Outcomes after breast cancer in an ethnically diverse cohort of high-risk patients: Differences in survival based on BRCA1/BRCA2 mutation status

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21116-21116
Author(s):  
R. Nanda ◽  
D. Huo ◽  
M. Cook ◽  
L. Chen ◽  
K. Hope ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Ethnically Diverse ◽  
European Ancestry ◽  
Rank Test ◽  
Brca1 And Brca2 ◽  
Brca2 Mutations ◽  
Brca1 Brca2

21116 Background: Most studies of hereditary breast cancer report that BRCA1 associated tumors are characterized by high grade and hormone receptor negativity, while those associated with BRCA2 are more similar to sporadic cases. Several groups have demonstrated that BRCA1 mutations, but not BRCA2 mutations, are associated with reduced survival in women with breast cancer. These studies have primarily included women of European and Ashkenazi Jewish heritage. No study to date has assessed outcomes in an ethnically diverse cohort of high-risk individuals. Methods: High-risk individuals were identified through the University of Chicago Cancer Risk Clinic (UCCRC). Clinicopathologic data was collected on all patients with breast cancer who had undergone genetic testing and consented to inclusion in research protocols. Recurrence-free survival (RFS) and overall survival (OS) for BRCA1, BRCA2 and non-carriers was compared using the log-rank test. Hazard ratios (HR) and 95% Confidence Intervals (95% CI) were calculated from Cox proportional hazard models. Results: 280 patients from 258 families were studied. 67 were BRCA1 mutation positive, 36 were BRCA2 positive and 177 were non-carriers. 65% of patients were non-Hispanic non-Jewish whites, 15% African American, 15% Ashkanazi Jewish, 3% Hispanic and 2% Asian. At a median follow up of 5 years, 40 patients had relapsed and 22 had died. HRs (95% CI) for RFS of the BRCA1 and BRCA2 carriers relative to non-carriers were 1.6 (0.77–3.33) and 1.3 (0.55–3.09) respectively, when adjusted for year at diagnosis. The adjusted HRs (95% CI) for OS for the BRCA1 and BRCA2 carriers relative to non-carriers were 1.82 (0.48–3.02) and 0.67 (0.15–3.04), respectively. Conclusions: In this study of an ethnically diverse cohort of high-risk individuals, BRCA1 mutation carriers had a poorer outcome as compared to those with BRCA2 mutations or those without identifiable mutations in either gene, although this difference was not statistically significant. This observation is consistent with previous studies of women of predominantly Ashkenzi Jewish and European ancestry. This study was funded by the Falk Medical Research Trust, the Breast Cancer Research Foundation and the Entertainment Industry Fund. No significant financial relationships to disclose.

scholarly journals The spectrum of the most common BRCA1/BRCA2 mutations in Lithuanian high risk families

Genetika ◽  
2017 ◽  
Vol 49 (1) ◽  
pp. 43-50
Author(s):  
Danielius Serapinas ◽  
Marius Sukys ◽  
Agne Bartkeviciute ◽  
Diana Barkauskiene ◽  
Daiva Bartkeviciene
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Brca2 Mutation ◽  
Health Science ◽  
University Hospital ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Incidence And Mortality ◽  
Brca2 Mutations ◽  
Brca1 Brca2

Breast cancer is the neoplasm with the highest incidence and mortality among women in Lithuania. The aim of the study was to determine the mutational incidence in BRCA1 and BRCA2 genes in high-risk breast and/or ovarian cancer families. After written informed consent, 36 participants from Lithuanian health science university hospital provided a blood sample for genetic analysis. Molecular diagnostics was done for 6 BRCA1and BRCA2 mutations. From 36 tested subjects for BRCA1/BRCA2 mutations. Positive test for BRCA1/BRCA2 mutations test was found in 12 (33%) cases. Most common BRCA1 mutation was 5328insC - 6 (50%) cases, other mutations: 185delAG - 1 (8,3%), 300t>6(c61G) - 4 (33,3%), 4153 del A - 1 (8,3%). All mutations were BRCA1, but none of the women were positive for the analyzed BRCA2 mutation. The mean age when the cancer was diagnosed in BRCA1 mutations group was 40.40?3.39 comparing with the group without mutations - 43.29 ?2.52. Rates of BRCA1 and BRCA2 mutation testing are increasing in young women with breast and ovarian cancer. Detected mutations in BRCA1 contribute to up to one-third of the families with breast and ovarian cancer in Lithuania.

Higher prevalence of BRCA2 mutations among Chinese breast cancer patients in a community oncology clinic.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12017-e12017
Author(s):  
Yi-Kong Keung ◽  
Adriana Hu ◽  
Annie Yeung ◽  
Amy Chan ◽  
Eddie Hu
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Small Sample ◽  
Brca1 And Brca2 ◽  
Similar Frequency ◽  
Nccn Guidelines ◽  
Uncertain Significance ◽  
Brca2 Mutations

e12017 Background: According to a large US population-based study, BRCA1 and 2 mutations occur in about 6 and 4% breast cancer cases age <45. Asians have the lowest prevalence of BRCA1 mutation among five US racial groups. The prevalence of BRCA1 and BRCA2 mutations was reported as 8.1% and 2.7% among pts with family history in Shanghai, compared to 4.9% and 7.5% respectively in Hong Kong. We would like to explore the BRCA mutations in a clinic located in an Asian-majority community in California. Methods: Consecutive female breast cancer pts selected for BRCA testing according to NCCN guidelines are retrospectively studied from 10/2009 to 10/2011. Sequencing of all translated exons and immediately adjacent intronic regions of the BRCA1 and BRCA2 was performed on the peripheral blood (Myriad, Utah). Results: Twenty-six pts were included in this study. Six pts have bilateral breast cancers; 2 synchronous and 4 metachronous with intervals of 11-13 years. Nine pts (34.6%) had BRCA2 germline mutations, of which 5 were considered deleterious and 4 of uncertain significance. Eleven pts (42.3%) had no BRCA mutation. BRCA results were unavailable in six pts because they were either not yet done or denied by health insurance. Conclusions: 1. High prevalence of BRCA2 mutation is seen in our pts selected according to NCCN guidelines. The presence of BRCA2 but not BRCA1 mutation in our study is intriguing. 2. Triple negative breast cancer is not more prevalent in BRCA2 mutation carriers. 3. Similar frequency of family history of breast/ovarian cancer is noted among pts with or without BRCA2 mutation, deleterious or of uncertain significance. The role of the BRCA2 mutation of uncertain significance needs to be further elucidated. 4. Due to the small sample size, further study is required to confirm our findings. [Table: see text]

Contralateral Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

2009 ◽  
Vol 27 (35) ◽  
pp. 5887-5892 ◽  
Author(s):  
Monika K. Graeser ◽  
Christoph Engel ◽  
Kerstin Rhiem ◽  
Dorothea Gadzicki ◽  
Ulrich Bick ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Contralateral Breast Cancer ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Contralateral Breast ◽  
Brca1 And Brca2 ◽  
Brca Gene ◽  
Brca2 Mutations

Purpose To estimate the risk for contralateral breast cancer in members of BRCA1- and BRCA2-positive families and to determine predictive risk factors. Patients and Methods A retrospective, multicenter, cohort study was performed from 1996 until 2008 and comprised 2,020 women with unilateral breast cancer (index patients, n = 978; relatives, n = 1.42) from 978 families who had a BRCA1 or BRCA2 mutation. Cox regression analysis was applied to assess the association of age at first breast cancer with time from first to contralateral breast cancer, stratified by the affected BRCA gene. Results The cumulative risk for contralateral breast cancer 25 years after first breast cancer was 47.4% (95% CI, 38.8% to 56.0%) for patients from families with BRCA1 or BRCA2 mutations. Members of families with BRCA1 mutations had a 1.6-fold (95% CI, 1.2-fold to 2.3-fold) higher risk of contralateral breast cancer than members of families with BRCA2 mutations. Younger age at first breast cancer was associated with a significantly higher risk of contralateral breast cancer in patients with BRCA1 mutation, and a trend was observed in patients with BRCA2 mutation. After 25 years, 62.9% (95% CI, 50.4% to 75.4%) of patients with BRCA1 mutation who were younger than 40 years of age at first breast cancer developed contralateral breast cancer, compared with only 19.6% (95% CI, 5.3% to 33.9%) of those who were older than 50 years of age at first breast cancer. Conclusion Contralateral breast cancer risk depends on age at first breast cancer and on the affected BRCA gene, and this risk should be considered in treatment planning.

scholarly journals Prevalence of BRCA1 and BRCA2 Mutations Among Patients With Ovarian, Primary Peritoneal, and Fallopian Tube Cancer in India: A Multicenter Cross-Sectional Study

2021 ◽  
pp. 849-861
Author(s):  
Sudeep Gupta ◽  
Senthil Rajappa ◽  
Suresh Advani ◽  
Amit Agarwal ◽  
Shyam Aggarwal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Family History ◽  
Newly Diagnosed ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Fallopian Tube Cancer ◽  
Cross Sectional ◽  
Brca2 Mutations ◽  
Brca1 Brca2

PURPOSE There are deficient data on prevalence of germline mutations in breast cancer susceptibility genes 1 and 2 ( BRCA1/ BRCA2) in Indian patients with ovarian cancer who are not selected by clinical features. METHODS This prospective, cross-sectional, noninterventional study in nine Indian centers included patients with newly diagnosed or relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer. The primary objective was to assess the prevalence of BRCA1/ BRCA2 mutations, and the secondary objective was to correlate BRCA1/ BRCA2 status with clinicopathologic characteristics. Mutation testing was performed by a standard next-generation sequencing assay. RESULTS Between March 2018 and December 2018, 239 patients with a median age of 53.0 (range, 23.0-86.0 years) years were included, of whom 203 (84.9%) had newly diagnosed disease, 36 (15.1%) had family history of ovarian or breast cancer, and 159 (66.5%) had serous subtype of epithelial ovarian cancer. Germline pathogenic or likely pathogenic mutations in BRCA1 and BRCA2 were detected in 37 (15.5%; 95% CI, 11.1 to 20.7) and 14 (5.9%; 95% CI, 3.2 to 9.6) patients, respectively, whereas variants of uncertain significance in these genes were seen in four (1.7%; 95% CI, 0.5 to 4.2) and six (2.5%; 95% CI, 0.9 to 5.4) patients, respectively. The prevalence of pathogenic or likely pathogenic BRCA mutations in patients with serous versus nonserous tumors, with versus without relevant family history, and ≤ 50 years versus > 50 years, were 40 of 159 (25.2%; 95% CI, 18.6 to 32.6) versus 11 of 80 (13.8%; 95% CI, 7.1 to 23.3; P = .0636), 20 of 36 (55.6%; 95% CI, 38.1 to 72.1) versus 41 of 203 (20.2%; 95% CI, 14.9 to 26.4; P < .0001), and 20 of 90 (22.2%; 95% CI, 14.1 to 32.2) versus 31 of 149 (20.8%; 95% CI, 14.6 to 28.2; P = .7956), respectively. CONCLUSION There is a high prevalence of pathogenic or likely pathogenic germline BRCA mutations in Indian patients with ovarian cancer.

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.

scholarly journals Prevalence of BRCA1 and BRCA2 Mutations Among High-Risk Saudi Patients With Breast Cancer

2018 ◽  
pp. JGO.18.00066 ◽  
Author(s):  
Omalkhair Abulkhair ◽  
Mohammed Al Balwi ◽  
Ola Makram ◽  
Lamia Alsubaie ◽  
Medhat Faris ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Novel Mutation ◽  
Brca Mutation ◽  
Brca1 Gene ◽  
Brca1 And Brca2 ◽  
Brca1 Mutations ◽  
Brca2 Mutations ◽  
Brca1 And Brca2 Mutations ◽  
Saudi Patients

Purpose Over the past three decades, the incidence rate of breast cancer (BC) among Arab women has continually increased. However, data on the prevalence of BRCA1/2 mutations are scarce. Although the population in Saudi Arabia is at large homogeneous and consanguinity is common, especially in the central, eastern, and southern regions of the country, the prevalence of BRCA1 and BRCA2 mutations and the characteristics of BC are not well studied in the country. Methods This prospective observational study intended to determine the prevalence of BRCA1 and BRCA2 mutations and sought to examine the clinicopathologic features of BC associated with these mutations. Results Of 310 patients, 270 (87%) had no mutation. BRCA mutations were identified in 40 patients; BRCA1 mutations were found in 11% of patients, and BRCA2 mutations were found in 2% of patients. Variants of unknown significance were found in 15% of patients (45 patients). Triple-negative BC (TNBC) accounted for 86% of all patients with BC and mutations. The following three recurrent deleterious founder BRCA1 mutations were observed: c.4136_4137delCT was observed in five unrelated patients, c.5530delC was observed in three unrelated patients, and c.4524G>A mutations were observed in five unrelated patients. One novel mutation was identified in the BRCA1 gene (c.5512 dup [p.Glu1838Glyfs*42]). Conclusion Among high-risk Saudi patients with BC, BRCA1 mutations are prevalent (11%). TNBC is the most common BC subtype. Furthermore, age alone does not have a significant association with mutation, but a combination of risk factors such as age, familial history, and TNBC has a significant association with BRCA mutation.

Contralateral Breast Cancer in BRCA1 and BRCA2 Mutation Carriers

2004 ◽  
Vol 22 (12) ◽  
pp. 2328-2335 ◽  
Author(s):  
Kelly Metcalfe ◽  
Henry T. Lynch ◽  
Parviz Ghadirian ◽  
Nadine Tung ◽  
Ivo Olivotto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Contralateral Breast Cancer ◽  
Brca Mutation ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Contralateral Breast ◽  
Second Primary ◽  
Brca1 And Brca2 ◽  
Breast Cancer Death ◽  
Actuarial Risk

Purpose To estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers after diagnosis and to determine which factors are predictive of the risk of a second primary breast cancer. Patients and Methods Patients included 491 women with stage I or stage II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up. Results The actuarial risk of contralateral breast cancer was 29.5% at 10 years. Factors that were predictive of a reduced risk were the presence of a BRCA2 mutation (v BRCA1 mutation; hazard ratio [HR], 0.73; 95% CI, 0.47 to 1.15); age 50 years or older at first diagnosis (v ≤ 49 years; HR, 0.63; 95% CI, 0.36 to 1.10); use of tamoxifen (HR, 0.59; 95% CI, 0.35 to 1.01); and history of oophorectomy (HR, 0.44; 95% CI, 0.21 to 0.91). The effect of oophorectomy was particularly strong in women first diagnosed prior to age 49 years (HR, 0.24; 95% CI, 0.07 to 0.77). For women who did not have an oophorectomy or take tamoxifen, the 10-year risk of contralateral cancer was 43.4% for BRCA1 carriers and 34.6% for BRCA2 carriers. Conclusion The risk of contralateral breast cancer in women with a BRCA mutation is approximately 40% at 10 years, and is reduced in women who take tamoxifen or who undergo an oophorectomy.

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