I am interested in BCS and Oncoplstic Surgery Department of Surgery. College of Medicine, Seoul National University, Graduated from School of Medicine, Seoul National University in 1973. 2011.5: Currently Director of Ewha Women’s University Cancer Center for Women, Seoul, Korea.2009.7-2011.4; President of Konkuk University Medical Center 2006-2008; President of Asian Breast Cancer Society 2006.7 ; Selected as one of the top 100 Health Professional as of Breast and Stomach Surgical Oncologist. International Biographical center of Cambridge, England 1982-2008; President, Chief Surgeon. Korea Cancer center Hospital. 2004.4; Currently Vice president of Korean Cancer Society.2001.6-2003.6;.President of Korean Breast Cancer Society 2000.6-2001.5. ; Organizing team leader of the 3rd Asian Breast Cancer Society congress. 2006.7; Selected as one of the top 100 Health Professional as of Breast and Stomach Surgical Oncologist. International Biographical Center of Cambridge, England
Breast cancer is the 2nd most female cancer followed by thyroid in Korea. Annual increasing breast cancer in States is about 1.1%, but 6.1% in Korea (22,000cases in 2015.) The survival rate of breast cancer patients in Korea was much improved with new diagnostic technology and treatment modalities (5yr and 10yr survival rates is 91% and 84% respectively). So breast cancer specialists started to consider about patients’ QOL, and developed new oncoplastic surgical technics without change of recurrence and survival. It’s meaning also includes the correction of unbalance to the natural unaffected breast. Surgery still remains the mainstay of treatment for breast cancer with the addition of adjuvant treatments such as chemotherapy, radiotherapy, hormonal therapy, target-therapy, immunotherapy, precision medicine and multimodality therapy. The principles of oncoplastic surgery of breast cancer are based on complete removal of breast cancer with minimal scarring and producing optimal breast shape and size. It includes careful preoperative planning as part of a multidisciplinary approach and a surgical plan that will result in optimal cancer management and the best possible aesthetic outcome. Neo-adjuvant chemotherapy or neo-endocrine therapy may, in appropriate cases, be used to shrink the tumor accordant to several biomarkers before surgery. In Korea I started BCS in 1986. Although it may be preferable to mastectomy in terms of psychologically and cosmetically, but sometimes It is more difficult to correct a deformity, especially after radiotherapy to the remnant-breast, that is, results of secondary shape-correction surgery are often not as good as expected, but patients don’t easily agree with delayed reshape due to fear of anesthesia and successful shape. So concurrent oncoplastic surgery should be considered with ADM (Acellular Dermal Metrix), Silicone or Water Implants) or autologous tissue reconstruction.
Germain Gillet is Professor at the Faculty of Medicine of Lyon and a group leader at Lyon Cancer Research Center. His current research focuses on the modifications of mitochondrial proteins in transformed cells and their consequences on cell death and metabolism. In 1995, Dr.Gillet described the antiapoptotic effect of the v-src oncogene and cloned the nr-13 gene, one of the few bcl-2 homologs known at that time. Later on, he characterized a number of Nr-13 related proteins in various species including mammals and zebrafish. Dr. Gillet made seminal contributions in the field, showing that the non-canonical roles of Bcl-2 proteins, in particular regarding calcium trafficking, are critical for the control of cell movements during the initial steps of development. This work has opened new avenues about the actual function of the Bcl-2 family proteins, including the context of breast cancer.
Bcl-2 is the prototypical member of a class of oncogenes that promote tumor progression by inhibiting cell death. Upregulation of apoptosis inhibitors in cancer is often correlated with chemotherapy resistance.
Bcl-2 proteins control mitochondrial outer membrane permeability increase and subsequent release of apoptotic factors. Thus, targeting mitochondria-based Bcl-2 proteins appears to be a promising strategy for the design of novel anticancer agents. To this end, a number of molecules referred to as BH3 mimetics are being developed whereas the BH4 domain of Bcl-2 proteins recently emerged as an additional target.
Actually, Bcl-2 proteins also reside at the endoplasmic reticulum (ER) where they control Ca2+ release from the ER lumen via IP3R channels. There is evidence that agents, including peptides, that disrupt Bcl/IP3R complexes, sensitizes cancer cells to chemotherapeutic compounds routinely used in the clinic and prevents tumor growth. Indeed, recent preclinical and clinical studies support the notion that such complexes are promising therapeutic targets to specifically prime cancer cells to death. Here I will review the current state of the art regarding the status of the apoptosis machinery as a therapeutic issue in the context of breast cancer.
Dr. Shiaw-Yih (Phoebus) Lin is a tenured professor and Deputy Chair of Department of Systems Biology at The University of Texas MD Anderson Cancer Center. Dr. Lin’s research efforts are focused within an overall theme of DNA damage response defects in cancer with the specific emphasis on systems and translational precision cancer therapy. Dr. Lin serves on editorial boards of ten international journals and has served on numerous grant review committees for NIH, DOD and other funding organizations both nationally and internationally.
The lack of specific targets for the treatment of triple-negative breast cancer (TNBC) is a major challenge as many patients with TNBC do not respond to conventional chemotherapy and develop recurrences within the first 5 years of follow-up. TNBC has significant overlap with basal-like breast cancer and shares clinicopathologic features with BRCA-mutated breast cancer. Because BRCA1 plays a major role in homologous recombination (HR) DNA repair, TNBC has long been known to exhibit dysfunctional HR repair. Intriguingly, among all of the potential HRD drivers that we identified, aberrations of RNA splicing factors were one of the top drivers in TNBC. Furthermore, we found that pharmacological inhibition of spliceosome synergized TNBC to PARP inhibitors and spliceosome inhibitors effectively overcame the resistance of TNBC to PARP inhibitors, demonstrating that spliceosome inhibitor/PARP inhibitor combination therapy may be effective in TNBC treatment.In addition, TNBC exhibited defects in the repair of stalled replication forks, another important function of BRCA1, which led to increased replication stress. In normal cells, replication stress activates the replication stress response (RSR) to maintain genome integrity. Defective RSR (RSRD) allows survival and proliferation of genomically unstable cancer cells. Intriguingly, we found that TNBCs display a gene signature that reflects RSRD and functionally confirmed dysfunctional RSR in TNBC. We have recently identified the underlying mechanisms that may mediate the RSRD in TNBC and develop novel therapeutic strategies, including immune checkpoint blockade to target TNBC based on their lack of intact RSR in cells.
Philippa Darbre is an academic scientist with a BSc Hons degree in biochemistry (University of Birmingham) and a Ph.D degree (University of Cambridge). Her postdoctoral research began at the Molecular Medicine Institute of the University of Oxford, and continued at the Cancer Research - UK laboratories in London where she became Head of the Cellular Endocrinology Laboratory. In 1991, she moved to the University of Reading where she is currently Professor Emeritus in Oncology. Her research over the past 37 years has been dedicated to studying the mechanisms by which oestrogens, antioestrogens and environmental endocrine disrupting chemicals regulate the growth of human breast cancer cells. She has published 3 books and 136 peer-reviewed scientific research papers. Her latest book was published by Elsevier in 2015 entitled “Endocrine Disruption and Human Health”.
In 2001, I proposed the hypothesis that regular topical application of chemical constituents contained in underarm cosmetics could be a contributory factor in the rising incidence of breast cancer and other breast diseases (Darbre. 2001. Euro J Cancer Prevention 10, 389). This was supported by the disproportionate incidence of breast cancer in the upper outer region of the breast where these chemicals are applied. This lecture will review subsequent research demonstrating that many of the constituent chemicals can be measured in human breast tissue and that the chemicals possess oestrogenic or genotoxic activity relevant to the development of the hallmarks of cancer in breast epithelial cells. For example, the alkyl esters of p-hydroxybenzoic acid (parabens), which are added as antimicrobials, have been measured in human breast tissue, and, through their oestrogenic activity, can increase proliferation, migration and invasion of oestrogen-responsive human breast cancer cells. Some chemical UV filters (benzophenone-3, octylmethoxycinnamate, 4-methylbenzilidenecamphor) have been recently measured in human breast tissue, and through their oestrogenic activity can also increase proliferation and migration of human breast cancer cells. Aluminium-based salts are used as an antiperspirant and have been measured in human breast tissue, breast cyst fluid and nipple aspirate fluid. Aluminium can increase proliferation and migration of breast epithelial cells. Epidemiological studies and animal models demonstrate a link between aluminium exposure and breast cancer development. Cyclic volatile methyl siloxanes are added as conditioning/spreading agents, and exposure of breast epithelial cells results in genotoxic consequences including loss of expression of the DNA repair gene BRCA1. If exposure to complex mixtures of oestrogenic and genotoxic compounds in personal care products is a factor in breast cancer development, then minimizing exposure could provide a strategy for breast cancer prevention.
Dr. Pusceddu Claudio is graduated in March 1986 from the University of Cagliari, with thesis title: “Mechanisms of induction of liver hyperplasia” and specialized at the same university in Diagnostic Radiology and Imaging Science in 1996 with thesis title “The Role of Computed Tomography in Staging of Endometrial cancer and in Medical Oncology with the thesis title “CT-guided percutaneous celiac plexus neurolysis in the treatment of visceral pain from cancer. He has worked in an oncological hospital since 1992, and he has specialized in extra-vascular interventional radiology in the field of oncological disease. Since 2004 he has been Director of Interventional Radiology Oncology at Businco hospital and since 2008 he has been Scientific Director responsible for refresher courses with CME (Continued Medical Education) accreditation “Brief Therapies and Interventional Radiology”. He is abmember of the following scientific societies: Italian Society of Medical Radiology (1993), Italian Society of Vascular Interventional Radiology, Italian Association of Medical Oncology, Italian Association of Neuroradiology, European Society of Radiology, European Society of Surgical Oncology, Cardiovascular and Interventional Radiology Society Europe and Interventional Radiology Society.
Background: Metastatic breast cancer is considered an incurable disease, and the main treatment goal is palliation, with the aim of maintaining or improving the quality of life and possibly improving survival.
Objectives: To evaluate the safety and efficacy of breast cryoablation (CRA) as local therapy for patient with metastatic breast cancer.
Methods: Thirty-nine breast lesions, mean size 2,1 (range 1 - 6,7 cm) in twenty-nine consecutive patients, mean age 51 (36-81) with core-needle biopsy-proven breast carcinoma and metastases were included in this study. Twenty-three patients had one lesion, 4 patients two lesions, 1 patient three lesions and 1 patient five lesions. Under local anaesthesia and mild conscious sedation, the tumour and surrounding breast tissue were ablated with percutaneous CT-guided CRA. Cryoablation consisted of 2 cycles each of 10 minutes of freezing followed by a 4-min active and 4-min passive thawing phase for each one. Twenty-four patients underwent one CRA session, four patients 2 CRA sessions and one patient underwent 3 CRA sessions.
Results: All CRA sessions were successfully completed and all breast tumors were ablated. Morbidity consisted in transient and mild ecchymotic changes and post-procedural oedema seen in ten cases. The therapeutic outcomes were evaluated by contrast-enhanced TC or MRI at 2-, 6-, 12-, and 18-month intervals. The absence of tumor enhancement TC or MR image was considered as indicating complete tumor necrosis. During the mean follow-up of 15 months (6- 28 months) 26 patients had shown complete response to the treatment. Only 3 patients out 29 (10%) showed relapse close to the treated lesion.
Conclusion: CRA of metastatic breast cancer is a safe and effective method which allows local control of the disease. This method can effectively be used with good local control of the disease in patients who present with metastases at the beginning of the illness.
Denise Senger native of Tulsa, Oklahoma, USA. She attended a private Catholic School and graduated in 1973. She attended the University of Oklahoma where I received a Bachelor of Science in Nursing in 1977. Her area of focus at that time was Maternal/Child Health and Public Health. She worked as an RN in Labor & Delivery for a short period of time until I was married and moved to Oklahoma City where She was employed by the Oklahoma City-County Health Department. She started their first multi-disciplinary maternal – child health high risk clinic in coordination with the University of Oklahoma Medical School.
Background: Oklahoma Project Woman (OPW) is a non-profit organization dedicated to providing free mammography and other breast diagnostic services for all Oklahoma women and men with no health insurance and limited income. The goal is to decrease the mortality rate of these women, who because of financial hardship, often delay seeking medical attention
Context: National: 68% uninsured women did not receive mammograms in 2005 (American Cancer Society, 2015).53 % of women in Oklahoma received a mammogram in 2012 (American Cancer Society, 2015).
Objective: Screen and distribute coupons, to women who qualify to enroll in the program; implemented by trained clinic staff
Veronica J James completed her PhD in Physics from the University of NSW in 1971. Working in crystallography, she published 40 papers on the molecular structures of small organic crystals, before moving into the fibre diffraction studies of collagen and keratin. In this area she has carried out the diffraction study that produced the successful structure for hard Î±-keratin and also pioneered the fi bre diffraction diagnostic tests for breast, colon, prostate cancers and for Alzheimer’s Disease. She was awarded an OAM for her Phones for the Deaf Program and her Advanced Physics Programs in 1996.
Certainly cutting five pubic hairs is a lot less painful than a mammogram. So why not use this simple method for diagnosing breast cancer. Since my first paper was published in Nature, March 4, 1999, many angry letters were published saying that my finding were not correct. Even a statement was published by a group of scientists saying that they were in my field and although they had never tried to do this experiment they did not believe my results.
Only one such group sent their samples to me and I did them, The results were delivered to Germany, where all were declared correct. The German scientists published a joint paper with me stating the results. 4000 samples have been tested since this time with the help of many assistants and no problems.
The hair test has many advantages chief among which is that it can detect the cancer as soon as it starts whereas mammograms can only detect the cancer when it is the size of a pea, about 2 years later.
Meanwhile this test has been cast aside and mammograms hold on. Let it get it back.
Hong Yan Wang has her
expertise in evaluation and passion in improving the health and wellbeing. She
has rich experience in breast ultrasonography
Backgrounds: We prospectively evaluated the performance of the vascular index (VI, defined as the ratio of Doppler signal pixels to pixels in the total lesion) measured via Smart 3D superb microvascular imaging (SMI) combined with ultrasound (US) Breast Imaging Reporting and Data System (BI-RADS) for breast lesions.
Methods: 232 consecutive patients with 236 breast lesions referred for biopsy at Peking Union Medical College Hospital were enrolled in the study from December 2016 to November 2017. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of VI, US BI-RADS and combination of the 2 methods were calculated with histopathologic results as the reference standard.
Results: Of the 236 breast lesions, 121 were malignant and 115 were benign. The mean VI was significantly higher in malignant lesions (9.7±8.2) than that in benign ones (3.4±3.3) (P<0.0001). Sensitivity, specificity, PPV, NPV and accuracy of VI (4.0 as the threshold), US BI-RADS and combination of the 2 methods were as follows respectively: 76.0%&90.9%&88.4%, 66.1%& 82.6%&94.8%, 70.2%&84.6%&94.7%, 72.4%&89.6%&88.6%, and 71.2%&86.9%& 91.5%. 17 US BI-RADS 4b lesions with VI less than 4.0 were downgraded to US BI-RADS 4a category, in which 14 (82.3%,14/17) were benign and three (17.7%, 3/17) were malignant.
Conclusion: VI combined with US BI-RADS improves the specificity, PPV and accuracy versus US BI-RADS used alone, and it can effectively downgrade BI-RADS 4b lesions to BI-RADS 4a. Smart 3D SMI may be a potentially useful imaging modality for accurately diagnosing breast lesions especially for US BI-RADS 4b lesions.
Time: 16:30 -17:00
Xiao Yan Zhang, with the
systematic professional theoretical basis and technical knowledge, she has been
engaged in clinical ultrasound diagnosis for many years. She is proficient in
the diagnosis and treatment of abdominal, gynecology and obstetrics, blood
vessels, superficial organs and other common diseases. She is familiar with the
clinical and research status and the latest progress of ultrasound
Purpose : To determine whether vascular index?VI?measured via Smart 3D superb microvascular imaging (SMI) in breast cancer correlates with immunohistochemically defined subtype and whether VI can predict molecular subtypes.
Materials and Methods: This prospective study involved 115 patients with 115 invasive breast cancers (mean size 2.65 cm, range 1.0–15.0 cm) who underwent superb microvascular imaging before therapy. The correlations between VI of breast cancers on Smart 3D SMI and molecular subtype, i.e. luminal A, luminal B (HER2-negative), luminal B (HER2-positive), HER2-positive and triple-negative were analyzed.
Results : The mean VI of the 115 tumors was 9.5±7.3 (range 0.0–32.9). Among the subtypes of the 115 tumors, 6 (5.2%) were luminal A with mean VI 7.4±8.1 (range 0.3–23.1), 7 (6.1%) were luminal B (HER2-negative) with mean VI 12.4±8.4 (range 4.1~26.2), 74 (64.3%) were luminal B (HER2-positive) with mean VI 8.9±6.4 (range 0.9±24.3), 14 (12.2%) were HER2-positive with mean VI 8.2±8.1 (range 0.9~24.3) and 14 (12.2%) were triple-negative with mean VI 16.4±8.5 (range 3.5~32.9). A cut-off value of 6.3 showed 71.4% sensitivity and 66.3%specificity with an AUC of 0.634 for predicting a HER2 positive subtype. A cut-off value of 18.4 yielded 66.7% sensitivity and 89.0% specificity with an AUC of 0.807 for predicting a triple-negative subtype.
Conclusion: VI shows a certain correlation with the molecular subtype of breast cancer?it is useful for predicting HER2-positive or triple negative subtype.
Dr. Kiven Erique
Lukong received his Ph.D. degree in biochemistry from the University of
Montreal in Canada and pursued his post-doctoral training first at Harvard
Medical School, U.S.A. and later at McGill University (Canada). He is currently
an Associate Professor in the Department of Biochemistry at the University of
Saskatchewan (U of S, Canada) since 2009 and a member of the Cancer Research
Cluster at the U of S. Since beginning his independent academic career at the U
of S, Dr. Lukong has obtained career awards from the Saskatchewan Health
Research Foundation (SHRF, Top New investigator 2010) and from the
Canadian Institutes of Health Research (CIHR, New investigator salary award). Dr.
Lukong’s research broadly involves elucidating the signaling mechanisms that
control the growth of normal and cancer cells. His lab is investigating the cellular and
physiological roles, and the mechanisms of action and modes of regulation of
the breast tumor kinase (BRK) family of non-receptor tyrosine kinases in breast
cancer and glioblastoma. The Lukong lab is also characterizing the diagnostic,
prognostic and therapeutic potential of the BRK family proteins in breast
cancer. Dr. Lukong holds or has held funding from SHRF, CIHR and the Canadian
Breast Cancer Foundation
Breast cancer is a heterogeneous disease that can be stratified based on the expression of molecular markers such estrogen receptor (ER), progesterone receptor and epidermal growth factor receptor 2. The movement toward targeted therapies has led to the development of drugs that block the function of some of these receptors as well as proteins associated with cancer formation and progression, including some non-receptor tyrosine kinases. Breast tumor kinase (BRK) is a non-receptor tyrosine kinase expressed in the majority of human breast tumors and breast cancer cell lines, but its expression has not been detected in the normal mammary gland. The overexpression of BRK has been shown to sensitize mammary epithelial cells to mitogenic signaling and to promote cell proliferation and tumor formation. However, there are still several unanswered questions about the cellular and physiological roles of BRK and its clinical implications in breast cancers. I will discuss our recent data highlighting the role of BRK in breast tumor progression, as well as the potential clinical implications of BRK in anti-hormonal drug-resistant ER-positive breast cancers.
Ajay Rana is the Director of Research in the Dept. of Surgery at the University of Illinois, Chicago. He is recognized in cell signaling, breast and pancreatic cancer fields. His research is funded through NIH and VA. Prof. Rana received several awards and honors for his research work and also received honorary visiting Professorship from many universities, including Iowa State University, Nanchang University and Windsor University School of Medicine. Prof. Rana has authored more than 70 peer- reviewed articles in prestigious journals and serves on multiple editorial boards of leading scientific journals, and as an expert member of the NIH, DOD and VA review committees.
Breast cancer (BC) is a heterogeneous disease and molecular analyses have classified BC under 5 sub-types. The discovery of new agents have certainly improved the clinical outcomes of BC, however, it is dismal in case of Triple Negative BCs (TNBCs) and has been attributed to a highly heterogeneous disease. The TNBC does respond to chemotherapy, but there is a high risk for recurrence and disease progression and therefore, the need still exists to develop more targeted, less toxic therapies for these specific sub-types of tumors. The majority of TNBCs are Basal-like disease, however detailed molecular analyses have identified TNBC cells that have characteristic like stem cells (classified as mesenchymal) with the propensity to cause recurrent metastatic disease.
We have identified a target in TNBC that plays a central role in cell survival. We observed that a kinase, called MLK3/MLKs was overexpressed and highly active in TNBC cell lines and tumors. Using human PDX and TNBC cell lines’ xenografts, we observed that the inhibitors of MLK3/MLKs were able to reduce tumor burden, however, some of the BC cell lines or their xenografts, especially mesenchymal sub-type were resistant to cell death. RNA-seq analyses were done and we identified a gene encoding TNFR family member, p75NTR was down regulated in tumors undergoing regression. The protein expression analyses confirmed that p75NTR expression was specifically low in mesenchymal compared to basal BC cell lines. Indeed, either overexpression of p75NTR or agonist of MLK3 that increased the expression of p75 in mesenchymal TNBCs, did sensitize to MLK3/MLKs inhibitors. Taken together, these results suggest that one of the strategies to promote cell death in mesenchymal TNBC will be to activate p75NTR (with an agonist) and then target with MLK3/MLKs inhibitors.
This work was supported by the National Institutes of Health grants CA176846 and CA216410 (to A.R.), and CA178063 (to B.R.).
The breast cancer care cost in the United States tops $16.00 billion annually and is rising. It is obviously, much larger in a global scale. Breast cancer is a multi-factorial disease. Therefore, to conquer the disease many overarching challenges need to overcome. The problem with the current treatment strategies they are narrowly focused and not necessarily using multi-disciplinary approaches. In many cases the therapeutics are targeted over and over again to the same axis of treatment while knowing fully when one pathway is blocked the cancer cell opens up another pathway. This certainly helps the pharmaceutical industries but not the patients or their families and friends who are in dire need of a cure.
Irrespective of the progress made in the area of glycoscience/glycobiology, the cancer researchers are from encashing the outcome of the discoveries. Dipak K. Banerjee’s laboratory at the University of Puerto Rico Medical School could see the gap and apply the niche to develop a glycotherapy which could serve as a next generation therapeutic to treat breast cancer in the clinic. The group has targeted the cancer holistically meaning both angiogenesis and the cancer cells received the same priorities. Using a pure protein N-glycosylation inhibitor tunicamycin Banerjee’s laboratory has categorically established that tunicamycin inhibits in vitro and in vivo angiogenesis, and the growth factors such VEGF cannot overcome the process. Also, the effect of tunicamycin cannot be washed out indicating there is a point of no-return. Similar results are obtained with nearly a half-a-dozen of human breast cancer cells. The humanized double negative and triple negative breast tumors in nude mice show a ~55%-65% reduction of tumor progression following tunicamycin treatment given by intravenous injection or administered orally. To see a similar effect by the FDA approved breast cancer therapeutic, taxol needs 15 times more. The molecular mechanism of tunicamycin is ER stress- induced unfolded protein response (upr)-mediated apoptotic cell death. Most importantly, tunicamycin alone inhibits the pathways targeted by all current therapeutics combined. Nano-formulated tunicamycin is three times more potent than the native tunicamycin. Thus, tunicamycin is going to the least expensive glycotherapy to treat breast cancer ever known with a least amount of side effect.
Dr.Dhanapal Sakthisekaran has joined as Lecturer in the Department of Medical Biochemistry, University of Madras in 1978. He has obtained his Ph.D., degree in 1988 and subsequently promoted as Reader and Professor in 1988 and 1994 respectively. He has published more than 140 research papers in reputed National and International journals He has received many awards for his contribution in Basic Medical Sciences. He has won Indian Council of Medical Research Award (Govt.of India) in 2003 and Tamil Nadu Scientist Award in 2005.He has also received SOMPS Poster Award from ICACT, Paris, France in 2008. He has guided 49 Ph.D students. He was the Editor in Chief of the journal BIOMEDICINE published by the Indian Association of Biomedical Scientists, India. He has retired in 2014 as Professor and Head and joined as UGC –BSR Faculty Fellow. Presently he is an Honorary Visiting Professor at the University of Madras.
Breast cancer has a major impact on the health of Women. Malignant progression of breast cancer involves a progressive deterioration of the normal mechanism of cell cycle. Chemotherapy is a treatment that uses anticancer drugs to kill cancer cells, or to stop them from multiplying. The side effects of chemotherapy depend mainly on the drugs, and the patient receives the doses. The natural antioxidants like Propolis, Thymoquinone, Plumbagin and Tangeretin are found to be very effective in minimizing the side effects induced by the anticancer drugs during chemotherapy. Therefore, researchers have focused diet and therapy as the best way in cancer chemoprevention and chemotherapy. The chemotherapeutic efficacy of these natural antioxidants in experimental breast cancer will be discussed.
Dr. Samir Attoub is Professor in the Department of Pharmacology, College of Medicine at the United Arab Emirates University. He obtained his Ph.D. from Paris VII University, France in 1998, and his Habilitation from Paris V University, France in 2002. Later, he served as a Senior Research Scientist at the National Institute of Health and Medical Research in Paris. In 2005, he joined the UAE University as an Assistant Professor and was promoted to the rank of Associate Professor in 2009 and to Full Professor in 2015. His current research is mainly in the field of cancer research (molecular biology of cancer and drug discovery) focused on the role of Akt/NF-K?/NOTCH signaling as a driving force behind solid tumor progression (survival, proliferation, invasion, angiogenesis, and metastasis).
Background: Breast cancer is the most common cancer seen in women worldwide and within this cancer, triple-negative breast cancers have the worst prognosis. The identification of new genes associated with triple-negative breast cancer progression is crucial for developing more specific anti-cancer targeted therapies, which could lead to better management of these patients. Invasion leading to metastasis represents the most devastating hallmark of cancer progression. Identification of genes associated with metastasis is crucial for the development of anti-metastasis targeted therapy.
The DEAD-BOX helicase DP103 was implicated in breast cancer invasion and metastasis. SMARCAD1 is also a DEAD/H box-containing helicase, suggested playing a role in genetic instability. However, its involvement in breast cancer progression has never been explored. The aim of this study was to investigate the impact of the stable knockdown of SMARCAD1 on breast cancer cell progression
Methods: Using two designs of shRNA targeting SMARCAD1, we investigated the impact of the stable knockdown of SMARCAD1 on human breast cancer cell migration, invasion, proliferation and colony growth in vitro and on tumor growth and metastasis in chick embryo and nude mouse xenograft models in vivo using the invasive breast cancer cell line MDA-MB-231 (ER-/PR-/HER2).
Results: We observed that SMARCAD1 knockdown in MDA-MB-231 cells was associated with increased cell-cell adhesion and a significant decrease in cell migration, invasion, and metastasis. We also found that SMARCAD1 knockdown resulted in a decrease in cancer cell proliferation and colony formation, leading to significant inhibition of tumor growth in both the chick embryo and nude mouse xenograft models. This inhibition was due, at least in part, to a decrease in IKK? expression and to a strong inhibition of STAT3 phosphorylation.
Conclusion: These results indicate that SMARCAD1 is involved in breast cancer progression and can be a promising target for breast cancer therapy.
Patriccia Anne Mae P. Paulino, MD. A graduate of
the University of Santo Tomas Faculty of Medicine and Surgery in 2015. She took
up Bachelors of Science in Nursing as my pre-med course also in the same
institution (University of Santo Tomas) in 2009. She had my post graduate
internship in UST Hospital from 2015-2016. Currently, She is on the 2nd year of
residency training, under General Surgery at University of Santo Tomas
Hospital. She aspires to be a Breast Cancer Specialist/Surgeon in the future.
Objective: In a developing country like the Philippines, mammography and breast ultrasound remains to be the key modalities for imaging breast lesions. Since the introduction of BI-RADS for ultrasonography and mammogram, breast lesions reporting was standardized, providing clinicians with guidance on the probability of malignancy of a given lesion. BI-RADS 4 lesions have been recommended for biopsy, however the wide range positive predictive value (PPV) (3%-94%) was problematic. It did not set out specific guidelines regarding the classification and the positive predictive value risk of malignancy for BI-RADS 4 subcategories (4A-4C). The present study aims to correlate between the sonomammographic findings of BI-RADS 4 lesion and its histopathologic results at the local setting.
Methods: A retrospective study was done in Filipino women who had mammogram and/or breast ultrasound with BI-RADS 4 score and underwent biopsy or surgery from January 2011 to December 2017 in a single institution. Total of two hundred three women (203) patients was included and was classified according to BI-RADS 4 subcategory (4a, 4b, 4c) and age groups (18-29, 30-49, ?50 years). Malignancy rate of each BI-RADS 4 subcategory was determined and among the three age groups were calculated on the basis of histopathological diagnosis and were compared using Chi square or Fisher’s exact test.
Results: Two hundred three BI-RADS 4
patients underwent either biopsy or surgery for histologic diagnosis but only
159 patients were subcategorised, 77 patients as Bi-RADS 4A, 39 patients as 4B
and 43 as 4C. Seven out of the 77 BI-RADS 4A patients (9%), 15 out of 39
BI-RADS 4B patients (38%) and 31 out of 43 BI-RADS 4C patients (72%) were found
to have malignant results. For age-related analysis, for ages 18-29 years old,
only 1 of 8 (14%) patients with BI-RADS 4A score had malignant lesion. For ages
30-49 years, 3 out of 37 BI-RADS 4A patients (8%), 3 out of 12 BI-RADS 4B patients
(25%), and 9 out of 15 BI-RADS 4C patients (60%) were found to have malignant
lesions. For ages ?50 years, 3 out of 33 BI-RADS 4A (9%), 12 out of 26 BI-RADS
4B patients (46%), and 22 out of 28 BI-RADS 4C patients (79%) were found to
have malignant lesions. In terms of presentation of the lesion, for
non-palpable lesions, 3 out of 55 BI-RADS 4A patients (5%), 11 out of 31
BI-RADS 4B patients (35%), and 17 out of 26 BI-RADS 4C patients (65%) were
found to have malignant lesions. For palpable lesions, 4 out of 22 BI-RADS 4A
patients (18%), 4 out of 8 BI-RADS 4B patients (50%), and 14 out of 17 BI-RADS
4C patients (82%) were found to have malignant lesions. Overall malignancy
rates were 9%, 38% and 72% for BI-RADS 4A, 4B and 4C respectively.
Conclusion: Malignancy rate of BI-RADS 4 lesions in Filipino women was comparable to the standard likelihood of malignancy world-wide. We validated the malignancy rate for non-palpable breast lesions to be also comparable to the standard likelihood of malignancy. On age-specific analysis, there is positive correlation between BI-RADS 4 subcategory score and malignancy rate for patients 30 years and above. Our data support the current recommendation for all BI-RADS 4 category regardless of subcategory especially for those 30 and above to acquire histologic diagnosis through biopsy.
Dr. Sveta Silverman, MD, conventional doctor with passion for education of disease prevention and health promotion. Dr. Sveta Silverman, MD FRCPC, surgical pathologist with breast pathology expertise, associate clinical professor, is a former pediatric surgeon from former USSR, and UofA medical school graduate, who completed surgical pathology fellowship and has an expertise in breast pathology. Dr. Sveta Silverman, MD is an accomplished author and presenter on breast cancer, NRF2 activation and mitochondria, one at at 8th world mitochondrial congress , Berlin 2017. Dr. Sveta Silverman, MD is on mission to educate and help millions of people to improve their health. Dr. Silverman, MD surgical pathologist by degree and teacher by call, invites you to a lecture:
Health and quality of life = choices and knowledge, cellular and microgut health and disease.
Background: Flat epithelial atypia (FEA) is a form of non-malignant
atypical hyperplasia of the breast. Historically, patients with FEA on breast
needle core biopsy have been advised to undergo open surgical excision to rule
out an underlying in-situ or invasive carcinoma. According to the literature,
the malignant upgrade rate of FEA diagnosed on core needle biopsy varies
between 0-30%. Excision versus observation with radiological follow-up for
these lesions remains controversial. We hypothesize that the local rate of FEA
is low and that close radiological surveillance is a reasonable treatment
option for patients diagnosed with pure FEA on breast needle core needle
Design: This study was a retrospective review of a prospectively-collated provincial pathology database. Patients diagnosed with FEA alone on needle core biopsy between 2006-2016 were included in our analysis. Patients who had FEA present together with either in-situ or invasive carcinoma within the same biopsy cores were excluded. Along with patient demographics, the size of the lesion on pre-operative imaging, the method of extraction and the presence of co-existing benign and malignant pathology on final excision biopsy were analyzed. An independent pathological review of a subset case was performed to confirm our results and help reduce inter-observer bias.
Results: The local rate of malignant upgrade when pure FEA is diagnosed on a breast needle core biopsy is 13%. Age at time of diagnosis, size of original lesion on the mammogram, presence of atypical ductal hyperplasia or atypical lobular hyperplasia on core needle biopsy, and the use of vacuum-assisted biopsy did not significantly correlate with malignant upgrade risk.
Conclusion: Our local malignant upgrade rate of 13% is consistent with published literature, but it is higher than expected. It is also unexpected that malignant upgrade occurs even after a diagnosis FEA only with VAB. Therefore, we currently recommend surgical excision for FEA given that appx 1 in 8 local women diagnosed with FEA on core or vacuum-assisted biopsy could harbor an underlying in-situ or invasive malignancy.
Mohamed Yousif Ibrahim is an assistant professor of Pharmacology and Toxicology at University of Sinnar, Sudan. He has obtained PhD in Pharmacology from University of Malaya, Malaysia. He was involved in many pharmacological and toxicological researches. Currently he is founder and the dean of pharmacy collage at Sinnar University, Sudan.
In this study, the chemotherapeutic effect of ?-mangostin (AM) isolated from Cratoxylum arborescens was assessed in rats injected with LA7 cancer cells to develop the mammary cancer. The rats received AM dosage orally at 30 and 60 mg/kg body weight twice a week for 4 weeks. Serum biomarkers such as: CEA, CA 15-3, ALT, ALP, and LDH were significantly lower (P < 0.05) in AM-treated rats than the untreated rats. Histopathological evaluations showed that AM protects the rat mammary gland from the carcinogenic effects of LA7 cells. Interestingly, AM significantly decreased (P < 0.05) the lipid peroxidation, increased the antioxidants enzymes to near normal level when compared to control. The mammary sections of the untreated rats showed abundant PCNA compared to the AM–treated rats (P < 0.05). Using the TUNEL test, there were significantly (P < 0.05) higher numbers of apoptotic cells in AM-cured animals than those not treated. AM dosage had also augmented Bax and diminished Bcl-2 protein expressions in the mammary of treated animals, which proposed augmented apoptosis. This report suggests that AM lessens oxidative stress, suppresses proliferation, prompts mitochondria-regulated apoptosis, and consequently minimizing LA7-induced mammary carcinogenesis. Therefore, AM has great potential in the treatment of breast cancer.
Consultant Medical Oncologist, King Faisal Specialist Hospital & Research Centre -Jeddah, Saudi Arabia and a Professor of Medicine (AL-FAISAL University) Prof. Zekri received his higher medical oncology training in UK where he was certified and practiced as a consultant. He acted as the deputy director of the research center (Jeddah) for 3 years. He is also an active member of National Cancer Management Guidelines Task Force for Gastrointestinal and Breast Cancers. He is a member of Africa and Middle East Uro-oncology group and a co-founder of the Red Sea Lung Cancer Group.
Prof. Zekri has published about 75 articles in peer-reviewed journals and 2 oncology chapters in a book. He presented more than 45 abstracts of original research at several international conferences. He is a peer reviewer in many scientific journals.
Oncotype-DX assay recurrence score (ODX-RS) cut-off values have recently changed after the results of the TAILOR-X trial published in June 2018. We aim to explore decisions for adjuvant chemotherapy (ACT) based on physicians’ clinical assessment and evolving ODX-RS.
Methodology: Patients who underwent ODX testing after curative surgical resection of estragon receptor positive (ER+), Her2 non-over-expressed (Her2-) and lymph node negative (LN-) BC were included. Data were collected retrospectively from the electronic and paper records. Management of these patients was guided by the results of the old ODX-RS-1 (<18, 18-30 & ?31) risk grouping. For the purpose of this study, treatment decisions were also assumed according to TAILOR-X results (ODX-RS-2). Decisions of 3 medical oncologists on ACT were solicited by blinding them to the RS to investigate concordance with ODXA RS-1&2 recommendations.
Results: Sixty-six consecutive patients fulfilled the inclusion criteria. The Median age was 50.5 (range: 21-73) years. There was one male patient and 37/65 females (56.9%) were pre-menopausal. Median tumor size was 21.5 (range: 10-55) mm and the grade were I, II and III in 6 (9.1%), 46 (69.7%) and 41 (21.2%) patients respectively. Among the 3 oncologists, recommendations for ACT based on clinical assessment were discrepant in 29 (43.9%) patients. Based on majority consensus (?2 oncologists), ACT would have been recommended to 22/41 (53.7%) and 22/46 (47.82%) patients with low risk tumours according to ODX-RS-1 and ODX-RS-2 respectively. Similar number of patients (n=12) would have received ACT based on ODX-RS-1 or ODX-RS-2.
Conclusion: Overtreatment and discrepancies in the management of patients with ER+/Her2-/LN- early BC can be prevented by the implementation of ODX genomic assay. Broadly, ODX-RS-1 and ODX-RS-2 seem to guide ACT decisions in similar proportions of patients.
Dr. Rania was granted her Ph.D. in 2010 after joint supervision between Ain Shams University and the University of Bath. She has also been granted a post-doc visit to Leiden University (2013). In 2016, she earned Lancaster University, young researchers career grant. She acquired a Pharmaceutical Bioinformatics certificate from Uppsala University (scored the highest grade). She has 48 international publications in prestigious journals. Dr. Rania is an awarder of the Egyptian Excellence Medal of the highest class (2017), the State award in the field of medicine and medical products (2017) , the State award in the field of medical genetics (2016) and the State Incentive award in the medical fields (2014) and the European Science Foundation award (2013). She also received Elsevier hottest article certificate in 2010 and Wiley publisher honorable certificate for a top-loaded article (2017-2018).
The objective of the presented approach was to exploit the biodegradable and safe gelatin nanoparticles after cholamine surface-modification (cationization) for the successful and efficient delivery of a genetic material viz. siRNA in order to silence the expression of AEG-1/Metadherin gene that is responsible for the metastatic breast cancer disease. MCF-7 cell model was utilized to test the proposed hypothesis using cytotoxicity studies, fluorescence labeling to track the uptake and internalization of the nanoparticles and by the use of ELISA technique to measure the protein silencing potential.
Paucity in research work utilizing this kind of nanoparticles was noticed despite the several merits that this kind of protein nano-carriers might pose in gene therapy. This may be attributed to the tedious preparation methods of these colloidal nanospheres. However, we believe that combining colloidal sciences with gene therapy would aid researches in achieving new horizons in breast cancer therapy.