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大約10%的晚期乳腺癌為激素受體陽性且HER2陽性，對于此類乳腺癌，多年來沒有證據(jù)表明一線治療應(yīng)該首選抗HER2治療＋內(nèi)分泌治療，還是抗HER2治療＋化療。 2022年2月15日，美國癌癥研究協(xié)會《臨床癌癥研究》正式發(fā)表中山大學(xué)腫瘤防治中心畢錫文、史艷俠、徐菲、郭穎、夏雯、洪若曦、蔣逵葵、薛聰、安欣、王樹森、黃嘉佳、袁中玉、中山大學(xué)孫逸仙紀(jì)念醫(yī)院趙健麗、中山大學(xué)附屬第一醫(yī)院林穎、中山大學(xué)附屬汕頭醫(yī)院吳智勇、廣東醫(yī)科大學(xué)附屬醫(yī)院張遠(yuǎn)起、廣州醫(yī)科大學(xué)附屬第二醫(yī)院章樂虹、廣東省婦幼保健院張安秦、廉江市人民醫(yī)院黃恒、中南大學(xué)湘雅醫(yī)學(xué)院附屬?？卺t(yī)院劉新梅的華南乳腺癌臨床研究協(xié)作組（SCBCG）SYSUCC-002研究報告，首次頭對頭比較了曲妥珠單抗＋內(nèi)分泌治療或化療一線治療激素受體陽性HER2陽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 該多中心非盲非劣效隨機(jī)對照三期臨床研究于2013年9月16日～2019年12月28日從9家醫(yī)院入組激素受體陽性HER2陽性晚期乳腺癌患者392例，根據(jù)既往輔助內(nèi)分泌治療和疾病狀態(tài)（復(fù)發(fā)疾病與新發(fā)轉(zhuǎn)移）進(jìn)行分層，按1∶1隨機(jī)分為兩組進(jìn)行一線治療： 
主要終點為無進(jìn)展生存，風(fēng)險比非劣效上限為1.35。對意向治療人群進(jìn)行主要終點和安全性分析。
結(jié)果，中位隨訪30.2個月（四分位15.0～44.7）后，內(nèi)分泌治療組與化療組相比： 中位無進(jìn)展生存：19.2個月比14.8個月（95%置信區(qū)間：16.7～21.7、12.8～16.8；風(fēng)險比：0.88，95%置信區(qū)間：0.71～1.09，非劣效P<0.0001） 中位總生存：33.9個月比32.5個月（95%置信區(qū)間：28.8～39.0、26.0～39.0；風(fēng)險比：0.82，95%置信區(qū)間：0.65～1.04，非劣效P=0.094）
不良事件發(fā)生率：顯著較低
亞組分析表明，無論患者雌孕激素受體是否同時陽性、內(nèi)臟是否轉(zhuǎn)移、既往輔助內(nèi)分泌治療方案、轉(zhuǎn)移數(shù)量、年齡>40歲、無病間隔>24個月，都有利于內(nèi)分泌治療；僅對患者年齡≤40歲、無病間隔≤24個月，有利于化療。
因此，該研究結(jié)果表明，對于激素受體陽性HER2陽性晚期乳腺癌患者，曲妥珠單抗＋內(nèi)分泌治療與曲妥珠單抗＋化療相比，無進(jìn)展生存毫不遜色，不良事件發(fā)生率顯著較低。HER2靶向治療＋內(nèi)分泌治療可取代標(biāo)準(zhǔn)的HER2靶向治療＋化療，作為激素受體陽性HER2陽性晚期乳腺癌患者一線治療的安全、有效、經(jīng)濟(jì)、實用方案。2021年6月，該研究被美國臨床腫瘤學(xué)會第57屆年會邀請進(jìn)行口頭報告。2021年12月，該研究還被第44屆圣安東尼奧乳腺癌大會年度回顧列入晚期乳腺癌一線治療重要研究。 相關(guān)鏈接
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
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