Patterns of recurrence and metastasis in BRCA1/BRCA2‐associated breast cancers

Abstract

BACKGROUND: Breast cancer subtypes are associated with distinct metastatic patterns. Whether germline BRCA1/BRCA2 mutation status is independently associated with central nervous system (CNS) relapse, controlling for tumor subtype, is unknown. METHODS: Patients who were treated at Dana-Farber Cancer Institute and diagnosed with a first locoregional recurrence (LRR) or metastasis between 1981 and 2014 were identified using 2 institutional registries: 1) patients treated for recurrent breast cancer and 2) patients who underwent BRCA testing. The frequencies of LRR, sites of metastasis, and breast cancer-specific survival from LRR or metastasis were calculated, and the factors associated with CNS recurrence were evaluated using multivariable logistic regression models. RESULTS: The final study cohort included 30 BRCA1 mutation carriers, 32 BRCA2 mutation carriers, and 270 noncarriers. Most BRCA1 carriers (73%) had triple-negative breast cancer; whereas most BRCA2 carriers (72%) had hormone receptor-positive tumors. BRCA1 carriers frequently experienced lung and distant lymph node metastasis, whereas BRCA2 carriers and noncarriers most often experienced bone metastasis. Although CNS disease occurred frequently in both BRCA1 and BRCA2 carriers (53% BRCA1, 50% BRCA2, 25% noncarriers; P < .001), only BRCA2 mutation (P = .006) was significantly associated with CNS metastasis in multivariable analysis controlling for tumor subtype. BRCA2 mutation (P = .01), triple-negative subtype (P < .001), and the involvement of CNS (P < .001) and other non-CNS distant sites (relative to locoregional recurrence or contralateral disease; P < .001) at presentation of recurrent breast cancer were associated with risk for mortality. CONCLUSIONS: CNS involvement is frequent in women with germline BRCA1/BRCA2 mutations who have metastatic breast cancer. BRCA2 mutation carriers had a significantly higher frequency of CNS metastasis than noncarriers when controlling for breast cancer subtype.

The relationship between BRCA-associated breast cancer and age factors: an analysis of the Japanese HBOC consortium database

“…Several studies have demonstrated that BRCA1-associated tumors are usually TNBC and BRCA2 mutation carriers commonly develop ER-positive breast cancer [43][44][45]. A similar pattern was reported in metastatic and recurrent breast cancer [46]. However, only a few reports have included age factors.…”

Homologous Recombination Repair Deficiency and the Immune Response in Breast Cancer: A Literature Review

“…However, BC subgroups with a higher TMB could be represented by TNBC [99] and g BRCA1/2 -mutated tumors, similar to what was observed with microsatellite unstable high (MSI-H) cases in colorectal cancer [100]. It is worth of note that up to 25% of TNBC harbors a g BRCA1/2 mutation and at least 75% and 25% of gBRCA1- and gBRCA2- mutated tumors, respectively, are TNBC [101,102].…”

The Genomic Landscape of Prostate Cancer Brain Metastases

“…PARP inhibitors, such as olaparib 37,38 or niraparib 39,40 , have shown to be active on brain metastases in patients with homologous recombination deficient (HRD) breast cancer and in murine models of brain metastases 41,42 . Moreover, HRD signatures have been reported to be enriched in breast cancer brain metastases compared with primary tumors 43 , and the occurrence of brain metastases is relatively frequent event in BRCA1/2 mutated cancers 44,45 . In a pancreatic xenograft model, niraparib has shown higher intracranial activity compared with olaparib 41 .…”