Day 2 :
Keynote Forum
Yvonne Paterson
University of Pennsylvania, USA
Keynote: HER-2/neu as a target for Listeria-based cancer immunotherapy for breast cancer
Time : 9.00 - 9-20
Biography:
Yvonne Paterson is Professor of Microbiology in the Perelman School of Medicine at the University of Pennsylvania, USA. As a Professor of Microbiology, Patersonrnis 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 firstrninvestigator to use Listeria monocytogenes, as a vector to target tumor-associated antigens to the immune system. She has pioneered the application of thisrnorganism in vaccine development for over 20 years. Her laboratory was the first to show that this bacterium could be genetically engineered to target antigensrnto the MHC class I pathway for antigen processing with the induction of cytotoxic T cells, the first to show that it could provide protective immunity against viralrnchallenge and the first to apply the technology for the immunotherapy of cancer. In partnership with Advaxis Inc., a company she founded in 2002, the Listeria basedrntechnology is now in a number of clinical trials. Overall, these trials have shown that Listeria based immunotherapeutics are safe to use in humans and result inrnsignificantly prolonged survival and, in some cases, complete and partial remissions.
Abstract:
We have been developing novel, live, highly attenuated bacterial vectors based on Listeria monocytogenes (Lm),rnbioengineered to secrete tumor-associated antigens and to present them to the immune system in a particularlyrnimmunogenic manner. The Lm vector itself, in addition to its major virulence factor listeriolysin O,(LLO), serves as its ownrnadjuvant and is phagocytized byAPC where it presents antigens through both MHC class I and II pathways,resulting in specificrnT-cell immunity to tumors. We have conducted extensive pre-clinical studies to determine the mechanism of action of Lm asrnan immunotherapeutic and its efficacy in numerous mouse models of cancer.Here we will describe the advancement of Lm-rnLLO immunotherapyinto the clinic for HER-2/neu over expressing tumors, such as breast cancer.Lm-LLO-cHER-2/neu,is anrnLm-LLO immunotherapy bioengineered to secrete a chimeric polypeptide consisting of three regions of HER-2/neu knownrnto contain most human HLA epitopes. This polypeptide, comprising 419 residues, about one third of the intact HER-2/neurnmolecule was fused to a truncated form of LLO for expression by Lm. Lm-LLO-cHER-2/neu has proven to be effective atrnlimiting tumor growth in pre-clinical mouse models of 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.
- 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 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.