Breast Center, Dept OB&GYN and CCCMunich, LMU University Hospital, Marchioninistrasse 15, 81377, Munich, Germany.
Breast. 2022 Mar;62 Suppl 1(Suppl 1):S12-S16. doi: 10.1016/j.breast.2022.01.006. Epub 2022 Jan 19.
The availability of HER2-targeted therapy has dramatically improved patient outcome in HER2-positive (HER2+) early breast cancer (EBC) as recently demonstrated by the EBCTCTG metaanalysis on trastuzumab in HER2+ EBC: Adding trastuzumab to chemotherapy has reduced recurrence rates and breast-cancer related mortality by a third [1]. Today, neoadjuvant therapy has become standard of care for women with stage II or III tumors as pathological complete response (pCR) status after surgery can be used to individualize adjuvant systemic therapy. pCR is correlated with favorable patient outcome, particularly in hormone receptor (HR) negative HER2+ EBC, as demonstrated by the FDA meta-analysis. Moreover, for patients with non-pCR, 14 cycles of adjuvant T-DM1 have become a new adjuvant therapy standard based on the results of the KATHERINE trial. Primary surgery can be offered to patients with low tumor burden (cN0 cT1). For this low-risk subgroup, 12 weeks of adjuvant paclitaxel + trastuzumab for one year are correlated with excellent outcome based on the APT trial results. A multidisciplinary team is essential right from the beginning for optimal locoregional and systemic therapy in such a complex neoadjuvant - adjuvant continuum of care. Clinical trials in HER2+ EBC are currently evaluating further therapy de-escalation in low-risk disease or patients with pCR whereas for patients with non-pCR, escalation trials are also ongoing. Newly approved drugs for HER2+ MBC like tucatinib or trastuzumab-deruxtecan or even immunotherapy combinations are being evaluated to improve upon efficacy of T-DM1 alone in the non-pCR setting. Regarding de-escalation, the WSG ADAPT trial demonstrated feasibility of avoiding overtreatment and individualizing neoadjuvant therapy without compromising outcome. Further de-escalation trials (e.g. DECRESCENDO, COMPASS-HER2) are currently ongoing.
曲妥珠单抗在 HER2+早期乳腺癌（EBC）中的应用：EBCTCG 荟萃分析的最新结果显示，HER2 靶向治疗的出现显著改善了 HER2 阳性（HER2+）EBC 患者的预后：曲妥珠单抗联合化疗可降低复发率和乳腺癌相关死亡率三分之一[1]。如今，新辅助治疗已成为 II 期或 III 期肿瘤患者的标准治疗方案，因为手术后的病理完全缓解（pCR）状态可用于个体化辅助全身治疗。pCR 与患者的良好预后相关，尤其是在 HR 阴性 HER2+EBC 中，这一结果已被 FDA 荟萃分析证实。此外，对于非 pCR 患者，基于 KATHERINE 试验结果，14 周期的辅助 T-DM1 已成为一种新的辅助治疗标准。对于肿瘤负荷低（cN0 cT1）的患者可选择进行原发灶手术。对于这一低危亚组，根据 APT 试验结果，12 周的辅助紫杉醇+曲妥珠单抗治疗一年与良好的预后相关。对于如此复杂的新辅助-辅助治疗连续体，从一开始就需要多学科团队为最佳局部和全身治疗提供支持。目前，HER2+EBC 的临床试验正在评估低危疾病或 pCR 患者的进一步降阶梯治疗，而对于非 pCR 患者，也在进行升阶梯试验。新批准的用于 HER2+MBC 的药物，如 tucatinib 或 trastuzumab-deruxtecan，甚至免疫治疗联合用药，正在评估中，以期在非 pCR 情况下提高 T-DM1 的疗效。关于降阶梯治疗，WSG ADAPT 试验证明了避免过度治疗和个体化新辅助治疗的可行性，而不会影响预后。进一步的降阶梯试验（如 DECRESCENDO、COMPASS-HER2）正在进行中。
