High incidence of germline BRCA mutation in patients with ER low‐positive/PR low‐positive/HER‐2 neu negative tumors

Abstract

Purpose 2015 NCCN guidelines recommend genetic counseling and germline BRCA mutation testing be offered to women under age 60 with triple negative breast cancer (TNBC). As a result of the 2010 ASCO/CAP guidelines in breast cancer, patients with breast cancers that are ER or PR low-positive (1–9% on immunohistochemistry) are no longer strictly considered to have TNBC and may not be referred for genetic counseling. However, the incidence of BRCA mutation in patients with hormone receptor (HR) low-positive breast cancers remains unknown, and current ASCO/CAP guidelines may result in under-testing for BRCA mutation. Methods We reviewed a prospectively maintained research database of breast cancer patients evaluated at UT MD Anderson Cancer Center between 2004 and 2014, identifying 314 patients with ER<10%, PR<10%, HER-2 neu negative breast cancers with known BRCA mutation status. Results 314 patients had breast cancers expressing ER and PR <10%; 238 (75.8%) had HR negative (ER and PR <1%) cancers and 76 (24.2%) had HR low-positive (ER and/or PR 1–9%) cancers. Among patients with HR negative tumors, 86 of 238 (36.1%) had a BRCA 1/2 mutation, while among the HR low-positive group, 30 of 76 (39.5%) had a BRCA 1/2 mutation. In multivariate analysis, HR status (HR<1% vs. HR 1–9%) was not significantly associated with BRCA 1/2 mutation. Conclusion The incidence of BRCA 1/2 mutation is similar in patients with HR low-positive and HR negative breast cancers. We recommend offering genetic counseling and BRCA testing to patients under age 60 with ER low-positive breast cancers.

High EGFR protein expression and exon 9 PIK3CA mutations are independent prognostic factors in triple negative breast cancers

“…A potential pitfall of our study could be linked to the choice of a European definition of TNBC, considering a <10 % negativity threshold for the determination of the hormone receptor status. However, the fact that the exclusion of the 11 cases with HR values between 1 and 9 % did not change the multivariate analysis results, and the fact that recent biological studies showed a close biologic similarity between the <1 % HR and 1–9 % HR population [ 39 ], both strengthen our results.…”

Differentially expressed genes and key molecules of BRCA1/2-mutant breast cancer: evidence from bioinformatics analyses

“…BRCA genes mutations, conferring increased risks for breast and high-grade serous cancer of the gynecological tract (fallopian tube, ovary and peritoneum), are closely associated with triple negative breast cancers (TNBC) (Foulkes, 2013;Sanford et al, 2015). Among the classifications of breast cancer, TNBC, manifested as early recurrence and poor survival, does not express estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).…”

“…Among the classifications of breast cancer, TNBC, manifested as early recurrence and poor survival, does not express estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Among patients with TNBC, the incidence of BRCA1/2 mutation is estimated to range from 11-37% (Sanford et al, 2015;Young et al, 2009). TNBC accounts for about 70% and 16-23% of BRCA1 and BRCA2 mutation carriers, respectively (Stevens & Couch, 2013), suggesting that TNBC is also inextricably linked to germline mutation in this breast cancer susceptibility gene.…”

Genetic and demographic factors of a brazilian population sample at-risk of hereditary breast and ovarian cancer

“…It is known that the association between the triple negative phenotype is more consistent in BRCA1 gene mutations than in BRCA2 ones 11 . A study conducted in a population consisting of 314 patients with triple negative breast cancer demonstrates this difference 11 : considering only patients with estrogen receptor (ER) and progesterone (PR) expression lower than 1%, the prevalence of BRCA1 mutations was 30%, whereas in BRCA2 it was 7% 11 .…”

“…It is known that the association between the triple negative phenotype is more consistent in BRCA1 gene mutations than in BRCA2 ones 11 . A study conducted in a population consisting of 314 patients with triple negative breast cancer demonstrates this difference 11 : considering only patients with estrogen receptor (ER) and progesterone (PR) expression lower than 1%, the prevalence of BRCA1 mutations was 30%, whereas in BRCA2 it was 7% 11 . Interestingly, these proportions were the same both for the group with ER and PR expressions of 1 to 9% and for less than 1%, which suggests that there are no biological differences between the two groups, with implications for the indication of tracing for HBOC and therapy 11 .…”