Biography:

Yun Gong has received her MD degree in 1984 and then finished her Postgraduate Pathology training in 1989 at Zhejiang Medical University in China. She then worked as a Post-doctor and Research Associate in the Shanghai Institute of Cell Biology, Chinese Academy of Sciences, Catholic University of Nijmegen, the Netherlands and the Scripps Research Institute, La Jolla, California. From 1998 to 2002, she has received her residency training in Anatomic and Clinical Pathology at Northwestern University Medical School in Chicago, followed by one-year cytopathology fellowship training at MD Anderson Cancer Center. From 2003, she became a Faculty Member at the Dept. of Pathology, MD Anderson Cancer Center, and currently is a Full Professor. She has numerous publications in the fields of breast cancer research and cytopathology (120 peer-review articles, 18 invited articles, 6 book chapters and 1 book, 118 abstracts). She is an important collaborator of two IBC research projects that were funded by Susan G Komen Promise Grant. She is a Guest Editor of Breast Diseases: Year Book of Oncology since 2011, a Member of the study section of MD Anderson Institutional Research Grant Program, and was a reviewer for NCI/NIH on Business Innovation Research Contract Proposals in 2009 and 2013

Abstract:

Inflammatory breast cancer (IBC) is rare but the most lethal type of breast cancer. IBC is often associated with early metastasis and resistance to conventional therapies. Understanding biological insights that underlie the aggressive behavior of IBC and identifying novel therapeutic strategies are highly desirable for improvement of clinical outcome in patients with IBC. This presentation will cover the clinic-pathologic significance of some important biomarkers expression in a cohort of IBC that have long-term clinical follow-up and treatment information. Our results indicated that EZH2 and PD-L1 (clone 28-8) expression status may be used to identify a subset of patients who have a relatively worse prognosis. Targeting EZH2 also may provide a novel strategy for improving the clinical outcome of patients with IBC. In addition, androgen receptor expression was significantly associated with lymphovascular invasion. Additional information and discussion will be presented.

Biography:

Steven M Hill received his PhD from the University of Arizona School of Medicine and Postdoctoral studies under Dr William L McGuire at The University of Texas Health Science Center in San Antonio. He is a Professor in the Department of Structural and Cellular Biology, the Edmond and Lily Safra Chair for Breast Cancer Research, and then Director of the Tulane Center for Circadian Biology at Tulane University School of Medicine. He has published more than 100 peer-reviewed papers in reputed journals and has been serving on the Editorial Board of the Journal of Pineal Research and Frontiers in Endocrinology.

Abstract:

Cancer patients with disrupted 24-hour (circadian) rhythms are reported to have poorer survival as compared to those with normal rhythms. We have reported that circadian/melatonin (MLT) disruption by exposure to dim light at night (dLAN) resulted in constitutive activation of ERK1/2, STAT3, and signaling nodes involved in epithelial to mesenchymal transition (EMT) in breast tumor xenografts promoting drug-resistance and that MLT can suppress the invasive activity of metastatic breast cancer. This study examined the scientific premise that dLAN-induced circadian/MLT disruption promotes EMT of epithelial MCF-7 breast tumor xenografts leading to the development of metastatic foci in the lungs, livers, and brains of circadian complete (MLT-producing) athymic nude female rats and mice. Employing athymic nude female rats and mice with ERa+ MCF-7 luciferase expressing tumor xenografts housed in LD, 12:12 (nighttime MLT) and LD, 12:12dLAN (dLAN) photoperiods or in dLAN supplemented with night time MLT, tumor from rats in dLAN showed increased growth and expression of signaling nodes involved in promoting EMT and metastasis vs. those from rats in LD: 12:12 dLAN+MLT or LD, 12:12. Nude mice exposed to dLAN showed metastatic outgrowth of MCF-7Luc xenografts forming identifiable metastatic foci in the lungs, livers, and brains of all mice, which was inhibited by MLT, as measured by IVIS small animal imaging system. CRISPR knock out of the MT1 MLT receptor in MCF-7 breast cancer cells induced a 9-fold increase in invasion as compared to parental control cells. This study is the first to show that circadian/MLT disruption by dLAN cab drive EMT and metastasis.

Biography:

Bashar Zeidan is a Clinical Lecturer in Surgery at the University of Southampton. He has a special interest in breast cancer research and oncoplastic breast surgery. He was awarded the first UK Academic Clinical Fellowship in Surgery in 2007. Following his fellowship he completed a higher degree focusing on breast cancer research and was granted a Doctorate of Philosophy Degree from the University of Southampton in 2013. He is an author of more than 15 papers and 2 book chapters in the field of surgery.

Abstract:

Introduction: Adjuvant hormonal therapy in oestrogen receptor (ER) positive breast cancer patients improves survival. In 2006 the original tamoxifen preparation (Nolvadex) was discontinued and patients were since gradually switched to alternative generic tamoxifen brands. The goal of this study is to evaluate factors affecting adjuvant tamoxifen related side effects and compliance including altering tamoxifen products.

Methods: Consecutive patients treated for ER positive breast cancer (stage I-III) in the Royal Hampshire County Hospital between January 1, 2007 and December 31, 2009 were included. 327 questionnaires were sent to eligible patients. Pearson’s c2 test was used for data analysis.

Results: 59% of patients experienced side effects associated with tamoxifen treatment out of which 53% were severe. Switching to generic tamoxifen was associated with more severe side effects (p=0.02). Non-prescribed supplements were taken by 42% of symptomatic patients with no significant improvement (p=0.05). Interestingly, the concomitant use of SSRI had no effect on side effects experienced by patients. A significant number of patients considered discontinuing tamoxifen because of the side effects (p=0.001), yet this did not translate into tamoxifen discontinuation or non adherence (p=0.8 and 0.08 respectively).

Conclusions: Severe tamoxifen side effects are commonly experienced by breast cancer patients and are altered by change in tamoxifen brand. Most patients will continue to take tamoxifen despite these side effects following clinicians’ advice to avoid cancer relapse. Supplementation and antidepressants did not improve tamoxifen related side effects. Further studies are needed to validate our preliminary findings.

Biography:

Jill Brook Hervik is currently working as a Physiotherapist, Acupuncturist and Researcher in hospital pain clinic (Vestfold Hospital Trust, Norway). Her areas of interest include integrative medicine, the importance of detailed clinical examination, multidisciplinary approach to pain syndromes and long term side effects of breast cancer treatments. She has published eight different articles in reputable medical journals.

Abstract:

Purpose: To access frequency and severity of adverse effects (AE) of non-hormonal drugs (NHD) for hot flashes in breast cancer survivors compared to controls and analyze adverse effect risk by reviewing published randomized trials.

Methods: Five data bases were searched, trials were included where participants were breast cancer survivors suffering from hot flashes, treatment was self-administered venlafaxine, gabapentin or clonidine, and AE’s were reported. AE frequency and severity was graded and a meta-analysis with sub-group analyses was conducted.

Results: 12/49 studies were included, 1467 participants experienced 772 adverse effects, 81% from treatment groups and 19% from control groups. 67% of AE’s was graded as mild and 33% as moderate. The frequency of AE for NHD was overall significant versus placebo. AE frequency and severity increased at higher doses for venlafaxine and gabapentin compared to placebo.

Conclusion: The odds for experiencing AE was significantly higher in patients randomized to high dose NHD than those randomized to controls, including placebo, low dose medication and acupuncture. These therapies should be considered as a potential treatment alternative.

Biography:

Amy Hong Zhang is an Associate Professor in the Department of Pathology and Translational Molecular Pathology in University of Texas-MD, Anderson Cancer Center in Houston, TX she is an American Board certified practicing Pathologist since 2003. She has expertise in diagnosing breast cancers and the interpretation of the biomarkers relevant to breast cancers for patient care. She is also actively supervising research scientists and trainees on translational and laboratory research, focusing on the characterization of tumor markers significant for breast tumorigenesis and the development of small molecule inhibitors and potential novel molecular targets for breast cancer treatment

Abstract:

The chromosome 17 is a frequent site of cancer-associated genetic anomalies and is strongly associated with poor prognosis. Previous studies of breast cancer have revealed the amplification of several genomic regions on 17q. These amplifications are typically discontinuous and complex in structure, suggesting that multiple oncogenes in this chromosomal segment may be co-selected during breast carcinogenesis. By integrative analysis of public genomic datasets of breast cancers from the cancer genome atlas (TCGA) including 910 tumor cases and 981 normal controls, we have found that FOXK2 in 17q25 displayed frequent genomic amplifications and correlated gene expression changes in all subtypes of breast cancers classified by PAM50 compared to normal controls. Its overexpression was associated with poor overall survival of breast cancer patients. FOXK2 knockdown using lentivirus mediated shRNAs inhibited breast cancer cell proliferation and anchorage-independent growth in four breast cancer cell lines with high FOXK2 expression status (MDA-MB-231, MCF-7, HCC1954 and MDA-MB-361). More importantly, overexpression of FOXK2 and oncogene RAS induced MCF10A cell colony formation, indicating that FOXK2 is an oncogene in breast cancer. The potential interacting molecules/pathways were explored using RNASeq technique on the FOXK2 knockdown breast cancer cells. Several pathways, including regulation of cell proliferation, regulation of cell division, cell adhesion and regulation of cell metabolism, were regulated by FOXK2 in breast cancer cells. Our data provide compelling evidence that FOXK2 is an oncogene in breast tumorigenesis, and it might be a novel therapeutic target and a biomarker predicting poor outcome.

Biography:

Abstract:

Biography:

Carole Verhoeven is a PhD holder. She is the Chief Scientific Officer (CSO) at Pantarhei Oncology BV, the company developing estetrol for the treatment of breast and prostate cancer. She has studied Chemistry at the Catholic University of Nijmegen (1989) and received her PhD on the metabolism of structurally related synthetic steroidal hormones in 2001 from the University of Groningen. From 1994-2011 she has been working for Organon/Schering-Plough/MSD in several positions in preclinical and clinical development. She has published 24 scientific papers in peer-reviewed journals

Abstract:

Efficacy of estrogens for treatment of advanced breast cancer was first described by Haddow in 1944. Results of Haddow were a paradox, as breast cancer was considered to be dependent on estrogens for growth. In the following years research on high dose estrogens (HDEs) was continued, making estrogens the standard of care in postmenopausal women with advanced breast cancer. In the 1970s, estrogen therapy was replaced by tamoxifen. Although not more effective than HDEs, tamoxifen was less toxic and therefore considered to be the preferred agent. In the 1990s, estrogen therapy has gained new interest as clinical studies showed anti-tumor efficacy with different estrogens (DES, EE, E2) in heavily pre-treated postmenopausal women in an estrogen deprived setting. The fact that estrogens can be used to treat breast cancer has almost been forgotten. Therefore, a review paper has been published, summarizing all literature data on this topic. The success of estrogen therapy is dependent on the menopausal status and how long the patient has been deprived of estrogens (gap hypothesis). Research on mechanism of action has shown that apoptosis induced by estrogens is regulated via the estrogen receptor. HDEs have a negative safety reputation, especially of having side effects related to the cardiovascular system. The fetal estrogen estetrol might be a new treatment option as estetrol has less interference with liver function as compared to other estrogens. A proof of concept study is ongoing in Germany to assess safety and anti‑tumor efficacy of estetrol in postmenopausal women with advanced ER⁺ breast cancer.

Biography:

Cohen-Armon working in an Academic position at the Tel-Aviv University Life Science, Neurobiochemistry and  Faculty of Medicine, Dept. of Physiology and Pharmacology and the Sagol School of Neuroscience . In 2001, she was appointed as visiting researcher in Columbia University, New York. She conferred with Human Frontiers award. She has published more than 30 papers in well reputed and high impact factor journals since 2000. Her research was supported by Novartis and the active molecule is prepared for use against triple negative breast cancers. She is an academic editor for several journals. Her interest lies in Signal transduction and Epigenetic mechanisms, protein modifications, drug discovery.

Abstract:

A newly - discovered mechanism involves the modification of specific proteins that affect the construction and stability of the spindle structure during mitosis. Their exclusive modification in human cancer cells prevented chromosomes segregation into daughter cells. Modifications of kinesins and NuMA, preventing their normal activity in the spindle of human cancer cells disrupted chromosomes alignment in the spindle mid-zone. This induces a rapid cell self-destruction while mitosis is prevented. Thus, the faster the cancer cells proliferate, the more quickly they die. Research was conducted using both cancer cell cultures and mice transplanted with human cancer cells. Mice transplanted with triple negative breast cancer cells revealed the arrest of tumor growth by agents causing their exclusive cell-death during mitosis, without affecting normal proliferating cells.

Biography:

De Francesco EM has completed her PhD in 2013 at the University of Calabria, where she has been involved in the characterization of estrogen signaling through GPER since 2009. She has published more than 25 papers in reputed journals and she has joined the University of Manchester in 2015, where her research is currently supported by an EU and AIRC (Associazione Italiana per la Ricerca sul Cancro) co-funded fellowship.

Abstract:

Compelling experimental evidence indicate that a member belonging to the G-protein coupled receptor superfamily, named GPER/GPR30, acts as a receptor for estrogens in diverse physio-pathological conditions, including breast cancer. Furthermore, GPER signaling has been shown to mediate stimulatory responses in breast cancer associated fibroblasts (CAFs), which are key components of the tumor microenvironment driving disease progression. In this context, we have recently demonstrated that GPER is involved in breast cancer cells adaptation to hypoxic microenvironment, through the activation of HIF-1α/VEGF transduction pathway and the angiogenic response. Worthy, a functional cross-talk between GPER- and growth factor (EGF, insulin and IGF1)-signaling has been demonstrated to integrate complex biological events in breast cancer, like cell proliferation and migration. Here, we evaluate the angiogenic-promoting role of GPER through the regulation of VEGF expression and function triggered by IGF1. Using estrogen receptor (ER)-negative and GPER positive SkBr3 breast cancer cells and CAFs derived from mammary ductal carcinomas, we demonstrate that IGF1 activates through IGF1R the ERK1/2 and AKT cascades, leading to the increase of HIF-1α and its targets GPER and VEGF. RT-PCR, western blotting, immunofluorescence and reporter assays, gene silencing strategies and in vitro angiogenesis studies show that a functional cross-talk between HIF-1α and GPER regulates VEGF expression and function, toward new blood vessel formation in breast cancer. Taken together, our findings demonstrate that targeting the interactions between GPER and IGF1/IGF1R may represent an innovative strategy for halting the angiogenic response in breast cancer.

Biography:

Manjeet Rao has completed his PhD from University of Delhi and Postdoctoral studies from MD Anderson Cancer Center, Houston, TX, USA. He is an Associate Professor at Greehey Children’s Cancer Research Institue, University of Texas Health Science Center, San Antonio. He has published more than 38 papers in reputed journals including cell, PNAS, blood, leukemia, oncogene and clinical cancer research

Abstract:

Defect in DNA damage response serves as a major factor predisposing normal cells to acquire oncogenic mutations. However, after tumor develops, cancer cells manage their survival by repairing DNA damage resulting from unchecked DNA replication. Moreover, the ability of cancer cells to repair chemotherapy-induced DNA damage also serves as one of the mechanisms for therapy resistance. Therefore, successful targeting of factors/pathways that are capable of inducing DNA damage and suppressing DNA repair responses of cancer cells will have promising therapeutic outcomes. We recently discovered that imipramine blue (IB), a novel analogue of anti-depressant imipramine that we recently synthesized, induces DNA damage and inhibits the ability of breast cancer cells to repair DNA. Using an innovative ex-vivo model of tumor explants from breast cancer patients, we demonstrate that IB inhibits breast cancer growth without affecting normal mammary epithelial cell proliferation. Notably, our studies revealed that systemic delivery of IB using nanoparticle-based drug delivery approach suppressed breast cancer growth and metastasis without inducing any toxicity in pre-clinical mouse models. Furthermore, our in vitro studies show that IB may improve the efficacy of doxorubicin and paclitaxel, a chemotherapeutic drug combination that is routinely used to treat TNBC patients. Importantly, our drug-interaction results suggest that IB may directly bind to and inhibit the activity of proto-oncogene FoxM1 and subsequently alter FoxM1-associated signaling that play critical roles in DNA repair and are known to mediate taxol resistance. We believe that our study will set the stage for a new paradigm of treating breast cancers using IB therapeutic. Our preliminary studies showing inhibition of breast cancer growth in orthotopic mouse model and explants from breast cancer patients by IB without targeting normal mammary epithelial cells suggest that IB may serve as a novel therapeutic with negligible toxicity. Since FoxM1 has been proposed to be a bonafide therapeutic target for several cancers including non-breast cancers, identification of a compound like IB that inhibits FoxM1 and FoxM1-dependnet mechanisms has immense translational potential for treating many aggressive cancers.

Biography:

Anne Ryhänen has completed her PhD from University of Turku. She is the Director of Nursing in Turku City Hospital and the Clinical Teacher in Department of Nursing Science in the University of Turku. She has published more than ten papers in reputed journals. She is a Member of Empowering Patient Education research group, where she is making her postdoc study.

Abstract:

This study was conducted to examine the effect of the breast cancer patient’s pathway program (BCPP) on breast cancer patients’ empowering process. The ultimate goal of this study was to develop breast cancer patient education in a more empowering direction by using the patient pathway as a patient education tool. The BCPP is an internet-based patient education program. The structure of the BCPP is based on a flow chart diagram picture of the patient pathway during the breast cancer care and treatment process and used with oral and written patient education. Newly diagnosed breast cancer patients were randomized to an intervention group (n=50) and control group (n=48). The patients’ knowledge expectations, perceptions of received knowledge, knowledge level, quality of life, anxiety, and treatment-related side effects were measured during the breast cancer treatment process. Breast cancer patients’ perceptions of received knowledge were not fulfilled; their knowledge expectations exceed the perceived amount of received knowledge. Statistical differences were not found between the groups in terms of quality of life, anxiety and treatment-related side effects. However, anxiety decreased faster in the intervention group when looking at internal differences between the groups at different measurement times. In the intervention group the relationship between the difference between knowledge expectations and perceptions of received knowledge correlated significantly with quality of life and anxiety. Their knowledge level was also significant higher than in the control group. These results support the theory that the empowering process requires patient’s awareness of knowledge expectations and perceptions of received knowledge.

Biography:

Qing-Xia Li has completed her PhD from The Fourth Military Medical University. She is the Associate Director of the 4th Department of Oncology, Hebei General Hospital. She has published more than 40 papers in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

Breast cancer is the most common cancer for women worldwide. Endocrine therapy has become one of the most important treatment options for hormone-sensitive patients, which accounts for approximately 70-80% of breast tumors. Many studies have explored the effect of high BMI on breast cancer patients with endocrine therapy, but the treatment efficacy is not clear in China. The relationships among BMI, SII and luminal subtype in endocrine therapy of breast cancer have been rarely explored .We analyzed the data from 161 breast cancer patients ,and demonstrated that the 5-year resistance rates of the patients in high BMI group and high SII group are significantly higher than that in the normal BMI group and low SII group, indicating that BMI and SII are closely related to endocrine therapy resistance of luminal type breast cancer. Further analysis shows that BMI and SII reveal the significantly positive correlation, suggesting that the increase of BMI may promote the increase of SII in a certain way, and both are involved in the resistance to endocrine therapy.BMI and SII can be the indicators for the prognosis of luminal type breast cancer, which can not only improve prognostic accuracy, but also reduce the physical pain and cost toxicity for patients.