Management ofPALB2‐associated breast cancer: A literature review and case report

Abstract

Key Clinical MessageGermline pathogenic variants (PV) of thePALB2tumor suppressor gene are associated with an increased risk of breast, pancreatic, and ovarian cancer. In previous research,PALB2‐associated breast cancer showed aggressive clinicopathological phenotypes, particularly triple‐negative subtype, and higher mortality regardless of tumor stage, type of chemotherapy nor hormone receptor status. The identification of this germline alteration may have an impact on clinical management of breast cancer (BC) from the surgical approach to the systemic treatment choice. We herein report the case of a patient with a germline PV ofPALB2, diagnosed with locally advanced PD‐L1 positive triple‐negative BC, who progressed after an immune checkpoint inhibitor (ICI)‐containing regimen and then experienced a pathologic complete response after platinum‐based chemotherapy. This case report hints a major role of the germlinePALB2alteration compared to the PD‐L1 expression as cancer driver and gives us the opportunity to extensively review and discuss the available literature on the optimal management ofPALB2‐associated BC. Overall, our case report and review of the literature provide additional evidence that the germline analysis ofPALB2gene should be included in routine genetic testing for predictive purposes and to refine treatment algorithms.