Anders Carey K, Abramson Vandana, Tan Tira, Dent Rebecca
From the Department of Medicine, Vanderbilt University, Vanderbilt-Ingram Cancer Center, Nashville, TN; Department of Medicine, National Cancer Center Singapore, Singapore; Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC; UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC.
Am Soc Clin Oncol Educ Book. 2016;35:34-42. doi: 10.1200/EDBK_159135.
Triple-negative breast cancer (TNBC) is clinically defined as lacking expression of the estrogen receptor (ER), progesterone receptor (ER), and HER2. Historically, TNBC has been characterized by an aggressive natural history and worse disease-specific outcomes compared with other breast cancer subtypes. The advent of next-generation sequencing (NGS) has allowed for the dissection of TNBC into molecular subtypes (i.e., basal-like, claudin-low). Within TNBC, several subtypes have emerged as "immune-activated," consistently illustrating better disease outcome. In addition, NGS has revealed a host of molecular features characteristic of TNBC, including high rates of TP53 mutations, PI3K and MEK pathway activation, and genetic similarities to serous ovarian cancers, including inactivation of the BRCA pathway. Identified genetic vulnerabilities of TNBC have led to promising therapeutic approaches, including DNA-damaging agents (i.e., platinum salts and PARP inhibitors), as well as immunotherapy. Platinum salts are routinely incorporated into the treatment of metastatic TNBC; however, best outcomes are observed among those with deficiencies in the BRCA pathway. Although the incorporation of platinum in the neoadjuvant care of patients with TNBC yields higher pathologic complete response (pCR) rates, the impact on longer-term outcome is less clear. The presence of immune infiltrate in TNBC has shown both a predictive and prognostic role. Checkpoint inhibitors, including PD-1 and PD-L1 inhibitors, are under investigation in the setting of metastatic TNBC and have shown responses in initial clinical trials. Finally, matching emerging therapeutic strategies to optimal subtype of TNBC is of utmost importance as we design future research strategies to improve patient outcome.
三阴性乳腺癌（TNBC）在临床上被定义为缺乏雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER2）的表达。从历史上看，与其他乳腺癌亚型相比，TNBC的特点是具有侵袭性的自然病程和更差的疾病特异性结局。新一代测序（NGS）技术的出现使得TNBC能够被细分为分子亚型（即基底样、Claudin低表达型）。在TNBC中，出现了几种“免疫激活”亚型，其疾病结局始终较好。此外，NGS还揭示了TNBC的一系列分子特征，包括TP53突变率高、PI3K和MEK通路激活，以及与浆液性卵巢癌的遗传相似性，包括BRCA通路失活。已确定的TNBC遗传脆弱性导致了有前景的治疗方法，包括DNA损伤剂（即铂盐和PARP抑制剂）以及免疫疗法。铂盐通常被纳入转移性TNBC的治疗中；然而，在BRCA通路缺陷的患者中观察到最佳疗效。尽管在TNBC患者的新辅助治疗中加入铂可提高病理完全缓解（pCR）率，但对长期结局的影响尚不清楚。TNBC中免疫浸润的存在已显示出预测和预后作用。包括程序性死亡受体1（PD-1）和程序性死亡配体1（PD-L1）抑制剂在内的检查点抑制剂正在转移性TNBC的治疗中进行研究，并且在初步临床试验中已显示出疗效。最后，在我们设计未来改善患者结局的研究策略时，将新兴治疗策略与TNBC的最佳亚型相匹配至关重要。
