Triple-negative breast cancer: BRCAness and concordance of clinical features with BRCA1-mutation carriers

E H Lips, L Mulder, A Oonk, L E van der Kolk, F B L Hogervorst, A L T Imholz, J Wesseling, S Rodenhuis, P M Nederlof, E H Lips, L Mulder, A Oonk, L E van der Kolk, F B L Hogervorst, A L T Imholz, J Wesseling, S Rodenhuis, P M Nederlof

Abstract

Background: BRCAness is defined as shared tumour characteristics between sporadic and BRCA-mutated cancers. However, how to exactly measure BRCAness and its frequency in breast cancer is not known. Assays to establish BRCAness would be extremely valuable for the clinical management of these tumours. We assessed BRCAness characteristics frequencies in a large cohort of triple-negative breast cancers (TNBCs).

Methods: As a measure of BRCAness, we determined a specific BRCA1-like pattern by array Comparative Genomic Hybridisation (aCGH), and BRCA1 promoter methylation in 377 TNBCs, obtained from 3 different patient cohorts. Clinicopathological data were available for all tumours, BRCA1-germline mutation status and chemotherapy response data were available for a subset.

Results: Of the tumours, 66-69% had a BRCA1-like aCGH profile and 27-37% showed BRCA1 promoter methylation. BRCA1-germline mutations and BRCA1 promoter methylation were mutually exclusive events (P=1 × 10(-5)). BRCAness was associated with younger age and grade 3 tumours. Chemotherapy response was significantly higher in BRCA1-mutated tumours, but not in tumours with BRCAness (63% (12 out of 19) vs 35% (18 out of 52) pathological complete remission rate, respectively).

Conclusion: The majority of the TNBCs show BRCAness, and those tumours share clinicopathological characteristics with BRCA1-mutated tumours. A better characterisation of TNBC and the presence of BRCAness could have consequences for both hereditary breast cancer screening and the treatment of these tumours.

Figures

Figure 1
Figure 1
Co-occurrence of aCGH BRCA1-like profile, BRCA1 mutation, and BRCA1 methylation. This pie chart shows the frequency of the combination of BRCAness characteristics and BRCA1 mutation status in 88 tumours from the neoadjuvant series. aCGH BRCA1-like tumours were either mutated (Mut), methylated (Meth) or showed no aberration (Other). The same applied to the non-BRCA1-like tumours.

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