scholarly journals Risk-Reducing Salpingo-Oophorectomy for the Prevention of BRCA1- and BRCA2-Associated Breast and Gynecologic Cancer: A Multicenter, Prospective Study

2008 ◽  
Vol 26 (8) ◽  
pp. 1331-1337 ◽  
Author(s):  
Noah D. Kauff ◽  
Susan M. Domchek ◽  
Tara M. Friebel ◽  
Mark E. Robson ◽  
Johanna Lee ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Gynecologic Cancer ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
Brca1 And Brca2 Mutations ◽  
Breast And Gynecologic Cancer

Purpose Risk-reducing salpingo-oophorectomy (RRSO) has been widely adopted as a key component of breast and gynecologic cancer risk-reduction for women with BRCA1 and BRCA2 mutations. Despite 17% to 39% of all BRCA mutation carriers having a mutation in BRCA2, no prospective study to date has evaluated the efficacy of RRSO for the prevention of breast and BRCA-associated gynecologic (ovarian, fallopian tube or primary peritoneal) cancer when BRCA2 mutation carriers are analyzed separately from BRCA1 mutation carriers. Patients and Methods A total of 1,079 women 30 years of age and older with ovaries in situ and a deleterious BRCA1 or BRCA2 mutation were enrolled onto prospective follow-up studies at one of 11 centers from November 1, 1994 to December 1, 2004. Women self-selected RRSO or observation. Follow-up information through November 30, 2005, was collected by questionnaire and medical record review. The effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model. Results During 3-year follow-up, RRSO was associated with an 85% reduction in BRCA1-associated gynecologic cancer risk (hazard ratio [HR] = 0.15; 95% CI, 0.04 to 0.56) and a 72% reduction in BRCA2-associated breast cancer risk (HR = 0.28; 95% CI, 0.08 to 0.92). While protection against BRCA1-associated breast cancer (HR = 0.61; 95% CI, 0.30 to 1.22) and BRCA2-associated gynecologic cancer (HR = 0.00; 95% CI, not estimable) was suggested, neither effect reached statistical significance. Conclusion The protection conferred by RRSO against breast and gynecologic cancers may differ between carriers of BRCA1 and BRCA2 mutations. Further studies evaluating the efficacy of risk-reduction strategies in BRCA mutation carriers should stratify by the specific gene mutated.

scholarly journals Aromatase Inhibitors and Contralateral Breast Cancer in BRCA Mutation Carriers: A long-term Follow-up

2021 ◽  
Author(s):  
Maryam Nemati Shafaee ◽  
Kristina Goutsouliak ◽  
Heather Lin ◽  
Therese B Bevers ◽  
Angelica Gutierrez-Barrera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Prophylactic Mastectomy ◽  
Brca Mutation ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Mutation Status ◽  
Mutation Carriers ◽  
Brca Mutation Carriers

Abstract Background: Deleterious BRCA mutations confer a significant lifetime risk of breast cancer (BC) as well as contralateral BC (CBC) in patients who do not undergo prophylactic mastectomy. Prior reports have suggested that tamoxifen reduces the risk of CBC in BRCA mutation carriers. Whether aromatase inhibitors (AI) have the same effect is unknown. Methods: This is a retrospective review of patients diagnosed with non-metastatic ER+ BC between 2004-2014 with known BRCA mutation status. Patients were followed from primary diagnosis until CBC diagnosis or death. Median follow up was 11.5 years. Risk of CBC was evaluated as time to event. Results: 935 subjects were included in this analysis, with 53 BRCA1 mutation carriers, and 94 BRCA2 mutation carriers. Median age at diagnosis was 42.7 years. Seventy-two percent (676) received tamoxifen and 43% (405) received AI. A total of 66 CBCs occurred, of which 10% (15/147) occurred in BRCA mutation carriers vs %6.5 (51/788) in BRCA wild type. Multivariate analyses indicated that BRCA status and AI use were significantly associated with CBC risk. AI use resulted in a significant reduction in risk of CBC (HR 0.44, p=0.004) regardless of the BRCA mutation status. Tamoxifen use was not associated with reduced risk of CBC. Conclusions: This is the first report showing that AIs reduce the risk of CBC in BRCA mutation carriers. The potential role of AIs as chemoprevention should be validated in larger independent cohorts.

Is mammography adequate for screening BRCA mutation carriers with low breast density?

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10014-10014 ◽  
Author(s):  
R. Bigenwald ◽  
E. Warner ◽  
A. Gunasekara ◽  
K. Hill ◽  
P. Causer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Density ◽  
Brca Mutation ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Brca1 And Brca2 ◽  
Younger Women ◽  
Mutation Carriers ◽  
Brca Mutation Carriers

10014 Background: Several large observational studies have demonstrated that magnetic resonance imaging (MRI) is much more sensitive than M (sensitivity 71–96% vs. 28–43%) for screening women > age 25 at high risk for hereditary breast cancer. However, MRI is much more costly and less specific than M. The extent to which the low sensitivity of M in these studies is due to the greater average breast density of younger women is unknown. Accordingly, we sought to determine the sensitivity of M and MRI according to breast density for the detection of breast cancer in a screening study of BRCA mutation carriers. Methods: Breast density was measured on the screening mammogram of the contralateral breast for all women who developed in-situ or invasive breast cancer on study. Density was measured in 2 ways: qualitatively according to the four categories characterized by the BIRADS system: 1) mostly fatty, 2) scattered fibroglandular tissue, 3) heterogeneously dense, 4) extremely dense; and semi-quantitatively using computer-aided techniques with subsequent classification as: A) ≤10%, B) 11–25%, C) 26%-50%, or D) >50% density. Results: Between 11/97 and 06/05 a total of 39 cases (12 in-situ and 27 invasive) were found in 36 mutation carriers (19 BRCA1 and 17 BRCA2). Mean age of the women with cancer was 48 (range 34 to 64). Average semi-quantitative breast density for BRCA1 mutation carriers was 28% and for BRCA2 was 27%. Sensitivity of M vs. MRI for in-situ cases was 25% vs. 83%, and for invasive cases was 30% vs. 93%. Sensitivities for BRCA1 and BRCA2 mutation carriers were similar. For BIRADS 1 to 4 respectively M detected 1/3 (33%), 5/11 (45%), 4/22 (18%), and 1/3 (33%) of cases; and for density groups A to D respectively detected 2/6 (33%), 7/15 (47%), 1/11 (9%) and, 1/7 (14%). Conclusion: Although there was a trend towards decreasing mammographic sensitivity with increasing density, even among BRCA mutation carriers with low breast density mammography is an inadequate screening tool. No significant financial relationships to disclose.

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.

Therapeutic radiation for breast cancer in BRCA mutation carriers and contralateral breast cancer (CBC) risk

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 611-611
Author(s):  
H. C. Moore ◽  
R. Wesolowski ◽  
T. K. Choueiri ◽  
L. Rybicki ◽  
A. G. Shealy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Treatment ◽  
Brca Mutation ◽  
Negative Group ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Mutation Carriers ◽  
Brca Mutation Carriers

611 Background: BRCA mutation carriers diagnosed with breast cancer are at high risk for contralateral second primary breast cancers. Mutations in BRCA1 and BRCA2 lead to defects in DNA repair. Radiation treatment for breast cancer is felt to increase risk of CBC, but the interaction between BRCA status and local radiation therapy with respect to their effects on CBC is unclear. Methods: Through an IRB approved database registry at the Cleveland Clinic, breast cancer patients tested for BRCA1 and BRCA2 mutations were identified and evaluated for CBC events and radiation treatment history. Patients with inadequate clinical follow-up, those with bilateral synchronous breast cancer and those undergoing bilateral mastectomy within one year of the original breast cancer diagnosis were excluded from the analysis. Chi-square test was used to compare CBC rates with or without prior radiation separately in patients testing positive and those testing negative for BRCA mutations. Results: Of 115 identified breast cancer patients tested for BRCA mutations, 57 met the inclusion criteria. Twenty-one carried BRCA1 or BRCA2 mutations and 36 tested negative for these mutations. Median follow-up for the two groups was 69.5 months (92 months in BRCA positive group and 51.5 months in BRCA negative group). Median age at diagnosis was 45 years (41 years in BRCA positive group and 48.5 in BRCA negative group). Among the 21 carriers, 9 patients (43%) developed CBC while only 3 of 36 patients (8%) testing negative for BRCA mutations developed CBC. Thirteen of 21 mutation carriers (62%) had received radiation treatment for the original cancer: CBC occurred in 3 of 13 (23%) radiated patients and 6 of 8 (75%) patients who had not received radiation (p= 0.02). Among 36 patients with negative BRCA testing, 30 (83%) had received radiation: CBC occurred in 3 of 30 (10%) mutation negative patients who had received prior radiation and in 0 of the 6 patients who had not received radiation (p = 0.42). Conclusions: CBC incidence was higher among BRCA mutation carriers than a control group suspected of having hereditary breast cancer but testing negative for these mutations. The use of radiation in the presence of a BRCA mutation, however, does not appear to further increase the risk for CBC. No significant financial relationships to disclose.

How to manage BRCA mutation carriers?

2020 ◽  
Vol 41 (3) ◽  
Author(s):  
Laura Sabiani ◽  
Julien Barrou ◽  
Jérome Mathis ◽  
Francois Eisinger ◽  
Marie Bannier ◽  
...  
Keyword(s):  
Brca Mutation ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Immediate Breast Reconstruction ◽  
Bilateral Mastectomy ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
The Impact ◽  
Risk Reducing

AbstractInherited mutations in BRCA1 and BRCA2 genes increase the risk of development of cancer in organs especially in breast and ovary. Prevention and screening in BRCA mutation carriers are of high importance. Prophylactic surgeries are possible but are still insufficiently performed because they require surgical procedures in healthy patients. Guidelines for the management of BRCA mutations carriers must absolutely be part of the standard practice of all those involved in the management of these patients to increase the impact of the implementation of these preventive measures. There is no screening recommended for ovarian cancer. A risk-reducing bilateral salpingo-oophorectomy should be performed from age 35 to 40 years for BRCA1 mutation carriers and 40 to 45 years for BRCA2 mutation carriers. A screening for breast cancer should be performed annually from 30 years old by breast MRI and mammography. A risk-reducing bilateral mastectomy is recommended with nipple sparing mastectomy and immediate breast reconstruction from 30 years and before 40 years. A multidisciplinary care must be implemented for these patients with an important psychological support.

scholarly journals The frequency and outcome of breast cancer risk-reducing surgery in finnish BRCA1 and BRCA2 mutation carriers

2013 ◽  
Vol 103 (1) ◽  
pp. 34-40 ◽  
Author(s):  
L. Koskenvuo ◽  
C. Svarvar ◽  
S. Suominen ◽  
K. Aittomäki ◽  
T. Jahkola
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Brca2 Mutation ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
Risk Reducing

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.

scholarly journals Breast Cancer Risk for Noncarriers of Family-Specific BRCA1 and BRCA2 Mutations: Findings From the Breast Cancer Family Registry

2011 ◽  
Vol 29 (34) ◽  
pp. 4505-4509 ◽  
Author(s):  
Allison W. Kurian ◽  
Gail D. Gong ◽  
Esther M. John ◽  
David A. Johnston ◽  
Anna Felberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Brca2 Mutation ◽  
Population Based ◽  
Brca1 And Brca2 ◽  
Breast Cancer Family ◽  
Cancer Family ◽  
Brca2 Mutations ◽  
Brca1 And Brca2 Mutations

Purpose Women with germline BRCA1 and BRCA2 mutations have five- to 20-fold increased risks of developing breast and ovarian cancer. A recent study claimed that women testing negative for their family-specific BRCA1 or BRCA2 mutation (noncarriers) have a five-fold increased risk of breast cancer. We estimated breast cancer risks for noncarriers by using a population-based sample of patients with breast cancer and their female first-degree relatives (FDRs). Patients and Methods Patients were women with breast cancer and their FDRs enrolled in the population-based component of the Breast Cancer Family Registry; patients with breast cancer were tested for BRCA1 and BRCA2 mutations, as were FDRs of identified mutation carriers. We used segregation analysis to fit a model that accommodates familial correlation in breast cancer risk due to unobserved shared risk factors. Results We studied 3,047 families; 160 had BRCA1 and 132 had BRCA2 mutations. There was no evidence of increased breast cancer risk for noncarriers of identified mutations compared with FDRs from families without BRCA1 or BRCA2 mutations: relative risk was 0.39 (95% CI, 0.04 to 3.81). Residual breast cancer correlation within families was strong, suggesting substantial risk heterogeneity in women without BRCA1 or BRCA2 mutations, with some 3.4% of them accounting for roughly one third of breast cancer cases. Conclusion These results support the practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to the family-specific BRCA1 or BRCA2 mutation.

The CYP17A1 −34T > C polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers

2010 ◽  
Vol 126 (2) ◽  
pp. 521-527 ◽  
Author(s):  
Bella Kaufman ◽  
Yael Laitman ◽  
Elad Ziv ◽  
Ute Hamann ◽  
Diana Torres ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Brca2 Mutation ◽  
Brca1 And Brca2 ◽  
Mutation Carriers
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