长期的治疗不足和肿瘤异质性导致了三阴性乳腺癌（TNBC），这是一种预后不良、病情进展迅速的亚型，占所有新乳腺癌病例的10%-15%。TNBC的特征是缺乏孕激素和雌激素受体表达，并且没有HER2的基因扩增或过表达。基因组测序发现，TNBC体细胞和生殖细胞修改的独特突变模式与其他乳腺肿瘤亚型极不相同。在TNBC中测序生殖BRCA1/2基因的临床效用已经得到了充分确立。然而，关于其他易感基因的穿透率和风险的报告相对较少。在TNBC中，复发性基因突变（如TP53和PIK3CA突变）与罕见突变共同出现，并且基因组修改的共同效应驱动了它的进展。鉴于该疾病的异质性和复杂性，对TNBC基因组修改的临床理解可以为其治疗铺平一条创新的道路。在本综述中，我们总结了与TNBC发育信号通路的潜在生物学相关的最新发现。我们还总结了近期在遗传学和流行病学方面的进展，并讨论了为TNBC提供个体化治疗的先进疫苗治疗策略。版权所有©2023年爱思唯尔公司。保留所有权利。

Long-standing scarcity of efficacious treatments and tumor heterogeneity have contributed to triple-negative breast cancer (TNBC), a subtype with a poor prognosis and aggressive behavior that accounts for 10-15% of all new cases of breast cancer. TNBC is characterized by the absence of progesterone and estrogen receptor expression and lacks gene amplification or overexpression of HER2. Genomic sequencing has detected that the unique mutational profile of both the somatic and germline modifications in TNBC is staggeringly dissimilar from other breast tumor subtypes. The clinical utility of sequencing germline BRCA1/2 genes has been well established in TNBC. Nevertheless, reports regarding the penetrance and risk of other susceptibility genes are relatively scarce. Recurring mutations (e.g., TP53 and PI3KCA mutations) occur together with rare mutations in TNBC, and the shared effects of genomic modifications drive its progression. Given the heterogeneity and complexity of this disease, a clinical understanding of the genomic modifications in TNBC can pave an innovative way toward its therapy. In this review, we summarized the most recent discoveries associated with the underlying biology of developmental signaling pathways in TNBC. We also summarize the recent advancements in genetics and epidemiology and discuss state-of-the-art vaccine-based therapeutic strategies for TNBC that will enable tailored therapeutics.Copyright © 2023 Elsevier Inc. All rights reserved.