Day 1 :
University of Texas Health Science Center at Houston, USA
Zhiqiang An is Professor of Molecular Medicine, the Robert A. Welch Distinguished University Chair in Chemistry, and Director of the Texas Therapeutics Institute at the UT Health Science Center at Houston. His laboratory focuses on breast cancer antibody drug resistance mechanisms and cancer antibody drug discovery Previously, he was Director of Biologics Research at Merck Research Laboratories. Dr. An received his Ph.D. degree from the University of Kentucky and his postdoctoral training at the University of Wisconsin-Madison. He is elected fellow of Society for Industrial Microbiology and Biotechnology (SIMB) and the American Academy of Microbiology (ASM).
The natural immune responses that patients develop to their own tumors, as well as therapeutic regimens employing the latest anti-cancer monoclonal antibodies, would reasonably be expected to suppress tumor growth. Yet, a perplexing resistance to both is widespread. The ineffectiveness of the immune system to prevail in these situations suggests that cancers possess tactics to evade antibodies that could otherwise eradicate them. With a clinical context in mind, we observed that tumor-associated protein-degrading enzymes can diminish, and in some cases negate, cell killing functions by inducing a single clip in a small part of the antibody structure. The structural modification is so subtle that it had not been previously recognized and would not have been anticipated to so profoundly impair the antibody. To be able to visualize and establish if such cleavage occurred in cancer, we had to develop innovative antibodies for that exact purpose. Indeed, the new antibodies readily enabled the visualization of antibody damage when incubated with cancer cells in the laboratory or within tumor tissues obtained from animals or human patients. More importantly, the same antibody tools possessed the additional and remarkable property of restoring the lost functions to the damaged antibodies. The “rescue” of lost function suggested that this could be exploited as a therapy in cases where tumors cause antibody damage in order to evade our immune system. This novel therapeutic strategy represents a potentially new direction in cancer immunotherapy.
University of Sydney, Australia
Keynote: : Pharmacological activity of an advanced formulation of curcumin for targeted therapy of triple negative breast cancer
Time : 10:45-11:30
Pegah Varamini is a lecturer and group leader in Cancer Theme within the Faculty of Pharmacy. She is the leader of Breast Cancer Targeting-Drug Delivery Group. Dr varamini was awarded the prestigious National Breast Cancer Foundation (NBCF) fellowship in Jan 2016. She completed her Doctorate degree in Pharmacy (PharmD) in May 2005 and was awarded her PhD degree in Medicinal Chemistry and Pharmacology in December 2012 (UQ, Australia). She won 2012 Dean’s Award for Research Higher Degree Excellence. Dr Varamini’s work was selected by the Australian Academy of Science in August 2016, resulting in her personal presentation at the inaugural Falling Walls Lab in Canberra (a gathering of 25 selected Australian and New Zealand researchers, entrepreneurs, engineers and innovators).
Breast cancer is the most common malignancy and the second leading cause of cancer-related death among Australian women despite existing progress in the development of novel therapeutic strategies. Triple-negative breast cancer (TNBC) accounting for 10-17% of all breast carcinomas, is an aggressive histological subtype. It represents an important clinical challenge because these cancers do not respond to the available targeted agents. Thus, there is an urgent demand for specific therapies that target other receptors that are overexpressed in TNBCs. We have designed and synthesized a novel drug delivery system, which targets curcumin to the breast cancer cells through a ligand of luteinizing hormone-releasing hormone (LHRH) receptors. LHRH receptors are overexpressed in breast cancer cells including MBC and TNBC cells while they are not expressed detectably in most visceral organs. We have taken advantage of this differential receptor expression by attaching a new derivative of the LHRH peptide (as a targeting moiety) to the outer surface of novel polymer nanoparticles. These nanoparticles encapsulate curcumin, a non-toxic plant extract that has recently attracted much attention in medicine due to its remarkable therapeutical actions. It is called the "next generation multipurpose drug" and is the active constituent of the Indian spice turmeric. However, it suffers from a very poor metabolic stability and bioavailabilty due to low water solubility. We have used an advanced formulation strategy to overcome hurdles to make it effectively used as a medication and also target it specifically to the TNBC cells via LHRH receptors.
- Breast Cancer-Present Perspective Screening, Treatment, and Diagnosing | Breast Cancer | Breast Cancer Nursing | Breast Cancer-Clinical Trials | Breast Cancer during Pregnancy
Royal Brisbane & Women’s Hospital, Australia
Will be updated soon..
Following the release of the ACOSOG Z0011 trial debate exists as to which patients with a positive sentinel lymph node biopsy (SLNB) should proceed to axillary lymph node dissection (ALND). We aim to identify predictors of positive non-sentinel lymph nodes in these patients.
All patients undergoing a Level I-III ALND for breast cancer between January 2008-December 2016 at the Royal Brisbane & Women’s Hospital were identified through an established database maintained by the Breast & Endocrine Surgery Unit. Ethics approval was obtained to conduct this retrospective review.
A total of 887 patients underwent SLNB for breast cancer during the study period. Of these, 179 (20.2%) progressed to a level I-III ALND. 67 patients had positive non-sentinel axillary nodes representing 37.4% of patients undergoing ALND. Level III nodes were positive in 18% of patients. Lymphovascular invasion was present in 59% of patients with a positive non-sentinel lymph node as opposed to 39% of patients with a negative ALND (p = 0.01). Additionally, Grade 3 tumours accounted for 40% of patients with positive non-sentinel lymph nodes in comparison to 25% of patients who were negative (P = 0.03). T stage, ER status, PR status and HER-2 status did not affect risk of non-sentinel disease
Axillary clearance remains an important therapeutic approach for management of axillary disease in breast cancer. Following a positive sentinel lymph node biopsy patients with lymphovascular invasion and grade 3 tumours should proceed to a Level I-III ALND given their increased risk of non-sentinel lymph node disease.
University of Texas Medical Science Center at Houston, USA
Ningyan Zhang was a protein biochemist and started my career in the pharmaceutical and biotechnology industry working on antibody engineering and drug discovery. After a 15-year research career in the biotechnology industry, I was recruited as a Texas ETF (Emerging Technology Fund) Scholar to join the faculty of the University of Texas Health Science Center at Houston (UTHealth) in 2010. My current research programs focus on cancer biology and translational research to bridge novel target discovery to drug discovery. I received my Ph.D. degree postdoctoral training from the University of Kentucky and the University of Wisconsin, respectively.
EGFL6, a member of the EGF like superfamily, is significantly upregulated in tumor- versus wound or normal endothelial cells. Our recent study and reported by others showed that EGFL6 plays important role in regulation of stem cell division and promoting angiogenesis. Using a series of in vitro and in vivo studies using orthotopic and genetically engineered mouse models, we demonstrated the mechanisms by which EGFL6 stimulates tumor growth and angiogenesis in both ovarian and breast cancer types. Significantly, EGFL6 blockage in vivo did not affect normal wound healing as shown by the existing anti-angiogenesis cancer therapy such as avastin. We have identified a panel of EGFL6 neutralizing monoclonal antibodies and investigated anti-EGFL6 antibody function in tumor inhibition. Results showed that blocking EGFL6 expression inhibited cell migration and invasion in cell culture studies. Targeting EGFL6 using our anti-EGFL6 antibodies also reduced the tumor growth in vivo. The results suggest that EGFL6 is a potential therapeutic target for breast cancer treatment and the anti-EGFL6 antibody presents a novel therapeutic strategy for blocking development of breast cancer metastasis.
International Medical University, Malaysia
Ebenezer Chitra completed her Ph.D. from National Institute of Immunology, Jawaharlal Nehru University, New Delhi, India. She did her post-doctoral fellowship in National Health Research Institutes, Taiwan working on cell signaling in cancer. Currently, she is a faculty in the School of Health Sciences in International Medical University. Her research interest is in cancer biology.
Breast cancer is the most common cancer affecting women; survival depends on early diagnosis and treatment. The common choices of treatment are surgery, radiotherapy, hormonal therapy and chemotherapy. Lactoferricin B (Lfcin B) is a 25-mer natural peptide obtained from milk protein lactoferrin and has demonstrated anti-cancer properties. Tumour was induced in the mammary pad of immunocompromised mice by injecting human breast cancer cells, MDA-MB-231 in the breast pad and allowing to develop into tumors. The establishment of tumor was confirmed by IVIS in vivo imaging system, which detects the GFP fluorescence from the implanted cells. Once the tumors were palpable, they were injected with lactoferricin B peptide intratumorally (3-5 mg/mouse/day) for 3 subsequent days. The mice were sacrificed 15 days post treatment. The harvested tumors injected with peptide showed a remarkable decrease in size and weight compared to tumors injected with vehicle control PBS. Our studies suggest that Lfcin B can be developed as a potential therapy for breast cancer, especially against drug resistant tumour cells.
The University of New South Wales, Australia
Bettina Meiser is and a Professor and Head of the Psychosocial Research Group, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia. She is a an internationally recognised expert in the area of psychosocial aspects of cancer genetics. She has published over 170 peer-reviewed articles. Her research program focuses on the psychological impact of cancer genetic counselling and testing, and the design and evaluation of interventions in this setting. She has undertaken research on the psychological impact of genetic testing a range of conditions including, amongst others, hereditary breast and/or ovarian cancer (HBOC), Lynch Syndrome, Familial Adenomatous Polyposis (FAP), and hereditary melanoma. She has also conducted innovative research on the psychosocial implications of new gene testing technologies, including the impact of treatment-focused genetic testing following a diagnosis of breast and/or ovarian cancer and the impact of testing for low-risk gene variants related to breast cancer. Bettina Meiser has been involved in the development and evaluation of a range of psycho-educational materials, including decision aids, for use in different settings in the cancer genetic counselling setting and oncology. All of the decision aids she has developed for people at increased genetic risk for hereditary disorders are being widely disseminated to familial cancer services around Australia. She is also undertaken extensive research on cultural aspects of cancer genetics.
Web-based point-of-care cancer genetics guidelines were launched across Australia in 2005 (http://www.eviq.org.au) to support the clinical decision-making in patient care. This project aimed to assess adherence to guidelines.
Materials and methods
Data collection was performed by trained genetic counsellors at 13 familial cancer clinics across Australia. (i) A file audit was carried out to assess compliance with guidelines regarding selection of patients for an offer of genetic testing for heritable mutations in the BRCA1/2 genes. (ii) From each familial cancer clinic, a random sample of unaffected carriers of BRCA1, BRCA2 and Lynch Syndrome-related mutations were selected. Patients were interviewed to assess their adherence to recommended risk management guidelines and barriers in compliance to guidelines.
(i) A total of 1,053 files were audited. Preliminary data analysis shows a high interrater reliability (k-statistics=0.89). Compliance of genetic testing uptake after the introduction of guidelines was around 70%. In more than 95% of noncompliant cases publicly funded genetic testing was used. (ii) 168 BRCA1, 161 BRCA2 and 215 Lynch Syndrome-related mutation carriers were interviewed. Twenty-eight percent to 32% of known mutation carriers for BRCA1/2 are in the younger age group and are waiting to complete their families before completing breast-cancer related risk-reducing surgery. Other reasons commonly cited for non-adherence were lack of awareness, past bad experience and fear of adverse effects.
This study provides data on the reasons for non-adherence to risk management recommendations amongst patients and thus provides the basis for the development of interventions to address such nonadherence.
Higher College of Technology, Sultanate of Oman
Manal Humaid Al Khanbashi has completed her PhD as join collaboration between Sultan Qaboos University (Oman) and Karolinska Institute (Sweden) and currently working as a “Lecturer” in Higher College of Technology. She developed some interests in the fields of methylation and miRNA expression changes in response to external factors like treatment, diet and physical activities as epigenetics elements in breast cancer. She has some publications in miRNA expression in locally advanced breast cancer in response to chemotherapy treatment. She initiated the “amaware” initiative for public awareness on healthy lifestyle, breast cancer, fitness and healthy diet (through workshops and social media).
Worldwide, breast cancer is the second leading cause of death in females exhibiting a significant global health burden. Piling evidences based on the reversibility nature of the epigenetics effects like physical activity and dietary habits may play a pivotal role in disease manifestation.
Among the most effective intervention that has an effect on cancer is the physical activity in which at moderate levels showed to reduce the risk of death from breast cancer and many other chronic diseases. Studies have showed high and low intensity supervised multimodal intervention exercises reduced cancer patients fatigues, muscular strength and improved patients’ wellbeing. Based on gene methylation expression data of breast cancer patients undergoing randomized clinical trial exercise revealed reduction in gene methylation of tumour suppressor genes in association with overall survival.
Herein, this study will give an overview on the predisposition of such exogenous epigenetic effects of physical activities on the potential reversibility and preventive possibilities of breast cancer.
Translational Research in Oncology, Uruguay
Gonzalo Spera is a practicing medical oncologist mostly dedicated to translational research. He has the position of Clinical Research Physician and Study Manager in Translational Research in Oncology (TRIO), an academic CRO fully dedicated to design and run clinical trials in patients with cancer. Gonzalo owns a Master in Basic Sciences of Medicine (UDELAR, Uruguay) and in Molecular Oncology (CNIO, Madrid). He is now pursuing a PhD degree within TRIO with his project “Beta-blockers: promissory anti-cancer agents in breast cancer ”.
Stress is usually considered among the numerous factors involved in the complex process of cancer carcinogenesis. However, how stressors or stress response impact on the natural history of this disease is still unknown. The adrenergic pathway is involved in stress responses in daily life being epinephrine and norepinephrine its key mediators. These hormones have been previously described as potent mitogens in normal and malignant cells. The blockage of this pathway by beta-adrenergic antagonists (BBs) has proven to disrupt cell proliferation and migration in malignant cell models. In the clinical setting, BBs have also been linked to improved cancer control rates in patients with localized and advanced breast cancer. Inconsistent results from different retrospective studies have encouraged the conduction of distinct meta-analyses from which, as of today, no clear conclusions can be made. Recently our team has shown significantly improved outcomes in patients with advanced triple negative breast cancer who received BBs for other comorbidities. We hypothesize that the discordance observed in the available evidence could be a consequence of methodological limitations and tumor heterogeneity. Consequently, we are now conducting a back-translational project in order to search consistent signals now in breast cancer pre-clinical models exposed to BBs, with the objective to improve the understanding of their mechanism of action. In addition to this, confirming the value of adding BB to standard therapies in a prospectively designed clinical trial is needed. Because BBs are inexpensive and well-established agents with an excellent safety profile, prospective controlled studies in this context are feasible.
Gujarat Cancer and Research Institute, India
Nikhil Garg has completed his MS in the year 2015. He is Gold medalist in his masters degree. He is now persuing super specialization degree, MCh in surgical oncology. He is working in Gujarat Cancer and Research Institute, Ahmedabad, India. It is a premier cancer institute in the country.
Post mastectomy radiotherapy (PMRT) reduces loco-regional recurrence (LRR) and improves overall survival.There is international consensus to recommend PMRT for patients with tumour size more than 5 cm, tumour invasion of the skin, pectoral muscle or chest wall and patients with > 4 positive lymph nodes. However, the role of PMRT for patients with T1 , T2 disease with 1–3 positive LN is still controversial. The side effects of radiotherapy and its associated morbidity have to be considered in the risk benefit ratio, thus difficult to arrive at consensus in early breast cancer.
101 patients treated between 2012 to 2015 were studied retrospectively, The inclusion criteria for this analysis were:(1) Female patients with unilateral breast cancer and no distant metastasis at initial diagnosis who underwent mastectomy and axillary lymph node dissection; (2) postoperative pathology indicated T1–2 and 1–3 positive axillary lymph nodes (T1–2N1M0) disease, at least 10 lymph nodes removed by axillary dissection; (3) complete surgical resection of the tumor and negative margins; (4) complete estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor family 2 (Her2) status; (5) No neoadjuvant chemotherapy was administered before surgery and endocrine therapy was performed based on the hormone receptor status. In order to study the research questions, we formulated hypotheses as follows,1. Radiotherapy does not have any impact on recurrence post mastectomy.2. There is no influence of Peri nodal extension on recurrence. The above hypotheses were tested using chi- square test.
Recurrences were obtained in 9 amongst radiotherapy and without radiotherapy in 16.When chi square was applied ,the value was highly significant.Hence our hypothesis was rejected.
Also in case of PNE with recurrence and radiotherapy,8 had PNE with radiotherapy and recurrence and 27 had no recurrence, p value was 0.013% hence highly significant.
Radiotherapy should be strongly considered in patients with 1-3 nodes post mastectomy as it decreases the chances of recurrence