Abstract P4-09-15: BRCAness and PD-L1 expression of basal-like and not basal-like triple negative breast cancer

Abstract

Abstract Background: Triple Negative Breast Cancer (TNBC) subtype occurs in approximately 20% of all patients with breast cancer and is associated with rapid growth, early metastasis and poor prognosis compared with other subtypes. TNBCs are a heterogeneous disease entity and further subclassification is needed, but still ongoing. In this study, we assessed BRCAness, defined as shared characteristics between sporadic and BRCA1-mutated tumors, in a cohort of basal-like and non-basal-like TNBCs. Patients and Methods: DNA was isolated from formalin-fixed paraffin-embedded tumor tissues and BRCAness status was analyzed in 262 patients with primary TNBCs resected at our three hospitals between 2004 and 2014. Classification of BRCAness was performed by using Multiple Ligation-dependent Probe Amplification (MLPA) with the probemix P376 BRCA1ness by MRC (Amsterdam, Holland). The tumor subtypes were routinely determined immunohistochemically by using resected specimens. Basal-like phenotype was defined as being positive for Epidermal Growth Factor Receptor (EGFR) and/or Cytokeratin 5/6 (CK5/6). Moreover, TNBCs were stained and analyzed for programmed cell death ligand-1 (PD-L1) expression as a target of new immune therapies. Results: Of 262 TNBCs, 232 tumors (88.5%) was a basal-like phenotype. The results of MLPA assay showed that 159 (68.5%) of 232 tumors had a BRCAness profile. Patients with basal-like BRCAness tumors were younger than patients with basal-like non-BRCAness tumors (p<0.0001). There was no significant difference between the two groups regarding pathological stage. The basal-like BRCAness group had shorter relapse-free survival (RFS) and overall survival (OS) than the basal-like non-BRCAness group (p=0.028 and p=0.13, respectively), and anthracycline-based regimens provided greater benefit to the basal-like BRCAness group significantly (p=0.01 in RFS and p=0.007 in OS). PD-L1 was expressed in 71 (44.7%) of 159 basal-like TNBCs with BRCAness. Conclusion: We reported the majority of basal-like TNBCs showed a BRCAness profile and PD-L1 expressed in approximately 50% of BRCAness tumors. It is known that about 30% of BRCAness tumors are BRCA1-mutated tumors. Those biomarkers are essential for subclassification of TNBCs and may offer not only platinum-based chemotherapy but also novel therapies, such as immune-targeted therapies of PD-1/PD-L1 inhibitors and PARP inhibitors, to patients with basal-like TNBCs with BRCAness. Citation Format: Mori H, Kubo M, Yamada M, Kai M, Osako T, Nishimura R, Arima N, Okido M, Kuroki S, Oda Y, Nakamura M. BRCAness and PD-L1 expression of basal-like and not basal-like triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-09-15.