scholarly journals Management Options after Prophylactic Surgeries in Women with BRCA Mutations: A Review

2007 ◽  
Vol 14 (4) ◽  
pp. 330-337 ◽  
Author(s):  
Dawn C. Allain ◽  
Kevin Sweet ◽  
Doreen M. Agnese
Keyword(s):  
Medical Management ◽  
Cancer Susceptibility ◽  
Brca Mutation ◽  
Brca2 Gene ◽  
Brca1 And Brca2 ◽  
Management Options ◽  
Cancer Susceptibility Genes ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Brca Mutation Carriers

Background Although breast cancer is relatively common, only about 5% of cases are due to inheritance of highly penetrant cancer susceptibility genes. The majority of these are caused by mutations in the BRCA1 and BRCA2 genes, which are also associated with an increased risk of ovarian cancer. Increased surveillance, chemoprevention, and prophylactic surgeries are standard options for the effective medical management of mutation carriers. However, optimal management of female carriers who choose to undergo prophylactic surgeries is still poorly understood. Methods The authors provide an overview of the current literature regarding medical management options for women carriers of BRCA1 and BRCA2 gene mutations and the implications for those individuals who have chosen to undergo prophylactic surgeries. Results BRCA mutation carriers who opt for prophylactic surgeries are still at risk for development of malignancy, and appropriate monitoring is warranted. Conclusions There are limited data on the appropriate medical management for BRCA mutation carriers after prophylactic surgeries. However, a management plan can be extrapolated from the general management recommendations for surveillance and other risk-reducing strategies in BRCA-positive individuals.

Comparison of risk-reducing surgery in women with BRCA and non-BRCA ovarian cancer susceptibility genes.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1547-1547
Author(s):  
Zachary Phillip Schwartz ◽  
Mae Zakhour ◽  
Andrew John Li ◽  
Christine S. Walsh ◽  
Bj Rimel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Susceptibility ◽  
Brca Mutation ◽  
Susceptibility Genes ◽  
Brca Mutations ◽  
Cancer Susceptibility Genes ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
History Of ◽  
Risk Reducing

1547 Background: Risk reducing gynecologic surgery (RRSO) is standard of care for women with BRCA mutations. The optimal management for women with non-BRCA ovarian cancer susceptibility mutations remains unclear. We sought to characterize the practice patterns for these women at our two institutions. Methods: Women with germline ovarian cancer susceptibility genes who had a RRSO were identified from 1/2000-1/2019 in an IRB approved study. All patients were asymptomatic with no suspicion for malignancy at time of RRSO. Clinico-pathologic characteristics were extracted from the medical records. Continuous variables were analyzed with Kruskal-Wallis and categorical variables analyzed with chi square and t-tests. Results: 152 BRCA1, 95 BRCA2, and 63 Non-BRCA mutation carriers were identified—50 Lynch (22 MLH1, 13 MSH2, 13 MSH6, 2 PMS2) and 13 Other (6 BRIP1, 2 RAD51C, 5 RAD51D). There was no difference between age at testing, age at RRSO, and interval between testing and RRSO between groups. Genetic counseling was higher in Non-BRCA patients. Family history of ovarian cancer was more common in women with BRCA1 and Other germline mutations compared to BRCA2 and Lynch. Family and personal history of breast cancer was high in all groups except Lynch carriers. Prophylactic mastectomy was seen mostly in BRCA mutation carriers. Concomitant hysterectomy was performed in the majority of women (BRCA1 59%, BRCA2 57%, and Other 62%), with the highest frequency in Lynch carriers (86%, p<.01). Occult cancer was only seen in BRCA mutation carriers: BRCA1 (7%), BRCA2 (2%), Lynch (0%), Other (0%). Conclusions: In this cohort, women with Non-BRCA mutations are managed similarly to women with BRCA mutations. We observed no occult cancers in Non-BRCA patients. The optimal role of surgery as a risk reducing strategy in this group requires further study. [Table: see text]

scholarly journals INHERITED MUTATION IN BRCA1 AND BRCA2 IN BREAST CANCER

2019 ◽  
Vol 3 (10) ◽  
Author(s):  
Diksha Mishra ◽  
Savita Kumari ◽  
Navneeta R. Kumar
Keyword(s):  
Breast Cancer ◽  
Cancer Susceptibility ◽  
Brca Mutation ◽  
Breast Cancer Susceptibility ◽  
Brca1 And Brca2 ◽  
Suppressive Function ◽  
Cancer Susceptibility Genes ◽  
Increased Risk ◽  
Tumor Suppressive Function ◽  
Damaged Dna

BRCA1 and BRCA2 are unrelated proteins, but both are normally expressed in the cells of breast and other tissue, where they help repair damaged DNA, or destroy cells if DNA cannot be repaired. They are involved in the repair of chromosomal damage with an important role in the error-free repair of DNA double-strand breaks. If BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer. BRCA1 and BRCA2 have been described as "breast cancer susceptibility genes" and "breast cancer susceptibility proteins". The predominant allele has a normal, tumor suppressive function whereas high penetrance mutations in these genes cause a loss of tumor suppressive function which correlates with an increased risk of breast cancer. Keywords: BRCA1; BRCA2; Breast cancer; Mutation; Gene.

Detecting prostate cancer in BRCA1 and BRCA2 mutation carriers: A role for EN2?

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4653-4653
Author(s):  
Emma Killick ◽  
Richard Morgan ◽  
Francesca Launchbury ◽  
Nicola E. Annels ◽  
Elizabeth Bancroft ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Group ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Digital Rectal Examination ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Brca Mutation Carriers ◽  
The Impact

4653 Background: EN2 is part of the HOX gene family and plays a role in foetal development. More recently a potential oncogenic role for the protein has been postulated and its utility as a cancer biomarker has been explored in prostate cancer (PrCa) and breast cancer. Carriers of mutations in the BRCA1 and BRCA2 genes have an increased risk of PrCa (1.8-fold and 5-fold respectively) and their tumours tend to be more aggressive and advanced than sporadic cases. Currently there is no national screening program for BRCA mutation carriers in the UK, and the IMPACT study was set up to evaluate PSA screening in this particular group. Here we analyse the efficacy of the urinary EN2 protein as a marker of early cancer detection within this higher risk group. Methods: First pass urine (without preceding digital rectal examination) was collected as part of the IMPACT screening study which enrolled individuals aged between 40 and 69 who were unaffected by PrCa at time of enrolment into the study (n= 418). All participants were from families harbouring a BRCA1 or BRCA2 mutation and were either BRCA mutation carriers themselves or controls with a negative predictive BRCA genetic test. They underwent annual PSA test with a PSA of > 3.0 ng/ml triggering a diagnostic biopsy. EN2 protein was measured in the urine using an ELISA; (positive = > 42.5ng/ml). Results: Our initial results demonstrated urinary EN2 had a sensitivity of 66.67% and a specificity of 89.29% when discriminating which men had been diagnosed with PrCa; the ROC AUC was 0.816. The difference in EN2 level between those diagnosed with cancer and those who were not was significant (p = <0.001). There was trend towards higher EN2 levels in those with more aggressive tumours (median EN2 84.5ng/mL in Gleason ≤3+4 vs 111ng/mL in Gleason ≥4+3), however this was not statistically significant. In one PrCa case EN2 rise preceded PSA rise by 2 years. Further samples are in the process of being analysed, results from these will be included. Conclusions: Urinary EN2 protein measurement warrants further investigation as a PrCa biomarker in this higher risk group with genetic predisposition to PrCa.

An exploratory study to determine if BRCA1 and BRCA2 mutation carriers have higher risk of cardiac toxicity.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1585-1585 ◽  
Author(s):  
Roohi Ismail-Khan ◽  
Monique Sajjad ◽  
Weihong Sun ◽  
Hatem Hussein Soliman ◽  
Hyo S. Han ◽  
...  
Keyword(s):  
Breast Cancer ◽  
General Population ◽  
Exploratory Study ◽  
Online Survey ◽  
Cardiac Toxicity ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Brca Mutation Carriers

1585 Background: Anthracycline related cardiac toxicity (CT) is a concern in treating women with breast cancer. The prevalence of heart failure (HF) affects 2% of the population, less so in women. Patients receiving anthracycline based therapy (ABT) have a dose-dependent risk of reduction in ejection fraction. Recent work by Dr. Verma suggests that BRCA-deficient mice manifest increased levels of cardiac failure. We sought to explore the risk for CT and evaluate the association between ABT and HF in female BRCA mutation carriers. Methods: An online survey was developed to collect information about breast cancer treatment (including HF) in BRCA mutation carriers through the national BRCA patient advocacy organization FORCE via their 2011 conference and their website as well as the Moffitt-based Inherited Cancer Registry (ICARE). The prevalence of CT and HF was calculated in both BRCA 1 and 2 breast cancer patients and compared to general population risks. Data from those that received ABT was compared to published HF rates from ABT. Results: Our sample included 227 BRCA1 carriers and 164 BRCA2 carriers in whom 6.4% reported cardiac toxicity (i.e., either HF and/or CT). This included similar proportions in BRCA1 vs BRCA2 carriers (i.e., 6.6% and 6.1%, respectively). These proportions are significantly higher than the published rate of 2% (all p-values < 0.001). Specifically regarding ABT, 112 mutation carriers had doxorubicin (Adriamycin) for treatment of whom 8% reported HF, similar to the 11 who had Epirubicin (11 patients), of whom 9% reported HF. Conclusions: Our data suggests that BRCA mutation carriers may have an increased risk of CT compared to the general population. In particular, women with BRCA mutations treated with ABT also appear to have a higher risk of developing CT and/or HF. This exploratory study provides the basis upon which larger retrospective and prospective studies are currently being planned. The high percentage of CT observed in this study requires confirmation as they could inform recommendation for cardiac screening and review of the current standard for ABT use in this population.

Unique genetic characteristics of BRCA mutation carriers in a cohort of Arab American women.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1541-1541 ◽  
Author(s):  
Seerin Viviane Shatavi ◽  
Lindsay Dohany ◽  
Mohammad Muhsin Chisti ◽  
Ishmael A. Jaiyesimi ◽  
Dana Zakalik
Keyword(s):  
Genetic Testing ◽  
Brca Mutation ◽  
Arab American ◽  
Deleterious Mutations ◽  
Brca1 And Brca2 ◽  
American Women ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
Arab American Women ◽  
Exon 11

1541 Background: Worldwide ethnic variations in the distribution of BRCA1 and BRCA2 mutations of breast cancer patients have been recently recognized. This has led to investigations of the epidemiology, genetics and clinical characteristics of BRCA positive individuals within specific populations. This study aims to describe the findings of BRCA genetic testing in a cohort of Arab American women. Methods: A total of 73 women of Arab ancestry were evaluated in the Beaumont Cancer Genetics Program from Jan 2008 to Jan 2013. Criteria for genetic testing included a personal or family history suggestive of Hereditary Breast and Ovarian Cancer Syndrome (HBOC). Patients underwent comprehensive genetic counseling, followed by full sequence analysis for germline mutations in BRCA1 and BRCA2. Results: 63 women of Arab ancestry underwent genetic testing for BRCA1 and BRCA2. 13 (21%) patients were found to be mutation carriers, of whom 10 (16%) of the 63 had deleterious mutations (7 in BRCA2, and 3 in BRCA1), and 3 (5%) had variants of undetermined significance (VUS) in BRCA2. Of the 10 patients with deleterious mutations, 4 (40%) unrelated individuals had the same mutation, 5804del4, in exon 11 of BRCA2. The remaining patients had deleterious mutations in exon 2, exon 20, and exon 13 of BRCA2; one patient had a BRCA1 and BRCA2 mutation (exon 18). 7 of 10 patients with deleterious mutations had a cancer diagnosis, of which 5 had breast cancer, 1 had ovarian cancer, 1 had pancreatic cancer, and 3 were unaffected. Conclusions: This study demonstrates that BRCA mutations (predominantly in BRCA2) were seen in a significant proportion of Arab American women undergoing genetic testing for HBOC. A mutation in BRCA2, 5804del4, was seen in nearly half (4/10) of the carriers of deleterious mutations. This mutation, in exon 11, has not previously been associated with Arab ethnicity and may represent a founder mutation. Knowledge of the genetic spectrum, frequency, and clinical characteristics of BRCA mutation carriers will lead to greater understanding of hereditary cancer in Arab American women.

scholarly journals BRCA1/BRCA2 mutation spectrum analysis in South Asia: a systematic review

2022 ◽  
Vol 50 (1) ◽  
pp. 030006052110707
Author(s):  
Sanjeev Kharel ◽  
Suraj Shrestha ◽  
Siddhartha Yadav ◽  
Prafulla Shakya ◽  
Sujita Baidya ◽  
...  
Keyword(s):  
South Asian ◽  
Cancer Susceptibility ◽  
Brca2 Mutation ◽  
Brca2 Gene ◽  
Mutation Spectrum ◽  
Quality Data ◽  
Brca1 And Brca2 ◽  
Exon 2 ◽  
Cancer Susceptibility Genes ◽  
Brca1 Brca2

Objective Breast cancer (BC) is the most common form of cancer among Asian females. Mutations in the BRCA1/ BRCA2 genes are often observed in BC cases and largely increase the lifetime risk of having BC. Because of the paucity of high-quality data on the molecular spectrum of BRCA mutations in South Asian populations, we aimed to explore these mutations among South Asian countries. Methods A systematic literature search was performed for the BRCA1 and BRCA2 gene mutation spectrum using electronic databases such as PubMed, EMBASE, and Google Scholar. Twenty studies were selected based on specific inclusion and exclusion criteria. Results The 185delAG (c.68_69del) mutation in exon 2 of BRCA1 was the most common recurrent mutation and founder mutation found. Various intronic variants, variants of unknown significance, large genomic rearrangements, and polymorphisms were also described in some studies. Conclusions The South Asian population has a wide variety of genetic mutations of BRCA1 and BRCA2 that differ according to countries and ethnicities. A stronger knowledge of various population-specific mutations in these cancer susceptibility genes can help provide efficient strategies for genetic testing.

scholarly journals Biological Role and Clinical Implications of microRNAs in BRCA Mutation Carriers

2021 ◽  
Vol 11 ◽  
Author(s):  
Chiara Tommasi ◽  
Benedetta Pellegrino ◽  
Daniela Boggiani ◽  
Angelica Sikokis ◽  
Maria Michiara ◽  
...  
Keyword(s):  
Brca Mutation ◽  
Scientific Evidence ◽  
Clinical Implications ◽  
Brca Mutations ◽  
Small Noncoding Rnas ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Modifiable Factors ◽  
Brca Mutation Carriers

Women with pathogenic germline mutations in BRCA1 and BRCA2 genes have an increased risk to develop breast and ovarian cancer. There is, however, a high interpersonal variability in the modality and timing of tumor onset in those subjects, thus suggesting a potential role of other individual’s genetic, epigenetic, and environmental risk factors in modulating the penetrance of BRCA mutations. MicroRNAs (miRNAs) are small noncoding RNAs that can modulate the expression of several genes involved in cancer initiation and progression. MiRNAs are dysregulated at all stages of breast cancer and although they are accessible and evaluable, a standardized method for miRNA assessment is needed to ensure comparable data analysis and accuracy of results. The aim of this review was to highlight the role of miRNAs as potential biological markers for BRCA mutation carriers. In particular, biological and clinical implications of a link between lifestyle and nutritional modifiable factors, miRNA expression and germline BRCA1 and BRCA2 mutations are discussed with the knowledge of the best available scientific evidence.

Hormone replacement therapy (HRT) among BRCA mutation carriers.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1561-1561
Author(s):  
Nicole Centers ◽  
Olga Ivanov ◽  
Cynthia Buffington ◽  
Aileen Caceres
Keyword(s):  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Brca Mutation ◽  
Hormone Replacement ◽  
Premature Menopause ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Brca Mutation Carriers ◽  
Risk Of Cancer ◽  
Risk Reducing

1561 Background: BRCA mutation carriers are often offered risk-reducing surgery (oophorectomy, hysterectomy) and medication regimens (hormone modulators, chemotherapy) in a preventative format. These therapies cause premature menopause and associated symptoms including reduced libido and sexuality. Hormone replacement therapy (HRT) is beneficial in alleviating climacteric symptoms of menopause. However, due to high risk for breast cancer in BRCA mutation carriers, many within the healthcare community oppose the use of HRT, despite recent studies that fail to demonstrate an adverse effect on oncologic outcomes. The purpose of this study was to identify current HRT practices among BRCA1,2 mutation carriers. Methods: The study population included 763 BRCA1,2 mutation carriers (52% previvors, 48% survivors) who are members of Facing Our Risk of Cancer Empowered, a support, education, and advocacy group for individuals with gene mutations. Data was collected via an online survey that included questions pertaining to patient characteristics, preventative procedures, menopausal status and symptoms, HRT use, and provider recommendations. Results: According to the survey findings, 73% of BRCA mutation carriers were postmenopausal (59% previvors, 88% survivors) and, among these, 81% had become menopausal prematurely due to risk-reducing surgery or medications. Major postmenopausal concerns of BRCA mutation carriers involved low libido/sexuality (78%) and an increased risk for weight gain (83%), cardiovascular disease (77%), and osteoporosis (65%). Despite the high incidence of premature menopause and associated symptomatology of the population, HRT usage was low (13% previvors, 28% survivors). According to the survey respondents, only 26% of healthcare providers for the previvors and 8% for the survivors favored HRT use. Conclusions: High rates of premature menopause with related symptoms occur among BRCA1,2 mutation carriers in association with cancer preventative therapies. Despite the young age of this postmenopausal population, only a small percentage are on HRT. These findings suggest the need for improved education to patients and providers regarding HRT and cancer risk, as well as the exploration of HRT options.

scholarly journals Update on chemoprevention in BRCA1 and BRCA2 mutation carriers

2005 ◽  
Vol 8 (9) ◽  
Author(s):  
M. Stumacher ◽  
S. M. Domchek
Keyword(s):  
Breast Cancer ◽  
Prophylactic Mastectomy ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Breast Cancers ◽  
Brca1 And Brca2 ◽  
Prophylactic Oophorectomy ◽  
Estrogen Exposure ◽  
Mutation Carriers ◽  
Increased Risk

Chemoprevention with tamoxifen and oophorectomy are thought to be effective in decreasing the incidence of breast cancer in women at increased risk for the disease. There is mounting data supporting the idea that hormonal interventions that reduce estrogen exposure to breast epithelium, such as prophylactic oophorectomy and tamoxifen, are effective in breast cancer prevention in both BRCA1 and BRCA2 mutations carriers. Several recent studies directly address the protective effect of tamoxifen and oophorectomy in BRCA mutation carriers and suggest that these endocrine manipulations decrease the risk of primary and secondary breast cancers. Ongoing studies aim to better define the effect of tamoxifen in these very high-risk women and determining whether factors, such as earlier age of use or prior prophylactic oophorectomy, impact tamoxifen's effect. Based on existing data, we recommend that women with deleterious mutations in BRCA1 or BRCA2 be informed of the beneficial effect of oophorectomy on breast cancer risk and that women who choose breast cancer screening instead of prophylactic mastectomy be offered tamoxifen as a prevention option.

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