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根据NEOSPHERE和TRYPHAENA研究的病理完全缓解增加，2012年美国食品药品管理局批准（注：中国至今尚未批准）帕妥珠单抗用于HER2阳性局部乳腺癌新辅助治疗。这些研究证实THP（多西他赛＋曲妥珠单抗＋帕妥珠单抗）与TH相比、FEC→THP（氟尿嘧啶＋表柔比星＋环磷酰胺→THP）与FEC→TH相比、TCHP（多西他赛＋卡铂＋曲妥珠单抗＋帕妥珠单抗）与TCH相比，病理完全缓解率显著提高。不过，在美国，虽然AC（多柔比星＋环磷酰胺）比FEC更受欢迎，但是缺少AC→THP、AC→TH、TCHP之间的新辅助治疗数据比较。 2018年9月15日，施普林格·自然旗下《乳腺癌研究与治疗》在线发表美国哈佛大学医学院麻省总医院癌症中心的研究报告，对AC→TH±帕妥珠单抗新辅助治疗局部HER2阳性乳腺癌患者的有效性和耐受性进行了比较。 该研究对2011～2016年美国哈佛大学医学院麻省总医院癌症中心（大型学术型医疗机构）和两家附属社区医院121例1～3期HER2阳性乳腺癌患者接受帕妥珠单抗新辅助治疗或剂量密集AC→TH治疗的临床病理特征进行回顾。病理完全缓解定义为术前新辅助治疗后病理检查肿瘤消失或未浸润（ypT0/is）且淋巴结未转移（ypN0）。通过费希尔精确检验和逻辑回归模型，进行统计学分析。 结果发现，有、无帕妥珠单抗的方案相比，病理完全缓解率较高：
THP与其他方案相比，毒性所致周期延迟显著较少（P=0.02）、剂量减少最少、住院率最低、治疗停止率最低。 因此，根据该研究结果，对于HER2阳性局部乳腺癌患者，有帕妥珠单抗的治疗方案（包括THP）与剂量密集AC→TH相比，病理完全缓解率较高，其中THP方案的耐受性最佳。由于新辅助治疗方案不同，需要进一步研究确定最佳治疗顺序和升级或降级策略，对HER2阳性局部乳腺癌的新辅助治疗方案进行个体化。 Breast Cancer Res Treat. 2018 Sep 15. Effectiveness and tolerability of neoadjuvant pertuzumab-containing regimens for HER2-positive localized breast cancer. Laura Spring, Andrzej Niemierko, Stephanie Haddad, Megan Yuen, Amy Comander, Kerry Reynolds, Jennifer Shin, Atul Bahn, Elena Brachtel, Michelle Specht, Barbara L. Smith, Alphonse Taghian, Rachel Jimenez, Jeffrey Peppercorn, Steven J. Isakoff, Beverly Moy, Aditya Bardia. Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA. PURPOSE: Based on improvement in pathologic complete response (pCR) in the NeoSphere and TRYPHAENA studies, the FDA approved neoadjuvant pertuzumab for HER2+ localized breast cancer. These studies demonstrated high pCR rates with THP (docetaxel + HP), FEC (5-fluorouracil, epirubicin, and cyclophosphamide)-THP, and TCHP (docetaxel, carboplatin + HP). However, in the United States, doxorubicin/cyclophosphamide (AC) is favored over FEC despite no data comparing neoadjuvant AC-THP with AC-TH or TCHP. Here we report outcomes for patients with localized HER2+ breast cancer treated with pertuzumab-containing neoadjuvant regimens and AC-TH. METHODS: We reviewed clinicopathological characteristics of patients with HER2+ breast cancer (Stage I-III) treated with either a neoadjuvant pertuzumab-containing regimen or dose-dense (dd) AC-TH, from 2011 to 2016 at a large academic medical institution and two affiliated community sites. pCR was defined as ypT0/is ypN0. Fisher's exact test and logistic regression analysis were used for statistical analysis. RESULTS: In this study (N = 121), pCR was numerically higher with pertuzumab-based regimens, including ddAC-THP (60%), TCHP (63%), THP (55%), as compared with ddAC-TH (46%). THP resulted in significantly less cycle delays due to toxicity compared to the other regimens (p = 0.02). THP also resulted in the least dose reductions, lowest rate of hospitalization, and lowest rate of treatment discontinuation. CONCLUSIONS: Pertuzumab-based regimens, including THP, resulted in higher pCR rates as compared to ddAC-TH, with the THP regimen associated with the best tolerability among patients with localized HER2+ breast cancer. Given the various neoadjuvant regimens, additional studies are needed to determine optimal treatment sequencing and escalation/de-escalation strategies to personalize neoadjuvant regimens for localized HER2+ breast cancer. KEYWORDS: Neoadjuvant HER2 Pathologic complete response Pertuzumab Trastuzumab DOI: 10.1007/s10549-018-4959-8
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