Day 3 :
Keynote Forum
Philippa D. Darbre
University of Reading, UK
Keynote: Role of environmental chemicals in the development of breast cancer
Time : 9.00 - 9.25
Biography:
Philippa Darbre is an academic scientist with a BSc Hons degree in Biochemistry (University of Birmingham) and a PhD degree (University of Cambridge). Herrnpostdoctoral research began at the Molecular Medicine Institute of the University of Oxford, and continued at the Cancer Research-UK laboratories in Londonrnwhere she became Head of the Cellular Endocrinology Laboratory. In 1991, she moved to the University of Reading where she is currently Associate Professor inrnOncology and has a research laboratory dedicated to studying the mechanisms by which oestrogens and environmental oestrogenic chemicals regulate growth ofrnhuman breast cancer cells.
Abstract:
This lecture will discuss the potential for combinations of low doses of environmental chemicals to act over the long term tornenable the hallmarks of cancer to develop in breast cells. It is not necessary for each chemical to impact on every hallmarkrnbut if a mixture of environmental chemicals can act together to impact on all the hallmarks, and to do so at concentrationsrnmeasurable in human breast tissues, then there is the potential for breast cancer development. Such chemicals may actrntogether through similar mechanisms or through complementary mechanisms. In view of the established role of oestrogenrnas a risk factor for breast cancer, there is a potential for environmental compounds which possess oestrogenic activity andrnwhich are measurable in the human breast to contribute to the development of multiple hallmarks of breast cancer. However,rnenvironmental compounds with genotoxic activity may contribute to genomic instability. Human exposure may be throughrnoccupational activities, diet, the indoor environment and personal care products, including cosmetics, and the range ofrnenvironmental chemicals now measureable in the human breast will be discussed. Specifically, evidence will be presented thatrnexposure to parabens and aluminium can have adverse effects on human breast epithelial cells at concentrations measured inrnsome human breast tissue samples. If exposure to complex mixtures of oestrogenic and/or genotoxic compounds in consumerrnproducts is a factor in breast cancer development, then a strategy for breast cancer prevention would be to minimise exposure.
Keynote Forum
Sidharth Sahni
Breast Surgeon
Indraprastha Apollo Hospital
India
Keynote: CHANGING PARDIGMS IN BREAST SURGERY
Time : 09:20 - 09:40
Biography:
Dr Sahni trained at the Edinburgh Breast Unit and the European Institute of Oncology, Milan. Dr.Sahni is a certified tutor at the Royal College of Surgeons Edinburgh. He is the specialist breast surgeon to the Embassy of the United States of America, Russia, Italy, Israel, Germany & The Australian High Commission. He is currently --Senior Consultant Breast Surgeon at the Indraprastha Apollo Hospital, New Delhi. Dr Sahni was appointed as an Auditor in the governing council of the S.I.S for the period of 2008-9. Dr Sahni is on the board of directors of EURAMA, as South Asian office President. Dr Sahni is on the editorial board of eCancer Medical Journal.
Abstract:
The saga of Breast Conservation, started by Umberto Veronesi in 1968 (QUART) and then ratified by NSABP-06,has changed over the decades not only the paradigm of managing early breast cancer but also recruited conservative treatments of the axilla and a quick and minimalistic approach to radiotherapy. Various new indications for conservation including multifocality and centricity as well as the development of Oncoplastic surgery is changing many concepts. The experience in Netherlands with multifocal and multicentric disease may well cause another shift in paradigm of disease management.The European Academy for Breast Surgery has now come forth with 6 established Oncoplastic techniques which are simple and allow adequate margins on resection as well as ensuring good cosmetic outcome. Sentinel Node biopsy, a currently established approach in a clinically negative axilla in early breast cancer is exploring new boundaries in the setting of neoadjuvant chemotherapy as well albeit so far with mixed results.However a recent study by Milan has thrown up interesting observations in the way results are and should be interpreted for “false negativity†in these patients. The latest data from the intraoperative trials (TARGIT & ELIOT) are extremely encouraging and have increased the scope of conservation as well as reducing costs and morbidity associated with other forms of radiation.
- Innovative Therapeutic Apporaches in Breast Cancer and Problem Areas
Session Introduction
Peter Weightman
University of Liverpool, UK
Title: A new approach to the diagnosis of cervical, oesophageal and prostate cancer based on a combination of infrared and terahertz techniques
Biography:
Professor Weightman is an experimental physicist with a track record in developing novel instruments. He was a co-applicant on the proposal to construct the ALICE machine which is an energy recovery linear accelerator, the first of its kind in Europe and the only one in the world equipped with a terahertz beamline designed for studies of cancer. ALICE is now operational and Weightman is leading a collaborative programme involving academic scientists and clinicians in exploiting the potential of ALICE for cancer research.
Abstract:
This lecture will describe a recently funded program [1] designed to advance the diagnosis of cervical, oesophageal and prostate cancers through the application of infrared, Raman and terahertz techniques. The programme will also clarify the potential of these techniques for the characterisation of cancerous tissue since conventional approaches appear to have reached the limit of their predictivity and none of these promising techniques have reached the stage of clinical trials. A key role is played by the 4th generation light source, ALICE [2], at the Daresbury laboratory in the UK that has unique capabilities for research in this field. Research using the infrared free electron laser driven by ALICE has already lead to a novel technique with the potential to diagnose adenocarcinoma from tissue extracted by endoscopy from patients with the precursor condition Barretts oesophagus [3]. The programme will also progress the development of two portable terahertz instruments, of novel design, with the potential for use in cancer diagnosis and explore the use of terahertz radiation as a new therapy for cancer. 1 http://gow.epsrc.ac.uk/NGBOViewGrant.aspx?GrantRef=EP/K023349/1 2 http://www.youtube.com/watch?v=d7Lbyuqor8A 3 Smith. et. al. App. Phys. Lett. 102 053701 (2013)
Lei Huo
The University of Texas MD Anderson Cancer Center, USA
Title: Diagnostic biomarkers in metastatic breast cancer
Biography:
Lei Huo received her Bachelor of Medicine degree at Beijing Medical University and her PhD in Molecular Biology and Genetics at Northwestern University, Chicago. A practicing breast pathologist in MD Anderson Cancer Center, she is actively involved in clinical and translational research in the field of breast cancer. Her research interests include molecular and immunohistochemical markers in the diagnosis and treatment of breast cancer, among others.
Abstract:
In patients with a history of breast cancer, determining the tissue origin of a tumor in another organ site is important due to its implication for clinical treatment. Conversely, the breast is an infrequent site of metastasis for tumors from other organs. Tissue-specific immunohistochemical biomarkers are helpful ancillary tools for the diagnosis of tissue origin. Traditionally used keratins have relatively site-specific expression profiles. More recently applied biomarkers such as WT-1 and PAX8 in ovarian carcinomas, TTF-1 and napsin A in lung carcinoma and CDX-2 in colon carcinoma provide additional utility when these sites are included in the differential diagnosis. Estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, which are routinely performed on invasive breast cancers as prognostic/predictive markers, can also serve as breast-specific markers in some clinical settings. However, in approximately 15% of breast carcinomas, these three markers are negative (triple-negative breast cancer); therefore other breast-specific markers may be needed. Gross cystic disease fluid protein-15, mammaglobin, and most recently, GATA-binding protein 3 are the best biomarkers to date that are associated with breast when a clinical question of tissue origin arises. While GATA-3 appears the most sensitive marker in this regard, a panel of markers should be performed to increase the diagnostic accuracy.
Jamal Zekri
Al-Faisal University, Saudi Arabia
Title: Management of skeletal health in patients with early breast cancer starting aromatase inhibitors
Biography:
Jamal Zekri has received his higher medical oncology training in Weston Park Hospital (Sheffield, England). He practiced as a consultant medical oncologist at Clatterbridge Centre for Oncology (Merseyside, England) until April 2008. Currently, he is an associate professor at Al Faisal University and the head of medical oncology services at King Faisal Specialist Hospital & Research Centre (Jeddah, Saudi Arabia). He has published more than 50 papers in peer reviewed journals and presented more than 30 abstracts of original research wok at international conferences.
Abstract:
Introduction: Adjuvant Aromatase Inhibitors (AIs) predispose breast cancer patients to accelerated bone loss. Consensus guidelines recommend screening and follow of bone mineral density (BMD) with dual energy X-ray absorptiometry (DEXA) scan in this setting. In this study we assessed the rate of adherence to these guidelines and introduced awareness measures to improve it. Methods: We conducted a single centre, retrospective study in patients who started adjuvant AIs for invasive breast cancer. As per World Health Organization criteria, normal BMD, osteopenia and osteoporosis were defined as T scores of >-1, -1 to >-2.5, and ≤-2.5 respectively. In addition, we measured the frequency of therapeutic intervention at T score cut-off of <-2 as recommended by most guidelines. Subsequently, 4 awareness sessions were conducted to encourage physicians to request a base line DEXA scan for new patients starting adjuvant AIs. The practice was re-audited 5 months later. Results: 554 women with early breast cancer on adjuvant hormonal therapy were identified. 367 of these patients were on AIs and are the subject of this report. Baseline DEXA scan was performed in 188 (51.2%) patients. Of these, 24 (12.8%) had normal BMD, 106 (56.4%) had osteopenia and 58 (30.8%) had osteoporosis. Therapeutic bisphosphonates were administered to 83 (78.3%) osteopenic and 41 (70.7%) osteoporotic patients. 89 patients had T score <-2, of whom 67(75.3%) received bisphosphonates. 40 out of these 89 (44.9%) had follow up DEXA scans.Twenty two new patients started AIs within the 5 months after the awareness sessions. All 22 (100%) had a DEXA scan requested Conclusion: This study of a sizable cohort adds to limited previous observations that adherence to skeletal health guidelines in this patient population is less than adequate. Adherence is improved dramatically by raising the awareness of relevant physicians.
Federico Cattin
Udine University School of Medicine, Italy
Title: Breast cancer: A comparison among different diagnostic and therapeutic protocols
Biography:
Federico Cattin has completed his graduation at the age of 25 in the Udine University, and post-graduate studies in the Surgical Department of the same University. He is engaged in the studies about breast cancer and has attended a scholarship in the European Institute of Oncology (IEO) in Milan, held by Prof. Umberto Veronesi. He has published 13 papers in reputed journals. Nowadays he works in the Sterzing General hospital in South Tyrol, in Italy.
Abstract:
Objectives: In breast cancer therapy diagnostic and therapeutic pathways may differ among different centres. The pathway chosen in our Department includes a stadiation through magnetic resonance imaging (MRI) for all the patients and the sentinel node biopsy (SNB) analysis made through an extemporaneous exam. This, even if more expensive at the beginning, allows in some cases to avoid further interventions. Aim of the study is the cost analysis of three different pathways. Methods: We studied the patients who underwent surgery for breast cancer in our department in the last 5 years (2006-2010); analyzed variables are: execution of MRI, kind and duration of surgery, duration of hospitalization. In case of mismatch MRI/ basic exams (mammography, ultrasonography) or positive SNB, we indicated the necessary second surgery or the axillary lymphadenectomy. We considered the costs of any single procedure and then their sum, hypothesizing then the application of other different pathways to the same group of patients, calculating each one’s cost. Results: 767 Patients, 489 quadrantectomies (63.7%) and 278 mastectomies (36.3%). Positive SNB in 90/559 cases (16.1%). Therapy modification after MRI happened in 63 cases (10.1% of 619 MRI). A single MRI costs 323€, hospitalization 570€/day. Operatory room cost/minute is 9.4€/quadrantectomy, 8.9€/mastectomy. SNB biopsy cost is 112€ if extemporaneous, 107€ if deferred. Surgery made for mistakes due to the absence of MRI exam costs 5394€, postponed axillary lymphadenectomy costs 4081€. The whole cost was 3.825.890€ for our pathway, 3.973.722€ for the one without MRI in every case, 4.339.588€ for the one without MRI in every case and without extemporaneous analysis of SN. Conclusions: Data considering avoided interventions and economic assessments show how, through a better organization, it is possible the objective to improve quality of health care and to cut down on costs.
Arghya Adhikary
University of Calcutta, India
Title: PEGylated-thymoquinone-nanoparticle mediated retardation of breast cancer cell migration by deregulation of cytoskeletal actin polymerization through miR-34a
Biography:
Arghya Adhikary has completed his PhD from Bose Institute and Postdoctoral studies from same institute. He is now DST INSPIRE Faculty, Assistant Professor at Centre for Research in Nanoscience and Nanotechnology, University of Calcutta. He has published more than 25 papers in reputed journals related to Cancer cell signaling, majorly on breast cancers and has been working on Nano-Bio interphase for the last two years. His research area is focused on the synthesis of biocompatible nanoparticles of different plant polyphenols to be used for cancer nanotherapeutics.
Abstract:
Thymoquinone (TQ), a major active constituent of black seeds of Nigella sativa, has potential medical applications including spectrum of therapeutic properties against different cancers. However, little is known about their effect on breast cancer cell migration, which is the cause of over 90% of deaths worldwide. Herein, we have synthesized TQ-encapsulated nanoparticles using biodegradable, hydrophilic polymers like polyvinylpyrrolidone (PVP) and polyethyleneglycol (PEG) to overcome TQ’s poor aqueous solubility, thermal and light sensitivity as well as consequently, minimal systemic bioavailability which can greatly improve the cancer treatment efficiency. Synthesized TQ-NPs were physico-chemically characterized by UV-Vis spectroscopy, DLS, zeta potential analyzer, FT-IR spectroscopy, XRD, FESEM, TEM, H1-NMR and TGA. Sizes of synthesized TQ-Nps were found to be below 50 nm and they were mostly spherical in shape with smooth surface texture. In the present investigation, we provide direct evidence that TQ-Nps showed more efficiency in killing cancer cells (MCF-7, HBL-100) as well as proved to be less toxic to normal cells at a significantly lower dose than TQ. Interestingly, evaluation of the anti-migratory effect of the TQ-Nps, revealed that PEG4000-TQ-Nps showed much potent anti-migratory properties than the other types. Further studies indicated that PEG4000-TQ-Nps could significantly increase the expression of miR-34a through p53. Moreover, NPs mediated miR-34a up-regulation directly down-regulated Rac1 expression followed by actin depolymerisation thereby disrupting the actin cytoskeleton which leads to significant reduction in the lamellipodia and filopodia formation on cell surfaces thus retarding cell migration. Considering the biodegradability, non-toxicity and effectivity of PEG4000-TQ-Nps against cancer cell migration, TQ-Nps may provide new insights into specific therapeutic approach for cancer treatment.
Saif Uddin Ahmed
BSM Medical University, Bangladesh
Title: Breast Cancer: Presentation & limitation oftreatment - Bangladesh perspective
Biography:
Saif Uddin Ahmedgraduated from Sylhet Medical College, Chittagong University, Bangladesh and Underwent Residency training at IPGMR, Dhaka. He is obtained fellowship from Bangladesh College of Physicians of Surgeons (BCPS), Dhaka. He is now Professor of Surgical Oncology, BSM Medical University, the only Medical University of the country. He has published 38 scientific papers and now appointed as focal point for Breast Cancer Screening Program at national level in Bangladesh funded by Government of Bangladesh and UNFPA.
Abstract:
In Bangladesh, 160 million people about half are female, 25% illiterate, 31% below poverty level and 45% female become illiterate. A breast lump when first identify already attains a big size. After identification of a lump often treated by hot compression, homeopath, and herbal medicine such as “Neempata†and lime. Large group presented with nipple discharge, nipple retraction, with axillary & supraclavicular lump, fumigating mass, with treated by local doctors keeping the cancer ignored. In tribal population, the ‘Chakma’ people there is tradition of application of hot water & iron. When they finally reach health care centre, they are diagnosed as breast cancer. The `Monipuri’ people do not consider a lump to be significant unless they are big. We are treating a huge number of breast cancers amidst many limitations within our capacity. Our patients do not come to early due to lack of awareness. They fail to understand the gravity and importance of the situation. When our patients are confused where to go. They shuttle between a surgeon, oncologist, gynecologist, general practitioner and also for a female doctor who are available nearer to their home.After Surgery, usual problems are fear of side effects of chemotherapy; inadequate post-operative radiotherapy facilities and improper post-operative follow up. Patients failed to avail timely treatment or discontinue treatment due to political turmoil, road blockage, strikes and natural calamities.There is no national management protocol and screening program of breast cancer in Bangladesh, Screening program and mass awareness is essential to overcome our social- religious bindings.
Fabienne Meier-Abt
University Hospital of Basel, Switzerland
Title: Mechanisms of Early Pregnancy-Mediated Breast Cancer Protection
Biography:
Fabienne Meier-Abt completed her MD at Yale University School of Medicine, New Haven, USA, and her PhD in experimental oncology at the Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. She is now working clinically in the Department of Internal Medicine at the University Hospital of Basel, Switzerland. Her scientific interests continue to be focused on translational cancer and stem cell research.
Abstract:
Pregnancy at early, but not late age, has a substantial and life-long protective effect againstbreast cancer. The expected overall increase in breast cancer incidence in the coming yearsdemands the development of strategies to mimic early-age pregnancymediated protection.Recently, converging results on molecular and cellular mechanisms underlying the protectiveeffect of early-age pregnancy were reported in rodent models and women. In particular, earlyparity induces differentiation and downregulates the Wnt/Notch signaling ratio and the in vitro and in vivo proliferation potential of basal stem/progenitor cells in mice. These early parityinducedchanges of gene expression and dynamics of mammary stem/progenitor cells werecaused primarily by a decrease in the proportion of hormone-sensitive and Wnt4-secretingluminal epithelial cells. Furthermore, they were of life-long duration and absent upon latepregnancy. Similar findings were made in humans confirming that decreased hormone- andWnt4-mediated Wnt signaling in mammary stem/progenitor cells plays a key role in theprotective effect of early-age pregnancy against breast cancer. However, in addition to decreased Wnt signaling, increased cellular quiescence induced by TGFβ signaling might also be involved in the breast cancer-protective effect of early pregnancy in humans. These congruent andcomplementary findings in mouse and human mammary epithelial stem/progenitor cells provide promising initial targets for translational studies directed toward the development ofpharmacological breast cancer prevention strategies.
K Ludwig
Tameside General Hospital, UK
Title: Targeting microtentacles on circulating breast tumor cells to reduce metastasis.
Biography:
My name is Katherine Ludwig, I graduate from Dundee Medical School in June 2014. I am currently an FY2 at Tameside General Hospital. During my foundation year 1 I undertook placements in gastroenterology, breast surgery and old age psychiatry. I hope to pursue a career in general surgery with an interest in breast surgery.
Abstract:
Background: After diagnosis with a breast tumor most patients can be offered breast conserving surgery by performing a wide local excision (WLE) rather than a mastectomy. This provides better breast cosmesis while maintaining the survival rates of a mastectomy. On reviewing the histology NICE guidelines suggest that if resection margins are less than 2mm that re-excision should take place after discussing the risks and benefits with the patient. Aims: This audit was undertaken in order to compare the WLE re-operation rates at a district general hospital with the national and global averages. Methods: Anonymous data was collected from patients who required re-excision after a WLE between 1st April 2012 and 21st August 2013. Data was collected anonymously from clinical, histology and radiology letters. Results:A total of 77 patients underwent WLE. 18% of which went on to have further operation, either a repeat WLE or mastectomy. 11 patients were found to have larger tumors on histology than initially suggested on radiography. Conclusion: Re-excision rate was 18%, with 54% of those going on to have a mastectomy. Wide local excision rate was 10.3%. Nearly all patients who underwent re-excision had the size of their tumor underestimated on radiology. With a large cohort study quoting a 20% re-excision rate this audit suggests that Tameside General Hospital is performing similarly with many other NHS trusts.
Shareef Alqahtani
Johns Hopkins Bloomberg School of Public Health, USA
Title: Illitracy and Breast Cancer Screening Utilization: A Case Study of Saudi Women over 60 Years of Age
Biography:
Shareef is a MBBS, MPH and a global surgery advocate. He completed two years of residency in general surgery before taking last year off to peruse a Master of Public Health (MPH) from Johns Hopkins University, concentrating in epidemiology and health care managment. Since June 2014 he is working as a research assistant at the Center of Surgical Trials and Outcomes Research (CSTOR) where he became interested in cancer epideiology and quality improvement in developing countries. His leadership experience includes serving as a Public Health Coalition Events Coordinator and Middle East Society Outreach coordinator at the School of Public Health (JHSPH). Shareef co-authored multiple research manuscripts primarily in the fields of cancer epidemiology and awareness in low and middle income countries.
Abstract:
Objective: Illiteracy is common among Saudi women over 60 years of age. The aim of this study was to evaluate whether illiteracy has an impact on breast cancer screening utilization among Saudi women over 60 years of age. Methods: Analysis was performed for women who were involved in The Health Care of The Saudi Elderly National Study which undertaken between 2012-2013. We compared the levels of breast cancer screening utilization between illiterate and non-illiterate women over 60 years of age. Logistic regression (multivariate and univarite) and adjusted probability were calculated. Results: Of 2183 women involved in the analysis, 1751 were illiterate and 432 were not illiterate, majority were between of 60 to 65 years (41%). Results of the multivariate logistic regression model showed a statistical significant effect of illiteracy on the utilization of breast cancer screening (OR=0.54, 95% CI: 0.30- 0.97, p= 0.038). According to our analysis, the adjusted probability of Saudi women over 60 years of age to get clinical breast examination and mammography is 0.08 for the illiterate and 0.37 for not illiterate women. Conclusion: Illiteracy among Saudi women over 60 years of age may contribute considerably to the low level of breast cancer screening utilization. These findings could help guide effective interventions and an attention to the needs of this cohort of the Saudi society.
Diaz-Rodriguez Lourdes
University of Granada, Spain
Title: Heart rate variability and the use of complementary therapies in breast cancer survivors
Biography:
DÃaz RodrÃguez is Nurse and has completed her PhD at the age of 30 years from University of Granada. She is a lecturer in the Department of Nursing of the Faculty of Health Sciences from 2007. She has published 40 papers in reputed journals and has been serving as a reviewer of different journals.
Abstract:
The same aggressive treatments that have led to a reduction in the breast cancer may also have adverse effects on cardiac autonomic balance. The cardiotoxic effects of oncologic treatments may affect vagal activity and therefore influence cardiac autonomic balance. There appears to be a bidirectional relationship between autonomic imbalance and cancer. Heart rate variability (HRV) is an important non-invasive index of vagal-nerve response and a potential stress marker. It may also be a useful test for autonomic imbalance.The index represents the time differences between beat-to-beat intervals, synonymous with RR variability. Research has shown that coadjuvant cancer treatments reduce HRV values after surgery, radiotherapy and chemotherapy. We have observed the presence of a cardiovascular imbalance in a descriptive case-controlled study with 22 breast cancer survivors during the first year post treatment in comparison to 22 healthy age-matched controls, evidenced by a higher resting heart rate and lower values for HRV time domains (SDNN, RMSSD, HRV index) and the high band (HF) of the HRV frequency domain. If further study confirms that HRV is a clinically useful tool to detect cardiovascular disease and predict prognosis in early-stage breast cancer survivors, various nonpharmacological therapies that improve altered cardiovascular balance may then be available for use among these patients. These therapies include manual therapy, reiki, physical exercise, relaxation exercises (e.g., guided imagery), meditation, yoga and controlled breathing.
Inge Verbrugge
The Netherlands Cancer Institute, The Netherlands
Title: Radio-immunotherapy of cancer: Therapeutic efficacy, underlying mechanisms and potential applications
Biography:
Inge Verbrugge is an Associate Staff Scientist, at The Netherlands Cancer Institute in Amsterdam. Her primary research interest is in understanding and exploiting potential synergy between localized radiotherapy and immune-modulatory antibodies (‘radio-immunotherapy’) in cancer treatment. She received her PhD from the University of Amsterdam in 2009 and was subsequently awarded two prestigious Fellowships (Dutch Cancer Society Post-Doctoral fellowship and ‘Bas Mulder Award’) to study the anti-cancer potential of radio-immunotherapy. This work was initiated at the Peter MacCallum Cancer Centre in Melbourne, Australia and continued at the Netherlands Cancer Institute. She published 14 papers as first or second author in reputed journals.
Abstract:
Radiotherapy is one of the most successful cancer therapies but may benefit from coincident or subsequent immunotherapy. We designed novel combinations of radiotherapy with immunomodulatory monoclonal antibodies (mAbs) that were evaluated in pre-clinical mouse breast cancer models. We demonstrate that in combination with both single-dose and fractionated radiotherapy, mAbs designed to enhance T-cell function [anti-(α)-CD137] and relieve immunosuppression through blocking T-cell inhibitory signaling [α-programmed death (PD)-1] induce tumor regression in up to 100% of mice. Radio-immunotherapy induced immunological memory in cured mice and CD8+ T-cells were critical for its therapeutic efficacy. Radiotherapy up regulates MHC class I (MHCI) expression on tumor cells, which may further support immune-mediated killing. We show that this involves mTOR activation by ionizing radiation by a still unresolved mechanism. Yet, mTOR is important as mTOR inhibition almost completely abrogated the therapeutic effect of radio-immunotherapy. We conclude that radio-immunotherapy effectively cures mice that bear established mammary tumors and that therapy response is critically dependent on the activity of cytotoxic T-lymphocytes as well as on mTOR signaling. We predict that other tumor types to which T-cells are present in the peripheral repertoire and in which radiotherapy is used as a primary course of treatment, will also respond to radio-immunotherapy.
- Biology of Breast Cancer
Chair
Shahla Masood
University of Florida College of Medicine-Jacksonville, USA
Co-Chair
Christopher Busby
Environmental Research SIA, Latvian Academy of Sciences, Latvia
Session Introduction
Christopher Busby
Environmental Research SIA, Latvian Academy of Sciences, Latvia
Title: The breast cancer epidemic: Evidence for a radiogenic cause
Biography:
Christopher Busby obtained a 1st class degree in Chemistry from London University and a PhD Chemical Physics from the University of Kent. He worked in the physical chemistry of molecular cell interactions for Welcome and began research in the biological effects of internal radionuclides in 1989. He was a member of two UK government committees on internal radiation and has published more than 30 research papers, many articles and three books on this issue. He is a reviewer for several journals on the issue of radiation and health. He was visiting Professor at the University of Ulster until his retirement and is currently Director of Environmental Research SIA, based in Riga, Latvia. He has been Scientific Secretary of the European Committee on Radiation Risk based in Brussels since 1998.
Abstract:
The marked increase in rates of breast cancer, together with the reduction in the age of onset of the disease which began in the 1980s, point to some environmental cause. An early analysis of cohort effects in breast cancer mortality in England and Wales was presented at the 1998 World Breast Cancer Conference in Ontario. Cohort effects suggest that the principal cause was exposure to radionuclides in atmospheric test fallout. This provided a basis for epidemiological studies of breast cancer mortality near three nuclear sites in England and Wales, the results of which are presented here. Using small area data supplied by the Office for National Statistics we found a statistically significant doubling of the risk of dying of breast cancer in census wards close to the offshore coastal sediment contaminated by routine releases from the Hinkley Point nuclear site in Somerset between 1994 and 2004. In a separate study using the same data source we found a significant doubling of breast cancer mortality in small area census wards adjacent to coastal sediment contaminated by releases from the Bradwell nuclear power station in Essex. A third study employed an epidemiological questionnaire approach to examine breast cancer incidence downwind of the nuclear power station at Trawsfynydd in Wales. Results showed a statistically significant 4-fold excess incidence in the ten years prior to the survey. Taken together and with other evidence these results support the belief that the increases in breast cancer seen in the last 30 years are principally radiogenic in origin.
Vicente Marco
Hospital Quirón Barcelona, Spain
Title: Changes in breast cancer pathology reports after second opinion
Biography:
Vicente Marco graduated from the University of Barcelona Medical School. He underwent residency training in Anatomic Pathology at the State University of New York, Buffalo, NY, USA. He is certified by The American Board of Pathology. Currently, he is Director of the Department of Anatomic Pathology at Hospital Quirón Barcelona, Barcelona Spain. He has published more than 25 papers in reputed journals and has been serving as an Editorial Board Member of Diagnostic Pathology.
Abstract:
A second opinion in breast cancer pathology reports may be requested when a patient is referred from another institution for treatment. This may uncover significant discrepancies that impact on patient management and prognosis. These discrepancies are related to the histologic diagnosis, the presence or absence of invasion in carcinomas, and the results of predictive factors of response (hormone receptors and HER2). A significant improvement in the concordance among pathologists in the assessment of breast cancer lesions can be achieved by careful histologic study, following standardized criteria and using high quality techniques. Also, complete and accurate clinical information is needed for pathological assessment.
San Ming Wang
University of Nebraska Medical Center, USA
Title: The unknown predisposition can lie deep in the family tree
Biography:
San Ming Wang completed his graduate training from Swiss Institute for Experimental Cancer Research, and Postdoctoral studies from Northwestern University and University of Chicago. He is an Associate Professor in UNMC, specializing in cancer genetics and genomics. He has published over 60 papers in reputed journals.
Abstract:
Genetic predisposition is the primary risk factor for hereditary breast cancer. For the majority of familial breast cancer, however, the genetic predispositions remain unknown. Currently, detection of the unknown predispositions is largely through screening large numbers of pooled individual cases, and the newly identified predispositions occur in disease population. Considering that family unit is the basic structure of genetics and hereditary breast cancer is an autosomal dominant disease, the disease family must carry the same genetic predisposition across generations. Therefore, focusing on the cases in lineages of familial breast cancer, rather than pooled, genetically-unrelated cases in disease population, is expected to provide high probability to identify the genetic predisposition for each family. We tested this concept by studying the family-specific variants in hereditary breast cancer families. We used exome sequencing to analyze three disease families and 22 probands with BRCAx (BRCA-negative) hereditary breast cancer. We observed the presence of family-specific, novel, deleterious germline variants in each family. Certain variants are putative deleterious genetic predispositions damaging functionally important genes involved in DNA replication and damaging repair, tumor suppression, signal transduction, and phosphorylation. Our study demonstrates that the unknown predispositions for many BRCAx hereditary breast cancer families can lie in each disease family. The application of a family-focused approach has the potential to detect those unknown predispositions.
Biography:
Gaspar Banfalvi studied pharmacy and received doctorate in Szeged (1972), spent two years at the Institute for Drug Research (Budapest, 1972-1974). He obtained degrees (CSc, DSc, Med. Habil.) at the Department of Medical Chemistry, Budapest and Habil. Biol. at University of Szeged. He took a biology chair at University of Debrecen (2000 - 2005). Teaching obligations: chemistry, biochemistry, cell biology, genetics, physiology. Longer visits: > 4 years Boston, 5 months Leiden, 6 mo NCTR, 8 mo Weizmann Institute. Research interest: DNA structure and function, genotoxicity, metastasis.
Abstract:
Abdominal organs (liver, kidney, spleen) are frequent targets of cancer cell invasion, but less known for their metastatic potential to other organs (e.g. breast). In spite of the possible connection between the pathogenesis of liver and breast cancers the study of this relationship was neglected. The spread of abdominal tumors to internal mammary lymph nodes has not been reviewed earlier. The idea of breast cancer being a metastasis rather than a primary btumor is based on the metastatic spread of rat tumor cells released by abdominal primary tumors (He/De, Ne/De) and leukemia (My1/De, My2/De) cells. The metastatic process starts with the peripheral disruptions of primary tumors. Tumor cells released into the abdomen cross the apertures of the diaphragm and enter the thoracal lymph nodes. Tumor cells accumulate in parathymic lymph nodes. Abdominal colloidal carbon particles faithfully mimic the migration of tumor cells and deposit in parathymic lymph nodes. Explanation is provided why the connection between abdominal tumors and mammary tumors escaped attention, notably rodent parathymic lymph nodes in humans were referred to as internal mammary or parasternal lymph nodes. These developments will impact future breast cancer diagnosis and therapy.
Tibor Tot
European Society of Pathology Sweden
Title: Multiparameter characterization of breast carcinoma: subgross, microscopy, proteins, and genes
Biography:
Tibor Tot, associate professor of pathology at the University of Uppsala and head of Laboratory Medicine Dalarna, Sweden, is faculty member of the breast pathology arm of the European School of Pathology (ESP), and scientific director in the European School of Oncology Certificate of Competence in Breast Cancer program. Publications: 6 textbooks, 20 book chapters, and 80 journal articles mostly on radiological – pathological correlation of breast diseases. He is repeatedly invited speaker on international congresses, member of the European Working Group for Breast Cancer Screening Pathology and past chair of the Working Group for Breast Pathology of the ESP.
Abstract:
The morphology of breast carcinoma is often very complex. Tumor characteristics which are detectable at the low resolution level of radiology and those detectable only with high resolution of microscopy or even higher resolution of gene sequencing are seemingly very different, but a close relationship between them can be evidenced. As the subgross morphological parameters and molecular phenotypes have been studied separately, this relationship has not received the attention it deserves. Tumor size, lesion distribution, disease extent, and intratumoral and intertumoral heterogeneity are subgross morphological parameters of breast carcinomas that are essential for proper diagnostic characterization of the disease. If assessed adequately by modern multimodality radiology and large-format histopathology, these parameters individually provide significant prognostic information. The molecular phenotype categories for breast carcinomas were recently defined and their prognostic and predictive power is determined. Luminal A tumors are often small and stellate (star-like) at radiology and rarely associated with calcifications. Luminal B, basal-like and triple negative cancers are most often round/oval and are significantly larger at average at the time of detection compared to Luminal A tumors. HER2 expressing tumors are more often multifocal and associated with a high-grade in situ component (casting type microcalcifications) than cancers with other molecular phenotypes. Diffuse invasive carcinomas are rare but have an unfavorable prognosis, despite having luminal phenotype. The interrelation of subgross, microscopic and molecular parameters indicate the necessity of multiparameter characterization of breast carcinomas for proper diagnosis and therapy.
Werner Boecker
University of Münster, and Hamburg, Germany
Title: Syringomatous tumour of the nipple and low-grade adenosquamous carcinoma: Evidence for a common origin
Biography:
Werner Boecker completed his dissertation at the age of 25 years at the Intitute of Pathology, University of Hamburg where he studied pathology under his teacher Gerhard Seifert. At the age of 34 he was appointed as Professor at the same institution. In 1997 he was appointed as Director and Professor of the Gerhard-Domagk-Institute of the University of Muenster. He has published more than 200 papers in reputed journals, has been serving as an editorial board member and published the books â€Breast Preneoplasia: A New conceptual approach†and the German Book “Pathologieâ€. .
Abstract:
Syringomatous tumour of the nipple and low-grade adenosquamous carcinoma (LGAdSC) of the breast are regarded as distinct entities. To clear the nature of these two lesions, we compared the expression of different lineage/differentiation markers in 12 syringomatous tumours of the nipple, 10 syringomas of skin and 9 LGAdSC, and normal breast epithelium. Using triple immunofluorescence labelling and quantitative RT-PCR studies for different keratins, p63 and SMA, we demonstrated that syringomatous tumour of the nipple and LGAdSC are identical or nearly identical lesions. Both contain p63+/K5/K14+ tumour progenitors from which, based on the sequential expression of these markers, K10+ squamous and K8/18+glandular lineage arise. In contrast , syringoma of skin does not express K8/18. Identical p63+/K5/14+ cells were also found in the normal breast duct epithelium. Based on our findings, we suggest that physiological p63+/K5/14+ counterparts of the normal breast duct epithelium or early related cells might play a key role in neoplastic transformation of both syringomatous tumour and LGAdSC. We propose that the differentiation patterns found in both lesions reflect the early ontogenetic stages of the normal breast epithelium.
Elena Bonanno
University of Rome Tor Vergata, Italy
Title: Microcalcification as an active phenomenon mediated by epithelial cells with mesenchymal characteristics
Biography:
Elena Bonanno, MD, PhD; (medical school degree in 1984; PhD degree in 1990) aggregate professor of pathology at University of Rome Tor Vergata, actually in charge of Cytopathology and breast pathology at Tor Vergata University Hospital. She published more than 80 scientific papers, 4 chapters in book. She actively participate to the Italian group of breast pathology study (GIPAM).
Abstract:
Mammary microcalcifications have a crucial role in breast cancer detection, but the processes that induce their formation are unknown. Moreover, recent studies have described the occurrence of the epithelial–mesenchymal transition (EMT) in breast cancer, but its role is not defined. Elemental analysis of microcalcifications by EDX revealed that the complex formation of calcium hydroxyapatite was strictly associated with malignant lesions whereas calcium-oxalate is mainly reported in benign lesions. Morphological studies demonstrated that epithelial cells with mesenchymal characteristics were significantly increased in infiltrating carcinomas with microcalcifications and in cells with ultrastructural features typical of osteoblasts close to microcalcifications. These data were strengthened by the rate of cells expressing molecules typically involved during physiological mineralization (i.e. BMP-2, OPN) that discriminated infiltrating carcinomas with microcalcifications from those without microcalcifications. Although the phenomenon of breast microcalcifications could be sustained by several mechanisms, the finding of osteoblast-like cells led us to hypothesize that microcalcifications in breast lesions could represent an active process related to epithelial to mesenchymal transition. New insights into the complex phenomenon of breast microcalcification could better define the pathophysiology of different microcalcifications. The introduction of mesenchymal markers such as vimentin and elemental analysis of breast lesions with microcalcifications may add further data to complete the clinical setting in the diagnosis and care of patients. The finding of a specific elemental composition associated with microcalcifications in cancer could enhance imaging technologies to discriminate microcalcifications in vivo, and thus act as a helpful tool in breast cancer screening.
Mieke Van Hemelrijck
King’s College London, London UK
Title: A role for lipids and statins in breast cancer risk and prevention?
Biography:
Following an MSc in Biomedical Sciences (2001-2005) and an MSc in Statistical Analysis (2005-2006) at Ghent University, Dr Van Hemelrijck obtained an MSc in Population & International Health at the Harvard School of Public Health (2006-2008). In 2010 she finished her PhD in Cancer Epidemiology at King’s College London. Her study findings, published in over 600 news articles to date, had a significant impact on the US Food and Drug Administration safety guidelines for commonly used prostate cancer drugs. In 2012, she was appointed as a Lecturer in Cancer Epidemiology at King’s College London, where she now runs the Cancer Epidemiology Group and has several PhD students working on breast cancer using data from Guy’s Hospital (London) and Uppsala University (Sweden).
Abstract:
Epidemiological evidence suggests a link between obesity and breast cancer. The lipid and glucose metabolisms have been postulated as possible intermediary mechanisms. Moreover, recent research suggests that statins, a group of drugs commonly prescribed to help lower serum cholesterol levels, may simultaneously reduce risk of fatal cancer. Here, we report on studies conducted based on several large Swedish cancer databases. Links between serum glucose and lipids and breast cancer severity at time of diagnosis were investigated in 35,017 women from the Swedish AMORIS cohort. Proportional odds models, with adjustment for interval time between serum measurement and diagnosis, were conducted. Despite the size and detail of the data in AMORIS, we only found a modest positive association between serum levels of glucose, apoB/ApoA-1 and BC severity, suggesting that these factors are not the main players in the link between obesity and BC aggressiveness. The effect of statins on cancer-specific death was assessed using two Swedish cancer databases. Marginal structural models based on inverse probability weights were applied to a pooled logistic regression model to estimate the causal effect of statins on cancer-specific death. These findings show that well-defined clinical trials are needed before the effect of a(ny) drug on cancer-specific mortality can be claimed, and observational research into drugs in relation to diseases other than their intended purpose should be interpreted cautiously. Despite increasing observations about a role for obesity in breast cancer carcinogenesis, more population-based studies and randomized clinical trials incorporating information on several factors of the lipid metabolism are needed to disentangle how targeting the lipid metabolism may fight breast cancer.
- Symposium on Immunotherapy of Breast Cancer
Session Introduction
Yvonne Paterson
University of Pennsylvania, USA
Title: HER-2/neu as a target forListeria-based cancer immunotherapy for breast cancer
Biography:
Yvone Paterson is Professor of Microbiology in the Perelman School of Medicine at the University of Pennsylvania, USA. As a Professor of Microbiology, Paterson is an active educator and trainer and is the PI of several training grants and programs. Her research is in the field of cancer vaccines where she was the first investigator to use Listeria monocytogenes, as a vector to target tumor-associated antigens to the immune system. She has pioneered the application of this organism in vaccine development for over 20 years.
Abstract:
We have been developing novel, live, highly attenuated bacterial vectors based on Listeria monocytogenes (Lm), bioengineered to secrete tumor-associated antigens and to present them to the immune system in a particularly immunogenic manner. The Lm vector itself, in addition to its major virulence factor listeriolysin O, (LLO), serves as its own adjuvant and is phagocytized by APC where it presents antigens through both MHC class I and II pathways, resulting in specific T-cell immunity to tumors. We have conducted extensive pre-clinical studies to determine the mechanism of action of Lm as an immunotherapeutic and its efficacy in numerous mouse models of cancer. Here we will describe the advancement of Lm-LLO immunotherapy into the clinic for HER-2/neu over expressing tumors, such as breast cancer. Lm-LLO-cHER-2/neu, is an Lm-LLO immunotherapy bioengineered to secrete a chimeric polypeptide consisting of three regions of HER-2/neu known to contain most human HLA epitopes. This polypeptide, comprising 419 residues, about one third of the intact HER-2/neu molecule was fused to a truncated form of LLO for expression by Lm. Lm-LLO-cHER-2/neu has proven to be effective at limiting tumor growth in pre-clinical mouse models of cancer.
Nicola Mason
University of Pennsylvania’s School of Veterinary Medicine, USA
Title: Pre-clinical studies evaluating the safety and efficacy of a recombinant Listeria expressing HER2/neu in dogs with spontaneous HER2+ bone cancer
Biography:
Nicola Mason is a graduate of the Royal Veterinary College, London and is board certified in Veterinary Internal Medicine. She earned her PhD in Immunology from the University of Pennsylvania where she performed her Post-doctoral fellowship in the laboratory of Dr. Carl June. She is an Associate Professor, the Pamela Cole Chair in Companion Animal Medicine and Associate Director of the Mari Lowe Center for Comparative Oncology in the University of Pennsylvania’s School of Veterinary Medicine. Her research focuses on developing immune therapeutic approaches to effectively target cancer and prevent metastatic disease in companion dogs, with the ultimate goal of identifying and accelerating successful therapies into the human and veterinary clinics. Her lab is currently focused on two main therapeutic strategies, recombinant listeria-based technologies and chimeric antigen receptor T cells (CAR-T) for canine osteosarcoma, lymphoma and hemangiosarcoma.
Abstract:
HER2/neu is a membrane bound receptor tyrosine kinase belonging to the erbB family. ErbB2 gene amplification and HER2/ neu over-expression is reported in 30-40% of patients with mammary carcinoma and serves as an important immune therapeutic target. HER2/neu is also expressed in 40% of pediatric osteosarcoma patients and we have found similar HER2 expression in pet dogs with spontaneous osteosarcoma (OSA). We have taken advantage of this naturally occurring spontaneous HER2+ tumor in dogs to evaluate the safety and efficacies of a recombinant Listeria expressing a chimeric human HER2/neu (Lm-LLO-cHuHer2) to generate potent HER2-specific T cell mediated immunity and prevent metastatic disease after standard of care amputation and chemotherapy. Administration of 3 doses of Lm-LLO-cHuHer2 at three-week intervals was found to be safe and effective at prolonging progression free survival and overall survival in dogs. Side effects that occurred were low grade and transient. IFN-γELISpot analysis revealed that Lm-LLO-cHuHer2 was able to break tolerance to HER2/neu supporting the hypothesis that HER2 specific T cell mediated immunity was preventing disease relapse. A second clinical trial was performed on dogs whose owners elected not to perform amputation or chemotherapy to determine the effects of combination radiotherapy and Lm-LLO-cHuHer2 immunotherapy on primary HER2+ appendicular OSA. Dogs received 16 Gyradiation, delivered as 2 fractions on consecutive days to the primary tumor site. Dogs then received a total of 8 doses of Lm-LLO-cHuHer2 administered intravenously at 3-week intervals and were then monitored for acute and chronic toxicities, primary tumor progression and development of metastatic disease. We found that repeat administrationsofLm-LLO-cHuHer2 were safe, broke tolerance to HER2/neu, delayed the progression of the primary tumor and delayed/prevented metastatic disease. In conclusion, we show that systemic administration ofLm-LLO-HER2/neuis well tolerated, breaks tolerance to HER2/neu, can prevent metastatic disease when administered in the setting of minimal residual disease, and can act synergistically with RT on HER2+ bone lesions to delay disease progression. These findings may have important translational relevance for human patients with HER2+ cancers such as mammary carcinoma.
Thomas Kieber-Emmons
University of Arkansas for Medical Sciences, USA
Title: Developing a first in man carbohydrate mimetic peptide vaccine for cancer: A translational story
Biography:
Thomas Kieber-Emmons, PhD is known for his work on developing peptide mimetics of carbohydrate antigens as vaccines in both the cancer and pathogen areas, and is an acknowledged pioneer in this field. He is Associate Director for Prevention Research at the Winthrop P. Rockefeller Cancer Institute and holds the Jossetta Wilkins Chair in Breast Cancer Research. His group has brought the first structurally designed carbohydrate mimetic peptide into the clinic for breast and other cancer types.
Abstract:
Tumor Associated Carbohydrate Antigens (TACAs) are pan-targets on tumor cells because they activate and regulate a network of signaling pathways associated with cell survival. Strategies that target TACAs, therefore, have potential benefit as cell-death therapies. In a dose escalation Phase I clinical trial, we analyzed the safety and immune response to a reverse engineeredCarbohydrate Mimetic Peptide (CMP), referred to as P10s, in 6 subjects with advanced breast cancer. P10s was developed as a pan-immunogen to induce responses to multiple TACAs with the intent being to induce antibodies that are proapoptotic. 16 women were consented, with 6 subjects receiving the CMP vaccine. 3 subjects completed the vaccination schedule at 300 μg P10s-PADRE per injection, and 3 completed immunizations at the 500 ug dose. Patients were evaluated for signs of toxicity during and after vaccination. All 6 subjects displayed a persistent IgG response to P10s after vaccination and induced serum and plasma antibodies displayed cross-reactivity to TACA expressing human breast cancer cell lines. Antibody induced by P10s in 5 of the 6 subjects displayed statistically significant apoptotic functionality to several human breast cancer cell lines, including a Trastuzumab-resistant one, and is caspase 3 dependent. Overall survival among the vaccinated subjects had a mean±SE (median) of 908±116 (928) days compared to 583±126 (312) days among the unvaccinated, consented subjects. P10s vaccination was well tolerated, with measurable immune responses and antitumor efficacy was noted.This is the first study to show that CMP vaccination is safe and can induce functional antibodies that potentially have therapeutic benefit in subjects immunized with this CMP-based vaccine.
Phillip K. Darcy
Cancer Immunology Program, Peter MacCallum Cancer Centre, Australia.
Title: Cancer immunotherapy utilizing gene-modified T cells: from the bench to the clinic.
Biography:
Phil is currently a NHMRC Senior Research Fellow and Group Leader at the Peter MacCallum Cancer Centre. His work has focused on developing novel T cell based immunotherapy approaches for cancer in preclinical mouse models and translating this into patients. His most recent studies have involved the development of combination immune based therapies which is showing tremendous promise. Phil has received project support from numerous national and international funding bodies to support his work and has published his work in premier cancer journals.
Abstract:
Adoptive immunotherapy involving genetic modification of T cells with chimeric antigen receptors (CAR’s) is a promising approach for treatment of cancer although has resulted in on target toxicity in some trials. To explore this more fully, we utilized a self-antigen mouse model that expresses human Her-2 as a self-antigen in brain and mammary tissue to assess the ability of T cells expressing an anti-Her-2 chimeric receptor to eradicate Her-2+ tumor. In adoptive transfer studies, we demonstrated significant improvement in the survival of mice bearing Her-2+ tumor following administration of anti-Her-2 T cells compared to control T cells. Importantly, anti-tumor effects were not associated with any autoimmune pathology in normal tissue expressing Her-2 antigen. The reduction in tumor growth correlated with localization of transferred T cells at the tumor site and an antigen-specific recall response could be induced in long term surviving mice following rechallenge with Her-2+ tumor. In further studies we have also utilized gene-engineered T cells in combination with other immune-based therapies such as anti-PD1 which resulted in significantly enhancing therapeutic effects in mice. We have recently completed a Phase I clinical trial in patients with acute myeloid leukaemia targeting the Lewis Y carbohydrate antigen and demonstrated that the therapy was well tolerated.
Paul A Beavis
Peter MacCallum Cancer Centre, Australia
Title: Adenosine receptor 2A blockade increases the efficacy of anti-PD-1 through enhanced anti-tumor T cell responses
Biography:
Paul A Beavis completed his PhD at Imperial College London, studying the biology of regulatory T cells in rheumatoid arthritis. He is currently a senior Post-Doc in Assoc. Prof. Phil Darcy’s Immunotherapy Group at the Peter MacCallum Cancer Centre. His current work is focused upon the application of combination immunotherapies and the use of chimeric antigen receptor transduced T cells to treat Breast Cancer. His work is already been published in PNAS, Trends in Immunology, OncoImmunology and the work presented in this meeting is currently under review at Cancer Immunology Research.
Abstract:
Immunotherapy is rapidly emerging as a cancer treatment with high potential. Recent clinical trials with anti-CTLA-4 and anti-PD-1/PDL-1 antibodies (mAbs) suggest that targeting multiple immunosuppressive pathways may significantly improve patient survival. The generation of adenosine by CD73 also suppresses anti-tumor immune responses through the activation of A2A receptors on T cells and NK cells. We have previously shown that blockade of A2A receptors can suppress tumour metastasis (1) and enhance responses to anthracycline therapy (2). Since A2A expression is enhanced on T cells following their activation, we hypothesised that A2A blockade would enhance the efficacy of anti-PD-1 mAb, an immunotherapy which acts through the liberation of anti-tumour immune responses. In the current study (3), we observed that the expression of CD73 by tumor cells limited the efficacy of anti-PD-1 mAb in two tumor models and that this was alleviated with concomitant treatment with an A2A adenosine receptor antagonist. The specificity of this effect for the A2A receptor was confirmed with the use of A2A knockout mice. The blockade of PD-1 enhanced A2A receptor expression on CD8+ tumour-infiltrating T cells, making them more susceptible to A2A mediated suppression. Thus, dual blockade of PD-1 and A2A significantly enhanced the expression of IFNγ and Granzyme B by tumor-infiltrating CD8+ T cells and accordingly, increased growth inhibition of CD73+ tumors and survival of mice. Moreover, A2A blockade was found to enhance the ability of PD-1 and TIM-3 to treat established 4T1.2 tumor metastases. Our study indicates that CD73 expression may constitute a potential biomarker for the efficacy of anti-PD-1 mAb in cancer patients and that the efficacy of anti-PD-1 mAb can be significantly enhanced by A2A antagonists. A2A antagonists, including SYN115 as utilized in our study, have undergone phase II trials for Parkinson\'s Disease and have been shown to be safe and well tolerated. Thus, this approach has high translational potential for the treatment of cancer patients.
Stefan B Eichmüller
German Cancer Research Center (DKFZ), Germany
Title: Identification of CD4+ T cell epitopes specific for the breast cancer associated antigen NY-BR-1
Biography:
Stefan B Eichmüller gained his PhD at the Free University of Berlin, where he continued his work as a Postdoc in the Dermatology Section of the Virchow Hospital Berlin. In 1997, he moved to the German Cancer Research Institute in Heidelberg, Germany, where he has been heading his own research group focusing on tumor-specific T cell immunology. Furthermore, he set up a GMP facility for the establishment of autologous immune cells as therapeutics, where he currently holds the positions as QP and head of QC. He has published more than 70 papers and is Editorial Board Member of several journals.
Abstract:
Adoptive transfer of autologous tumor antigen-specific T cells provides an innovative strategy for cancer immunotherapy. The differentiation antigen NY-BR-1 is over-expressed in approx. 60% of all invasive mammary carcinomas, thus representing a potential target for T cell based immunotherapy. As efficient immune attack of tumors depends on the activity of tumor antigen-specific CD4+ effector T cells, NY-BR-1 was screened for the presence of HLA-restricted CD4+ T cell epitopes that could be included in immunological treatment approaches. Splenocytes from HLA-transgenic (HLAtg) mice immunized with recombinant adenovirus (Ad.NY-BR-1) were screened ex vivo for specific activity against a NY-BR-1-derived peptide library. In silico predicted candidate epitopes present among recognized library peptides were used to establish murine CD4+ T cell lines whose HLA-restriction was determined in vitro on peptide loaded T2/DR3 and T2/DR4 target cells. Natural processing of these epitopes by human cells was proven upon specific recognition of human dendritic cells loaded with cell lysates from Ad5. NY-BR-1 infected melanoma cells through the established murine HLA-restricted CD4+ T cell lines. Importantly, reactive CD4+ T cells specific for the identified NY-BR-1-derived epitopes were detected among PBMC of HLA-matched breast cancer patients after long term in vitrorestimulation with synthetic 15mers by intracellular cytokine staining. Moreover, deep sequencing performed on the murine HLA-restricted CD4+ T cell lines established with the new epitopes identified two NY-BR-1-specific TCRs that could potentially serve tools for the generation of autologous TCR-transduced T cells lines for future NY-BR-1-specific adoptive immunotherapy approaches against breast cancer.
- Symposium on “Implementing recent advances in breast cancer diagnosis and treatment: The University of Tennessee Medical Center at Knoxville experience"
Session Introduction
Amila Orucevic
University of Tennessee Medical Center, USA
Title: Prognostic value of ER, PR, and HER2 breast cancer biomarkers and AJCC’s TNM staging system on overall survival of Caucasian females with breast cancer: An institution’s 10 year experience
Biography:
Amila Orucevic obtained MD degree from Medical School of University of Sarajevo, Bosnia and Herzegovina (1983) and PhD from The University of Western Ontario, London, Ontario, Canada (1996). She is a board certified pathologist for Anatomic and Clinical Pathology by The American Board of Pathology (2002), and board certified pathologist for Anatomic Pathology by The Royal College of Physicians and Surgeons of Canada (2002). Currently, she is Attending/Staff pathologist, Associate Professor, and Director of Research at the Department of Pathology, The University of Tennessee Medical Center, Knoxville, TN, USA. She published 21 papers in reputed peer reviewed journals.
Abstract:
The Breast Cancer Task Force and many recently published studies questioned relevance of AJCC’s TNM staging system in predicting outcomes in breast cancer because of the increasing understanding of prognostic impact of breast cancer biomarkers (ER/PR/HER2). Inclusion of biomarkers into the TNM system (bTNM) with goal of improving the TNM staging accuracy was suggested. We tested whether any of three recently proposed bTNM systems could improve the prognostic accuracy of breast cancer staging in our institution’s breast cancer patient population (>90% are Caucasians). 1253 Caucasian women diagnosed with primary invasive breast carcinoma from 1/1998-7/2008 entered our study. Breast cancers were grouped according to their TNM stage, or recently proposed bTNM systems: #1-bTNM-triple negative ER/PR/HER2 phenotype (TNP) vs. non-TNP; #2-bTNM ER status/grade/TNM stage; #3-bTNM-five-group ER/PR/HER2 subtype classification system recommended by St. Gallen International Consensus Panel in 2011.Overall survival (OS) was measured. TNM stage was significant predictors of OS in any bTNM used (#1-#3). In #1-bTNM, TNP significantly worsened prognosis/survival only in higher TNM stages (III&IV). In #2-bTNM, ER/grade and in #3-bTNM, five-group ER/PR/HER2 subtype classification had no significant impact on OS. Our data support the traditional TNM staging as a continued relevant predictive tool for breast cancer outcomes and show that biomarkers may improve the accuracy of TNM staging in advanced stages of breast cancer, but are dependent on classification system used. We propose systematic analyses of proposed bTNM ER/PR/HER2 classification systems in different study environments (both nationally and internationally) before biomarkers are fully incorporated into the TNM staging system (bTNM).
Daniel H. Snyder
The University of Tennessee Medical Center, USA
Title: Breast cancer in young age (≤40 years): The University of Tennessee Medical Center at Knoxville 10 year experience
Biography:
Dr. Daniel Snyder received his Bachelor of Science degree in Biology at Tennessee Technological University in Cookeville, TN in 2010, and earned his medical degree from Lincoln Memorial University-DeBusk College of Osteopathic Medicine in Harrogate, TN in 2014. Currently, Dr. Snyder is a PGY-1 resident in the Anatomic and Clinical Pathology Residency Program at the University of Tennessee Medical Center in Knoxville, Tennessee. His research interests include breast cancer, biomarkers, and patient outcomes.
Abstract:
Young age at diagnosis of breast carcinoma (BC), triple negative ER/PR/HER2 phenotype, and non-Caucasian race have all been reported to have a negative impact on patient outcome. We evaluated the prognostic value of ER/PR/HER2 subtypes, pathologic tumor characteristics, and TNM stage on overall survival (OS) of young Caucasian female patients (≤40y/o) with invasive BC from our institution over a 10 year period (1/1/1998-7/1/2008), and analyzed the type of therapy received (last follow-up day 8/1/2013). Eighty ≤40y/o patients (6.3% of study population) had complete ER/PR/HER2 data and were divided into five-ER/PR/HER2 groups per 2011 St. Gallen International Consensus Panel classification system. The effect of ER/PR/HER2 subtype on OS was measured using a Kaplan-Meier curve. A multivariate Cox regression was used when ER/PR/HER2 subtype was controlled for grade and TNM stage. 41% of patients were ER+/PR+/HER2- subtype, 31% ER+/PR+/HER2+ or ER-/PR-/HER2+, and 28% ER-/PR-/HER2-. The majority presented with grade 3 invasive BC (67.5%) and TNM stage II (50%). Only 17% had negative lymph nodes. 50% underwent modified radical mastectomy, 29% had breast conserving surgery, 46% had radiation, 82% received adjuvant chemotherapy and 80% of ER+ patients received hormonal therapy. Patients with ER+/PR+/HER2- subtype had significantly better OS than ER-/PR-/HER2- or ER+/PR+/HER2+ (p=.035) in a univariate analysis. However, when ER/PR/HER2 subtype was controlled for TNM stage and grade, only TNM stage was a significant predictor of OS (p<.001). These results are in concordance with our previously published data on the effects of ER/PR/HER2 on OS, and will be compared/contrasted to results from literature.
James M. McLoughlin
University of Tennessee Medical Center, USA
Title: The role of intraoperative fluoroscopy to improve negative margin resection of partial mastectomies: a single institution experience
Biography:
James McLoughlin earned his MD from Rush University in Chicago, IL and completed a general surgery residency at Baylor University Medical Center in Dallas, TX. He completed a surgical oncology fellowship at the H. Lee Moffitt Cancer in Tampa, FL. His practice is primarily focused on the care of breast cancer patients. His research interest is in improving clinical and surgical outcomes and identifying disparities in cancer outcomes.
Abstract:
The estimated positive margin rate for partial mastectomies for in situ or invasive breast cancer is between 15% - 24% though reported rates widely vary. In an attempt to decrease the positive margin rate for partial mastectomies, intraoperative fluoroscopy was added to the pre-incision operative planning as an additional tool to improve intraoperative accuracy. Beginning in January 2011 – December 2014, 220 women underwent a wire guided partial mastectomy with the pre-incision aid of intraoperative fluoroscopy. Surgical planning was based on the fluoroscopic images as well as the mammographic images taken post wire placement. All excised specimens were immediately evaluated with a specimen radiograph. Final margin status was assessed on permanent section. Positive margins were defined as tumor on ink. Close margins were considered negative if no tumor was seen on the inked margin. Margin status was compared to national rates as well as institutional rates prior to the addition of fluoroscopy. Despite vigorous fluoroscopic mapping, the overall positive margin rate did not decrease compared to the historic rates. It specifically had no impact on margins for DCIS or invasive lobular carcinoma. Overall, intraoperative fluoroscopy did not improve the negative margin rate compared to standard techniques for a partial mastectomy. The role for intraoperative fluoroscopy was most beneficial for planning surgery in difficult locations such as deep tumors in large breasts. It was also a useful teaching tool for junior residents learning three dimensional surgical planning. The role of intraoperative fluoroscopy should be determined on an individual patient basis.
Heather Gage
The University of Tennessee Medical Center, USA
Title: HER2+ breast cancer: Pre and post adjuvant anti-HER2 therapy era - the University of Tennessee Medical Center at Knoxville 11 year experience
Biography:
Dr. Heather Gage received a Bachelor of Arts degree in Physics from Bryn Mawr College, Pennsylvania in 2008, and received her medical degree from University College Cork, Ireland in 2013. Currently, Dr. Gage is a PGY 1 resident in the Anatomic and Clinical Pathology Residency Program at the University of Tennessee Medical Center in Knoxville, Tennessee. Research interests include breast cancer, biomarkers, and outcomes.
Abstract:
Large randomized trials have shown that adjuvant anti-HER2 therapy is efficient in reducing the risk of recurrence and improving the survival in patients with HER2+ breast cancer (BC). We evaluated whether the introduction of adjuvant anti-HER2 therapy for treatment of HER2+ BC patients in an academic institution settings outside of clinical trials had similar effect on overall survival (OS). Two-hundred-fifteen of 309 Caucasian females diagnosed with HER2+ invasive BC at our academic institution from 1998-2009 were studied. They were divided into 2 groups based on the time of diagnosis (before or after 11/2005, the start date of adjuvant anti-HER2 therapy administration as standard practice for operable HER2+ BC at our institution). Group 0 (G0) included 119 HER2+ patients diagnosed before 11/2005; Group 1 (G1) included 95 HER2+ patients diagnosed after 11/2005. Both groups were further subdivided based on ER/PR/HER2 subtype: G0 had 72 ER+/PR+/HER2+ and 48 ER-/PR-/HER2- patients. G1 had 56 ER+ PR+/HER2+ and 39 ER-/PR-/HER2+ patients. Ninety-four patients from G0 followed for >120 months were excluded from the study, to balance the G0 and G1 groups’ follow-up time. OS was measured by Kaplan-Meier curve. Although only 2/3 of G1 patients received anti-HER2 therapy, OS significantly improved (p<.003), largely due to an effect on the ER-/PR-/HER2+ group. This was also reflected in five-year survival (G0:ER-/PR-/HER2+=68.8%, G1:ER-/PR-/HER2+=84.6%; G0:ER+/PR+/HER2+=83.3%, G1:ER+/PR+/HER2+=85.7%). Our results are comparable to results from the clinical trials for anti-HER2 therapy in adjuvant settings. Similarities and differences will be discussed including the role of ER/PR positivity in HER2+ BC.
John L. Bell
University of Tennessee Graduate School of Medicine, USA
Title: Using USA guidelines and standards of breast cancer care in an academic medical center: screening to survivorship
Biography:
Dr. John L. Bell, received his medical degree from the University of Alabama/Birmingham, where he stayed to do his general surgical training, completed in 1986. A surgical oncology fellowship was completed in 1988 at the MD Anderson Cancer Center. Dr. Bell was recruited by the University of Tennessee to develop a Division of Surgical Oncology and an oncology program. He belongs to organizations such as the Southern Surgical Association, the American College of Surgeons, and the American Society of Breast Surgeons. He is the immediate past-president of the National Consortium of Breast Centers 2011-2013. He is certified by the American Board of Surgery, a Professor in the Department of Surgery, and Director of the UT Medical Center Cancer Institute.
Abstract:
The cost of healthcare in the United States is higher than all other developed countries. Despite these expenditures, outcomes lag behind others especially the United Kingdom, when looking at variables such as quality, access, efficiency, equity and healthy lives. The National Comprehensive Cancer Network, The American Society of Clinical Oncology, The United States Preventive Services Task Force, The National Cancer Institute, along with other organizations are increasing their focus on value-based, evidence-based cancer care as the United States transitions to the era of the Affordable Care Act (ACA). The ACA in some ways mimics the successful program now in place for many years in the United Kingdom which ranks number 1 in three of the five categories noted above. The full discussion of this abstract will review the latest cancer facts and figures in the United States and contrast those to other developed countries such as the United Kingdom. Appropriate risk reduction and prevention strategies, cancer screening controversies, diagnostic testing, treatment options, surveillance and survivorship data will be tabulated, reviewed, and discussed with an economic focus.
Matthew Curzon, M.D.
The University of Tennessee Medical Center, USA
Title: Breast cancer in elderly patients (70 years and older): The University of Tennessee Medical Center at Knoxville 10 year experience
Biography:
Dr. Curzon received a BSc degree in Physiological Science from the University of California, Los Angeles in 2008, and his Medical degree from the American University of the Caribbean in 2012. Currently, Dr. Curzon is a Chief Resident and a PGY-3 resident in Anatomic and Clinical Pathology Residency Program at the University of Tennessee Medical Center in Knoxville, Tennessee. He has research interest in breast cancer, biomarkers and improving patient outcomes.
Abstract:
Breast cancer (BC) incidence increases with age, however, there is still a paucity of data on cancer biology, standardized treatment, and outcomes in elderly (≥70 y/o) patients. We evaluated whether ER/PR/HER2 subtype and TNM stage of invasive BC had significant impact on overall survival (OS) in a study population of 232 elderly Caucasian female patients (≥70 y/o) from our institution at the 10 year interval (01/1998-7/2008), and analyzed treatments that they received (last follow-up date 8/1/2013). Patients were grouped according to TNM stage and ER/PR/HER2 subtype using 5-group classification system per 2011 St. Gallen International Consensus Panel recommendations. OS was measured comparing these categories using Kaplan Meier curves and Cox regression analysis. The majority of patients (178/232=76.7%) were in the traditionally considered “favorable†BC subtype (ER+/PR+/HER2-); 23.3% were in “unfavorable†subtype [HER2+=12% (28/232) and triple negative (TNP) =11.3% (26/232)]. Interestingly, a trend for better survival was noted in HER2+ patients, the group that is only nowadays considered worth reclassifying to “favorable†due to advantageous effects of anti-HER2 treatment (HER2+ OS=68%; ER+/PR+/HER2- OS=56% and TNP OS=58%). However, no ER/PR/HER2 subtype was significantly predictive of better OS (p=.73). TNM stage was predictive of OS (p<.001). Our previously published data on non-significant effects of ER/PR/HER2 on OS in our Caucasian BC patient population are concordant to results obtained in our elderly patient subgroup. Discussion of this abstract will include the treatments that our patients received and compare/contrast them to the literature data in an attempt to reconcile and stratify given therapy with outcomes.
- Chemotherapy for Breast Cancer
Chair
Aysegul A Sahin
The University of Texas MD Anderson Cancer Center, USA
Co-Chair
Robert-Alain Toillon
Universite Lille 1, France
Session Introduction
Aysegul A. Sahin
The University of Texas | MD Anderson Cancer Center, USA.
Title: Histopathologic evaluation of breast specimens after neoadjuvant chemotherapy
Biography:
Dr. Aysegul Sahin is an internationally recognized breast pathology expert who is a faculty member at M. D. Anderson Cancer Center since 1988. She received her medical doctor degree from University of Ankara in 1980, completed Anatomic and Clinical Pathology Residency at Oregon Health Science University, and did Surgical and Oncologic Surgical Pathology Fellowships at the University of Iowa Hospital and Clinics and the UT M. D. Anderson Cancer Center. Currently, she is the Section Head of Breast Pathology and Director of Education in the Department of Pathology and Breast Pathology Fellowship Program. She is also the Director of the Breast Tumor Bank. Dr. Sahin has also published multiple book chapters on pathology of breast lesions. She is an executive committee member of International Society of Breast Pathology and member of national and international pathology societies.
Abstract:
Neoadjuvant chemotherapy refers to chemotherapy administered before surgery and it is the standard treatment in locally advanced breast cancer. In the last decade the indications for neoadjuvant chemotherapy has broadened to include its use in the treatment of earlier stages of breast cancer with the aim to obtain tumor shrinkage and improve the rate of breast-conserving surgery. More recently, this treatment modality is increasingly used to obtain a quantifiable evaluation of sensitivity or resistance to chemotherapy. The potential of tumor response might also allow individualization of systemic treatments and therapid assessment of new drugs. Furthermore, clinical trials in neoadjuvant setting are increasingly being utilized for the evaluation of new drugs and novel therapeutic strategies using pathological complete response, a surrogate marker for survival, as the primary endpoint. Complete eradication of invasive tumor cells in the primary tumor bed following neoadjuvant therapy is strongly correlated with improved disease-free survival and overall survival. The excision or mastectomy specimens display a range of histopathologic changes after neoadjuvant chemotherapy. Appropriate specimen handling is essential to evaluate response to neoadjuvant chemotherapy and includes not only careful assessment of specimens but also requires correlation with clinical and imaging findings. There are different methods to quantitate residual tumor. In this presentation the author will review methods to evaluate breast resection specimens after neoadjuvant chemotherapy and discuss the classifications systems of residual tumor burden, and tumor biomarkers related to response to neoadjuvant chemotherapy.
Robert-Alain Toillon
University of Lille, France
Title: Implication of tyrosine kinase receptor networks in therapy resistance
Biography:
Robert-Alain Toillon has completed his PhD at the age of 28 years from Lille University and Postdoctoral studies from Université Libre de Bruxelles. He is the Director of “Neurotrophin signaling and therapy resistance†team in INSERM U908 lab. He was hired as Cell Biology Professor of Lille University in 2013 and published more than 30 papers in reputed journals.
Abstract:
During the past years, we showed that neurotrophins, especially the nerve growth factor (NGF), well known for its involvement in the survival and differentiation of neurons, are also of importance in breast tumor development. In light of the role of Trks in cancer cell biology, strategies aimed at targeting the Trk tyrosine kinase domain have been tested. For instance, CEP-701 (Lestaurtinib) has been shown to exhibit some efficiency in preclinical models when used as a single agent or in combination with other cytotoxic drugs. Nevertheless, clinical trials fail to demonstrate the efficiency of Trk tyrosine kinase inhibitors in cancer treatment, as cancer relapse occurs rapidly with a burst of tumor cell growth. The rapid relapse indicates that resistance mechanism should already exist in cancer cells at the beginning of the treatment. Indeed, Tyrosine Kinase Receptor-mediated signaling pathways share multiple elements and inhibiting one type of TKR can result in the compensatory recruitment of downstream components by other co-receptors. Our results showed that tumor cell resistance to Trk inhibitors is driven by membrane receptor signaling platforms. Our findings of the existence and the importance of TrkA phosphorylation independent signaling constitute a real change of paradigm on the comprehension of Trk-mediated neurotrophins effects. So, our scientific projects are focused on the study of integrated signaling networks of neurotrophins and proneurotrophins as well as their contributions in increasing aggressive phenotype of cancer cells.
Graham Ross
Roche Products Limited, UK
Title: Neoadjuvant therapy for early stage breast cancer: A new pathway to registration?
Biography:
Graham Ross was trained in Durban, South Africa in the Department of Radiotherapy and Oncology. For 20 years he has worked in medicines development in the pharmaceutical industry, the last nine years as the Global Clinical Science Leader for the development of pertuzumab. He has worked on the development of several compounds in various indications including small cell lung cancer, ovarian cancer, breast cancer and the management of emesis. He is a Fellow of the Faculty of Pharmaceutical Medicine.
Abstract:
One of the paradoxes in oncology research is that the more successful we are, the longer it takes to prove the clinical value of new treatments. Breast cancer is a very good example: from the time docetaxel was registered as a treatment for metastatic breast cancer, it took five years to define its role in the adjuvant treatment of early stage breast cancer; from the time trastuzumab was registered as a treatment for metastatic HER2 positive breast cancer it took eight years to establish its role in adjuvant therapy. It is imperative that we come up with strategies to accelerate the development process and to make new active therapies available to patients, especially in the era of molecular sub-typing and targeted therapies. Both the FDA and the EMA issued draft guidelines in 2014 on the potential for accelerated approval or approval with agreed conditions, respectively, based on the use of pathological Complete Response (pCR) following neoadjuvant therapy, provided that there certain criteria are met (for example the population treated needs to be at high risk of relapse, there has to be a convincing increase in the rate of pCR preferably by “adding on†to standard therapy in randomized studies, the mode of action has to be well characterized, the additional toxicity must be “minor†and a suitable confirmatory study needs to well underway). HER2 positive breast cancer is a good model for testing this potential new pathway, and the positive lessons as well as caveats and disappointments will be discussed.
Sitanshu Sekhar Lahiri
Amity Inst. of Biotechnology, Amity University, India
Title: A novel oral formulation for cancer therapy, loaded in a slow release matrix for targeted delivery
Biography:
Sitanshu Sekhar Lahiri from New Delhi India is the Professor Emeritus in the Amity University NOIDA. He superannuated as a Scientist and Jt. Director from the Institute of Nuclear Medicine & Allied Sciences, Defense R&D Organization. He is a Gold Medalist, a CommonWealth awardee, Resource Person in the “State-of –the- art†Workshops of Govt. of India. His interest is in Drug Development & Delivery, DNA Diagnostics, Radiation Biology & Protection, Animal Sciences, Herbal remedy and Toxicity research. Sitanshu Sekhar Lahiri has 16 patents, 42 publications and is the Reviewer of 35 reputed international journals. He has received several international appreciations.
Abstract:
The present invention, provide an anti-cancer formulation, incorporated in the hydrogel. It selectively causes apoptosis of cancer cells, leaving the healthy cells unaffected. The anti-cancer formulation comprises of aqueous leaf extracts of Belada mara (Aegle marmelos), Oxalis corniculata; cotyledons of the seed of custard apple (Annona reticulate), seeds of Fenugreek (Trigonella foenum-graecum), Ginseng from the plant Panax ginseng and Newcastle disease virus suspended in 1X Phosphate buffer saline, all at declared proportions. Its hydrogel based targeted oral delivery for slow release in the intestine has been developed. The hydrogel comprises agarose and protein in phosphate buffer saline, polyethelene glycol and glycerol. The contents of the hydrogel are non-toxic and are consumed as food or for therapy. The hydrogel can be made for target specific (pH specific) release in intestine or in stomach by altering the buffer pH during the production.
Penelope Ottewell
University of Sheffield, UK
Title: Inhibition of RANK/RANKL interactions preventovariectomy-induced growth of disseminated breast cancer cells in bone
Biography:
Ottewell is a lecturer in the Academic Unit of Clinical Oncology, University of Sheffield UK. She was awarded a PhD from the Department of Gastroenterology at The University of Liverpool in 2005. Ottewell first arrived in Sheffield in 2005 when she took up a position as a post-doctoral scientist working on breast cancer. During her time here Dr Ottewell has carried out international collaborative work spending time at INSERM (University of Lyon), France and at TUFTS University in Boston, USA. Her multi-award winning research focuses on advanced breast cancer with particular emphasis on looking at how and why breast cancer cells spread from the primary site to the skeleton. Ottewell has been awarded a total of 10 prizes for her research including the prestigious Breast Cancer Campaign Research Team of the year award in 2008 and the International Bone and Mineral Society Gregory Mundy Research Fellowship in 2011.
Abstract:
Dormant disseminated tumour cells can be detected in the bone marrow of breast cancer patients several years after resection of the primary tumour. The majority of these patients will remain asymptomatic, however, approximately 15% will go on to develop overt bone metastases and this condition is currently incurable. The reason why these dormant cells are stimulated to proliferate and form bone tumours in some patients and not others remains to be elucidated. We have recently shown that in an in vivo model, increasing bone turnover by ovariectomy stimulated proliferation of disseminated tumour cells, resulting in formation of bone metastasis. This awakening of MDA-MB-231 tumour cells in bone from a dormant to a proliferative state was prevented following administration of the antiresorptive drug zoledronic acid and therefore appeared to be driven by osteoclast mediated mechanisms. In agreement with this hypothesis we have also shown that disruption of RANK-RANKL interactions following administration of OPG-Fc inhibits growth of these dormant tumour cells in vivo. Our pre-clinical data support early intervention with anti-resorptive therapy in a low-oestrogen environment to prevent development of bone metastases.
Biography:
Anne Marie Lunde Husebø is a PhD candidate from Department of Health Studies at University of Stavanger (UiS), Norway. She is conducting the PhD-project: “Exercise during breast cancer treatment. A study of physical and psychosocial outcomes, and motivational challengesâ€, and has published 4 papers from the study. She is a registered nurse and holds a master’s degree in Health Science from UiS. She represents the research area Health promotion in long-term illness.
Abstract:
Women with breast cancer may experience a decrease in physical activity following the cancer diagnosis, and adhering to exercise interventions can be a challenge. Research is needed to identify motivational factors and barriers for exercise adherence among women during breast cancer treatment. This study aimed to explore factors influencing exercise adherence amongbreast cancer patients while following an exercise program. A qualitative design was applied to explore patient’s perceptions of the challenges to exercise adherence during a randomized, controlled trial. Twenty-seven women with early stage breast cancer were purposively sampled for focus group interviews from their participation in the exercise intervention group. Five focus groups were performed. Five main themes were identified from the analysis which described factors participants perceived to influence their adherence to exercise during chemotherapy, and were: ‘side-effects of breast cancer treatment as a barrier to exercise’, ‘restoring and maintaining normality in daily life motivates exercise’, ‘other valued activities compete with exercise‘, ‘constructive support enhances exercise’ and ‘positive beliefs about efficacy and outcomes motivate exercise’. Adherence to the exercise intervention were challenged by internal and external conditions, and may be improved by attention to the impact of treatment side-effects, and by supporting patient self-efficacy towards changing health behavior. Health professionals should be aware that exercise adherence could be a challenge among women with breast cancer. They should help identify obstacles to exercise for women and ways to overcome them, as well as support them in their beliefs that they are capable of changing their health behavior.
Biography:
Stephen Assinder completed his Doctorate studies at the University of Bristol, UK in 1996. He now leads the Bosch Institute’s Andrology Research Group, at the University of Sydney. Research interests include: the roles of structural proteins in cancer development; signaling pathway integration and dysregulation in cancers; the actions of oxytocin in both benign and malignant prostate disease; identification of prognostic markers of prostate disease and treatment. He is also a founding member of the Copper Biology Research Group which is focused on chemotherapeutic implications of copper transproters.
Abstract:
Influx of reduced copper into cells is mediated by the copper transporters CTR1 and CTR2. CTR1 and 2 are also thought to be responsible for the influx of platinum-based cytotoxic drugs used in the treatment of cancers. Evidence suggests that the sensitivity of a cell to such drugs (eg. cisplatin) might relate to the amount of CTR2 present. Immunohistochemical analysis of breast cancer tissue microarrays demonstrated an increased amount of CTR2 relative to CTR1 in both invasive ductal and invasive epithelial carcinomas as compared to normal breast tissue.We than tested the hypothesis thatgreater amounts of CTR2 reduced sensitivity of breast cancer cells tocisplatin. Levels of CTR2 proteins were assayed in a normal breast epithelial cell line (184B5), and 3 representative breast cancer cell lines (MCF7, HCC1806, MDA-MB-468) by western blot. Western blot analysis detected monomeric and dimericCTR2. In the relatively cisplatin insensitive MCF7 cell line (IC50 > 20 μmol.L-1) there is predominantly dimeric form. Cisplatin sensitive HCC1806 and 184B5 (IC50=5 μmol.L-1), have predominantly monomeric CTR2. The highly cisplatin sensitive (IC50=0.5 μmol.L-1) MDA-MB-468 breast cancer cells have significantly less total CTR2 protein, butsimilar amounts of CTR2 monomer and dimer. Confocal imaging demonstrated that cisplatin resistant MCF7 cells exhibit peri-nuclear CTR2 while more sensitive cell linesshow an unexpected CTR2 nuclear localisation. We conclude that the amount of total CTR2, its quarternary structure and sub-cellular localisation may determine cisplatin sensitivity. Dimerisation of CTR2 might prevent localisation to the nucleus in turn preventing cisplatin from trafficking to the nucleus and resultant DNA damage and apoptosis.
Susumu Ohya
Kyoto Pharmaceutical University, Japan
Title: Downregulation of Ca2+-activated Cl- channel TMEM16A by histone deacetylase inhibition in breast cancer cells
Biography:
Susumu Ohya has started ion channel research in Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan. Since 2012, he has been the Professor of Department of Pharmacology, Kyoto Pharmaceutical University, Japan. Currently, he is working on the physiological significance of Ca2+, K+ and Cl- channels in cancer cell growth, apoptosis, migration and invasion. He is on an Editorial Board Member of Biological and Pharmaceutical Bulletin of Japanese Pharmaceutical Society.
Abstract:
TMEM16A (also known as ANO1 or DOG1) was identified as a pore-forming subunit of the Ca2+-activated Cl- channel, and plays an important role in driving the amplification of 11q13 in many types of human cancer.TMEM16A is responsible for facilitating cell growth and metastasis of TMEM16A-expressing,HER2-positive breast cancer cells. Recently, we found a significant decrease in TMEM16A expression and its functional activity induced by vorinostat, a pan-histone deacetylase inhibitor (HDACi) in HER2-positive breast cancer cell line YMB-1. Both pharmacological blockade and siRNA-induced inhibition of HDAC3 elicited a large decrease in TMEM16A expression and its functional activity in YMB-1. Additionally, we recently found that genetic and pharmacological inhibition of TMEM16A is responsible for the regulation of HER2 expression. Taken together, TMEM16A is epigenetically regulated by HDAC inhibition and in malignancies with a frequent gene amplification of TMEM16A, HDAC3 inhibition exerts the suppressive effects on cancer cell viability via a downregulation of TMEM16A.
Ashok Jain
Albany State University, USA
Title: Role of dietary additives in suppressing the PhIP induced cytotoxicity
Biography:
A Jain has completed his PhD from Agra University, India. He was a visiting scientist at Texas A&M University. Currently he is a Professor at Albany State University, GA and program coordinator for Biotechnology program. He has received research funding from NIH, DOD and USDA. He served as Director, Center for Undergraduate Research and currently he is serving as MARC U*STAR project director. He has published more than 25 papers in reputed journals and has been serving as reviewer for six journals of international repute.
Abstract:
The 2-amino-1-methyl-6-phenylimidazo[4-5-b]pyridine (PhIP) is mutagenic and carcinogenic heterocyclic amine formed during the cooking of meat. Several studies have shown that PhIP can induce tumors in breast, prostate and colon cells and in rodent models. Metabolism of PhIP results in the formation of free radicals (ROS) and PhIP metabolites are known to produce DNA adduct and DNA strand breaks. The metabolism and mutational effects of PhIP are well defined. Phytochemicals are known to inhibit cytotoxic and genotoxic effects. Therefore, we hypothesized that the right combination of antioxidants and or phytochemical (naturally present in fruits, vegetables and spices) along with grilled meat should be capable of suppressing the PhIP induced cytotoxicity and breast cancer. Therefore, a model system using human breast epithelial cells (MCF 10A) was developed to test various antioxidants in presence or absence of PhIP. We have tested four vitamin (C, K3, D3, and E), Gingerol (6 and 10), N-acetyl cysteine, glutathione and curcumin at varying concentrations. The protective effect of these compounds was evaluated using cell viability assay, DCF assay to quantify ROS production, Comet assay to quantify the DNA damage and DNA adduct formation by immunofluorescence method. Results indicate that presence of these compounds improves cell viability as compared to PhIP treated group. However, curcumin co-treated cells showed significant differences and PhIP induced cell cytotoxicity was consistently reverted to normal. Gene expression analysis indicates that curcumin interact via multiple molecular targets, suggesting that curcumin appears to be an effective anti-PhIP food additive.
Mona Abd Elazeem
Tanta University, Egypt
Title: Claudin-4 Expression in Triple Negative Breast Cancer: Correlation with Androgen Receptors and Ki-67 Expression
Biography:
Mona A. AbdElazeem has completed her PhD in December, 2006 from Tanta University and postdoctoral studies from Tanta University. She is an Ass. Prof. of pathology in Pathology Department, Faculty of Medicine, Tanta University. She is a member in The Egyptian Society of Pathology.
Abstract:
Breast cancer is the most common malignancy in women and the leading cause of cancer mortality worldwide. Triple-negative breast cancer (TNBC) is an important phenotype of breast cancer that accounts for a relatively small number of breast cancer cases, but still represent a focus of increasing interest at the clinical, biological and epidemiological level. Claudins are the major component of the tight junction and only a few studies have addressed the role of claudins in breast cancer, especially triple negative breast cancer. Androgen receptors (AR) as members of the nuclear receptor superfamily are known to be involved in a complex network of signaling pathways that collectively regulate cell proliferation. However, roles of AR in breast cancer development and progression have not been very clearly understood. The proliferation marker Ki-67 has been confirmed as an independent predictive and prognostic factor in early breast cancer. The aims of this study are to identify the clinic-pathological associations and prognostic value of claudin-4 expression in triple negative breast cancer and to correlate claudin-4 expression with AR status and Ki-67 expression.
- Breast Cancer Tests: Screening, Diagnosis and Monitoring
HER2 Positive and Other Types of Breast Cancers
Session Introduction
Diptendra K Sarkar
President Elect, Association Breast Surgeons of India, India
Title: Role of NFKB as a prognostic marker in breast cancer: a new tool in the horizon
Biography:
Professor Sarkar is the Chief of the Breast Service and Research Unit at IPGMER, Kolkata, India. He is a Founder member and presently the Honorary Secretary of The Association of Breast Surgeons of India. He has delivered more than 150 lectures and orations in various national and international conferences. He has published more than 30 articles and has contributed as author to two different text books. He is the Associate Editor of Indian Journal of Surgery and Surgical Oncology. He is part of the esteemed Governing Council of Association of Surgeons of India.He is the one of the pioneers of Breast Surgery in Eastern India.
Abstract:
The nuclear factor kB (NFkB) is a superfamily of transcription factors. Activation of the signaling pathway leads to induction of target genes that inhibits apoptosis, dysregulates cell cycle, promotes cellular invasion. It regulates tumorogenesis , inflammation and metastasis. It is hypothesized that study of a single factor, instead of multiple proliferative genes, can prognosticate breast cancer to same extent. A prospective study was conducted at the Comprehensive breast service and Breast cancer research Unit, IPGME&R,Kolkata, India. The patients were divided into two groups, first group (Group A) comprised of 57 patients with primary breast cancer and second group (Group B) comprised of 54 patients of fibroadenomas. NFkB was measured in both groups by Western Blot and RT-PCR technique using p65 protein of NFkB family.ER , PR and Her2 neu were measured by immunohistochemistry methods. NF-kB was expressed in 71.8% of breast cancer patients while none of the Group B patients expressed it.NF-kB / p65 expression is significantly associated with large tumor size(>5 cm.)(p-value 0.012),Grade III tumors(p=0.002),ER and PR negative tumors(p=0.002 and 0.001 respectively) and Her2 neu positive tumors(p=<0.001).Correlation is poor with lymph node status(p0.393) and menopausal status(p=0.973).The results were correlated with NPI.(higher NPI of more than 5.4 was statistically significant with p=0.002). The study puts forward the fact that NF-kB is a valid prognostic marker. Being a transcription factor, it controls multiple pathways and thus has the potential to replace costly multigene prognostication models. This can have a major impact in developing countries in prognosticating breast cancer.
Syeda Zakia Hossain
Faculty of Health Sciences, University of Sydney, Australia
Title: What factors affect breast screening practices among Muslim women living in Sydney metropolitan area?
Biography:
Dr Syeda Zakia Hossain has completed her PhD from the University of Queensland, Australia. She is a health sociologist and a demographer, expert in women’s health. She has worked extensively on women’s health and wellbeing. Her research focuses on health inequalities, chronic disease and disability, i.e., breast cancer, diabetes, health inequalities, South East Asia and Middle East. Dr Hossain has presented her research in national and international conferences and published more than 30 papers in reputed journals. Dr Hossain has been serving as an Executive editor of the Journal of Community Medicine and Health Education.
Abstract:
Breast cancer is one of the most commonly occurring malignant neoplasms among women. Survival from breast cancer has improved steadily over time in many developed countries. Ethnic differences in survival of breast cancer were reported in the USA. Limited evidence suggests that people from culturally and linguistically diverse (CALD) background have lower than average rates of population in cancer screening in Australia. The aim of this research is to understand breast cancer knowledge and screening practices among Muslim migrant women (MMW) living in Sydney metropolitan area. Participants of the study are Muslim migrant women (N=101), over the age of 35 living in metropolitan Sydney; were recruited using convenient and snowball techniques. Survey instrument was used to gather data. Results show that the mean age of the participants’ was 44.9 years, 54% had tertiary education, 57% were unemployed and mostly married (84%). Bivariate results show that education, employment and religious priority are significantly associated with breast cancer knowledge (P<0.05). Breast screening participation was significantly associated with age, residency, English ability, refusal to see male practitioners and breast cancer knowledge (P<0.05). Notable barriers of screening include pain, unnecessary radiation, lack of GP recommendation and something negative may be discovered, suggesting policy implications.
Medhat Faris
King Fahad Specialist Hospital, Dammam, KSA
Title: Patient advocacy program for breast cancer patients in the eastern province
Biography:
Prof. Medhat Faris is a professor of Medical Oncology, King Fahad Specialist Hospital, Dammam KSA. Trained in Medical Oncology at the Beatson Oncology Center, Glasgow, UK. He worked at Velindre Hospital, Maidstone Hospital, and Addenbrooke’s Hospital UK. He was offered the opportunity to establish the Oncology service in the sultanate of Oman (1998-2008). He is the founder of the patient’s advocacy program “We Careâ€. His work focusing on breast cancer research and patient’s care. Prof. Medhat Faris is also certified by the European Society for Medical Oncology (ESMO) since Sept. 1999. Moreover, he participated in international, regional and national clinical trials and has more than 70 publications & Reviewer of several Indexed Journals.
Abstract:
Patient advocate is a person who helps a patient work with others who have an effect on the patient's health, including doctors, nurses, insurance companies, employers, case managers, and lawyers. A patient advocate helps resolve issues about health care, and job discrimination related to a patient's medical condition. Cancer advocacy groups try to raise public awareness about important cancer issues. The following important points will be discussed including: Why Is being an advocate Important now?, Why you should be an advocate? And What are the obstacles of patient advocacy? Explanation of the Goals of the Advocate to Inform, enhance autonomy and respect the decisions of others, even if we don’t agree with it will be addressed. I will highlight the Efforts by physicians, cancer foundations, cancer survivors, patients and their families to improve cancer management and provide comprehensive evidence based treatment, education, early detection and support to patients and their relatives in our region. Details of our advocacy group “we care†to communicate with the patients and their relatives will be explained. It is now well recognized the important role that patients, patient advocates, and other members outside of the traditional science community play in advancing cancer care and research.
Caigang Liu
The Second Hospital of Dalian Medical University, China
Title: FSIP1: A new potential early screening marker for breast cancer
Biography:
Caigang Liu has completed his Doctor’s degree at the age of 33 years from China Medical University. He is the Director of the Breast Disease and Reconstruction Center and Breast Cancer Key Lab of Dalian of the Second Hospital of Dalian Medical University. He has published more than 100 papers, 39 of those were included in SCI.
Abstract:
This study is aimed at investigating the expression status of FISP1 in breast cancer. Wound fluid and serum samples from 122 female primary breast cancer patients and 112 recrudescent and metastatic breast cancer patients and 38 female benign cases were enrolled for the protein concentration analysis. 496 paraffin-embedded tissues with 5-year follow-up were enrolled for prognosis analysis. It was observed that FSIP1 protein was expressed significantly higher in breast cancer tissues compared to benign tissues. The cases with high FSIP1 expression intended to develop into better postoperative disease-specific survival (P<0.001). FSIP1 expression levels were significantly higher in primary breast cancer patients compared to benign group (4713±3065 pg/ml vs. 1798±1943 pg/ml, p<0.0001), in recrudescent and metastatic breast cancer compared to primary breast cancer group (7713±3065 vs. 4713±3065 pg/ml, p=0.003), in DCIS compared to IDCgroup (6172±2432 pg/ml vs. 4381±3019 pg/ml, p=0.0493), in lymphonodus negative group compared to positive group (5132±3216 pg/ml vs. 3943±2630 pg/ml, p=0.0401), in ER, PR positive breast cancer compared to negative group (5286±3152pg/ml vs. 3445±2458pg/ml, p=0.0018), and in luminal B breast cancer patients compared to triple-negative group (5383±3170pg/ml vs. 3697±2683pg/ml, p=0.0268). Similarly, FSIP1 in wound fluid of lymphonodus negative patients was significantly higher than those of positive group (4937±2914 pg/ml vs. 3273±2647 pg/ml, p=0.0384).
Biography:
I was born in 1985 in Konya. I graduated from Istanbul University, Cerrahpasa Medical Faculty (English Program). Between 2007-2009 I served on the student representative council. I began my General Surgery residency at the same faculty in 2011. In 2014, I was elected as President of the Turkish Surgical Society’s Resident Committee. I’m currently listed as an editor in the journal Medicine. In addition, I’m one of the founding members of the Turkish Young Doctors’ Platform and Association and currently their vice President. My research interests are endocrine surgery new technologies in medicine in terms of diagnostics and treatment modalities.
Abstract:
Breast cancer is the most common malignancy in women. Most effective method for treatment is early removal of cancer tissue. Widely used modalities in detection of breast cancer are mammography, magnetic resonance imaging (MRI), and ultrasonography. An alternative technique, which is in clinical trials phase, is microwave breast tomography (MMT). MMT is specific for cancer tissues. It relays on high contrast of dielectric coefficient between healthy and cancer tissue. This study aims to compare MRI and MMT with histopathology (HP) reports. Methods To evaluate the MMT in clinical settings, pre-operative MMT measurements are obtained from patients who has planned surgery and have a breast MRI, after informed consent was obtained. By using MMT outcomes, images were drawn using jet color mapping. A group of doctors blind to MRI and HP results were evaluated MMT images. MMT and MRI measurements of each patient is compared with HP reports of specimen. Results: When dimensions of lesions detected in MMT compared with MRI and HP reports, MMT dimensions were more congruent with HP results. Median (minimum-maximum) lesion dimensions of MMT, HP, and MRI respectively are: 28.05 (11 – 35.7), 24 (10 - 35), and 25 (8 - 44). Median MMT/HP and MRI/HP ratios are 103% and 91%. Conclusion: MMT results are more congruent with HP results than MRI, but larger series are required for further analysis.
Domenico Samorani
Santarcangelo Hospital, Italy
Title: Screening of Breast Cancer from Mammography to MR Imaging
Biography:
Dr. Domenico Samorani, Medical Doctor, now is Chief of General and Breast Surgery at Santarcangelo Hospital (RN) AUSL Romagna, Italy, Degree in Medicine and Surgery, Specialist in General Surgery at Bologna University. Expert in oncoplastic breast surgery. Author of several publications in particolar regarding the use of indocyanine green to detect the sentinel lymph node . He was a speaker at the 14th annual meeting of the American Society of Breast Surgeons ( Chicago 1 to 5 May 2013).
Abstract:
The use of Indocyanine Green (ICG) to detect the Sentinel Lymph Node (SLN) in breast cancer (BC) has been widely discussed in literature. As compared with Technetium (Tc) , ICG has different possible advantages: 1) Organisational: involvement of a nuclear medicine department is not necessary; 2) Social: patients no longer need to have Tc or other radioactive material injected at a nuclear medicine department). Further, the ICG technique can be performed in the operating room immediately after the induction of general anaesthesia and without any discomfort to the patient. 3) Operative: when radio-guided occult lesion localisation (ROLL) is combined with SN biopsy, SN detection with ICG avoids the superposition of 2 radioactive tracings at the injection site, favouring tumour detection. Some studies pointed out that the SLN detected via ICG coincides with that detected via Tc. After more than 300 surgeries during which we detected the SLN via ICG associated with Tc, thus refining our technique, in the last 4 months we have been using only ICG without combining it with any other tracers. So far, in 112 surgery cases, we have had 100% detection of the SLN with a median of 2 lymph nodes per patient (range: from 1 to 4). We inject a variable quantity of ICG that spans from 0.4 to 0.7 ml depending on the breast volume and on the distance between neoplasia and axilla or between areola and axilla. The time between the injection of the ICG and the incision varies from patient to patient (from 2 to 8 minutes), with a median of 4 minutes. Therefore, it is necessary to follow the subcutaneous migration of the tracer using an infrared torch and make the incision only when the tracer has visibly reached the axilla, not before, otherwise, by interrupting the vessels too soon, the detection of SLNs becomes much more difficult. As we have already reported, ICG increases the average number of detected SLNs as compared to Tc, without increasing complications. This fact does not seem to be a limit, rather, in certain cases – and according to what Giuliano also stated – it allows us to avoid axillary dissections when, out of three harvested lymph nodes, only a metastatic lymph node is detected. Our experience in using only ICG to detect the SLN demonstrates the use of ICG only, once the technique is mastered, allows, always and in every case, the removal of the SLN in BC
Lubna Mushtaque Vohra
Ziauddin University Hospital, Pakistan
Title: Metaplastic carcinoma of the breast and p16 positivity: What does it mean?
Biography:
Lubna Mushtaque Vohra is an Assistant professor in Ziauddin University Hospital, Karachi Pakistan. She is a dedicated qualified breast surgeon with special interest in oncoplastic, aesthetic and reconstructive breast surgery. She did her post graduation in general surgery followed by fellowship in breast surgery from Aga Khan University Hospital. She also did European board in breast surgery. Recently, did fellowship in Oncoplastic, aesthetic and reconstructive breast surgery under supervision of Prof. Werner Audretsch. She has also been actively participating in research and so many research articles published as authors.
Abstract:
Metaplastic breast cancer are a group of breast cancer subsets which display the coexistence of breast cancer of the usual varieties along with other components such as squamous, sarcomatoid ,chondroid or other tissue types in the same specimen. The presence of p16 positivity by immunohistochemistry as a surrogate marker in HPV related oropharangeal cancer is now well accepted. Whether this is related to other such cancers of the HPV spectrum needs more research. It is with this background that five sequential cases of meta plastic breast cancer were tested for p16 positivity by IHC.
Jose Roberto Piato
University of São Paulo, Brazil
Title: Improved frozen section examination of the retroareolar margin for prediction of nipple involvement in breast cancer
Biography:
Shyng-Shiou F. Yuan received M.D. degree from Kaohsiung Medical University, Taiwan and has completed his PhD and postdoctoral training from University of Texas Health Science Center at San Antonio, USA. He is currently the director of Translational Research Center, Kaohsiung Medical University Hospital. He has published more than 60 papers in reputed journals and has been serving as an editorial board member of Cancer Letters since 2007.
Abstract:
Introduction: Development of the nipple-sparing mastectomy (NSM) technique has constituted a significant advance in the surgical treatment of selected cases of breast cancer. The most important aspect of areolar complex preservation is the exclusion of carcinoma involving the nipple. The retroareolar surgical margin is usually sampled and subjected to an intraoperative evaluation by frozen section examination in order to avoid a second procedure. However, this method is not standardized resulting in variable rates of false-negative results.Here, a new technique is proposed for the intraoperative study of the retroareolar margin. This ex vivo study was conducted by performing a simulated NSM procedure for patients undergoing total mastectomy to assess the impact of these measures on the accuracy of retroareolar frozen section examination. Materials and Methods: Between September 2012 and April 2014, we studied 158 mastectomy specimens from patients undergoing total mastectomy for breast cancer at the Cancer Institute of the State of São Paulo. Inclusion criteria were stage Tis-T3 tumors, multifocal and multicentric breast carcinoma, unicentric carcinoma not suitable to quadrantectomy. Patients submitted to neoadjuvant chemotherapy were also included. To obtain the entire sample area, the terminal retroareolar milk duct bunch was isolated. Fragments approximately 1.5 cm in length were excised and sectioned in parallel at the base of the nipple using a cold bistoury. Three transverse histological sections (4 mm each) at 200 mm intervals that included the entire isolated fragments were subjected to frozen section examination. The sections were stained with hematoxylin-eosin (H&E) and were evaluated. The remainder of each fragment was embedded in paraffin and 4 mm sections were subsequently stained with H&E and examined. Results: A total of 158 mastectomy specimens involving mammary carcinoma of no special type were examined. These included 15 (9.5%) in situ stage tumors, 36 (22.8%) stage I tumors, 71 (44.9%) stage II tumors, and 36 (22.8%) stage IIIA tumors. Paraffin examinations identified 25 retroareolar fragments compromised by carcinoma, resulting in 16.1% prevalence. Of the frozen sections examined, 2/158 (1.3%) had false-negative results and 5/158 (3.1%) had false-positive results. For the former two cases, the corresponding paraffin examinations detected low-grade carcinoma in situ and a residual cell cluster with a diameter less than 1 mm. The latter was found in a mastectomy specimen from a patient that underwent neoadjuvant chemotherapy. For the three cases involving false-positive results, the corresponding paraffin examinations revealed no atypical ductal hyperplasia present, one sclerosingintraductal papilloma and one nipple syringomatous adenoma. Statistical analysis revealed that the frozen section examinations performed had a sensitivity rate of 92.0% and a specificity rate of 96.2%. In addition, the positive predictive value (PPV) was 82.1%, the negative predictive value (NPV) was 98.4%, and the accuracy was 95.4%. Conclusion: The frozen section examination technique described here detected nipple involvement in breast cancer with greater accuracy than the frozen section usually performed by most surgeons.
Yi-Cheng Hu
National Yang-Ming University, Taiwan
Title: Detection of a negative correlation between prescription of Chinese herbal products containing coumestrol, genistein or daidzein and risk of subsequent endometrial cancer among tamoxifentreated female breast cancer survivors in Taiwan between 1998 and 2008: A population-based study
Biography:
Yi-Cheng Hu completed his double majoring in traditional Chinese medicine and modern medicine in Taiwan and later with his residency in department of acupuncture in Chang Gung Memorial Hospital. Currently, he is the attending physician in China Medical University Hospital, Taipei branch and doing researches in the field of traditional Chinese medicine utilization on cancer patients.
Abstract:
Tamoxifen users sometimes seek complementary and alternative medicine advice for treatment of a variety of illness and co-administer with phytoestrogen-containing herbs, resulting in an increasing concern of its influence in subsequent endometrial cancer risk. Our study aims to determine the prevalence of Chinese herbal products containing coumestrol, genistein, or daidzein and their association with subsequent endometrial cancer risk among tamoxifen-treated breast cancer survivors in Taiwan. We selected all patients who were newly diagnosed with invasive breast cancer and received tamoxifen treatment between January 1, 1998, and December 31, 2008, from the National Health Insurance Research Database. Among the 26,656 tamoxifen-treated breast cancer survivors, we evaluated the usage, frequency of service, and prescription of Chinese herbal products containing coumestrol, genistein, or daidzein. The logistic regression method was employed to calculate the odds ratios for utilization of those herbal products. Cox proportional hazard regression was set to calculate the hazard ratios of endometrial cancer associated with such usage. Of the patients surveyed, 36.2% (n = 9,652) of the tamoxifen-treated breast cancer survivors examined in the study had consumed Chinese herbal products containing coumestrol, genistein, or daidzein during the study period. Among those tamoxifen-treated female breast cancer survivors in Taiwan, consumption of Chinese herbal products containing coumestrol, genistein, or daidzein is negatively correlated with subsequent endometrial cancer risk.
- Breast Cancer Surgery & Radiotherapy for Breast Cancer
Chair
Chintamani
The Association of Breast Surgeons of India, India
Co-Chair
Vicente Marco Molina
Hospital Quirón Barcelona, Spain
Session Introduction
Helena K Puonti
Savonlinna Central Hospital, Finland
Title: Breast reconstruction with own tissue after mastectomy. A new microneurovascular technique with muscle sparing TRAM flap
Biography:
Plastic surgeon Helena K. Puonti has worked as microsurgeon since 1991. She has dedicated her work history for the development of surgical breast cancer treatment. She performed the first microneurovascular breast reconstruction with free ms-TRAM flap in 2001, and is preparing her thesis study from it. She has worked as the head of the plastic surgery department at Savonlinna Central Hospital since 1987, and fifteen years in her private own clinic Helena performing all kind of reconstructive plastic surgery. Cancer Society of Finland selected her for the oncologist of the year 2003 in Finland. Many plastic surgeons have started their career in her guidance and she gives yearly many lectures about the oncological surgery.
Abstract:
In previous studies, it has been shown that a breast reconstruction with own tissue gives the best possible result in the long run. Furthermore, sensibility following innervated free TRAM flap for breast reconstruction improves patient-rated quality of life. In this study, we were looking for the most efficient neurorraphy technique for sensory recovery in microneurovascular muscle sparing TRAM (ms-TRAM) reconstructions after a mastectomy for breast cancer patients. All together ninety six breast cancer patients undergoing breast reconstruction by free ms-TRAM were included in the study. Both sensibility of the reconstructed breast and sensibility of abdominal skin were evaluated by neurophysiological examinations and patient questionnaire at baseline before ms-TRAM reconstruction and after 12 and 24 months postoperatively. Quantitative sensory testing (QST) was performed for tactile, vibratory and thermal sensory modalities, sharp-blunt discrimination, and spatial acuity using two-point discrimination. Results were analyzed with SPSS, and Mann-Whitney test was used. In our pilot retrospective study, twenty patients, who underwent unilateral neurorraphy, showed significantly better results when compared with the control group of twenty patients without neurorraphy. Prospective study was started in 2006. Neurorraphy technique (unilateral, bilateral or no-neurorraphy) did not compromise abdominal skin sensibility when it was compared between different groups and no major problems or pain could be detected in donor area. The sensory recovery of the reconstructed breast was significantly better in neurorraphy groups comparing with no neuro group. Our interest in the future is to investigate the results for bilateral neurorraphy.
Inge Verbrugge
The Netherlands Cancer Institute, The Netherlands
Title: Radio-immunotherapy of cancer: Therapeutic efficacy, underlying mechanisms and potential applications
Biography:
Inge Verbrugge is an Associate Staff Scientist, at The Netherlands Cancer Institute in Amsterdam. Her primary research interest is in understanding and exploiting potential synergy between localized radiotherapy and immune-modulatory antibodies (‘radio-immunotherapy’) in cancer treatment. She received her PhD from the University of Amsterdam in 2009 and was subsequently awarded two prestigious Fellowships (Dutch Cancer Society Post-Doctoral fellowship and ‘Bas Mulder Award’) to study the anti-cancer potential of radio-immunotherapy. This work was initiated at the Peter MacCallum Cancer Centre in Melbourne, Australia and continued at the Netherlands Cancer Institute. She published 14 papers as first or second author in reputed journals.
Abstract:
Radiotherapy is one of the most successful cancer therapies but may benefit from coincident or subsequent immunotherapy. We designed novel combinations of radiotherapy with immunomodulatory monoclonal antibodies (mAbs) that were evaluated in pre-clinical mouse breast cancer models. We demonstrate that in combination with both single-dose and fractionated radiotherapy, mAbs designed to enhance T-cell function [anti-(α)-CD137] and relieve immunosuppression through blocking T-cell inhibitory signaling [α-programmed death (PD)-1] induce tumor regression in up to 100% of mice. Radio-immunotherapy induced immunological memory in cured mice and CD8+ T-cells were critical for its therapeutic efficacy. Radiotherapy up regulates MHC class I (MHCI) expression on tumor cells, which may further support immune-mediated killing. We show that this involves mTOR activation by ionizing radiation by a still unresolved mechanism. Yet, mTOR is important as mTOR inhibition almost completely abrogated the therapeutic effect of radio-immunotherapy. We conclude that radio-immunotherapy effectively cures mice that bear established mammary tumors and that therapy response is critically dependent on the activity of cytotoxic T-lymphocytes as well as on mTOR signaling. We predict that other tumor types to which T-cells are present in the peripheral repertoire and in which radiotherapy is used as a primary course of treatment, will also respond to radio-immunotherapy.
Carolina Alonso-González
University of Cantabria, Spain
Title: Melatonin sensitizes human breast cancer cells to ionizing radiation
Biography:
Carolina Alonso-González has finished her PhD from University of Cantabria in 2009, where she has received various research awards, and she completed a Postdoctoral fellowship at University of London, School of Pharmacy. Currently, she is an Associate Professor at the School of Medicine, University of Cantabria (Spain). Her recent research is focused on the sensitization effects of melatonin to chemotherapy and radiotherapy, studying the molecular changes that modulate the process. She has published over 30 articles and book chapters in peer-reviewed journals in the field of breast cancer research and have present her research at national and international conferences.
Abstract:
Nowadays radiotherapy and adjuvant endocrine therapy represent a standard treatment option in management of breast cancer. Melatonin exerts oncostatic actions on human breast cancer cells. Therefore, the purpose of this study was to investigate the effects of a combination of radiotherapy and melatonin on human breast cancer cells. Radiation inhibited MCF-7 cell proliferation in a dose-dependent manner, and pretreatment with melatonin one week before radiation led to a significantly decrease of cell proliferation compared with radiation alone. Melatonin pretreatment also decrease G2-M phase arrest compared with radiation alone, with a higher percentage of cells in G0-G1 phase and a lower percentage of cells in S phase. Regarding double-strand DNA break repair proteins, melatonin led to a significantly greater decrease in RAD-51 and DNA-PKcs mRNA gene expression compared with radiation alone. Melatonin pretreatment also upregulated the tumor suppressor p53. We have also demonstrated that melatonin pretreatment induced a greater decrease in aromatase and sulfatase, two main enzymes involved in the tumoral synthesis of estrogens, compared with radiation alone. Therefore, melatonin reduces active estrogens levels at tumoral cell. This is an important finding since anti-estrogens and anti-aromatase drugs have potential application with radiotherapy. Our findings suggest that melatonin may act as a radiaosensitizer in breast cancer cells by inhibiting tumor alestrogen production, decreasing cell proliferation, inducing cell cycle arrest and down-regulating proteins involved in double-strand DNA break repair through its regulatory action on p53. Thus, these results may have high translational potential for the adjuvant therapy in breast cancer patients.
Sribatsa Kumar Mahapatra
Veer Surendra Sai Institute Of Medical Science & Research, India
Title: Triple ABC Technique in Clinical Assessment in Breast Cancer Diagnosis
Biography:
Prof.Sribatsa Kumar mahapatra and Prof.Brajamohan Mishra both are working as professor of general surgery at V.I.M.S.A.R.Burla with teaching,treating and research activity in a busy 1000 beded institute hospital.
Abstract:
Triple assessment is the standard assessment for breast cancer diagnosis.This includes:Clinical examination,radiological assessment and pathological asessment.Clinical examination remains the corner stone in diagnosis around the world as it is cost effective, in contrast to radiological assessment and pathological assessment and it can be easily learned and applied anywhere anytime.But unfortunately there is no standardisation of this clinical assessment.In this paper we have devised a standard method called TRIPLE ABC METHOD for clinical assessment. For early diagnosis of breast cancer our TRIPLE ABC assessment can be easily learnedand applied by beginner and expert Surgeons.TWO ABC’s are completed in examination for both sides of breast with the following technique: A-AXILLA examination, B-BREAST examination and C-CERVICAL (neck) examination.The THIRD ABC is completed using the following technique:A-ABDOMEN examination, B-BONES examination and C-CHEST examination.For easy recall, each A ,B and C are given 5 Sites Of specific Examination LIKE A5, B5, C5 which will be disussed in detail in this paper.This completes the TRIPLE ABC technique.
Merdan Fayda
Istanbul University, Turkey
Title: Is Sentinel Lymph Node Biopsy Enough for Axillary Macrometastasis?
Biography:
Merdan Fayda is an associate professor at Istanbul University, Institute of Oncology, Dept. Of Radiation Oncology. He has been working in the field of radiation oncology since 1999, when he began his education at Istanbul University‘s Institute of Oncology Dept. of Radiation Oncology. Since then, Dr. Fayda has been involved with the Italian Hospital Dept. of Radiation Oncology, Gulhane Military Medical Academy, Dept. of Radiation Oncology, Kocaeli University Faculty of Medicine, Department of Radiation Oncology, and his current affiliation with Istanbul University Institute of Oncology, Department of Radiation Oncology. Dr. Fayda is a member of the Turkish Society of Radiation Oncology, ASTRO and ESTRO.He has several publications which include his thesis on Patient and treatment related factors affecting locoregional recurrence after post-mastectomy adjuvant radiotherapy’, Axillary versus sentinel-lymph-node dissection for micrometastatic breast cancer and his most recent publication of The diagnostic, predictive, and prognostic role of serum epithelial cell adhesion molecule (EpCAM) and vascular cell adhesion molecule-1 (VCAM-1) levels in breast cancer.
Abstract:
Although omission of further treatment to axilla inclinical N0 T1-2 breast cancer patients with conserved breast and positive micrometastatic 1-2 sentinel lymph node(s) is relatively well established, optimal management of the axilla in macrometastatic disease is controversial. Z0011 (micro- and macromets), International Breast Cancer Study Group (IBCSG) 23-01 (micromets), and AMAROS (micro- and macromets)are randomized trialstry to determine best management. According to Z0011 axillary lymph node dissection (ALND) isn’t necessary and sentinel lymph node dissection (SLND) could be the appropriate choice.IBCSG 23-01not only further strengths this idea for the micrometastatic cases but also shows that quality of life could be improved with SLND. In Saint Gallen consensus report 2013, 73%of the experts state that avoiding full axillaryclearance after 1-2 positive sentinel nodes is endorsed in situationsofconservative surgery and radiotherapy (RT).AMAROS announced at ASC0 2013 Meeting and showedthat both axillary RT and ALND were equally effective but less lymphedema with axillary RT.Although Z0011 changes the practice, details of radiotherapy fields have recently been announced at the San Antonio 2013 Meeting. In review of patients with evaluable detailed radiotherapy records, roughly 70% of them receivedsome form of lymphatic RT.Omission of further treatment to axilla with macrometastatic sentinel lymph node isn’t appropriate and either ALND or axillary RT can be an effective optiontreating patients but with less lymphedema in RT arm.It’s still not clear whether these suggestions could be applicable to the patients treated with mastectomy.
Farid Meybodi
Westmead Breast Cancer Institute, Sydney, Australia
Title: Use of 3D photography to measure breast volume prior to breast reconstruction.
Biography:
Dr Farid Meybodi is a Breast, Endocrine and General surgeon recently appointed as staff specialist at Westmead Breast Cancer Institute (BCI).Dr Meybodi completed his general surgery training in 2005 in Iran and experienced two years as a consultant surgeon in Shaheed Beheshti University of Medical Science before migrating to Australia. He was awarded FRACS in 2013 following further training and assessment by the Royal College of Surgeons. He spent three years as a Breast and Endocrine Fellow in Nepean, St George and Westmead hospitals. Dr Meybodi has a special interest in oncoplastic surgery and particularly post mastectomy implant based breast reconstruction. His research projects are focused on application of 3D Imaging technology in breast analysis, surgical planning, simulation and patient education in breast surgery.
Abstract:
Introduction: Assessment of breast volume is an important component of preoperative planning for breast reconstruction. Currently this is mainly based on clinical assessment and relies on surgeons’ experience and chest wall measurements. 3D photography (3DP) is a newer and more objective method for volumetric assessment. The aim of this study is to determine the accuracy of this method and factors influencing it. Methods: A retrospective review of 52 patients (64 breasts) who had undergone simple mastectomy (SM) N=10, nipple sparing mastectomy (NSM) N=23, skin reducing mastectomy (SRM) N=16, and skin sparing mastectomy (SSM) N= 15 and had pre op 3DP between Jan 2013 to Dec 2014 was performed. Calculation of volume with 3DP (3DPV) was based on surface acquisition and creation of virtual chest wall as anterior and posterior breast boundaries. Mastectomy specimen volume (MV) was assumed to equate specimen weight, measured intra operatively. MV and 3DPV were compared. Results: There was a strong linear association between MV and 3DPV (r= 0.89, p<0.001). The predicted MV can be calculated by equation MV= (68.7+ 0.92 x* 3DPV). The mean error between 3DPV and MV was 70 +/- 50 ml for NSM and SRM compared to 135 +/- 95 ml for SM and SSM. (p<0.001). The difference between MV-3DPV tended to decrease with BMI in NSM group (r=0.69, p=0.007) and increase with BMI in SRM (r=0.70, p=0.008). Conclusion: 3D photography is a reliable method for volumetric assessment, which may be useful in preoperative planning of breast reconstruction. Factors such as mastectomy type, breast weight, and patient BMI should be taken into consideration.
Nicolae Bacalbasa
University of Medicine and Pharmacy, Romania
Title: The benefits of surgery for breast cancer liver metastases – a single center experience
Biography:
Nicolae Bacalbasa is a professor at the University of Medicine and Pharmacy, Romania.
Abstract:
predictors of survival. Method: Forty-nine patients diagnosed with breast cancer liver metastases were submitted to hepatic resection for breast cancer liver metastases in “Dan Setlacec†Center of Gatrointestinal Disease and Liver Transplantation, between 2002-2015. Results: At the moment of liver resection the mean age was 53.2 years; 87.7% of cases received neo-adjuvant chemotherapy or hormone-therapy before liver resection. Four patients were diagnosed with synchronous liver metastases while in the other 45 cases metachronous hepatic lesions were found. Multiple liver lesions were found in 24 cases; in 12 cases the largest tumor dimension surpassed 5 cm. Major hepatic resections defined as resections of more than 3 segments) were performed in 14 cases while in the other 29 cases minor hepatic resections ( of less than 3 segments) were needed. The overall morbidity rate was 10.2% while early postoperative mortality rate was 0. The median overall survival was 34,2 months for unique hepatic lesions versus 24.3 months for multiple lesions, p=0.005 respectively 34.5 months for tumors smaller than 5 cm versus 22.8 months for larger lesions, p=0.006); major hepatectomies were not associated with a poorer outcome when compared to minor resections (p=0.08). Conclusions: Hepatic resection for breast cancer liver metastases is safe and can provide survival benefit especially in patients with solitary, lesser than 5 cm lesions.
Daisuke Ota
Mitsui Memorial Hospital, Japan
Title: The clinical outcome of reconstruction with tissue expander for breast cancer patients with mastectomy
Biography:
Daisuke Ota had completed his PhD from Tokyo Medical University. He is the Deputy Director of breast and endocrine surgery of Mitsui Memorial Hospital.
Abstract:
Purpose: We analyzed the outcomes and complications of reconstruction with tissue expanders (TEs) and permanent implants (PIs). Patients & Methods: From 2000 to 2009, 197 patients with unilateral, primary breast cancer who required mastectomy concurrent with reconstruction using TEs (TE group) and 540 patients with breast cancer who underwent mastectomy without reconstruction (MT group) were examined. Moreover, from 1997 to 2009, a retrospective review was performed of 234 primary breast cancer patients undergoing 239 postmastectomy breast reconstructions with TEs / PIs. Results: The incidence of local recurrence in the TE and the MT group were 4.1% vs. 4.1% (p=0.9936). In the TE vs. the MT groups, relapse-free-survival and overall survival at 120 months were 80.8% vs. 74.7% (p=0.1288) and 85.9% vs. 81.9% (p=0.2305), respectively. The incidence of infection was significantly higher in the TE than in the MT group, 13.2 % vs. 4.1% (p<0.0001). Removal of TEs / PIs was observed in 15.5% (37/239) of reconstructions. The completion rate was significantly higher in reconstructions without TE infection than with infection (96% vs. 54%, p<0.0001). Patients with BMI ≥25 kg/m2 and seroma aspiration were more likely to develop TE infections, and seroma aspiration was a significant independent risk factor (p<0.0001). Conclusion: Compared with mastectomy alone, immediate reconstruction with TEs did not impair prognosis, although the incidence of surgical site infection in the TE group was significantly higher than in the MT group. To improve completion rates of breast reconstruction, prevention of TE infection plays a key role.
Giorgio Berna
The Regional Hospital of Treviso, Italy
Title: No pec touch: a pre-shaped ADM for subcutaneous one-step breast reconstruction
Biography:
G Berna graduated from the University of Padua, Faculty of Medicine in 1989. He continued his preparation as a Plastic Surgeon obtaining the degree in 1994. Since 1993, he has been working at the Regional Hospital of Treviso. In 2006, he became the Director of the Plastic Surgery Unit. He is an active Member of the Sicpre (Italian Society of Plastic Surgeons) and International Member of the American Society of Plastic Surgeons. His expertise includes breast reconstruction and aesthetic surgery; and post trauma reconstructions.
Abstract:
Introduction: Implant-based breast reconstruction is becoming increasingly popular because of the widespread adoption of Acellular Dermal Matrix (ADM), which allows good aesthetic results with fewer operations. A preliminary study was carried out from November 2012 to January 2014, in order to verify the effectiveness of the new immediate muscle-sparing breast reconstruction technique. The patented Braxon, ADM enables subcutaneous positioning of the implant without detaching the pectoralis major muscle. Between April 2014 and April 2015 another European multicenter study was performed to confirm the preliminary outcomes. We report the results of the two experiences, from November 2012 to date. Material & Methods: The muscle-sparing surgical technique involves the use of a pre-shaped porcine ADM which totally wraps the breast implant. The device is positioned in a subcutaneous plane, without detaching the pectoral major muscle. This procedure decreases post-operative complications and betters outcomes. Results: The preliminary study was carried out on 19 patients (25 implants). Encouraging results were obtained by improving the characteristics of ADM and the surgical technique. The following European multicenter experience on 90 implants reported a reduction of early complications. Symmetrical and natural breasts with good shape and ptosis were observed. No cases of capsular contracture were detected in both studies. Conclusions: After more than two years, the muscle-sparing breast reconstruction can be safely proposed as a new option for patients who fit the inclusion criteria. The use of an ADM for the complete coverage of the implant prevents from capsular contracture. Longer evaluations and histological examinations are planned.
Sribatsa Kumar Mahapatra
Veer Surendra Sai Institute Of Medical Science & Research, India
Title: Triple ABC Technique in Clinical Assessment in Breast Cancer Diagnosis
Biography:
Prof.Sribatsa Kumar mahapatra and Prof.Brajamohan Mishra both are working as professor of general surgery at V.I.M.S.A.R.Burla with teaching,treating and research activity in a busy 1000 beded institute hospital.
Abstract:
Triple assessment is the standard assessment for breast cancer diagnosis.This includes:Clinical examination,radiological assessment and pathological asessment.Clinical examination remains the corner stone in diagnosis around the world as it is cost effective, in contrast to radiological assessment and pathological assessment and it can be easily learned and applied anywhere anytime.But unfortunately there is no standardisation of this clinical assessment.In this paper we have devised a standard method called TRIPLE ABC METHOD for clinical assessment. For early diagnosis of breast cancer our TRIPLE ABC assessment can be easily learnedand applied by beginner and expert Surgeons.TWO ABC’s are completed in examination for both sides of breast with the following technique: A-AXILLA examination, B-BREAST examination and C-CERVICAL (neck) examination.The THIRD ABC is completed using the following technique:A-ABDOMEN examination, B-BONES examination and C-CHEST examination.For easy recall, each A ,B and C are given 5 Sites Of specific Examination LIKE A5, B5, C5 which will be disussed in detail in this paper.This completes the TRIPLE ABC technique.
Mervi Siekkinen
University of Turku, Finland
Title: Effect of e-feedback on knowledge about radiotherapy of breast cancer patients
Biography:
Mervi Siekkinen has completed her MNSc (2006) and PhD (2014) from University of Turku, Faculty of Medicine at Department of Nursing Science. She is the coordinator of Turku University Hospital Cancer Center and National Cancer Center of Finland (FICAN). She has published 10 papers in reputed journals and has been serving as an Editorial Board Member of repute.
Abstract:
The growing number of women with breast cancer and their unmet knowledge expectations of radiotherapy pose a challenge to develop effective electronic patient education. Development efforts should be focused on e-feedback on knowledge because of its positive effects. In this study, we evaluated how an e-feedback knowledge intervention (e-Re-Know) before first radiotherapy improves breast cancer patients’ knowledge of radiotherapy and identified the associations with patients’ characteristics. Women with breast cancer were randomized prior to the radiotherapy period either to the intervention group or control group. The outcome measured three months after the radiotherapy period was knowledge level of radiotherapy. The increase in knowledge level was higher in the intervention group after adjustment for baseline knowledge level, and a significantly higher increase in knowledge level was seen in one subdomain, side-effect self-care, compared to the control group. The results of this study indicate that the e-Re-Know can be used in patient education to support empowerment. Future research should target new applications of e-Re-Know available on the Internet for those interested in the subject.
Guldeniz Karadeniz Cakmak
Bulent Ecevit University School of Medicine, Turkey
Title: The importance of intraoperative ultrasound guidance to achieve negative margins for palpable and nonpalpable breast cancer
Biography:
Güldeniz Karadeniz Cakmak is an Associate Professor in the Department of General Surgery at BülentEcevit University The School of Medicine. She is also Director of the General Surgery Department and Vice-President of the Surgical Sciences Division. She earned her MD from Istanbul University, Cerrahpasa Medical School. Her research interests include breast cancer, oncoplastic breast surgery, intraoperative breast ultrasound and sentinel node mapping. Her laboratory and clinical research include surgical treatment modalities for early stage breast cancer. She has authored more than 50 scientific research papers and presented numerous papers, lectures and workshops nationally and internationally.
Abstract:
Margin positivity is one of the most conflicting issues in breast conserving surgery (BCS) with a reported rate up to 25%. In an attempt to achieve negative margins intraoperative ultrasound guidance (IUG) was performed during BCS for palpable and nonpalpable breast cancer. Between 2011 and 2015, 259 patients underwent IUG-BCS with the diagnosis of in situ or invasive carcinoma. Intraoperative localization protocol includes ultrasound visualization of the lesion, tumor margin determination under real-time sonographic guidance, and image confirmation of specimen and tumor bed. Sonographic and macroscopic assessment of the surgical margins by surgeon was followed by frozen section analysis of each margin. Of the 259 patients, 45.1% had palpable and 54.9 % had nonpalpable tumors. The sensitivity of intraoperative ultrasound localization was 100%. Negative margins were achieved in 92.2 % of nonpalpable and 91.4% of palpable lesions at the initial procedure. The involved margins were correctly identified via specimen sonography in 95.4% of the cases. According to frozen section analysis of the 1554 ultrasonographically clear margins, re-excisions were required for 2.3% of cases with the majority of these proved to have significant degrees of DCIS. A second operation was required only in five cases, for either determination of close margins or multifocality at cavity shaved margins, without residual cancer on pathological examination of the reoperative specimens. The cost-time analysis and calculated resection ratio determined nothing significant between groups. IUG-BCS is an invaluable and effective modality for both palpable and nonpalpable breast cancer in obtaining clear surgical margins with optimum resection volumes and reducing re-operations. Furthermore, frozen section analysis of the specimen margins together with shaving cavity margins of the tumor bed for permanent analysis could be a feasible method for minimizing the requirement for reoperations.
Afsar Rahbar
Karolinska University Hospital, Sweden
Title: Studies of the importance of Cytomegalovirus infection in breast cancer
Biography:
Afsar Rahbar completed her PhD in 2004 and did her Postdoctoral studies at Karolinska Institutet, Stockholm, Sweden. During this period, I studied occurrence and significance of cytomegalovirus infection in patients with Glioblastoma Multiforme. Results from these studies are published in leading international journals. Currently, she works as a senior researcher at the Karolinska Institute with research focus on the significance of cytomegalovirus in patients with breast cancer. She has published 45 papers in leading international journals and she is a member of steering board for the Foundation Cure Cancer.
Abstract:
Recently, Human cytomegalovirus (HCMV) infection has been found in breast cancer. Our research group has recently detected HCMV in most neoplastic cells in sentinel lymph nodes and brain metastases (BMs) of breast metastases of breast cancer. The exact mechanism by which BMs develop is unknown. Several risk factors are associated with BMs. These include human epidermal growth factor receptor 2–positive breast cancer, triple-negative breast cancer and COX-2 expression, as well as enhanced expression of integrin αvβ3, CXCR4/SDF-1 and CD44. COX-2 expression is thought to mediate impaired bloodbrain barrier functions, while CXCR4/SDF-1, CD44, and integrin αvβ3 are thought to mediate increased metastatic potential to the brain and promote angiogenesis, which may contribute to the development of BM. HCMV infection induces CD40 on the surface of the infected cells that interact with CD40L and results in VEGF production. Moreover, increased expression of integrin αvβ3, CXCR4/SDF-1, and CD44 may promote angiogenesis and initiate metastasis formation. High expression of HCMV-US27, another putative chemokine receptor, has been associated with enhanced expression of CXCR4 and induces cellular migration. In addition, HCMV infection increase expression of CD44, which increases cell–cell interactions, cell adhesion, and migration of infected cells. The prevalence of HCMV proteins and nucleic acids is very high in primary and metastatic tumors and may drive the development of metastasis; therefore, this virus may represent a potential therapeutic target in metastatic cancer. The long term goal of my study is to further understand the oncomodulatory role of HCMV in breast cancer and metastasization.