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.