Abstract
BRCAness is defined as a phenotypic copy of germline BRCA mutations, which describes presence of homologous recombination defects in sporadic cancers. We detected BRCAness by multiplex ligation-dependent probe amplification (MLPA) and explored whether BRCAness can be used as a predictor of prognosis. BRCAness status was classified for total 121 breast cancer patients. Forty-eight patients (39.7%) were identified as BRCAness positive. Tumors of BRCAness were more likely to be hormone receptors negative (95.8% vs. 50.7%, P < 0.001), nuclear grade III (76.1% vs. 48.4%, P = 0.001) and triple-negative breast cancer subtype (91.6% vs. 42.5%, P < 0.001). Five-year disease free survival (DFS) (54.0% vs. 88.0%, P < 0.001) and overall survival (OS) (76.3% vs. 93.1%, P = 0.002) were significantly lower in BRCAness patients. In neoadjuvant chemotherapy subgroup analysis, clinical response rate for taxane-based regimen was significantly lower in BRCAness patients (58.3% vs. 77.8%, P = 0.041). Cox regression multivariate analysis showed that BRCAness was the independent prognostic factor for DFS (HR 2.962, 95%CI 1.184–7.412, P = 0.020), but not for OS (HR 2.681, 95%CI 0.618–11.630, P = 0.188). BRCAness is associated with specific characteristics and may suggest resistance to taxane-based chemotherapy. BRCAness can be used as a negative prognostic indicator for breast cancer.
Highlights
Germline mutations in BRCA1 and BRCA2 have been confirmed to associate with increased risk of developing breast and ovarian cancers since two decades a go[1,2,3]
BRCAness positive patients showed a significantly higher nuclear grade and lower hormone receptor positive rate compared to the BRCAness negative patients (P < 0.001 and P < 0.001, respectively)
Since BRCA genes were identified, it has been confirmed that germline BRCA mutation breast cancer has some distinctive clinicopathological features compared to sporadic breast cancer
Summary
Germline mutations in BRCA1 and BRCA2 have been confirmed to associate with increased risk of developing breast and ovarian cancers since two decades a go[1,2,3]. This high risk might be related to the functions of BRCA1 and BRCA2 genes in DNA repair. Our previous research confirmed the result that same as germline BRCA mutations, BRCAness predicts resistance to taxane-containing regimens in triple negative breast cancer (TNBC) during neoadjuvant chemotherapy (NAC)[6,7].
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