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.

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.

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.

Risk-reducing salpingo-oophorectomy and breast cancer incidence among BRCA-mutation carriers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10548-10548
Author(s):  
Tamar Perri ◽  
Shani Naor-Ravel ◽  
Perry Eliassi-Revivo ◽  
Dror Lifshitz ◽  
Eitan Friedman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Incidence ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Breast Cancer Incidence ◽  
Mutation Carriers ◽  
Age At Surgery ◽  
Significant Difference ◽  
Brca Mutation Carriers ◽  
Risk Reducing

10548 Background: Uncertainty exists with regard to the role of bilateral salpingo-oophorectomy in altering the risk of breast cancer in BRCA-mutation carriers. Methods: Included were 1645 healthy Jewish Israeli BRCA1/2 -mutation carriers from a single center without prophylactic mastectomy. Carriers with and without risk-reducing bilateral salpingo-oophorectomy (RRBSO) were matched according to BRCA-mutation type (BRCA1 vs. BRCA2) and year of birth (±1 year). Hormonal and reproductive variables were compared and incidence of breast cancer recorded. Association between RRBSO and breast cancer was studied. Results: Seventy-seven and 50 matched-pairs had BRCA1 and BRCA2 mutation respectively. Fifty-two carriers had breast cancer, 21 in RRBSO-group and 31 in no- RRBSO group, with no statistically significant difference. When analysing each mutation group separately, stratified by age at surgery, no association between RRBSO and breast cancer incidence was found among BRCA1-mutation carriers. However, in BRCA2 mutation carriers, RRBSO was associated with a statistically significant decreased overall incidence of breast cancer, HR = 0.2 (confidence interval 0.44-0.913, p = 0.038). Breast cancer incidence was lower after 5, 10,15 and 20 years in BRCA2-mutation carriers with RRBSO compared to no-RRBSO. Age at menarche, age at surgery, parity and oral contraceptive use were not significant risk factors for breast cancer. Hormone replacement therapy was used by 62 mutation carriers, 52 in the RRBSO group and 10 in the no-RRBSO group, and its use did not alter breast cancer risk (p = 0.463). Conclusions: According to our findings, RRBSO is associated with a reduced risk of breast cancer only in BRCA2 mutation carriers, regardless of HRT use.

scholarly journals Prophylactic Surgery in the BRCA+ Patient: Do Women Develop Breast Cancer While Waiting?

2021 ◽  
Vol 28 (1) ◽  
pp. 702-715
Author(s):  
Sheina A. Macadam ◽  
Karen Slater ◽  
Rona E. Cheifetz ◽  
Leigh Jansen ◽  
Stephen Chia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Reconstruction ◽  
Prophylactic Mastectomy ◽  
Brca Mutation ◽  
Prophylactic Surgery ◽  
Historical Cohort ◽  
Patient Journey ◽  
Time To Surgery ◽  
Mutation Carriers ◽  
Brca Mutation Carriers

Breast cancer susceptibility gene (BRCA) mutation carriers have an increased risk of breast cancer. Mitigation of this risk can be achieved via surveillance or prophylactic mastectomy with or without breast reconstruction. Those that choose surgery expect to reduce their chance of developing cancer. The purpose of this study was to determine the incidence of patients developing breast cancer prior to surgery and to identify modifiable contributing factors within the patient journey. This is a historical cohort study of all BRCA mutation carriers identified through the British Columbia Cancer Hereditary Cancer Program between 2000 and 2012. Patients were divided into two groups: surveillance (S) and prophylactic mastectomy with immediate breast reconstruction (PM/IBR). The incidence of cancer, time to PM/IBR and patient journeys were analyzed. A total of 333 women were identified. The time to surgery from mutation disclosure was a median of 31 (5.3, 75.7) months. During this period, 6% of patients developed breast cancer compared with a 14% incidence of breast cancer in patients choosing surveillance. The majority of time to surgery was attributed to the period between mutation disclosure and the decision to proceed with surgery. Strategies to facilitate decision-making as well as wait list prioritization and dedicated operative time should be targeted to this population to decrease the number of women developing an interval cancer prior to surgery.

Increased risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers after breast-conserving therapy compared to mastectomy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1512-1512
Author(s):  
R. K. Schmutzler ◽  
M. K. Graeser ◽  
K. Rhiem ◽  
B. Schlehe ◽  
W. Hofmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Contralateral Breast Cancer ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Breast Conserving Therapy ◽  
Contralateral Breast ◽  
Cox Regression Analysis ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Brca Mutation Carriers

1512 Background: BRCA mutation carriers affected by breast cancer face an elevated risk of contralateral breast cancer (clBrCa). We here aimed at estimating the influence of breast conserving therapy (BCT) versus mastectomy (MXT) on the rik of clBrCa. Methods: We conducted a retrospective cohort study in 3810 index patients (pts) collected within the CHBOC. Deleterious BRCA1 or BRCA2 mutations were detected in 921 pts and medical records were obtained from 532 pts (344 BRCA1, 184 BRCA2 mutation carriers, 4 both) of whom 261 (49%) underwent BCT and 271 (51%) MXT. Pts were followed from the initial diagnosis of breast cancer until clBrCa or censored at time of prophylactic contralateral mastectomy, oophorectomy, death, or date of last visit. Median age at first diagnosis was 39.9 years (range 17.5 to 79.0) and median follow up 48.84 months (3413 person years). The hazard ratio (HR) was estimated using multivariate Cox regression analysis adjusting for conduct of radiotherapy, age at first breast cancer, and affected BRCA gene. Results: In the univariate analysis the risk of clBrCa was 12.2% (95% CI 7.6 to 16.8) at 5 years and 24.9% (95% CI 18.0 to 31.9) at 10 years for pts treated with MXT and 25.9% (95% CI 18.8 to 33.1) at 5 years and 45.7% (95% CI 35.0 to 56.5) at 10 years for pts treated with BCT. In the multivariate analysis, the HR was 1.8 for BCT versus MXT (95% CI 1.2 to 2.7). Neither age at diagnosis of the first primary nor BRCA mutation status were significantly predictive. A subgroup analysis comparing BCT plus radiotherapy with MXT minus radiotherapy revealed a HR of 1.6 (95% CI 1.02 to 2.56) for the BCT group. Conclusions: We report for the first time a 1.8-fold increased risk of clBrCa in BRCA mutation carriers undergoing BCT versus MXT. Scattered radiation is the most probable causation. Although results from further studies such as the WECARE study should be awaited, our results provide evidence that recommendations for primary brCa treatment of BRCA mutation carriers must to be reconsidered. No significant financial relationships to disclose.

scholarly journals Risk-Reducing Bilateral Salpingo-Oophorectomy for BRCA Mutation Carriers and Hormonal Replacement Therapy: If It Should Rain, Better a Drizzle than a Storm

Medicina ◽  
2019 ◽  
Vol 55 (8) ◽  
pp. 415
Author(s):  
Maria Luisa Gasparri ◽  
Katayoun Taghavi ◽  
Enrico Fiacco ◽  
Veronica Zuber ◽  
Rosa Di Micco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Replacement Therapy ◽  
Brca Mutation ◽  
Brca1 Mutation ◽  
Effective Strategy ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
Risk Reducing

Women carrying a BRCA mutation have an increased risk of developing breast and ovarian cancer. The most effective strategy to reduce this risk is the bilateral salpingo-oophorectomy, with or without additional risk-reducing mastectomy. Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is recommended between age 35 and 40 and between age 40 and 45 years for women carriers of BRCA1 and BRCA2 mutations, respectively. Consequently, most BRCA mutation carriers undergo this procedure prior to a natural menopause and develop an anticipated lack of hormones. This condition has a detrimental impact on various systems, affecting both the quality of life and longevity; in particular, women carrying BRCA1 mutation, who are likely to have surgery earlier as compared to BRCA2. Hormonal replacement therapy (HRT) is the only effective strategy able to significantly compensate the hormonal deprivation and counteract menopausal symptoms, both in spontaneous and surgical menopause. Although recent evidence suggests that HRT does not diminish the protective effect of RRBSO in BRCA mutation carriers, concerns regarding the safety of estrogen and progesterone intake reduce the use in this setting. Furthermore, there is strong data demonstrating that the use of estrogen alone after RRBSO does not increase the risk of breast cancer among women with a BRCA1 mutation. The additional progesterone intake, mandatory for the protection of the endometrium during HRT, warrants further studies. However, when hysterectomy is performed at the time of RRBSO, the indication of progesterone addition decays and consequently its potential effect on breast cancer risk. Similarly, in patients conserving the uterus but undergoing risk-reducing mastectomy, the addition of progesterone should not raise significant concerns for breast cancer risk anymore. Therefore, BRCA mutation carriers require careful counselling about the scenarios following their RRBSO, menopausal symptoms or the fear associated with HRT use.

scholarly journals Penetrance of Breast and Ovarian Cancer in Women Who Carry a BRCA1/2 Mutation and Do Not Use Risk-Reducing Salpingo-Oophorectomy: An Updated Meta-Analysis

2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Jinbo Chen ◽  
Eunchan Bae ◽  
Lingjiao Zhang ◽  
Kevin Hughes ◽  
Giovanni Parmigiani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Meta Analysis ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Breast And Ovarian Cancer ◽  
Mutation Carriers ◽  
Risk Reducing ◽  
Good Calibration

Abstract Background Use of risk-reducing Salpingo-oophorectomy (RRSO) substantially reduces the risk of ovarian and breast cancer for women who carry a BRCA1/2 mutation. It is important to adjust for RRSO use in the estimation of BRCA1/2 penetrance of breast and ovarian cancer. Methods We searched PubMed for penetrance estimates of breast and ovarian cancer from studies that genotyped individual patients and explicitly adjusted for RRSO use by censoring follow-up at the age of RRSO. We meta-analyzed penetrance estimates from 7 identified studies. We implemented the resulting penetrance estimates in a Mendelian risk prediction model as iplemented in the software package BRCAPRO, which we applied to estimate carrier probabilities in 2 BRCA cohorts. Results Penetrance estimates by age 70 years for breast cancer were 64.6% (95% confidence interval [CI] = 59.5% to 69.4%) for BRCA1 mutation carriers and 61.0% (95% CI = 48.1% to 72.5%) for BRCA2 mutation carriers, and for ovarian cancer they were 48.3% (95% CI = 38.8% to 57.9%) and 20.0% (95% CI = 13.3% to 29.0%), respectively. When integrated into BRCAPRO, our estimates led to good calibration and different estimates of carrier probabilities for some individuals when evaluating the models in 2 cohorts. Conclusions The report updates penetrance estimates for BRCA1/2-associated cancer. We report higher estimates than previously reported, which did not adjust for RRSO. Differential use of RRSO may partially explain heterogeneity in the currently available penetrance estimates. For some individuals, using our estimates in BRCAPRO may result in changes in estimated carrier probabilities, which warrants validation in future studies.

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.

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