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Brca ovarian cancer

Francesca Vena, Ruochen Jia, Arman Esfandiari, Juan J Garcia-Gomez, Manuel Rodriguez-Justo, Jianguo Ma, Sakeena Syed, Lindsey Crowley, Brian Elenbaas, Samantha Goodstal, John A Hartley, Daniel Hochhauser
Targeting the DNA damage response (DDR) in tumors with defective DNA repair is a clinically successful strategy. The RAS/RAF/MEK/ERK signalling pathway is frequently deregulated in human cancers. In this study, we explored the effects of MEK inhibition on the homologous recombination pathway and explored the potential for combination therapy of MEK inhibitors with DDR inhibitors and a hypoxia-activated prodrug. We studied effects of combining pimasertib, a selective allosteric inhibitor of MEK1/2, with olaparib, a small molecule inhibitor of poly (adenosine diphosphate [ADP]-ribose) polymerases (PARP), and with the hypoxia-activated prodrug evofosfamide in ovarian and pancreatic cancer cell lines...
February 20, 2018: Oncotarget
(no author information available yet)
The FDA authorized 23andMe to market the first direct-to-consumer test to check for three BRCA1/2 mutations associated with a higher risk of developing breast, ovarian, and prostate cancers. The mutations are most commonly found in about 2% of women of Ashkenazi Jewish descent.
March 14, 2018: Cancer Discovery
Belinda Rahman, Anne Lanceley, Rebecca S Kristeleit, Jonathan A Ledermann, Michelle Lockley, Mary McCormack, Tim Mould, Lucy Side
BACKGROUND: Ovarian cancer is the fifth most common cause of cancer death for women in the UK. Up to 18% of cases can be attributed to germline mutations in BRCA1 and BRCA2 genes. Identifying patients who carry a BRCA mutation provides important information about potential response to treatment and eligibility for therapies such as poly ADP ribose polymerase (PARP) inhibitors. Implementation of systematic genetic testing of patients with ovarian cancer via oncology clinics (mainstreamed genetic testing, MGT) is increasing...
March 13, 2018: Journal of Medical Genetics
Isabella Faraoni, Francesca Aloisio, Antonio De Gabrieli, Maria Irno Consalvo, Serena Lavorgna, Maria Teresa Voso, Francesco Lo-Coco, Grazia Graziani
Olaparib is a potent orally bioavailable poly(ADP-ribose) polymerase inhibitor (PARPi), approved for BRCA-mutated ovarian and breast cancers. We recently showed that olaparib at clinically achievable concentrations exerts anti-proliferative and pro-apoptotic effects in vitro as monotherapy against primary acute myeloid leukemia (AML) blasts, while sparing normal bone marrow (BM) hematopoietic cells. Since AML expresses low levels of death receptors that may contribute to apoptosis resistance, in this study we investigated whether the anti-leukemia activity of olaparib involves modulation of FAS and TRAIL receptors DR5 and DR4...
March 8, 2018: Cancer Letters
Laura Cortesi, Angela Toss, Iole Cucinotto
The standard of treatment for advanced ovarian cancer is represented by optimal surgical debulking preceded or followed by chemotherapeutic regimens including taxanes and platinum agents, possibly associated with bevacizumab and/or intraperitoneal therapy. Despite this comprehensive treatment strategy, almost 75% of patients relapse or progress and are therefore candidates for a second-line treatment, showing, at this point, less chemo-sensitivity and worse prognosis. An interesting approach to improve outcomes of these patients has been developed in the last decade, in BRCA-related ovarian cancer...
March 7, 2018: Current Cancer Drug Targets
Gloria Mittica, Eleonora Ghisoni, Gaia Giannone, Sofia Genta, Massimo Aglietta, Anna Sapino, Giorgio Valabrega
BACKGROUND: Treatment of Epithelial Ovarian Cancer (EOC), historically based on surgery and platinum doublet chemotherapy, is associated with high risk of relapse and poor prognosis for recurrent disease. In this landscape, the innovative treatment with PARP inhibitors (PARPis) demonstrated an outstanding activity in EOC, and is currently changing clinical practice in BRCA mutant patients. OBJECTIVES: To highlight the mechanism of action, pharmacokinetics, clinical activity, indications and current strategies of development of Olaparib, Niraparib, Rucaparib, Talazoparib and Veliparib, the 5 most relevant PARPis...
March 5, 2018: Recent Patents on Anti-cancer Drug Discovery
Gillian E Hanley, Jessica N McAlpine, Dianne Miller, David Huntsman, Kasmintan A Schrader, C Blake Gilks, Gillian Mitchell
BACKGROUND: Identifying female carriers of BRCA1 and BRCA2 mutations is imperative for prevention of ovarian cancer and breast cancer. There are five major histologic subtypes of ovarian cancer and high grade serous cancer (the most common) is reported in 75-100% of BRCA1 and BRCA2 mutation carriers. We examined histology-based referral to the Hereditary Cancer Program following an educational prevention campaign recommending BRCA1 and BRCA2 mutation screening for all high-grade serous cancer patients...
March 5, 2018: BMC Cancer
Ava Kwong, John C W Ho, Vivian Y Shin, Allison W Kurian, Edmund Tai, Laura J Esserman, Jeffery N Weitzel, Po-Han Lin, Michael Field, Susan M Domchek, Jessica Lo, Hextan Y S Ngan, Edmond S K Ma, Tsun L Chan, James M Ford
BRCA1/2 mutations are significant risk factors for hereditary breast and ovarian cancer (HBOC), its mutation frequency in HBOC of Chinese ethnicity is around 9%, in which nearly half are recurrent mutations. In Hong Kong and China, genetic testing and counseling are not as common as in the West. To reduce the barrier of testing, a multiplex SNaPshot genotyping panel that targeted 25 Chinese BRCA1/2 mutation hotspots was developed, and its feasibility was evaluated in a local cohort of 441 breast and 155 ovarian cancer patients...
January 30, 2018: Oncotarget
David A Barrington, Macie L Champion, Teresa K L Boitano, Christen L Walters-Haygood, Meagan B Farmer, Ronald D Alvarez, Jacob M Estes, Charles A Leath
OBJECTIVES: Describe patient characteristics in African American (AA) women seen for gynecologic cancer related genetic counseling at a large southeastern comprehensive cancer center. METHODS: We reviewed an IRB approved, prospective observational cohort of patients from a Gynecologic Cancer Risk Assessment Clinic. Data evaluated included personal cancer history, family history, frequency of genetic testing, frequency/type of genetic mutations, and frequency of surgical intervention...
February 24, 2018: Gynecologic Oncology
Amanda Ewart Toland, Andrea Forman, Fergus J Couch, Julie O Culver, Diana M Eccles, William D Foulkes, Frans B L Hogervorst, Claude Houdayer, Ephrat Levy-Lahad, Alvaro N Monteiro, Susan L Neuhausen, Sharon E Plon, Shyam K Sharan, Amanda B Spurdle, Csilla Szabo, Lawrence C Brody
Clinical testing of BRCA1 and BRCA2 began over 20 years ago. With the expiration and overturning of the BRCA patents, limitations on which laboratories could offer commercial testing were lifted. These legal changes occurred approximately the same time as the widespread adoption of massively parallel sequencing (MPS) technologies. Little is known about how these changes impacted laboratory practices for detecting genetic alterations in hereditary breast and ovarian cancer genes. Therefore, we sought to examine current laboratory genetic testing practices for BRCA1 / BRCA2 ...
2018: NPJ Genomic Medicine
Jaya Singh, Nishita Thota, Suhasini Singh, Shila Padhi, Puja Mohan, Shivani Deshwal, Soumit Sur, Mithua Ghosh, Amit Agarwal, Ramesh Sarin, Rosina Ahmed, Sachin Almel, Basumita Chakraborti, Vinod Raina, Praveen K DadiReddy, B K Smruti, Senthil Rajappa, Chandragouda Dodagoudar, Shyam Aggarwal, Manish Singhal, Ashish Joshi, Rajeev Kumar, Ajai Kumar, Deepak K Mishra, Neeraj Arora, Aarati Karaba, Satish Sankaran, Shanmukh Katragadda, Arunabha Ghosh, Vamsi Veeramachaneni, Ramesh Hariharan, Ashraf U Mannan
PURPOSE: Breast and/or ovarian cancers are among the most common cancers in women across the world. In the Indian population, the healthcare burden of breast and/or ovarian cancers has been steadily rising, thus stressing the need for early detection, surveillance, and disease management measures. However, the burden attributable to inherited mutations is not well characterized. METHODS: We sequenced 1010 unrelated patients and families from across India with an indication of breast and/or ovarian cancers, using the TruSight Cancer panel which includes 14 genes, strongly associated with risk of hereditary breast and/or ovarian cancers...
February 22, 2018: Breast Cancer Research and Treatment
Dong Hoon Suh, Miseon Kim, Kyung Hun Lee, Keun Yong Eom, Maj Kamille Kjeldsen, Mansoor Raza Mirza, Jae Weon Kim
In 2017, 10 topics were selected as major clinical research advances in gynecologic oncology. For cervical cancer, efficacy and safety analysis results of a 9-valent human papillomavirus (HPV) vaccine and long-term impact of reduced dose of quadrivalent vaccine were updated. Brief introduction of KEYNOTE trials of pembrolizumab, a monoclonal antibody that blocks the interaction between programmed death (PD)-1 and its ligands, PD-L1 and PD-L2, followed. Tailored surveillance programs for gynecologic cancer related with Lynch syndrome and update on sentinel lymph node mapping were reviewed for uterine corpus cancer...
March 2018: Journal of Gynecologic Oncology
Kelsey E Lewis, Karen H Lu, Amber M Klimczak, Samuel C Mok
Current ovarian cancer screening guidelines in high-risk women vary according to different organizations. Risk reducing surgery remains the gold standard for definitive treatment in BRCA mutation carriers, but research advancements have created more short-term options for patients to consider. The decisions involved in how a woman manages her BRCA mutation status can cause a great deal of stress and worry due to the imperfect therapy options. The goal of this review was to critically analyze the screening recommendations and alternative options for high-risk ovarian cancer patients and evaluate how these discrepancies and choices affect a woman's management decisions...
February 21, 2018: Cancers
Sanghamitra Mylavarapu, Asmita Das, Monideepa Roy
Recent years have seen cancer emerge as one of the leading cause of mortality worldwide with breast cancer being the second most common cause of death among women. Individuals harboring BRCA mutations are at a higher risk of developing breast and/or ovarian cancers. This risk is much greater in the presence of germline mutations. BRCA1 and BRCA2 play crucial role in the DNA damage response and repair pathway, a function that is critical in preserving the integrity of the genome. Mutations that interfere with normal cellular function of BRCA not only lead to onset and progression of cancer but also modulate therapy outcome of treatment with platinum drugs...
2018: Frontiers in Oncology
Christine Mau, Michael Untch
Risk-reducing surgery has proved to be a reasonable procedure in healthy women with a definitely elevated risk of developing cancer. Here we consider the elevated risk of breast and ovarian cancer. There is a clear indication for such surgery in healthy women with a pathogenic BRCA1/2 mutation. For these patients, a risk-reducing bilateral mastectomy leads to a verifiable reduction in mortality from breast cancer, particularly for young patients. In most cases, surgery is combined with breast reconstruction...
December 2017: Breast Care
Kevin H Eng, J Brian Szender, John Lewis Etter, Jasmine Kaur, Samantha Poblete, Ruea-Yea Huang, Qianqian Zhu, Katherine A Grzesik, Sebastiano Battaglia, Rikki Cannioto, John J Krolewski, Emese Zsiros, Peter J Frederick, Shashikant B Lele, Kirsten B Moysich, Kunle O Odunsi
Given prior evidence that an affected woman conveys a higher risk of ovarian cancer to her sister than to her mother, we hypothesized that there exists an X-linked variant evidenced by transmission to a woman from her paternal grandmother via her father. We ascertained 3,499 grandmother/granddaughter pairs from the Familial Ovarian Cancer Registry at the Roswell Park Cancer Institute observing 892 informative pairs with 157 affected granddaughters. We performed germline X-chromosome exome sequencing on 186 women with ovarian cancer from the registry...
February 2018: PLoS Genetics
Mohammed Ibrahim, Siddhartha Yadav, Foluso Ogunleye, Dana Zakalik
BACKGROUND: Mutations in BRCA1 and BRCA2 (BRCA1/2) genes are associated with an increased risk of breast and ovarian cancers in women. The cancer characteristics of men with BRCA1/2 mutations are less well studied. This study describes the unique cancer characteristics of male BRCA1/2 mutation carriers at our institution. METHODS: We performed a retrospective chart review on male patients who were seen between January 2004 and December 2014 and tested positive for a BRCA1/2 mutation...
February 13, 2018: BMC Cancer
J Ventriglia, I Paciolla, S C Cecere, C Pisano, M Di Napoli, L Arenare, S V Setola, N S Losito, D Califano, M Orditura, S Pignata
In patients with recurrent ovarian cancer, the choice of second-line therapy is complex. Several factors have to be considered, such as platinum-free interval (PFI), residual toxicity from the previous treatments, BRCA1/2 gene mutation status. Trebectedin is a minor groove DNA binder derived from a marine organism that has shown efficacy in different settings in ovarian cancer therapy. It has been approved in the treatment of partially platinum sensitive (PPS) (PFI between 6 and 12 months) relapsed ovarian cancer according to the statistically significant progression-free survival (7...
February 8, 2018: Clinical Oncology: a Journal of the Royal College of Radiologists
Stephanie A Cohen, Courtney Lynam Scherr, Dawn M Nixon
Women with BRCA mutations, at significantly increased risk for breast and ovarian cancer, do not consistently adhere to management guidelines due to lack of awareness and challenges tracking appointments. We developed an iPhone application (app) to help BRCA carriers manage their surveillance. We explored baseline awareness and adherence to surveillance guidelines and analytic data from 21 months of app use. Descriptive statistics were calculated on responses (N = 86) to a survey about surveillance awareness and practices...
February 10, 2018: Journal of Genetic Counseling
Hikmat Abdel-Razeq, Amal Al-Omari, Farah Zahran, Banu Arun
BACKGROUND: Breast cancer is the most common malignancy and the leading cause of cancer-related deaths among Jordanian women. With a median age of 50 years at diagnosis, a higher prevalence of hereditary breast cancer may be expected. The objective of this pilot study is to evaluate, for the first time, the contribution of germline mutations in BRCA1/2 to breast cancer among Jordanian patients. METHODS: Jordanian breast cancer women with a selected high risk profile were invited to participate...
February 6, 2018: BMC Cancer
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