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https://www.readbyqxmd.com/read/28314837/risk-reducing-strategies-for-ovarian-cancer-in-brca-mutation-carriers-a-balancing-act
#1
Roi Tschernichovsky, Annekathryn Goodman
OBJECTIVE: The objective of this study was to review the role of bilateral salpingo-oophorectomy in BRCA mutation (mBRCA) carriers and alternative interventions in risk reduction of ovarian cancer (OC). MATERIALS AND METHODS: A systematic review using PubMed, MEDLINE, EMBASE, and the Cochrane library was conducted to identify studies of different strategies to prevent OC in mBRCA carriers, including bilateral salpingo-oophorectomy, prophylactic salpingectomy with delayed oophorectomy, intensive surveillance, and chemoprevention...
March 17, 2017: Oncologist
https://www.readbyqxmd.com/read/28277317/brca1-2-germline-missense-mutations-a-systematic-review
#2
Giovanni Corso, Irene Feroce, Mattia Intra, Antonio Toesca, Francesca Magnoni, Manuela Sargenti, Paola Naninato, Pietro Caldarella, Gianmatteo Pagani, Annarita Vento, Paolo Veronesi, Bernardo Bonanni, Viviana Galimberti
Hereditary breast and ovarian cancer is an inherited syndrome associated with BRCA1/2 germline defects. The identified mutations are classified as missense, large deletion, insertion, nonsense and splice-site variants with a deleterious impact on BRCA1/2 function. Part of these forms the well-documented truncating mutations, and missense variants represent a clinical dilemma as the pathogenic role is yet to be clearly shown. In this systematic review, we collected these missense variations with a documented deleterious function...
March 8, 2017: European Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28250726/parp-inhibitors-review-of-mechanisms-of-action-and-brca1-2-mutation-targeting
#3
REVIEW
Karolina N Dziadkowiec, Emilia Gąsiorowska, Ewa Nowak-Markwitz, Anna Jankowska
Poly(ADP-ribose) polymerases have shown true promise in early clinical studies due to reported activity in BRCA-associated cancers. PARP inhibitors may represent a potentially important new class of chemotherapeutic agents directed at targeting cancers with defective DNA-damage repair. In order to widen the prospective patient population that would benefit from PARP inhibitors, predictive biomarkers based on a clear understanding of the mechanism of action are required. In addition, a more sophisticated understanding of the toxicity profile is required if PARP inhibitors are to be employed in the curative, rather than the palliative, setting...
December 2016: Przeglad Menopauzalny, Menopause Review
https://www.readbyqxmd.com/read/28216025/pi3k-akt-mtor-inhibitors-in-breast-cancers-from-tumor-cell-signaling-to-clinical-trials
#4
REVIEW
Dey Nandini, De Pradip, Leyland-Jones Brian
Breast cancer (BC) is the most common women cancer and second most common cause of cancer death in women. A woman living in the United States has 12.3% lifetime risk of being diagnosed with BC. From the genomics point of view, the most common three subtypes of BC encountered in clinics are HR+, HER2+, and TNBC or basal-like BC. Estrogen receptor (ER) status or HER2 amplification or chemotherapy is not sufficient to understand the underlying mechanisms of disease progression and resistance (de novo or acquire)...
February 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28162234/mainstreaming-cancer-genetics-a-model-integrating-germline-brca-testing-into-routine-ovarian-cancer-clinics
#5
Maira Kentwell, Eryn Dow, Yoland Antill, C David Wrede, Orla McNally, Emily Higgs, Anne Hamilton, Sumitra Ananda, Geoffrey J Lindeman, Clare L Scott
OBJECTIVE: Owing to the rapid increase in clinical need, we aimed to implement and review the performance of a mainstreaming model of germline BRCA1/2 genetic testing in eligible women with high grade non-mucinous epithelial ovarian cancer via a Genetic Counselor embedded in the gynecology oncology clinic. METHODS: The model implemented involved a specialized referral form, weekly genetics-lead multidisciplinary review of referrals, and pre- and post-test genetic counseling provided by an embedded genetic counselor during chemotherapy chair time...
February 3, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28152805/a-multidisciplinary-team-approach-to-efficient-breast-cancer-diagnosis
#6
Melissa Shelby, Shefali Birdi, Stephanie Costa Byrum, Julie Annie Yee Billar, Kevin McCabe, Jignesh Patel, Vilert A Loving
88 Background: System inefficiencies result in delayed breast cancer diagnoses. Inefficiencies include any non-value added steps between symptom onset/imaging abnormality to cancer diagnosis and treatment. Diagnostic delays can lead to more advanced disease and may negatively impact survival. Further, optimizing the efficiency of diagnostic evaluation models can reduce barriers to care and improve patient satisfaction. To achieve these efficiency goals, Banner MD Anderson Cancer Center (BMDACC) instituted the Undiagnosed Breast Clinic (UBC)...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28117679/the-potential-of-targeting-ribosome-biogenesis-in-high-grade-serous-ovarian-cancer
#7
REVIEW
Shunfei Yan, Daniel Frank, Jinbae Son, Katherine M Hannan, Ross D Hannan, Keefe T Chan, Richard B Pearson, Elaine Sanij
Overall survival for patients with ovarian cancer (OC) has shown little improvement for decades meaning new therapeutic options are critical. OC comprises multiple histological subtypes, of which the most common and aggressive subtype is high-grade serous ovarian cancer (HGSOC). HGSOC is characterized by genomic structural variations with relatively few recurrent somatic mutations or dominantly acting oncogenes that can be targeted for the development of novel therapies. However, deregulation of pathways controlling homologous recombination (HR) and ribosome biogenesis has been observed in a high proportion of HGSOC, raising the possibility that targeting these basic cellular processes may provide improved patient outcomes...
January 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28094039/cisplatin-can-be-safely-administered-to-ovarian-cancer-patients-with-hypersensitivity-to-carboplatin
#8
A Bergamini, C Pisano, M Di Napoli, L Arenare, C Della Pepa, R Tambaro, G Facchini, P Gargiulo, S Rossetti, G Mangili, S Pignata, S C Cecere
OBJECTIVE: Hypersensitivity reactions (HSR) are frequently reported in patients rechallenged with carboplatin for recurrent ovarian cancer (ROC) and represent a critical issue, since discontinuation of the platinum-based therapy could affect prognosis. Several strategies to allow platinum rechallenge have been described, with controversial outcomes. The aim of this study is to illustrate a 10-year experience with cisplatin in patients with a previous HSR to carboplatin or at risk for allergy...
January 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28078645/parp-inhibitors-in-reproductive-system-cancers-current-use-and-developments
#9
REVIEW
Geraldine O'Sullivan Coyne, Alice P Chen, Robert Meehan, James H Doroshow
The repair of DNA damage is a critical cellular process governed by multiple biochemical pathways that are often found to be defective in cancer cells. The poly(ADP-ribose) polymerase (PARP) family of proteins controls response to single-strand DNA breaks by detecting these damaged sites and recruiting the proper factors for repair. Blocking this pathway forces cells to utilize complementary mechanisms to repair DNA damage. While PARP inhibition may not, in itself, be sufficient to cause tumor cell death, inhibition of DNA repair with PARP inhibitors is an effective cytotoxic strategy when it is used in patients who carry other defective DNA-repair mechanisms, such as mutations in the genes BRCA 1 and 2...
February 2017: Drugs
https://www.readbyqxmd.com/read/28055979/-back-to-a-false-normality-new-intriguing-mechanisms-of-resistance-to-parp-inhibitors
#10
REVIEW
Lorena Incorvaia, Francesc Passiglia, Sergio Rizzo, Antonio Galvano, Angela Listì, Nadia Barraco, Rossella Maragliano, Valentina Calò, Clara Natoli, Marcello Ciaccio, Viviana Bazan, Antonio Russo
Several evidences have shown that BRCA mutations increased tumor-cells sensitivity to PARP inhibitors by synthetic lethality leading to an accelerated development of several compounds targeting the PARP enzymes system as anticancer agents for clinical setting. Most of such compounds have been investigated in ovarian and breast cancer, showing promising efficacy in BRCA-mutated patients. Recently clinical studies of PARP-inhibitors have been extended across different tumor types harboring BRCA-mutations, including also "BRCA-like" sporadic tumors with homologous recombination deficiency (HRD)...
December 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/28049253/prostate-cancer-in-a-patient-with-a-family-history-of-brca-mutation-a-case-report-and-literature-review
#11
Won Hoon Song, Sung Han Kim, Jae Young Joung, Weon Seo Park, Ho Kyung Seo, Jinsoo Chung, Kang Hyun Lee
One of the most significant risk factors for prostate cancer (PC) is a family history of the disease, with germ-line mutations in the breast cancer predisposition gene (BRCA) 2 conferring the highest risk. We here report a 56-year-old man presented with painful gait disturbance and diagnosed PC with multiple disseminated bone metastases. The patient had a strong family history of breast cancer with his 2 nieces affected. Furthermore, his aunts and uncles from both sides were diagnosed with stomach, ovarian, and colorectal cancers...
February 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28012689/oncofertility-for-women-with-gynecologic-malignancies
#12
REVIEW
Jessica L Chan, Erica T Wang
The emerging field of oncofertility addresses fertility and the reproductive health needs for cancer patients, a key topic in cancer survivorship. Given that the standard treatment for gynecologic malignancies involves removal of reproductive organs, pelvic radiation, or chemotherapy, the effect of such treatment on fertility and options for fertility preservation are even more relevant than for other malignancies. In young women with new diagnoses of cervical, endometrial, or ovarian cancers, viable strategies for fertility preservation without compromising oncological outcome exist and should be considered...
March 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/27981507/emerging-diagnostic-prognostic-and-therapeutic-biomarkers-for-ovarian-cancer
#13
REVIEW
Khalid El Bairi, Abdul Hafeez Kandhro, Adel Gouri, Wafaa Mahfoud, Noureddine Louanjli, Brahim Saadani, Said Afqir, Mariam Amrani
BACKGROUND: In spite of various treatment options currently available, ovarian cancer (OC) still remains a leading cause of death in women world-wide. Diagnosis at an early stage is one of the most important factors that determines survival. Current clinical diagnostic tools have, however, a limited efficacy in early OC detection. Therefore, there is a critical need for new (early) diagnostic biomarkers and tools. Through advances in genomic, proteomic and metabolomic techniques, several novel molecular OC biomarkers have recently been identified...
December 15, 2016: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/27978798/combination-platinum-based-and-dna-damage-response-targeting-cancer-therapy-evolution-and-future-directions
#14
Spyridon P Basourakos, Likun Li, Ana M Aparicio, Paul G Corn, Jeri Kim, Timothy C Thompson
Maintenance of genomic stability is a critical determinant of cell survival and is necessary for growth and progression of malignant cells. Alkylating factors, i.e., interstrand crosslinking (ICL) agents, including platinum-based agents, are first-line chemotherapy treatment for many solid human cancers. In malignant cells, ICL triggers the DNA damage response (DDR) including DNA repair, and mainly involves the nucleotide excision repair (NER) pathway. When the damage burden is high and lesions cannot be repaired, malignant cells are unable to divide and ultimately undergo cell death either through mitotic catastrophe or apoptosis...
December 14, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27958297/delivering-widespread-brca-testing-and-parp-inhibition-to-patients-with-ovarian-cancer
#15
REVIEW
Angela George, Stan Kaye, Susana Banerjee
The treatment of patients with ovarian cancer is rapidly changing following the success of poly [ADP-ribose] polymerase (PARP) inhibitors in clinical trials. Olaparib is the first PARP inhibitor to be approved by the EMA and FDA for BRCA-mutated ovarian cancer. Germ line BRCA mutation status is now established as a predictive biomarker of potential benefit from treatment with a PARP inhibitor; therefore, knowledge of the BRCA status of an individual patient with ovarian cancer is essential, in order to guide treatment decisions...
December 13, 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27931006/brca-mutation-genetic-testing-implications-in-the-united-states
#16
REVIEW
Soley Bayraktar, Banu Arun
BRCA mutation carriers have a very high risk of breast and ovarian cancer by age 70, in the ranges 47%-66% and 40%-57%, respectively. Additionally, women with BRCA mutation-associated breast cancer also have an elevated risk of other or secondary malignancies. Fortunately, the breast and ovarian cancer outcome for BRCA1/2 mutation carriers is at least as good as for non-carriers with chemoprevention, prophylactic surgeries and appropriate use of therapies. Therefore, identification of those who might have a mutation is important so that genetic counseling, testing, screening and prevention strategies can be applied in a timely manner...
February 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/27922795/breast-cancer-risk-reduction-decisions-of-the-brca-positive-patient-an-observational-study-at-a-single-institution
#17
Dana Johns, Jay Agarwal, Layla Anderson, Jian Ying, Wendy Kohlmann
BACKGROUND: BRCA1 and BRCA2 gene mutations carry with them a 50%-80% risk of developing breast cancer. The best choice for managing breast cancer risk in patients with a BRCA1/2 mutation is a highly personal decision. Options for risk management include surveillance with multiple modalities or prophylactic surgical intervention. The goal of this study was to gain a better understanding of contributing factors affecting the decision for managing breast cancer risk made by patients who are BRCA mutation positive and cancer free...
December 6, 2016: Journal of Women's Health
https://www.readbyqxmd.com/read/27917619/practical-guidance-on-the-use-of-olaparib-capsules-as-maintenance-therapy-for-women-with-brca-mutations-and-platinum-sensitive-recurrent-ovarian-cancer
#18
REVIEW
Michael Friedlander, Susana Banerjee, Linda Mileshkin, Clare Scott, Catherine Shannon, Jeffrey Goh
Olaparib is the first oral poly(ADP-ribose) polymerase inhibitor to be approved as maintenance monotherapy for treatment of patients with platinum-sensitive relapsed BRCA-mutated (BRCAm) serous ovarian cancer. This review provides practical guidance on the use of olaparib (capsule formulation) in the maintenance setting. The article focuses on the key toxicities that can arise with olaparib therapy and recommendations for their management. Nausea, vomiting, fatigue and anemia are the most commonly reported adverse events in olaparib clinical trials and are generally mild to moderate and transient in nature in most patients...
December 2016: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27906166/which-brca-genetic-testing-programs-are-ready-for-implementation-in-health-care-a-systematic-review-of-economic-evaluations
#19
Elvira D'Andrea, Carolina Marzuillo, Corrado De Vito, Marco Di Marco, Erica Pitini, Maria Rosaria Vacchio, Paolo Villari
PURPOSE: There is considerable evidence regarding the efficacy and effectiveness of BRCA genetic testing programs, but whether they represent good use of financial resources is not clear. Therefore, we aimed to identify the main health-care programs for BRCA testing and to evaluate their cost-effectiveness. METHODS: We performed a systematic review of full economic evaluations of health-care programs involving BRCA testing. RESULTS: Nine economic evaluations were included, and four main categories of BRCA testing programs were identified: (i) population-based genetic screening of individuals without cancer, either comprehensive or targeted based on ancestry; (ii) family history (FH)-based genetic screening, i...
December 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/27899185/genetic-predisposition-in-gynecologic-cancers
#20
REVIEW
Molly S Daniels, Karen H Lu
This review article discusses the diagnosis and management of hereditary ovarian cancer and hereditary uterine cancer. The key recommendations highlighted are: All women with high grade non-mucinous epithelial ovarian cancer should be offered at least BRCA1 and BRCA2 genetic testing. The care of women with BRCA-associated ovarian cancer should be tailored to their mutation status. Risk-reducing bilateral salpingo-oophorectomy is recommended for women with BRCA1/2 mutations. Women with endometrial cancer should be assessed for the possibility of Lynch syndrome...
October 2016: Seminars in Oncology
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