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Abstract：
Germline pathogenic variants (PV) of the PALB2 tumor 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 of PALB2, 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 germline PALB2 alteration 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 of PALB2-associated BC. Overall, our case report and review of the literature provide additional evidence that the germline analysis of PALB2 gene should be included in routine genetic testing for predictive purposes and to refine treatment algorithms.
摘要：
PALB2抑癌基因的种系致病变异体（PV）与乳腺癌风险增加有关，胰腺,和卵巢癌。在以前的研究中，PALB2相关乳腺癌显示侵袭性临床病理表型，特别是三阴性亚型，和更高的死亡率，无论肿瘤分期，化疗类型或激素受体状态。从手术方法到全身治疗选择，这种种系改变的鉴定可能会对乳腺癌（BC）的临床管理产生影响。我们在此报告了PALB2种系PV的患者，诊断为局部晚期PD-L1阳性三阴性BC，患者在接受含有免疫检查点抑制剂(ICI)的方案后进展,然后在铂类化疗后出现病理性完全缓解.该病例报告暗示了与PD-L1表达相比，种系PALB2改变作为癌症驱动因子的主要作用，并使我们有机会广泛回顾和讨论有关PALB2相关BC的最佳管理的现有文献。总的来说,我们的病例报告和文献综述提供了更多证据,表明PALB2基因的种系分析应纳入常规基因检测中,以达到预测目的和改进治疗算法.
