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.

BRCA mutation status and risk of secondary malignancy following chemotherapy for breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11017-11017
Author(s):  
R. Wesolowski ◽  
T. K. Choueiri ◽  
L. Rybicki ◽  
A. G. Shealy ◽  
G. Casey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Brca Mutation ◽  
Cleveland Clinic ◽  
Secondary Malignancy ◽  
Negative Group ◽  
Breast Cancer Patients ◽  
Positive Group ◽  
Brca Negative

11017 Background: Since the BRCA gene is responsible for excisional DNA repair, we hypothesized that breast cancer patients with BRCA mutation would be more susceptible to the induction of second malignancies following chemotherapy treatment than breast cancer patients who tested negative for BRCA mutations. Methods: Breast cancer patients tested for BRCA1 and BRCA2 mutations at the Cleveland Clinic were identified and evaluated for history of neoadjuvant or adjuvant chemotherapy and for the occurrence of subsequent non-breast primary invasive cancer. Patients with inadequate follow-up and those with inoperable disease at diagnosis were excluded from the analysis. Fisher’s exact test was used to compare different cohorts. The IRB at Cleveland Clinic approved the study. Results: Of 115 identified breast cancer patients tested for BRCA mutations, 77 met the inclusion criteria. Twenty-seven of these patients carried BRCA1 or BRCA2 mutations and 50 tested negative for these mutations. Twelve patients (44%) in the BRCA positive group and 8 patients (16%) in the BRCA negative group underwent prophylactic oophorectomy. Median follow-up for the two groups was 53.5 months (75 months in the BRCA positive group and 48.5 months in the BRCA negative group). Median age at diagnosis was 42 years (40.5 years in the BRCA positive group and 44.5 in the BRCA negative group). In the BRCA positive group 3 of 25 patients (12%) treated with chemotherapy developed second malignancies (ovarian cancer, transitional cell cancer in urinary tract and renal cell carcinoma) compared with none of the 2 patients who did not get chemotherapy (p= 1.0). In the BRCA negative group, 2/34 patients (6%), treated with chemotherapy developed second cancers compared with 2/16 patients (12%), who were not treated with chemotherapy (p=0.58). Cancers in the BRCA negative group included two bladder carcinomas in the chemotherapy treated patients and in the non-chemotherapy group, non-small cell lung cancer, uterine, ovarian, endometrial and peritoneal cancers. Conclusions: At more than 4-years of follow up, chemotherapy in operable breast cancer patients was not associated with an increase in the risk of secondary malignancy or with a differential effect on this endpoint by BRCA mutation status in this retrospective study. No significant financial relationships to disclose.

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.

Comparison of guidelines, BRCAPRO, and genetic counsellors estimates for the identification of BRCA1 and BRCA2 mutations in pancreatic cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15784-e15784
Author(s):  
Robert C Grant ◽  
Spring Holter ◽  
Ayelet Borgida ◽  
Melania Pintile ◽  
Mohammad R Akbari ◽  
...  
Keyword(s):  
Brca Mutation ◽  
Area Under The Curve ◽  
Brca1 And Brca2 ◽  
Degree Relative ◽  
Brca Mutations ◽  
Term Care ◽  
Predictive Values ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
Incident Cases

e15784 Background: Germline BRCA1 and BRCA2 (BRCA) mutation carriers with pancreatic adenocarcinoma (PDAC) are eligible for precision therapy trials and their relatives should undergo genetic testing and tailored cancer prevention. We assessed the performance of strategies to identify BRCA mutation carriers in PDAC. Methods: Incident cases of PDAC were prospectively recruited for BRCA sequencing in a multidisciplinary PDAC clinic. Probands were evaluated according to the National Comprehensive Cancer Network 2017 (NCCN) and the Ontario Ministry of Health and Long-Term Care (MOHLTC) guidelines for BRCA testing. The probability of each proband carrying a BRCA mutation was estimated using BRCAPRO and by surveying genetic counsellors. Guidelines were compared across sensitivity, specificity, and positive and negative predictive values (PPV and NPV). Estimates from BRCAPRO and the genetic counsellors were compared using the area-under-the-curve (AUC) for discrimination and the Hosmer-Lemeshow test for calibration. Results: 22/484 (4.5%) of probands carried a BRCA mutation. The mutation rate was higher in probands with Ashkenazi Jewish ancestry (7/57, p=0.009) or a first-degree relative with breast cancer (8/83, p=0.036). 119 genetic counsellors responded to the survey and each proband was assessed by a mean of 5.9 genetic counsellors. The Table displays the performance of the guidelines. Discrimination was similar for the estimates from genetic counsellors and BRCAPRO (AUC 0.755 and 0.775, respectively, p=0.701). Genetic counsellors generally overestimated (p=0.008), whereas BRCAPRO severely underestimated (p<0.001), the probability that each proband carried a mutation. Conclusions: The NCCN 2017 guidelines and estimates from genetic counsellors accurately identify BRCA mutations in PDAC. The MOHLTC guidelines and BRCAPRO should be updated to account for the association between PDAC and BRCA mutations. [Table: see text]

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.

Costs of breast cancer surveillance in BRCA mutation carriers

2008 ◽  
Vol 6 (7) ◽  
pp. 94-95
Author(s):  
Y.J.L. Kamm ◽  
C. Boetes ◽  
E.M.M. Adang ◽  
P. Bull ◽  
H.J. Bonenkamp ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brca Mutation ◽  
Cancer Surveillance ◽  
Mutation Carriers ◽  
Brca Mutation Carriers

scholarly journals Prophylactic irradiation to the contralateral breast for BRCA mutation carriers with early-stage breast cancer

2019 ◽  
Vol 30 (3) ◽  
pp. 412-417 ◽  
Author(s):  
E. Evron ◽  
A.M. Ben-David ◽  
H. Goldberg ◽  
G. Fried ◽  
B. Kaufman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Brca Mutation ◽  
Contralateral Breast ◽  
Early Stage Breast Cancer ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
Prophylactic Irradiation
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