Selection of Intensive Adjuvant Therapy for Triple-positive Breast Cancer
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摘要: 三阳性乳腺癌（triple-positive breast cancer，TPBC）是以激素受体（hormonereceptor，HR）阳性（HR+）和人类表皮生长因子受体（humanepidermalgrowthfactorreceptor 2，HER2）阳性（HER2+）共表达的一类特殊类型的乳腺癌。因其同时受HR信号通路和HER2信号通路共同调控影响，TPBC的治疗策略选择一直是临床关注的热点。TPBC患者强化辅助治疗选择不一，序贯、联合，内分泌治疗和靶向治疗如何精准的谋局落子，尚缺少系统性理论的支持。综述查阅了PUBMED、美国临床试验数据库（ClinicalTrials.gov）、知网等，梳理出近年来TPBC治疗方面的11项随机对照试验结果，为TPBC的辅助强化治疗策略的选择提供临床参考依据。Abstract: Triple-positive breast cancer （TPBC） is a special type of breast cancer characterized by the co-expression of hormone receptors （HR+） and human epidermal growth factor receptor 2 （HER2+）. Due to the regulation of the HR signaling pathway and the HER2 signaling pathway, the treatment strategy for TPBC has been a hot topic of clinical attention. There is currently a lack of systematic theoretical support for the selection of intensive adjuvant therapy for TPBC patients, including sequential or combination therapy, endocrine therapy, and targeted therapy. This review article examines 11 randomized controlled trials on TPBC treatment in recent years, obtained from database such as PUBMED, ClinicalTrials.gov, and CNKI, in order to provide clinical reference for the selection of neoadjuvant therapy strategies for TPBC.
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图 1 ER通路和HER2信号通路之间的串扰机制（1）
图片由Figdraw绘制。
Figure 1. Crosstalk mechanism between ER pathway and HER2 signaling pathway （1）
图 2 ER通路和HER2信号通路之间的串扰机制（2）
图片由Figdraw绘制。
Figure 2. Crosstalk mechanism between ER pathway and HER2 signaling pathway （2）
表 1 TPBC临床研究
Table 1. Clinical Research about TPBC
研究信息 入组人群 入组人数（n） 研究设计 结局 Katherine研究[22]
Ⅲ期试验在曲妥珠单抗进行新辅助化疗后未达到pCR的HER2+患者 1486（其中TPBC有
1074）T-DM1组
曲妥珠单抗组3a DFS率为88.3%VS77.0%，*P < 0.001 ExteNET研究[26]
多中心、随机、双盲
Ⅲ期试验Ⅱ～Ⅲ期、淋巴结阳性、新辅助治疗后未达pCR的HER2+患者 2840（其中TPBC有
1631）曲妥珠单抗辅助治疗后继续使用1 a奈拉替尼
曲妥珠单抗辅助治疗后继续使用1年安慰剂
2 a PFS率为93.9%VS 91.6%，*P = 0.0091
5a PFS率为90.2% VS 87.7%，*P = 0.0083
HR阳性亚组的侵袭性无病生存的HR为0.60（95%CI 0.43～0.83）SYSUCC-002研究[29]
NCT01950182
开放、非劣性、随机
Ⅲ期试验
一线转移性TPBC患者 392 曲妥珠单抗+内分泌治疗组（ET组）
曲妥珠单抗+化疗组（CT组）PFS：ET组为19.2个月，CT组为14.8个月，
*P < 0.0001PERTAIN研究[30]
NCT01491737
随机、双臂、开放、多中心Ⅱ期研究转移性TPBC患者 258 曲妥珠单抗+帕妥珠单抗联合AI
曲妥珠单抗联合AI
PFS：双靶组18.89个月VS单靶组15.80个月，*P =
0.0070
ALTERNATIVE研究[31]
大规模随机对照研究以前接受内分泌治疗、曲妥珠单抗治疗和化疗的转移性TPBC患者 355 曲妥珠单抗+拉帕替尼联合AI（L+T组）
拉帕替尼联合AI（L组）
曲妥珠单抗联合AI（T组）PFS：
L+T组11.0个月 VS L组8.3个月，*P= 0.0063
L组8.3个月VS T组5.7个月， P= 0.3159monarcHER研究[36]
NCT02675231
Ⅱ期试验既往晚期阶段接受过至少二线抗HER2靶向治疗的TPBC局部晚期不可手术或转移性患者 237 阿贝西利+曲妥珠单抗+氟维司群（A组）
阿贝西利+曲妥珠单抗（B组）
曲妥珠单抗+化疗（C组）PFS： A组8.3个月VS C组5.7个月，P= 0.051；B组5.7个月VS C组5.7个月， P= 0.77
OS：A组31.1个月VS C组20.7个月，P= 0.086；B组29.2个月 VS C组20.7个月，P= 0.365TAnDEM研究[40]
NCT00022672
Ⅲ期
曾用他莫昔芬治疗的转移性TPBC 207 阿那曲唑+曲妥珠单抗
阿那曲唑PFS：4.8个月VS 2.4个月，*P= 0.0016 eLEcTRA研究[39]
NCT00171847
Ⅲ期转移性TPBC 57 来曲唑
来曲唑+曲妥珠单抗TTP：3.3个月VS 14.1个月，P= 0.23 SOLTI-1303 PATRICIA
研究[32]
Ⅱ期、开放标签、多中心
研究已使用2-4个抗HER2方案（至少包括曲妥珠单抗）治疗后的HER2+局部晚期或转移性乳腺癌患者 71（其中TPBC有37） 曲妥珠单抗+哌柏西利
曲妥珠单抗+哌柏西利+来曲唑PFS6率：
42.8%（12/28）VS 46.4%（13/28），*P= 0.003NCT02657343[23]
Ib/Ⅱ期临床试验已接受过曲妥珠单抗、帕妥珠单抗和T-DM1作为（新）辅助或转移治疗的HER2+患者 Ⅰ期12（其中TPBC有8） 瑞博西尼+T-DM1
瑞博西尼+曲妥珠单抗
瑞博西尼+曲妥珠单抗+氟维司群仅有Ⅰ期结果：仅1例
（ 8.3 % ）患者病情稳定 > 24周；mPFS = 1.33个月LORDSHIPS研究[33]
NCT03772353
Ⅱ期临床试验
复发或转移的HR+/HER2+晚期乳腺癌 Ⅰ期15 CDK4/6抑制剂达尔西利 + 酪氨酸激酶抑制剂吡咯替尼 + 芳香酶抑制剂来曲唑三药联合方案 总体ORR 66.7 %
经过HER2靶向治疗一线（1L）和二线（2L）ORR：85.7 % VS 50.0 %
总体mPFS 11.3个月，1 L组PFS尚未达到，2 L组PFS为10.9个月*P < 0.05。 
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