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https://www.readbyqxmd.com/read/28800469/immunotherapy-in-ovarian-endometrial-and-cervical-cancer-state-of-the-art-and-future-perspectives
#1
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...
July 31, 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
#2
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...
August 11, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28794804/brca-mutation-in-ovarian-cancer-testing-implications-and-treatment-considerations
#3
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
#4
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
https://www.readbyqxmd.com/read/28782087/germline-brca-mutations-in-asian-patients-with-pancreatic-adenocarcinoma-a-prospective-study-evaluating-risk-category-for-genetic-testing
#5
Kyoungmin Lee, Changhoon Yoo, Kyu-Pyo Kim, Kyoung-Jin Park, Heung-Moon Chang, Tae Won Kim, Jae-Lyun Lee, Woochang Lee, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dong Wan Seo, Sung Koo Lee, Myung-Hwan Kim, Sang Hyun Shin, Dae Wook Hwang, Ki Byung Song, Jae Hoon Lee, Song Cheol Kim, Baek-Yeol Ryoo
Introduction Germline BRCA mutations may have therapeutic implications as surrogate markers of DNA-damage repair status in pancreatic ductal adenocarcinoma (PDAC). We performed a prospective study to evaluate the efficiency of risk criteria based on personal or family history of breast and ovarian cancer for determining germline BRCA mutations in PDAC patients with Asian ethnicity. Methods Between November 2015 and May 2016, we screened consecutive PDAC patients with locally advanced unresectable or metastatic disease who were referred for systemic chemotherapy...
August 7, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28770827/discovery-of-potent-2-4-difluoro-linker-poly-adp-ribose-polymerase-1-inhibitors-with-enhanced-water-solubility-and-in-vivo-anticancer-efficacy
#6
Wen-Hua Chen, Shan-Shan Song, Ming-Hui Qi, Xia-Juan Huan, Ying-Qing Wang, Hualiang Jiang, Jian Ding, Guo-Bin Ren, Ze-Hong Miao, Jian Li
Poly (ADP-ribose) polymerase 1 (PARP1) is overexpressed in a variety of cancers, especially in breast and ovarian cancers; tumor cells that are deficient in breast cancer gene 1/2 (BRCA1/2) are highly sensitive to PARP1 inhibition. In this study, we identified a series of 2,4-difluorophenyl-linker analogs (15-55) derived from olaparib as novel PARP1 inhibitors. Four potent analogs 17, 43, 47, and 50 (IC50=2.2-4.4 nmol/L) effectively inhibited the proliferation of Chinese hamster lung fibroblast V-C8 cells (IC50=3...
August 3, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28766223/differences-among-a-modern-cohort-of-brca-mutation-carriers-choosing-bilateral-prophylactic-mastectomies-compared-to-breast-surveillance
#7
Elizabeth Gilbert, Emily C Zabor, Michelle Stempel, Debra Mangino, Alexandra Heerdt, Melissa Pilewskie
BACKGROUND: Women with a BRCA mutation have significantly elevated breast cancer risk, which can be reduced by >90% with bilateral prophylactic mastectomy (BPM). We sought to compare a cohort of BRCA mutation carriers choosing BPM versus breast surveillance to better elucidate factors that may impact decision making. METHODS: Women with a BRCA mutation were retrospectively identified from a prospectively maintained database. The surveillance cohort (n = 313) consisted of women seen in a high-risk clinic between 2014 and 2016, while the surgery cohort (n = 142) consisted of women who underwent BPM between 2010 and 2016...
August 1, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28763368/veliparib-monotherapy-to-patients-with-brca-germ-line-mutation-and-platinum-resistant-or-partially-platinum-sensitive-relapse-of-epithelial-ovarian-cancer-a-phase-i-ii-study
#8
Karina Dahl Steffensen, Parvin Adimi, Anders Jakobsen
OBJECTIVE: A new treatment principle, which seems to radically change the treatment approach in ovarian cancer (OC), has developed over the past few years. Poly(ADP-ribose) polymerase inhibitors work by interfering with mechanisms important to DNA damage repair. Cancer cells that already have defects in the BRCA genes are particularly sensitive to treatment with poly(ADP-ribose) polymerase inhibitors. The main purpose of this study was to investigate the effect of veliparib in patients with known BRCA1/2 mutations and with a platinum-resistant or intermediate sensitive relapse of OC...
August 1, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28751443/fda-approval-summary-rucaparib-for-the-treatment-of-patients-with-deleterious-brca-mutation-associated-advanced-ovarian-cancer
#9
Sanjeeve Balasubramaniam, Julia A Beaver, Sara Horton, Laura L Fernandes, Shenghui Tang, Hisani N Horne, Jinzhong Liu, Chao Liu, Sarah J Schrieber, Jingyu Yu, Pengfei Song, William Pierce, Kim J Robertson, Todd R Palmby, Haw-Jyh Chiu, Eunice Y Lee, Reena Philip, Robert Schuck, Rosane Charlab, Anamitro Banerjee, Xiao Hong Chen, Xing Wang, Kirsten B Goldberg, Rajeshwari Sridhara, Geoffrey Kim, Richard Pazdur
On December 19, 2016, the U.S. Food and Drug Administration granted accelerated approval to rucaparib (RUBRACA, Clovis Oncology, Inc.) for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies. FDA also approved the FoundationFocus™ CDx BRCA test (Foundation Medicine Inc.), the first next-generation sequencing-based companion diagnostic, for identifying patients with advanced ovarian cancer eligible for treatment with rucaparib based on detection of deleterious BRCA1 and/or BRCA2 mutations in tumor tissue...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28740454/genetic-counselling-brca1-2-status-and-clinico-pathologic-characteristics-of-patients-with-ovarian-cancer-before-50-years-of-age
#10
Mirjam Cvelbar, Marko Hocevar, Srdjan Novakovic, Vida Stegel, Andraz Perhavec, Mateja Krajc
BACKGROUND: In Slovenia like in other countries, till recently, personal history of epithelial ovarian cancer (EOC) has not been included among indications for genetic counselling. Recent studies reported up to 17% rate of germinal BRCA1/2 mutation (gBRCA1/2m) within the age group under 50 years at diagnosis. The original aim of this study was to invite to the genetic counselling still living patients with EOC under 45 years, to offer gBRCA1/2m testing and to perform analysis of gBRCA1/2m rate and of clinico-pathologic characteristics...
June 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/28723660/poly-adp-ribose-polymerase-inhibitors-as-radiosensitizers-a-systematic-review-of-pre-clinical-and-clinical-human-studies
#11
REVIEW
Paul Lesueur, François Chevalier, Jean-Baptiste Austry, Waisse Waissi, Hélène Burckel, Georges Noël, Jean-Louis Habrand, Yannick Saintigny, Florence Joly
BACKGROUND: Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors are becoming important actors of anti-neoplasic agents landscape, with recent but narrow FDA's approvals for ovarian BRCA mutated cancers and prostatic cancer. Nevertheless, PARP inhibitors are also promising drugs for combined treatments particularly with radiotherapy. More than seven PARP inhibitors have been currently developed. Central Role of PARP in DNA repair, makes consider PARP inhibitor as potential radiosensitizers, especially for tumors with DNA repair defects, such as BRCA mutation, because of synthetic lethality...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28709830/pathologic-findings-in-breast-fallopian-tube-and-ovary-specimens-in-non-brca-hereditary-breast-and-or-ovarian-cancer-syndromes-a-study-of-18-patients-with-deleterious-germline-mutations-in-rad51c-bard1-brip1-palb2-mutyh-or-chek2
#12
J Kenneth Schoolmeester, Ann M Moyer, McKinsey L Goodenberger, Gary L Keeney, Jodi M Carter, Jamie N Bakkum-Gamez
Germline BRCA mutations account for a significant proportion of genetic/familial risk of breast and ovarian cancer (GBOC) susceptibility, but a broader spectrum of GBOC susceptibility genes has emerged in recent years. Genotype to phenotype correlations are known for some established forms of GBOC, however whether such correlations exist for less common GBOC variants is unclear. We reviewed our institution's experience with non-BRCA GBOC, looking specifically for trends in pathologic and clinical features. Eighteen women with deleterious germline mutations in RAD51C (5 patients), BARD1 (1 patient), BRIP1 (2 patients), PALB2 (3 patients), MUTYH (2 patients) or CHEK2 (5 patients) were identified between January 2011 and December 2016...
July 11, 2017: Human Pathology
https://www.readbyqxmd.com/read/28706762/metastatic-breast-cancer-with-brca-mutation-discovered-by-next-generation-sequencing-responding-to-olaparib
#13
Wajeeha Rizvi, Phu Truong, Quoc Truong
Breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) mutations are associated with hereditary breast and ovarian cancer syndromes (HBOC). However, certain individuals with breast cancer do not meet high-risk factors for hereditary breast cancer screening based on age, family history, and biology of malignancy. We present a patient with relapsed breast cancer who developed progressive disease with significant tumor burden causing a recurrent pleural effusion. Next-generation sequencing (NGS) done on a tumor biopsy was positive for the BRCA2 mutation...
June 11, 2017: Curēus
https://www.readbyqxmd.com/read/28699130/cost-effectiveness-of-risk-reducing-mastectomy-versus-surveillance-in-brca-mutation-carriers-with-a-history-of-ovarian-cancer
#14
Charlotte Gamble, Laura J Havrilesky, Evan R Myers, Junzo P Chino, Scott Hollenbeck, Jennifer K Plichta, P Kelly Marcom, E Shelley Hwang, Noah D Kauff, Rachel A Greenup
BACKGROUND: The appropriate management of breast cancer risk in BRCA mutation carriers following ovarian cancer diagnosis remains unclear. We sought to determine the survival benefit and cost effectiveness of risk-reducing mastectomy (RRM) among women with BRCA1/2 mutations following stage II-IV ovarian cancer. DESIGN: We constructed a decision model from a third-party payer perspective to compare annual screening with magnetic resonance imaging (MRI) and mammography to annual screening followed by RRM with reconstruction following ovarian cancer diagnosis...
July 11, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28695914/genetics-brca-mutant-breast-ovarian-cancer-revealed
#15
Peter Sidaway
No abstract text is available yet for this article.
July 11, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28692916/discovery-mechanism-and-metabolism-studies-of-2-3-difluorophenyl-linker-containing-parp1-inhibitors-with-enhanced-in%C3%A2-vivo-efficacy-for-cancer-therapy
#16
Wenhua Chen, Ne Guo, Minghui Qi, Haiying Dai, Minghuang Hong, Longfei Guan, Xiajuan Huan, Shanshan Song, Jinxue He, Yingqing Wang, Yong Xi, Xinying Yang, Yanyan Shen, Yi Su, Yiming Sun, Yinglei Gao, Yi Chen, Jian Ding, Yun Tang, Guobin Ren, Zehong Miao, Jian Li
Poly (ADP-ribose) polymerase 1 (PARP1) is overexpressed in a variety of cancers, especially breast and ovarian cancers, and tumor cell lines deficient in breast cancer gene 1/2 (BRCA1/2) are highly sensitive to PARP1 inhibition. In this study, with the help of molecular docking, we identified a novel series of 2,3-difluorophenyl-linker analogues (15-54) derived from olaparib (1) as PARP1 inhibitors. Lead optimization led to the identification of 47, which showed high selectivity and high potency against PARP1 enzyme (IC50 = 1...
June 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28692889/dynamic-real-time-in-vivo-confocal-laser-endomicroscopy-of-the-fallopian-tube-during-laparoscopy-in-the-prevention-of-ovarian-cancer
#17
Gautier Chene, Lauriane Chauvy, Annie Buenerd, Stéphanie Moret, Béatrice Nadaud, Philippe Chabert, Gery Lamblin
OBJECTIVES: Recently it has been postulated that most ovarian cancers have a tubal origin. The identification of preinvasive tubal lesions would be of great interest in the early diagnosis of ovarian cancer. Optical biopsy has been developed and validated in the detection of precancerous lesions (such as Barrett's oesophagus). The first objective of this study was to assess the feasibility of optical biopsy in the study of fallopian tubes during laparoscopy. The second objective was to describe the images in benign premalignant and malignant tubes with a histopathological and immunohistochemical (p53 and Ki67 expressions) correlation...
July 5, 2017: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/28692638/the-first-nationwide-multicenter-prevalence-study-of-germline-brca1-and-brca2-mutations-in-chinese-ovarian-cancer-patients
#18
Xiaohua Wu, Lingying Wu, Beihua Kong, Jihong Liu, Rutie Yin, Hao Wen, Ning Li, Hualei Bu, Yanling Feng, Qingli Li, Xuesong Lu, Jia Wei, Xuehua Zhu, John Mills, Gillian Ellison, Thorsten Gutjahr, Yuzhen Liu
OBJECTIVE: Subjects with germline BRCA1/2 mutations (gBRCAm) have an increased risk of developing ovarian cancer and enhanced sensitivity to platinum-containing agents and PARP (poly[ADP-ribose] polymerase) inhibitors. BRCA mutations in Asian patients are poorly understood compared with other populations. We aimed to investigate gBRCAm prevalence and characteristics in Chinese ovarian cancer patients. METHODS: We conducted the first nationwide multicenter gBRCAm prevalence study in China...
July 7, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28690658/influence-of-the-angelina-jolie-announcement-and-insurance-reimbursement-on-practice-patterns-for-hereditary-breast-cancer
#19
Jihyoun Lee, Sungwon Kim, Eunyoung Kang, Suyeon Park, Zisun Kim, Min Hyuk Lee
Lack of awareness, the stigma of carrying a genetic mutation, and economic factors are barriers to acceptance of BRCA genetic testing or appropriate risk management. We aimed to investigate the influence of Angelina Jolie's announcement of her medical experience and also health insurance reimbursement for BRCA gene testing on practice patterns for hereditary breast and ovarian cancer (HBOC). A survey regarding changes in practice patterns for HBOC before and after the announcement was conducted online. The rate of BRCA gene testing was obtained from the National Health Insurance Review and Assessment Service database...
June 2017: Journal of Breast Cancer
https://www.readbyqxmd.com/read/28669566/recent-patterns-in-genetic-testing-for-breast-and-ovarian-cancer-risk-in-the-u-s
#20
Xuesong Han, Ahmedin Jemal
INTRODUCTION: Mutations in BRCA genes are strongly associated with increased risk of breast and ovarian cancer, and it is recommended that women at high risk for these mutations be referred for genetic counseling and testing. The Affordable Care Act (ACA) provision implemented in 2010 eliminated cost sharing for BRCA genetic testing for privately insured women with family history of BRCA-related cancers. METHODS: Using a nationally representative sample from the National Health Interview Survey, this study examined trends in genetic testing for breast and ovarian cancer risk from 2005 to 2015 among women by family history and insurance status...
June 29, 2017: American Journal of Preventive Medicine
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