转移性三阴性乳腺癌临床治疗进展

Clinical Advances in the Treatment of Metastatic Triple Negative Breast Cancer

摘要: 三阴性乳腺癌(TNBC)的复发风险高，预后差。超过三分之一的TNBC患者在发病过程中会出现远处转移。尽管长久以来化疗为主要治疗转移TNBC方案，然而，随着用于携带BRCA基因突变(BRCAmut)的患者的聚腺苷二磷酸核糖聚合酶抑制剂(PARPis)的问世，以及PD-L1阳性肿瘤患者的免疫治疗结果，这种情况发生了变化。本文在现有相关文献的基础上，综述了一种针对转移性TNBC患者的治疗方法。对于BRCAmut患者和能够耐受化疗的患者，我们建议使用铂(卡铂/顺铂)开始治疗，并在疾病进展时开始使用PARPis。对于PD-L1阳性肿瘤患者(PD-L1在肿瘤浸润免疫细胞上的表达≥1%)，我们建议在可行的情况下，采用紫杉醇钠和阿特珠单抗一线治疗。对于无BRCA突变和PD-L1阴性肿瘤的患者，我们建议单用紫杉醇(紫杉醇或多西他赛)作为一线治疗。在疾病负担高或症状严重的患者中，联合使用蒽环类药物加环磷酰胺或铂类药物与紫杉烷类药物是有效的选择。化疗应持续到疾病进展或限制毒性的发生。对于一线化疗后进展的患者，蒽环类药物是接受紫杉烷类药物治疗后的患者的一种选择，反之亦然。对于进展到紫杉醇和蒽环类药物的患者，或对上述药物有禁忌症的患者，氟尿嘧啶/卡培他滨、艾里布林、吉西他滨、顺铂/卡铂、长春瑞滨和伊沙哌酮是替代药物。TNBC的治疗正在不断发展，应鼓励患者纳入正在进行的评估新的靶向药物、免疫治疗和预测生物标志物的试验，以改善转移性TNBC治疗的结果。

Abstract: Triple-negative breast cancer (TNBC) is associated with a high risk of recurrence and generally a bad prognosis. More than one-third of patients with TNBC will present distant metastases during the course of their disease. Although chemotherapy has been the main treatment option for meta-static TNBC for a long time, this scenario has changed recently with the advent of the polyaden-osinediphosphate-ribose polymerase inhibitors (PARPis) for patients harbouring a mutation in the BRCA genes (BRCAmut) and also with the results of immunotherapy in patients with PD-L1-positive tumours. The present manuscript proposes a treatment algorithm for patients with metastatic TNBC based on the currently available, most relevant literature on the topic. For patients with a BRCAmut and able to tolerate chemotherapy, we recommend initiating treatment with platins (carboplatin/cisplatin) and to start PARPis at disease progression. For patients with PD-L1-positive tumours (PD-L1 expression on tumour-infiltrating immune cells ≥1%), we recommend first-line treatment with nab-paclitaxel and atezolizumab, when available. In patients without a BRCA mutation and with PD-L1-negative tumours, we recommend single agent chemotherapy with taxanes (paclitaxel or docetaxel) as a first-line treatment. In patients with a high disease burden or who are very symptomatic, combinations such as anthracyclines plus cyclophosphamide or platins with taxanes are valid options. Chemotherapy should be maintained until the occurrence of disease progression or limiting toxicities. After progression to first-line chemotherapy, anthracyclines are an option for patients who received taxanes and vice versa. For patients who progressed to taxanes and anthracyclines, or who present contraindications to these agents, fluorouracil/capecitabine, eribulin, gemcitabine, cisplatin/carboplatin, vinorelbine and ixabepilone are alternatives. The treatment of TNBC is constantly evolving, and the inclusion of patients in ongoing trials evaluating new targeted agents, immunotherapy and predictive biomarkers should be encouraged, in an attempt to improve metastatic TNBC treatment outcomes.