Clinical outcome of triple negative breast cancer in BRCA1 mutation carriers and noncarriers

Abstract

BACKGROUND Women with BRCA1 mutations develop breast cancer with similar pathologic features to sporadic triple negative (TN) breast cancer, a subtype associated with early disease relapse and poor outcome. We compared the clinical outcome of women with and without BRCA1 mutations who had TN breast cancer treated with conventional chemotherapy. METHODS Women with stage I-III TN breast cancer who had BRCA1 testing within 36 months of diagnosis and received alkylating chemotherapy were identified from clinical databases and a SPORE specimen bank. BRCA2 mutation carriers were excluded, resulting in a study cohort of 46 BRCA1 carriers and 71 non-carriers. Sites of metastasis, relapse rates and survival were compared among carriers and non-carriers. The median follow-up was 75 months. RESULTS BRCA1 carriers were younger at diagnosis (p<0.001) and had smaller tumors (p=0.03) than non-carriers. Freedom from distant metastasis at 5 years was 76% for carriers and 70% for non-carriers (HR 0.79, p=0.5). Sites of distant recurrence did not differ significantly (p=0.15), although BRCA1 carriers had a propensity for brain relapse (58% vs. 24%, p=0.06). Overall survival at 5 years was 82% for carriers and 74% for non-carriers (HR 0.64, p=0.25). Adjusting for age and stage, BRCA1 mutation status was not an independent predictor of survival (HR 0.73, p=0.48). CONCLUSION BRCA1 mutation carriers with TN disease have similar survival rates to non-carriers when treated with alkylating chemotherapy. Women with BRCA1-related breast cancer may benefit from novel therapies that target DNA repair, and further study is needed to identify sporadic TN breast cancers with a BRCA-deficient phenotype.

CNS Metastases in Breast Cancer: Old Challenge, New Frontiers

“…3,18,19). However, in contrast to patients with HER2-positive breast cancer, CNS involvement in patients with triple-negative breast cancer typically occurs in the setting of simultaneous extracranial disease progression, and tends to cluster relatively early in a patient's disease trajectory (6,(19)(20)(21).…”

“…In a study of lapatinib among patients with HER2-positive breast cancer, reductions in the FDG uptake in brain metastases were seen in a subset of women, providing some of the first in vivo evidence that the drug reaches levels in patients with brain metastases sufficient to influence cellular signaling (93). 18 F-FLT (3 0 -fluoro-3 0 deoxythymidine)-PET imaging is a noninvasive tool for measuring in vivo tumor cell proliferation. 18 F-FLT is a pyrimidine analogue.…”

“…18 F-FLT (3 0 -fluoro-3 0 deoxythymidine)-PET imaging is a noninvasive tool for measuring in vivo tumor cell proliferation. 18 F-FLT is a pyrimidine analogue. After its uptake by proliferating cells, it is phosphorylated by thymidine kinase 1 and becomes trapped in the cells (94).…”

“…After its uptake by proliferating cells, it is phosphorylated by thymidine kinase 1 and becomes trapped in the cells (94). 18 F-FLT PET imaging may allow tracking of therapeutic-associated cell-cycle arrest before morphologic changes become measurable. Several studies in breast, lung, and brain tumors have demonstrated that retention of 18 F-FLT correlated with tumor proliferation and have studied it for monitoring early response to therapies (95)(96)(97)(98)(99).…”

“…18 F-FLT PET imaging may allow tracking of therapeutic-associated cell-cycle arrest before morphologic changes become measurable. Several studies in breast, lung, and brain tumors have demonstrated that retention of 18 F-FLT correlated with tumor proliferation and have studied it for monitoring early response to therapies (95)(96)(97)(98)(99). Although 18 F-FLT has been used to image and stage several tumor types, the standardized uptake value is generally lower than that obtained with 18 F-FDG (100).…”