Characteristics of individuals with breast cancer rearrangements in BRCA1 and BRCA2

Abstract

; and the Northwestern Cancer Genetics Group BACKGROUND: Large rearrangements in BRCA1 and BRCA2 occur in a small percentage (< 1%) of patients tested for hereditary breast (BC) and ovarian cancer. It is unclear what factors predict BRACAnalysis Large Rearrangement Test (BART) positivity. METH-ODS: Data from 6 centers were included in this analysis. Individuals with negative Comprehensive BRACAnalysis tested for BART were included. RESULTS: From 1300 individuals, 42 (3.2%) were BART positivity. Factors positively associated with BART positivity were Myriad score, first-degree relatives with BC, infiltrating BC with ductal carcinoma in situ, younger age at BC diagnosis, estrogen receptor-negative BC for both the first and second BC, and Latin American/Caribbean ethnicity. Presence of unilateral BC was inversely associated with BART positivity. Several analyses were performed on the variables available to find the model that best predicts for BART positivity. The BART predictive model, including first BC, ovarian cancer, primary maternal ancestry being Latin America/Caribbean, number of first-degree relatives with BC of 1 or more versus 0, and family history of prostate and pancreatic cancer, had good predictive ability with an area under the curve of 0.77. CONCLUSIONS: Several factors are significantly associated with BART positivity. Among them we have found that Latin American/Caribbean ancestry, Myriad score, first degree relatives with BC, younger age at BC diagnosis, estrogen receptor-negative status of BC, and infiltrating ductal carcinoma with ductal carcinoma in situ features are significantly associated with BART positivity. A BART predictive model may help in a clinical setting. Cancer 2014;120:1557-64.

Phase I/Ib study of olaparib and carboplatin in women with triple negative breast cancer

“…They are more likely to be identified with copy number assays, or whole exome and whole genome approaches, now more commonly applied. Jackson et al reported rearrangements in 42 of 1300 (3.2%) patients referred for BRCA mutation testing and only 10 of the 42 had met Myriad criteria [ 34 ]. Our patient’s outcome of an over 5-year olaparib-maintained CR identifies her as an exceptional responder, remarkable even for patients with BRCA mutation-associated breast cancer.…”

Identification of a new BRCA2 large genomic deletion associated with high risk male breast cancer

“…The majority of mutations found to date in the BRCA1/BRCA2 genes in breast and/or ovarian cancer families are point mutations or small insertions and deletions scattered over the coding sequence and splice junctions. Large rearrangements in BRCA1 and BRCA2 occur in a small percentage (<1%) of patients tested for hereditary breast and ovarian cancer [ 15 ]. Moreover, the mutation was detected in a male patient.…”

Recent advances of therapeutic targets based on the molecular signature in breast cancer: genetic mutations and implications for current treatment paradigms

“…To the best of our knowledge, the majority of mutations of the BRCA1/BRCA2genes in breast and/or ovarian cancer families are point mutations or small insertions and deletions spread over the coding sequence and splice site junctions. It is noteworthy that large rearrangements in BRCA1and BRCA2 accounted for less than 1% of evaluated patients suffering from hereditary breast and ovarian cancer [21]. All of these mutations are capable of shortening BRCA1 protein, leading to failing to its physiologic function [9].…”