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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
#1
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/28903158/surgeon-influence-on-variation-in-receipt-of-contralateral-prophylactic-mastectomy-for-women-with-breast-cancer
#2
Steven J Katz, Sarah T Hawley, Ann S Hamilton, Kevin C Ward, Monica Morrow, Reshma Jagsi, Timothy P Hofer
Importance: Rates of contralateral prophylactic mastectomy (CPM) have markedly increased but we know little about the influence of surgeons on variability of the procedure in the community. Objective: To quantify the influence of the attending surgeon on rates of CPM and clinician attitudes that explained it. Design, Setting, and Participants: In this population-based survey study, we identified 7810 women with stages 0 to II breast cancer treated in 2013 to 2015 through the Surveillance, Epidemiology, and End Results registries of Georgia and Los Angeles County...
September 13, 2017: JAMA Surgery
https://www.readbyqxmd.com/read/28881597/tgfbeta-and-mirna-regulation-in-familial-and-sporadic-breast-cancer
#3
Katia Danza, Simona De Summa, Rosamaria Pinto, Brunella Pilato, Orazio Palumbo, Massimo Carella, Ondina Popescu, Maria Digennaro, Rosanna Lacalamita, Stefania Tommasi
The term 'BRCAness' was introduced to identify sporadic malignant tumors sharing characteristics similar to those germline BRCA-related. Among all mechanisms attributable to BRCA1 expression silencing, a major role has been assigned to microRNAs. MicroRNAs role in familial and sporadic breast cancer has been explored but few data are available about microRNAs involvement in homologous recombination repair control in these breast cancer subgroups. Our aim was to seek microRNAs associated to pathways underlying DNA repair dysfunction in breast cancer according to a family history of the disease...
August 1, 2017: Oncotarget
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
#4
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/28879638/impact-of-etoposide-on-brca1-expression-in-various-breast-cancer-cell-lines
#5
Xi Zhang, Simone Hofmann, Nadia Harbeck, Udo Jeschke, Sophie Sixou
Breast cancer 1 (BRCA1), as a tumor suppressor, exerts an effective influence on protecting DNA integrity to suppress the development of breast cancer (BC). BRCA1 expression is induced in response to DNA-damaging agents such as etoposide. Germline BRCA1 gene mutations are associated with development of hereditary BC. However, besides BRCA-mutated BCs, some sporadic cancers may also exhibit a BRCA-like phenotype, displaying so-called 'BRCAness'. This common phenotype may respond to similar therapeutic approaches as BRCA-mutated tumors and may thus have important implications for the clinical management of these cancers...
September 6, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28875097/sustained-long-term-maintenance-of-remission-with-single-agent-veliparib-in-recurrent-triple-negative-breast-cancer
#6
Karthik Kota, Shannon Puhalla
Triple-negative breast cancers (TNBC) have poorer outcomes than hormone positive or human epidermal growth factor receptor 2 (HER2)-positive breast cancers, with chemotherapy being the usual standard of care. Veliparib, a poly ADP-ribose polymerase (PARP) inhibitor, has been studied in both breast cancer susceptibility genes 1 and 2 (BRCA)-mutation related and sporadic cancers as a single agent and in combination with chemotherapy. Here, we describe a patient whose metastatic recurrence of TNBC was treated with combination chemotherapy and veliparib followed by maintenance single-therapy veliparib...
July 4, 2017: Curēus
https://www.readbyqxmd.com/read/28874104/ovarian-stimulation-in-patients-with-cancer-impact-of-letrozole-and-brca-mutations-on-fertility-preservation-cycle-outcomes
#7
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
#8
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/28856077/exceptional-responses-to-standard-therapy-in-a-patient-with-metastatic-her2-positive-breast-cancer
#9
Carsten Nieder, Bård Mannsåker, Ellinor Haukland
Patients with metastatic breast cancer involving the liver and brain often have short overall survival. Here, we report a case of de novo metastatic breast cancer with multiple liver metastases at initial diagnosis in February 2011 in a 35-year-old Caucasian female patient. The histology was poorly differentiated invasive ductal carcinoma (estrogen and progesterone receptor negative, HER2 positive) and the patient was negative for germline BRCA 1 and 2 mutations. Systemic therapy with trastuzumab and docetaxel was given for six months and then switched to trastuzumab only because of peripheral neuropathy...
June 29, 2017: Curēus
https://www.readbyqxmd.com/read/28841600/determining-the-oncologic-safety-of-autologous-fat-grafting-as-a-reconstructive-modality-an-institutional-review-of-breast-cancer-recurrence-rates-and-surgical-outcomes
#10
Oriana Cohen, Gretl Lam, Nolan Karp, Mihye Choi
BACKGROUND: The increasing use of autologous fat grafting in breast cancer patients has raised concerns regarding its oncologic safety. This study evaluated patient outcomes and tumor recurrence following mastectomy reconstruction and autologous fat grafting. METHODS: Retrospective chart review identified patients who underwent mastectomy followed by breast reconstruction from 2010 to 2015. Eight hundred twenty-nine breasts met inclusion criteria: 248 (30.0 percent) underwent autologous fat grafting, whereas 581 (70...
September 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28830795/indications-for-postmastectomy-radiation-after-neoadjuvant-chemotherapy-in-ypn0-and-ypn1-3-axillary-node-positive-women
#11
Barbara Fowble, Abhishek Keshav Jairam, Frederick Wang, Anne Peled, Michael Alvarado, Cheryl Ewing, Laura Esserman, Catherine Park, Ann Lazar
INTRODUCTION: Downstaging with neoadjuvant chemotherapy (NAC) might obscure indications for postmastectomy radiation (PMRT). The degree of downstaging that results in local-regional recurrence (LRR) rates low enough to omit PMRT remains controversial. We examined the rate of LRR in women who received NAC who underwent mastectomy without PMRT. PATIENTS AND METHODS: Between 2004 and 2013, 81 women with stage I to IIIA breast cancer had NAC and mastectomy; 48 patients (59%) were clinical N0 and 33 patients (41%) were clinical N1; median age was 45 years; 33 patients (41%) had hormone receptor-positive (HR(+))HER2(-), 21 patients (26%) HR(+)HER2(+), 19 patients (23%) HR(-) HER2(-), and 7 patients (9%) HR(-)HER2(+) disease...
August 1, 2017: Clinical Breast Cancer
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
#12
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/28802254/tdp1-is-critical-for-the-repair-of-dna-breaks-induced-by-sapacitabine-a-nucleoside-also-targeting-atm-and-brca-deficient-tumors
#13
Muthana Al Abo, Hiroyuki Sasanuma, Xiaojun Liu, Vinodh N Rajapakse, Shar-Yin N Huang, Evgeny Kiselev, Shunichi Takeda, William Plunkett, Yves Pommier
2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine (CNDAC) is the active metabolite of the anticancer drug, sapacitabine. CNDAC is incorporated into the genome during DNA replication and subsequently undergoes beta-elimination that generates single-strand breaks with abnormal 3'-ends. Because tyrosyl-DNA phosphodiesterase 1 (TDP1) selectively hydrolyzes non-phosphorylated 3'-blocking ends, we tested its role in the repair of CNDAC-induced DNA damage. We show that cells lacking TDP1 (avian TDP1-/- DT40 cells and human TDP1 KO TSCER2 and HCT116 cells) exhibit marked hypersensitivity to CNDAC...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28790837/rucaparib-the-past-present-and-future-of-a-newly-approved-parp-inhibitor-for-ovarian-cancer
#14
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/28790402/h-ferritin-nanocaged-olaparib-a-promising-choice-for-both-brca-mutated-and-sporadic-triple-negative-breast-cancer
#15
S Mazzucchelli, M Truffi, F Baccarini, M Beretta, L Sorrentino, M Bellini, M A Rizzuto, R Ottria, A Ravelli, P Ciuffreda, D Prosperi, F Corsi
Poly(ADP-ribose) polymerase (PARP) inhibitors represent a promising strategy toward the treatment of triple-negative breast cancer (TNBC), which is often associated to genomic instability and/or BRCA mutations. However, clinical outcome is controversial and no benefits have been demonstrated in wild type BRCA cancers, possibly due to poor drug bioavailability and low nuclear delivery. In the attempt to overcome these limitations, we have developed H-Ferritin nanoformulated olaparib (HOla) and assessed its anticancer efficacy on both BRCA-mutated and non-mutated TNBC cells...
August 8, 2017: Scientific Reports
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
#16
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
#17
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
#18
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/28758101/brca-population-screening-for-predicting-breast-cancer-for-or-against
#19
Giuseppe Lippi, Camilla Mattiuzzi, Martina Montagnana
The pathogenesis of breast cancer, the most frequent female malignancy, entails both genetic and acquired risk factors. Among the various oncogenetic mutations, those involving the BReast Cancer 1 (BRCA1) and BReast Cancer 2 (BRCA2) genes are associated with an extremely high risk of developing breast cancer, with a penetration approximating 70% in women with a positive family history for this malignancy. This important evidence elicits some pragmatic considerations, such as the clinical effectiveness of screening for the most penetrant BRCA mutations in women with or without a positive familial history, but also raises important issues related to the most appropriate clinical management of these patients...
July 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28757302/-i-ve-just-never-gotten-around-to-doing-it-men-s-approaches-to-managing-brca-related-cancer-risks
#20
Emily A Rauscher, Marleah Dean
OBJECTIVE: To examine men's approaches to managing BRCA-related cancer risks. METHODS: 25 Qualitative interviews were conducted with men who are at risk for BRCA-related cancers. Thematic analysis was conducted using the constant comparison. RESULTS: Qualitative analysis revealed two different approaches for how men managed their BRCA-related cancer risks. Men were engaged when: (1) initially seeking information, (2) uptake of genetic testing, and (3) population screening procedures...
July 23, 2017: Patient Education and Counseling
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