Prevalence of BRCA Mutations Among Women with Triple-Negative Breast Cancer (TNBC) in a Genetic Counseling Cohort

Department of Surgery, Duke University, Durham, NC, USA, .
Annals of Surgical Oncology (Impact Factor: 3.93). 08/2013; 20(10). DOI: 10.1245/s10434-013-3205-1
Source: PubMed


Revised NCCN guidelines recommend that women ≤60 years with triple-negative breast cancer (TNBC) be referred for consideration of genetic counseling. Small, homogeneous samples have limited evaluation of BRCA mutation prevalence among different ethnicities affected by TNBC subtype. We sought to determine whether the prevalence of BRCA mutations within a TNBC cohort differs by demographic factors.
We performed a retrospective review of patients with TNBC referred for genetic counseling at two academic Hereditary Cancer Clinics between 2000 and 2012. Demographic data were collected, including age at diagnosis and race/ethnicity. Race was categorized as African American (AA), Ashkenazi Jewish (AJ), Asian, Caucasian, Hispanic, or other. Primary outcome was BRCA mutation status, analyzed by race/ethnicity and age at diagnosis.
A total of 469 patients with TNBC who underwent testing for BRCA genetic mutations were identified, of which 450 patients had evaluable BRCA testing results; 139 (30.8 %) had confirmed BRCA1 (n = 106) or BRCA2 (n = 32) mutations. BRCA mutation prevalence differed by ethnicity and race: AA (20.4 %), AJ (50 %), Asian (28.5 %), Caucasian (33.3 %), and Hispanic (20 %). The prevalence of genetic mutations also differed by age at diagnosis: <40 years (43.8 %), 40-49 years (27.4 %), 50-59 years (25.3 %), 60-69 years (12.5 %), and >70 years (16.6 %).
The prevalence of genetic mutations among women with TNBC referred for genetic counseling is high and differs significantly by ethnicity/race and age. This data helps to refine mutation risk estimates among women with TNBC, allowing for more personalized genetic counseling potentially aiding in improved patient decision-making.

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    • "which is strongly connected with the loss of function of BRCA1/2 genes (Greenup et al., 2013). The association of TNBC with BRCA1 and BRCA2 mutations allows early identification of patients who were affected by hereditary cancer syndromes and it has important treatment implications for patients and their families (Greenup et al., 2013). To date, studies about miRNA alterations in TNBC were commonly performed in cell lines and clinical samples which have not been tested for BRCA mutations, and these studies were focused on determination of aberrant miRNA expression in this disease (Radojicic et al., 2011; Howe et al., 2012; Cascione et al., 2013; D'Ippolito and Iorio, 2013). "
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    ABSTRACT: Triple negative breast cancer (TNBC) is the most aggressive and poorly understood subclass of breast cancer (BC). Over the recent years, miRNA expression studies have been providing certain detailed overview that aberrant expression of miRNAs is associated with TNBC. Although TNBC tumors are strongly connected with loss of function of BRCA genes, there is no knowledge about the effect of BRCA mutation status on miRNA expressions in TNBC cases. The aims of this study were to evaluate the expression profile of miRNAs that plays role in TNBC progression and the role of BRCA mutations in their regulation. The expression level of BC associated 13 miRNAs was analyzed in 7 BRCA mutations positive, 6 BRCA mutations negative TNBC cases and 20 non-tumoral tissues using RT-PCR. According to RT2 Profiler PCR Array Data Analysis, let-7a expression was 4.67 fold reduced in TNBCs as compared to normal tissues (P=0.031). In addition, miR-200c expression was 5.75 fold reduced in BRCA mutation positive TNBC tumors (P=0.005). Analysis revealed a negative correlation between miR-200c and VEGFA expressions (r=-468). Thus, miR-200c may be involved in invasion and metastasis in TNBC cases with BRCA mutation. In this study we provide the knowledge on the first report of association between microRNA-200c and BRCA mutations in TNBC. Further studies and evaluations are required, but this miRNA may provide novel therapeutic molecular targets for TNBC treatment and new directions for the development of anticancer drugs. Copyright © 2014. Published by Elsevier B.V.
    Gene 11/2014; 556(2). DOI:10.1016/j.gene.2014.11.047 · 2.14 Impact Factor
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    • "Germline mutations in the BRCA1 and BRCA2 breast cancer susceptibility genes have been associated with up to 15% of TNBC, and TNBC accounts for 70% of breast tumors arising in BRCA1 mutation carriers and 16–23% of breast tumors in BRCA2 carriers (8). Because BRCA1 and BRCA2 tumor suppressor genes play a key role in the control of genomic stability through regulation of DNA repair and centrosome duplication (9–11), these findings explain the causal role of BRCA1 and BRCA2 mutations in the development of high CIN commonly observed in TNBC tumors. "
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    International Journal of Oncology 06/2014; 45(3). DOI:10.3892/ijo.2014.2523 · 3.03 Impact Factor
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    ABSTRACT: While the 5-year survival rate of breast cancer is at an all-time high of 90%, this disease remains the second most common cause of cancer-related death, surpassed only by lung cancer in the US. The reasons for this discrepancy stem from cancer subtypes which become resistant to current therapies. These subtypes: "Triple negative" and ErbB2-overexpressing, are discussed in this review.
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