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https://www.readbyqxmd.com/read/29228641/brca-mutations-in-the-manifestation-and-treatment-of-ovarian-cancer
#1
REVIEW
Zimin Pan, Xing Xie
BRCA genes are important for the integrity and stability of genetic material and play key roles in repairing DNA breaks via high fidelity homologous recombination. BRCA mutations are known to predispose carriers to gynecological malignancies, accounting for a majority of hereditary OC cases. Known to be lethal, OC is difficult to detect and control. Testing for BRCA mutations is a key step in the risk assessment, prognosis, treatment and prevention of OC and current clinical guidelines recommend BRCA mutation testing for all OCs of epithelial origin...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29205122/parp-inhibitors-in-epithelial-ovarian-cancer
#2
Kristin N Taylor, Ramez N Eskander
Background Ovarian cancer remains the most common lethal gynecologic malignancy. The therapeutic gains with use of traditional cytotoxic chemotherapy in advanced stage disease remain limited, reflecting the need for novel therapies. Poly(ADP-ribose) polymerase (PARP) inhibitors have recently demonstrated a significant therapeutic effect in patients with recurrent, high grade serous ovarian cancer, both in the treatment of existing disease and in prolonging the disease-free interval. Objective The purpose of this article is to discuss PARP inhibitor use in patients with advanced stage ovarian cancer, and to extensively review the existing clinical literature and related patents...
December 3, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29202431/triple-negative-breast-cancer-emerging-therapeutic-modalities-and-novel-combination-therapies
#3
REVIEW
Alice Lee, Mustafa B A Djamgoz
Triple negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer which lacks oestrogen receptors, progesterone receptors and HER2 amplification, thereby making it difficult to target therapeutically. In addition, TNBC has the highest rates of metastatic disease and the poorest overall survival of all breast cancer subtypes. Resultantly, development of targeted therapies for TNBC is urgently needed. Recent efforts aimed at molecular characterisation of TNBCs have revealed various emerging therapeutic targets including PARP1, receptor and non-receptor tyrosine kinases, immune-checkpoints, androgen receptor and epigenetic proteins...
November 13, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29187427/the-role-of-the-androgen-receptor-signaling-in-breast-malignancies
#4
REVIEW
Panagiotis F Christopoulos, Nikolaos I Vlachogiannis, Christiana T Vogkou, Michael Koutsilieris
Breast cancer (BrCa) is the most common malignancy among women worldwide, and one of the leading causes of cancer-related deaths in females. Despite the development of novel therapeutic modalities, triple-negative breast cancer (TNBC) remains an incurable disease. Androgen receptor (AR) is widely expressed in BrCa and its role in the disease may differ depending on the molecular subtype and the stage. Interestingly, AR has been suggested as a potential target candidate in TNBC, while sex hormone levels may regulate the role of AR in BrCa subtypes...
December 2017: Anticancer Research
https://www.readbyqxmd.com/read/29171761/new-agents-for-the-management-of-resistant-metastatic-breast-cancer
#5
Jesus Anampa, Joseph A Sparano
Metastatic breast cancer (MBC) is an incurable disease and treatment is directed towards symptom palliation and survival prolongation. Treatment selection in patients is based on tumor biology, age, comorbidities, performance status, tumor burden, and prior treatment history. Areas covered: This present review summarizes the recent treatment strategies in the management of MBC, highlighting regimens after first-line therapy. Topics discussed include new strategies for endocrine therapy, anti-HER2 therapy, and promising strategies for the management of triple negative breast cancer...
November 24, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29166829/rucaparib-a-poly-adp-ribose-polymerase-inhibitor-for-brca-mutated-relapsed-ovarian-cancer
#6
Donald C Moore, J Tanner Ringley, Jolly Patel
OBJECTIVE: To review the pharmacology, safety, efficacy, and the role of rucaparib in the treatment of relapsed, advanced ovarian cancer. SUMMARY: A total of 2 phase I/II trials and 1 phase II trial have evaluated the safety and efficacy of oral rucaparib in ovarian cancer. In patients with deleterious BRCA1/2 mutation, an overall response rate of 80% was achieved in the phase II trial Assessment of Rucaparib in Ovarian CancEr Trial 2 (ARIEL2). In the same trial, progression-free survival was higher in patients with BRCA1/2 mutation and BRCA wild types with high loss of heterozygosity (LOH) than BRCA wild types with low LOH...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/29164974/clinical-and-molecular-characterization-of-brca-associated-breast-cancer-results-from-the-dbcg
#7
I M H Soenderstrup, A V Laenkholm, M B Jensen, J O Eriksen, A M Gerdes, T V O Hansen, T A Kruse, M J Larsen, I S Pedersen, M Rossing, M Thomassen, B Ejlertsen
BACKGROUND: In breast cancer (BC) patients a cancer predisposing BRCA1/2 mutation is associated with adverse tumor characteristics, risk assessment and treatment allocation. We aimed to estimate overall- (OS) and disease-free survival (DFS) according to tumor characteristics and treatment among women who within two years of definitive surgery for primary BC were shown to carry a mutation in BRCA1/2 . MATERIAL AND METHODS: From the clinical database of the Danish Breast Cancer Group we included 141 BRCA1 and 96 BRCA2 BC patients...
November 22, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29163536/drug-hypersensitivity-and-anaphylaxis-in-cancer-and-chronic-inflammatory-diseases-the-role-of-desensitizations
#8
REVIEW
Mariana Castells
Drug allergy is a rising problem in the twenty-first century which affects all populations and races, children, and adults, and for which the recognition, diagnosis, management, and treatment is still not well standardized. Classical and new chemotherapy drugs, monoclonal antibodies (MoAbs), and small molecules to treat cancer and chronic inflammatory diseases are aimed at improving quality of life and life expectancy of patients, but an increasing number of reactions including anaphylaxis precludes their use in targeted populations...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29152070/the-role-of-brca-status-on-prognosis-in-patients-with-triple-negative-breast-cancer
#9
Yuxin Xie, Qiheng Gou, Qianqian Wang, Xiaorong Zhong, Hong Zheng
Studies have showed that dysfunction in the breast cancer susceptibility gene (BRCA) is associated with triple-negative breast cancer (TNBC); however, its effect on patient survival remains controversial. We investigated the distribution of BRCA1/2 mutations in unselected Chinese patients with TNBC and explored their roles in prognosis. Then a systematic review and meta-analysis were performed to evaluate the prognostic role of BRCA dysfunction, including BRCA1/2 germline/somatic mutations, BRCA1 promoter methylation, and low BRCA1 protein expression in TNBC patients...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150351/combined-hormonal-contraceptive-use-and-risk-of-breast-cancer-in-a-population-of-women-with-a-family-history
#10
Giovanni Grandi, Angela Toss, Angelo Cagnacci, Luigi Marcheselli, Silvia Pavesi, Fabio Facchinetti, Stefano Cascinu, Laura Cortesi
BACKGROUND: We estimated the association between combined hormonal contraceptive (CHC) use and breast cancer (BC) incidence in a well-selected population of women at familial risk of BC at the Modena Family Cancer Clinic. MATERIALS AND METHODS: We performed a retrospective cohort study by reviewing the data from 2527 women (4.5% BRCA mutation carriers, 72.2% high risk, and 23.3% intermediate risk using the Modena criteria and the Tyrer-Cuzick model). RESULTS: We did not find any specific feature of breast cancer (infiltration, hormone receptor and HER2 status, onset before age 35 years, multiple diagnoses) in the CHC users (P > ...
November 14, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29147896/genetic-diagnosis-before-surgery-has-an-impact-on-surgical-decision-in-brca-mutation-carriers-with-breast-cancer
#11
Sungmin Park, Jeong Eon Lee, Jai Min Ryu, Issac Kim, Soo Youn Bae, Se Kyung Lee, Jonghan Yu, Seok Won Kim, Seok Jin Nam
BACKGROUND: The first aim of our study was to evaluate surgical decision-making by BRCA mutation carriers with breast cancer based on the timing of knowledge of their BRCA mutation status. The second aim was to evaluate breast cancer outcome following surgical treatment. METHODS: This was a retrospective study of 164 patients diagnosed with invasive breast cancer, tested for BRCA mutation, and treated with primary surgery between 2004 and 2015 at Samsung Medical Center in Seoul, Korea...
November 16, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/29147583/patterns-of-progression-in-metastatic-estrogen-receptor-positive-breast-cancer-an-argument-for-local-therapy
#12
Patrick Kelly, Zhe Ma, Said Baidas, Rebecca Moroose, Nikita Shah, Roi Dagan, Eleftherios Mamounas, Justin Rineer
Purpose: Despite advances in endocrine therapy (ET), metastatic estrogen receptor positive breast cancer (BrCA) remains incurable. Though the mechanisms of resistance to ET have been studied extensively, the anatomic pattern of disease progression remains poorly characterized. The purpose of this study was to characterize the pattern of progression for patients receiving ET for metastatic BrCA. Methods: The records of 108 patients with metastatic BrCA who progressed on ET were reviewed...
2017: International Journal of Breast Cancer
https://www.readbyqxmd.com/read/29138572/current-status-of-poly-adp-ribose-polymerase-inhibitors-and-future-directions
#13
REVIEW
Akihiro Ohmoto, Shinichi Yachida
Inhibitors of poly(ADP-ribose) polymerases (PARPs), which play a key role in DNA damage/repair pathways, have been developed as antitumor agents based on the concept of synthetic lethality. Synthetic lethality is the idea that cell death would be efficiently induced by simultaneous loss of function of plural key molecules, for example, by exposing tumor cells with inactivating gene mutation of BRCA-mediated DNA repair to chemically induced inhibition of PARPs. Indeed, three PARP inhibitors, olaparib, rucaparib and niraparib have already been approved in the US or Europe, mainly for the treatment of BRCA-mutant ovarian cancer...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29128106/who-are-the-long-term-survivors-of-high-grade-serous-ovarian-cancer
#14
REVIEW
Claire Hoppenot, Mark A Eckert, Samantha M Tienda, Ernst Lengyel
Although the median survival for epithelial ovarian cancer (EOC) is <5years, approximately 15% of patients will survive for >10years. A better understanding of these exceptional responders could reveal opportunities to improve the dismal prognosis of most EOC patients. In this review, we examine the clinical and genomic features that have been associated with long-term survival, which is generally defined as survival of >7-10years after initial diagnosis. Clinical features influencing long-term survival have been best reported in large retrospective population-based studies...
November 8, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29110151/patient-reported-factors-associated-with-adherence-to-adjuvant-endocrine-therapy-after-breast-cancer-an-integrative-review
#15
REVIEW
Leah K Lambert, Lynda G Balneaves, A Fuchsia Howard, Carolyn C Gotay
BACKGROUND: Adjuvant endocrine therapy (AET) significantly reduces recurrence and mortality in women with breast cancer (BrCa). Despite the efficacy of AET in improving BrCa outcomes, up to 50% of women do not adhere to prescribed AET regimens. While numerous demographic and clinical predictors influence adherence and persistence, few studies have identified the patient-reported factors that influence AET adherence and persistence. PURPOSE: The aim was to examine the patient-reported personal, social, and structural factors influencing BrCa survivors' adherence and persistence with AET...
November 6, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29109859/candidate-synthetic-lethality-partners-to-parp-inhibitors-in-the-treatment-of-ovarian-clear-cell-cancer
#16
Naoki Kawahara, Kenji Ogawa, Mika Nagayasu, Mai Kimura, Yoshikazu Sasaki, Hiroshi Kobayashi
Inhibitors of poly(ADP-ribose) polymerase (PARP) are new types of personalized treatment of relapsed platinum-sensitive ovarian cancer harboring BRCA1/2 mutations. Ovarian clear cell cancer (CCC), a subset of ovarian cancer, often appears as low-stage disease with a higher incidence among Japanese. Advanced CCC is highly aggressive with poor patient outcome. The aim of the present study was to determine the potential synthetic lethality gene pairs for PARP inhibitions in patients with CCC through virtual and biological screenings as well as clinical studies...
November 2017: Biomedical Reports
https://www.readbyqxmd.com/read/29069866/germline-mutations-in-pancreatic-cancer-and-potential-new-therapeutic-options
#17
REVIEW
Rille Pihlak, Juan W Valle, Mairéad G McNamara
Due to short-lived treatment responses in unresectable disease, pancreatic ductal adenocarcinoma (PDAC) continues to be one of the deadliest cancers. There is availability of new information about germline and sporadic mutations in the deoxyribonucleic acid (DNA) damage repair pathway in PDAC in recent decades and the expectation is that novel targeted therapies will thus be developed. A variety of germline mutations (BRCA2, BRCA1, PALB2, CDKN2A, ATM, TP53 and mismatch repair genes MLH1, MSH2, MSH6) have been reported in these patients with the highest prevalence being BRCA1/2...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29063517/parp-inhibitors-in-the-treatment-of-triple-negative-breast-cancer
#18
REVIEW
Jill J J Geenen, Sabine C Linn, Jos H Beijnen, Jan H M Schellens
Breast cancer is a heterogeneous disease, manifesting in a broad differentiation in phenotypes and morphologic profiles, resulting in variable clinical behavior. Between 10 and 20% of all breast cancers are triple negative. Triple-negative breast cancer (TNBC) lacks the expression of human epidermal growth factor receptor 2 (HER2) and hormone receptors; therefore, to date, chemotherapy remains the backbone of treatment. TNBC tends to be aggressive and has a high histological grade, resulting in a poor 5-year prognosis...
October 23, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29061774/immune-checkpoint-inhibitors-in-gynecological-cancers-update-of-literature-and-perspectives-of-clinical-research
#19
REVIEW
Angiolo Gadducci, Maria Elena Guerrieri
The presence of tumor infiltrating lymphocytes (TILs) influences the clinical outcome of cancer patients and immune checkpoint inhibitors (ICPI) have been approved for treating different types of malignancies. In this review, we assess the scanty data from literature and the perspectives of clinical research about the use of ICPI in gynecological cancers. These agents have obtained objective response rates ranging from 5.9% to 15% in early phase Ib-II trials, including patients with platinum-resistant ovarian cancer, whereas only anecdotal data are available for patients with recurrent, heavily pretreated endometrial cancer...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29058922/-satisfaction-and-overall-quality-of-life-in-brca-positive-women-after-prophylactic-surgeries
#20
P Šašková, D Pavlišta, L Dostálek
INTRODUCTION: Genetic mutations are responsible for 5-10% of all breast and ovarian carcinomas, while most of them are caused by a mutation of the BRCA gene. Women with this type of mutation have a lifetime risk of breast and ovarian cancer and therefore, they require very intensive medical care, including surgical prevention. Specifically, prophylactic bilateral mastectomy and prophylactic salpingo-oophorectomy are done, which undoubtedly decrease the riskof cancer. The aim of this review article is to inform healthcare professionals and the general public about the satisfaction of BRCA positive women with their decision to undergo these prophylactic surgeries, and also about the impact of these procedures on sexuality, menopausal symptoms, mental health and the overall quality of life...
2017: Rozhledy V Chirurgii: Měsíčník Československé Chirurgické Společnosti
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