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Brca ovarian cancer

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https://www.readbyqxmd.com/read/28930807/breadth-of-genetic-testing-selected-by-patients-at-risk-of-hereditary-breast-and-ovarian-cancer
#1
J Brian Szender, Jasmine Kaur, Katherine Clayback, Mollie L Hutton, June Mikkelson, Kunle Odunsi, Cara Dresbold
OBJECTIVE: The aim of this study was to evaluate the ability of patients at risk of hereditary breast and ovarian cancer (HBOC) syndrome to select the extent of genetic testing personally preferred and the impact of demographic factors on the breadth of testing pursued. METHODS: A single-institution cohort was enumerated consisting of patients referred for clinical genetic counseling secondary to risk of HBOC syndrome. This was a retrospective study of consecutive patients seen for genetic counseling; all patients completed an epidemiologic questionnaire and provided personal and family medical histories...
September 19, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28925391/ezh2-contributes-to-the-response-to-parp-inhibitors-through-its-parp-mediated-poly-adp-ribosylation-in-breast-cancer
#2
H Yamaguchi, Y Du, K Nakai, M Ding, S-S Chang, J L Hsu, J Yao, Y Wei, L Nie, S Jiao, W-C Chang, C-H Chen, Y Yu, G N Hortobagyi, M-C Hung
Inhibitors against poly (ADP-ribose) polymerase (PARP) are promising targeted agents currently used to treat BRCA-mutant ovarian cancer and are in clinical trials for other cancer types, including BRCA-mutant breast cancer. To enhance the clinical response to PARP inhibitors (PARPis), understanding the mechanisms underlying PARPi sensitivity is urgently needed. Here, we show enhancer of zeste homolog 2 (EZH2), an enzyme that catalyzes H3 lysine trimethylation and associates with oncogenic function, contributes to PARPi sensitivity in breast cancer cells...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28916367/rucaparib-maintenance-treatment-for-recurrent-ovarian-carcinoma-after-response-to-platinum-therapy-ariel3-a-randomised-double-blind-placebo-controlled-phase-3-trial
#3
Robert L Coleman, Amit M Oza, Domenica Lorusso, Carol Aghajanian, Ana Oaknin, Andrew Dean, Nicoletta Colombo, Johanne I Weberpals, Andrew Clamp, Giovanni Scambia, Alexandra Leary, Robert W Holloway, Margarita Amenedo Gancedo, Peter C Fong, Jeffrey C Goh, David M O'Malley, Deborah K Armstrong, Jesus Garcia-Donas, Elizabeth M Swisher, Anne Floquet, Gottfried E Konecny, Iain A McNeish, Clare L Scott, Terri Cameron, Lara Maloney, Jeff Isaacson, Sandra Goble, Caroline Grace, Thomas C Harding, Mitch Raponi, James Sun, Kevin K Lin, Heidi Giordano, Jonathan A Ledermann
BACKGROUND: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries...
September 12, 2017: Lancet
https://www.readbyqxmd.com/read/28914396/the-expected-benefit-of-preventive-mastectomy-on-breast-cancer-incidence-and-mortality-in-brca-mutation-carriers-by-age-at-mastectomy
#4
Vasily Giannakeas, Steven A Narod
PURPOSE: Preventive breast surgery is offered to unaffected BRCA mutation carriers to prevent breast cancer incidence and mortality. The clinical benefit of preventive mastectomy can be measured in several ways, including extension of life expectancy (mean years of life gained) and by estimating the probability of surviving until age 80. We sought to estimate the expected benefit of a preventive mastectomy at various ages, using these indices of mortality, by simulating hypothetical cohorts of women...
September 15, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28884397/brca1-gene-function-and-deficiency
#5
REVIEW
Miho Takaoka, Yoshio Miki
The BRCA1 protein, a hereditary breast and ovarian cancer-causing gene product, is known as a multifunctional protein that performs various functions in cells. It is well known, along with BRCA 2, to cause hereditary breast and ovarian cancer, but here we will specifically focus on BRCA1. We introduce the mechanism and the latest report on homologous recombination repair, replication, involvement in checkpoint regulation, transcription, chromatin remodeling, and cytoplasmic function (centrosome regulation, apoptosis, selective autophagy), and consider the possibility of carcinogenesis from inhibition of the intracellular functions in each...
September 7, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28881380/missed-therapeutic-and-prevention-opportunities-in-women-with-brca-mutated-epithelial-ovarian-cancer-and-their-families-due-to-low-referral-rates-for-genetic-counseling-and-brca-testing-a-review-of-the-literature
#6
Paul J Hoskins, Walter H Gotlieb
Answer questions and earn CME/CNE Fifteen percent of women with epithelial ovarian cancer have inherited mutations in the BRCA breast cancer susceptibility genes. Knowledge of her BRCA status has value both for the woman and for her family. A therapeutic benefit exists for the woman with cancer, because a new family of oral drugs, the poly ADP-ribose polymerase (PARP) inhibitors, has recently been approved, and these drugs have the greatest efficacy in women who carry the mutation. For her family, there is the potential to prevent ovarian cancer in those carrying the mutation by using risk-reducing surgery...
September 7, 2017: CA: a Cancer Journal for Clinicians
https://www.readbyqxmd.com/read/28880857/brca-genetic-testing-and-receipt-of-preventive-interventions-among-women-aged-18-64-years-with-employer-sponsored-health-insurance-in-nonmetropolitan-and-metropolitan-areas-united-states-2009-2014
#7
Katherine Kolor, Zhuo Chen, Scott D Grosse, Juan L Rodriguez, Ridgely Fisk Green, W David Dotson, M Scott Bowen, Julie A Lynch, Muin J Khoury
PROBLEM/CONDITION: Genetic testing for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) gene mutations can identify women at increased risk for breast and ovarian cancer. These testing results can be used to select preventive interventions and guide treatment. Differences between nonmetropolitan and metropolitan populations in rates of BRCA testing and receipt of preventive interventions after testing have not previously been examined. PERIOD COVERED: 2009-2014...
September 8, 2017: MMWR. Surveillance Summaries: Morbidity and Mortality Weekly Report. Surveillance Summaries
https://www.readbyqxmd.com/read/28874104/ovarian-stimulation-in-patients-with-cancer-impact-of-letrozole-and-brca-mutations-on-fertility-preservation-cycle-outcomes
#8
Volkan Turan, Giuliano Bedoschi, Volkan Emirdar, Fred Moy, Kutluk Oktay
BACKGROUND: Aromatase inhibitors (AI) have been introduced to reduce estrogen exposure in women with estrogen-sensitive cancer undergoing ovarian stimulation for oocyte/embryo cryopreservation. There have been questions regarding whether the addition of AI and the presence of BRCA mutations affect cycle outcomes. We sought to determine the impact of letrozole and BRCA mutations on fertility preservation (FP) cycle outcomes of patients undergoing ovarian stimulation with an antagonist protocol...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28870960/risk-reducing-salpingo-oophorectomy-in-women-at-higher-risk-of-ovarian-and-breast-cancer-a-single-institution-prospective-series
#9
Enzo Ricciardi, Federica Tomao, Giovanni Aletti, Luca Bazzurini, Luca Bocciolone, Sara Boveri, Fabio Landoni, Maria Teresa Lapresa, Matteo Maruccio, Gabriella Parma, Fedro Peccatori, Maria Cristina Petrella, Vanna Zanagnolo, Nicoletta Colombo, Angelo Maggioni
BACKGROUND/AIM: Occult cancers' reported rates vary from 2-12% and serous tubal intraepithelial carcinomas (STICs) have been identified in 3-12% of the prophylactically removed tubes of women carrying a BRCA mutation. The aim of this study was to evaluate the incidence of tubal minor epithelial atypia (STIL), STIC, and occult invasive cancer and to evaluate the cancer-specific mortality in a prospective series of women at higher risk of ovarian and breast cancer undergoing risk-reducing salpingo-oophorectomy (RRSO) n a tertiary cancer center...
September 2017: Anticancer Research
https://www.readbyqxmd.com/read/28868023/next-generation-sequencing-in-order-to-better-characterize-a-brca-variant-of-uncertain-significance
#10
Steven Sorscher, Shakti Ramkissoon
BRCA germline mutations are the most common predisposing factor in familial breast-ovarian cancer syndrome families. However, many screened patients are identified as harboring BRCA variants of uncertain significance (VUS), rather than carrying deleterious germline mutations [Calo et al.: Cancers 2010; 2:1644-1660]. While such VUSs are typically reclassified as benign polymorphisms, this may occur years after the VUS is first identified [Murray et al.: Genet Med 2011; 13; 998-1005]. Loss of heterozygosity (LOH) of BRCA is nearly always the gatekeeper event in inherited BRCA-related breast cancer and LOH of BRCA is rare in sporadic cancers [Osorio et al...
May 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28863070/evaluation-of-microscopic-changes-in-fallopian-tubes-of-brca-mutation-carriers-by-morphometric-analysis-of-histologic-slides-a-preliminary-pilot-study
#11
Amnon Amit, Edmond Sabo, Yaniv Zohar, Einat Trugman, Irena Pranovich, Ari Reiss, Emad Matanes, Geula Klorin
Mutations in BRCA genes increase the risk of ovarian cancer, yet no method for early diagnosis is available. Some serous ovarian tumors are hypothesized to stem from cells of the fallopian tube fimbria. Using a novel method of computerized morphometry of the fimbrial epithelium, this study aimed to detect morphologic differences in noncancerous fimbriae between BRCA mutation carriers and noncarriers, and between healthy and serous ovarian cancer patients. Twenty-four fimbriae from healthy women (13 BRCA+, 11 BRCA-) and 21 fimbriae from women with serous ovarian cancer (10 BRCA+, 11 BRCA-), all reported as "normal" by hematoxylin and eosin examination, were subjected to computerized histomorphometric analysis...
August 31, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/28832487/committee-opinion-no-716-the-role-of-the-obstetrician-gynecologist-in-the-early-detection-of-epithelial-ovarian-cancer-in-women-at-average-risk
#12
(no author information available yet)
Ovarian cancer is the second most common type of female reproductive cancer, and more women die from ovarian cancer than from cervical cancer and uterine cancer combined. Currently, there is no strategy for early detection of ovarian cancer that reduces ovarian cancer mortality. Taking a detailed personal and family history for breast, gynecologic, and colon cancer facilitates categorizing women based on their risk (average risk or high risk) of developing epithelial ovarian cancer. Women with a strong family history of ovarian, breast, or colon cancer may have hereditary breast and ovarian cancer syndrome (BRCA mutation) or hereditary nonpolyposis colorectal cancer (Lynch syndrome), and these women are at increased risk of developing ovarian cancer...
September 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28832478/committee-opinion-no-716-summary-the-role-of-the-obstetrician-gynecologist-in-the-early-detection-of-epithelial-ovarian-cancer-in-women-at-average-risk
#13
(no author information available yet)
Ovarian cancer is the second most common type of female reproductive cancer, and more women die from ovarian cancer than from cervical cancer and uterine cancer combined. Currently, there is no strategy for early detection of ovarian cancer that reduces ovarian cancer mortality. Taking a detailed personal and family history for breast, gynecologic, and colon cancer facilitates categorizing women based on their risk (average risk or high risk) of developing epithelial ovarian cancer. Women with a strong family history of ovarian, breast, or colon cancer may have hereditary breast and ovarian cancer syndrome (BRCA mutation) or hereditary nonpolyposis colorectal cancer (Lynch syndrome), and these women are at increased risk of developing ovarian cancer...
September 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28831036/brca-locus-specific-loss-of-heterozygosity-in-germline-brca1-and-brca2-carriers
#14
Kara N Maxwell, Bradley Wubbenhorst, Brandon M Wenz, Daniel De Sloover, John Pluta, Lyndsey Emery, Amanda Barrett, Adam A Kraya, Ioannis N Anastopoulos, Shun Yu, Yuchao Jiang, Hao Chen, Nancy R Zhang, Nicole Hackman, Kurt D'Andrea, Robert Daber, Jennifer J D Morrissette, Nandita Mitra, Michael Feldman, Susan M Domchek, Katherine L Nathanson
Complete loss of BRCA1 or BRCA2 function is associated with sensitivity to DNA damaging agents. However, not all BRCA1 and BRCA2 germline mutation-associated tumors respond. Herein we report analyses of 160 BRCA1 and BRCA2 germline mutation-associated breast and ovarian tumors. Retention of the normal BRCA1 or BRCA2 allele (absence of locus-specific loss of heterozygosity (LOH)) is observed in 7% of BRCA1 ovarian, 16% of BRCA2 ovarian, 10% of BRCA1 breast, and 46% of BRCA2 breast tumors. These tumors have equivalent homologous recombination deficiency scores to sporadic tumors, significantly lower than scores in tumors with locus-specific LOH (ovarian, P = 0...
August 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28829366/understanding-resistance-mechanisms-and-expanding-the-therapeutic-utility-of-parp-inhibitors
#15
REVIEW
Joline S J Lim, David S P Tan
Poly-(ADP-ribose) polymerase (PARP) inhibitors act through synthetic lethality in cells with defects in homologous recombination (HR) DNA repair caused by molecular aberrations such as BRCA mutations, and is approved for treatment in ovarian cancer, with promising clinical activity against other HR defective tumors including breast and prostate cancers. Three PARP inhibitors have been FDA approved, while another two have shown promising activity and are in late stage development. Nonetheless, both primary and secondary resistance to PARP inhibition have led to treatment failure, and the development of predictive biomarkers and the ability to identify and overcome mechanisms of resistance is vital for optimization of its clinical utility...
August 22, 2017: Cancers
https://www.readbyqxmd.com/read/28821472/surgical-findings-and-outcomes-in-premenopausal-breast-cancer-patients-undergoing-oophorectomy-a-multicenter-review-from-the-fellows-pelvic-research-network
#16
Lara F B Harvey, Vandana G Abramson, Jimena Alvarez, Christopher Destephano, Hye-Chun Hur, Katherine Lee, Patricia Mattingly, Beau Park, Carolyn Piszczek, Farinaz Seifi, Mallory Stuparich, Amanda Yunker
STUDY OBJECTIVE: Since publication of the Suppression of Ovarian Function Trial (SOFT) data, some women with premenopausal breast cancer have been recommended to undergo bilateral oophorectomy to facilitate breast cancer treatment with aromatase inhibitors. These women may be at higher risk of occult abdominal pathology than the general population. Our objective is to describe the procedures performed, intra-abdominal findings, and surgical pathology of this population. DESIGN: Multi-center retrospective chart review...
August 15, 2017: Journal of Minimally Invasive Gynecology
https://www.readbyqxmd.com/read/28800469/immunotherapy-in-ovarian-endometrial-and-cervical-cancer-state-of-the-art-and-future-perspectives
#17
REVIEW
Jole Ventriglia, Immacolata Paciolla, Carmela Pisano, Sabrina Chiara Cecere, Marilena Di Napoli, Rosa Tambaro, Daniela Califano, Simona Losito, Giosuè Scognamiglio, Sergio Venanzio Setola, Laura Arenare, Sandro Pignata, Chiara Della Pepa
The tumors of the female genital tract represent a leading cause of morbidity and mortality among women worldwide. Substantial progresses have been made in ovarian cancer, with the increasing knowledge about BRCA mutated tumors and the recent development of PARP inhibitors, and in cervical cancer, thanks to extensive screening and widespread of vaccination against Human Papilloma Virus. Nevertheless many needs remain unmet, advanced stage diseases are still incurable and cervical and endometrial carcinoma, as well as platinum-resistant ovarian carcinoma, can certainly be classifiable among the cancers with poor sensitivity to conventional chemotherapy...
September 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28799806/elevated-serum-level-of-ca125-is-a-biomarker-that-can-be-used-to-alter-prognosis-determined-by-brca-mutation-and-family-history-in-ovarian-cancer
#18
Weiling Liu, Zhizhong Wang, Jie Ma, Yangyang Hou, Jiuzhou Zhao, Bing Dong, Shichun Tu, Li Wang, Yongjun Guo
AIMS: In this study, we determined whether serum tumor markers (STMs), including CA125, are associated with BRCA mutation status and if they can be used prognostically in sporadic ovarian cancer (SOC) and familial ovarian cancer (FOC). METHODS: BRCA gene mutations were screened using next-generation sequencing (NGS) in 31 FOC and 66 SOC patients enrolled between 2013 and 2014. The serum levels of STM CEA, CA125, CA199, and HE4 were also measured in these patients to determine the prognostic potential of these markers and their association with BRCA mutations...
September 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28794804/brca-mutation-in-ovarian-cancer-testing-implications-and-treatment-considerations
#19
REVIEW
Robert T Neff, Leigha Senter, Ritu Salani
Ovarian cancer is a heterogeneous disease that encompasses a number of different cellular subtypes, the most common of which is high-grade serous ovarian cancer (HGSOC). Still today, ovarian cancer is primarily treated with chemotherapy and surgery. Recent advances in the hereditary understanding of this disease have shown a significant role for the BRCA gene. While only a minority of patients with HGSOC will have a germline BRCA mutation, many others may have tumor genetic aberrations within BRCA or other homologous recombination proteins...
August 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28790837/rucaparib-the-past-present-and-future-of-a-newly-approved-parp-inhibitor-for-ovarian-cancer
#20
REVIEW
L E Dockery, C C Gunderson, K N Moore
Rucaparib camsylate (CO-338, AG-014699, PF-01367338) is a potent PARP-1, PARP-2, and PARP-3 inhibitor. Phase I and II studies demonstrated clinical efficacy in both BRCA-mutated (inclusive of germline and somatic) ovarian tumors and ovarian tumors with homologous recombination deficiency (HRD) loss of heterozygosity (LOH). Rucaparib has received the US Food and Drug Administration (FDA) approval for patients with deleterious BRCA mutation (germline and/or somatic)-associated advanced ovarian cancer who have been treated with two or more chemotherapies...
2017: OncoTargets and Therapy
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