大约10%的晚期乳腺癌为激素受体阳性且HER2阳性，对于此类乳腺癌，多年来没有证据表明一线治疗应该首选抗HER2治疗＋内分泌治疗，还是抗HER2治疗＋化疗。
2022年2月15日，美国癌症研究协会《临床癌症研究》正式发表中山大学肿瘤防治中心毕锡文、史艳侠、徐菲、郭颖、夏雯、洪若曦、蒋逵葵、薛聪、安欣、王树森、黄嘉佳、袁中玉、中山大学孙逸仙纪念医院赵健丽、中山大学附属第一医院林颖、中山大学附属汕头医院吴智勇、广东医科大学附属医院张远起、广州医科大学附属第二医院章乐虹、广东省妇幼保健院张安秦、廉江市人民医院黄恒、中南大学湘雅医学院附属海口医院刘新梅的华南乳腺癌临床研究协作组（SCBCG）SYSUCC-002研究报告，首次头对头比较了曲妥珠单抗＋内分泌治疗或化疗一线治疗激素受体阳性HER2阳性晚期乳腺癌的有效性和安全性。
SYSUCC-002 (NCT01950182): A Multicentre, Randomized Study of Trastuzumab Combined With Chemotherapy or Endocrine Therapy as the First Line Treatment for Patients With Metastatic Luminal B2 Breast Cancer Subtype 该多中心非盲非劣效随机对照三期临床研究于2013年9月16日～2019年12月28日从9家医院入组激素受体阳性HER2阳性晚期乳腺癌患者392例，根据既往辅助内分泌治疗和疾病状态（复发疾病与新发转移）进行分层，按1∶1随机分为两组进行一线治疗：
主要终点为无进展生存，风险比非劣效上限为1.35。对意向治疗人群进行主要终点和安全性分析。
结果，中位随访30.2个月（四分位15.0～44.7）后，内分泌治疗组与化疗组相比：
亚组分析表明，无论患者雌孕激素受体是否同时阳性、内脏是否转移、既往辅助内分泌治疗方案、转移数量、年龄>40岁、无病间隔>24个月，都有利于内分泌治疗；仅对患者年龄≤40岁、无病间隔≤24个月，有利于化疗。
因此，该研究结果表明，对于激素受体阳性HER2阳性晚期乳腺癌患者，曲妥珠单抗＋内分泌治疗与曲妥珠单抗＋化疗相比，无进展生存毫不逊色，不良事件发生率显著较低。HER2靶向治疗＋内分泌治疗可取代标准的HER2靶向治疗＋化疗，作为激素受体阳性HER2阳性晚期乳腺癌患者一线治疗的安全、有效、经济、实用方案。2021年6月，该研究被美国临床肿瘤学会第57届年会邀请进行口头报告。2021年12月，该研究还被第44届圣安东尼奥乳腺癌大会年度回顾列入晚期乳腺癌一线治疗重要研究。
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Clin Cancer Res. 2022 Feb 15;28(4):637-645.Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002).Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY; South China Breast Cancer Group (SCBCG).Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; Affiliated Shantou Hospital, Sun Yat-sen University, Shantou, China; Affiliated Hospital of Guangdong Medical College, Zhanjiang, China; The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Maternal and Child Health Care Hospital of Guangdong Province, Guangzhou, China; Lianjiang Pepole's Hospital, Lianjiang, China; Haikou People's Hospital, Haikou, China.PURPOSE: There is no research evidence demonstrate which is the better partner strategy, endocrine therapy or chemotherapy, to combine with anti-HER2 therapy as the first-line management of hormone receptor (HR)-positive (HR ) and HER2-positive (HER2 ) metastatic breast cancer (MBC). We wished to ascertain if trastuzumab plus endocrine therapy is noninferior to trastuzumab plus chemotherapy.PATIENTS AND METHODS: We conducted an open-label, noninferiority, phase III, randomized, controlled trial (NCT01950182) at nine hospitals in China. Participants, stratified by previous adjuvant endocrine therapy and disease status (recurrent disease vs. de novo metastasis), were assigned randomly (1:1) to receive trastuzumab plus endocrine therapy (per investigator's choice of oestrogen-receptor modulators or aromatase inhibitor, with/without concurrent ovarian suppression) or chemotherapy (per investigator's choice of taxanes, capecitabine, or vinorelbine). The primary endpoint was progression-free survival (PFS) with a noninferiority upper margin of 1.35 for the HR. The intention-to-treat population was used in primary and safety analyses.RESULTS: A total of 392 patients were enrolled and assigned randomly to receive trastuzumab plus endocrine therapy (ET group, n = 196) or trastuzumab plus chemotherapy (CT group, n = 196). After a median follow-up of 30.2 months [interquartile range (IQR) 15.0-44.7], the median PFS was 19.2 months [95% confidence interval (CI), 16.7-21.7)] in the ET group and 14.8 months (12.8-16.8) in the CT group (hazard ratio, 0.88; 95% CI, 0.71-1.09; Pnoninferiority < 0.0001). A significantly higher prevalence of toxicity was observed in the CT group compared with the ET group.CONCLUSIONS: Trastuzumab plus endocrine therapy was noninferior to trastuzumab plus chemotherapy in patients with HR HER2 MBC.TRANSLATIONAL RELEVANCE: Hormone receptor (HR)-positive (HR ) and HER2-positive (HER2 ) account for approximately 10% of all metastatic breast cancer (MBC). Over the years, there are no evidence that showed which first-line regimens were preferred, either anti-HER2 therapy plus endocrine therapy or chemotherapy for HR HER2 MBC. This is the first randomized, phase III study to compare, in a head-to-head manner, the efficacy and safety of trastuzumab combined with endocrine therapy or with chemotherapy as first-line treatment for HR HER2 MBC. The final analysis showed that trastuzumab plus endocrine therapy was noninferior to trastuzumab plus chemotherapy in patients with HR HER2 MBC. HER2-targeted therapy combined with endocrine therapy could be an alternative to standard HER2-targeted therapy combined with chemotherapy— the priority principle of endocrine therapy is also applicable to patients with HR HER2 MBC.DOI: 10.1158/1078-0432.CCR-21-3435
