ImportanceOver the past 2 decades, systemic therapy for early-stage breast cancer has gradually moved from the adjuvant to the neoadjuvant setting. Administration of systemic therapy before surgery leads to potential improvements in surgical outcomes and allows for the assessment of the pathologic response to treatment. For patients with residual disease (RD), 3 adjuvant strategies have been shown to improve outcomes: (1) adjuvant trastuzumab emtansine for ERBB2-positive disease, (2) adjuvant capecitabine for triple-negative disease, and (3) adjuvant olaparib for patients with germline BRCA variants. Furthermore, studies are testing novel drugs in the postneoadjuvant setting. Given the potential to tailor adjuvant therapy based on the response to preoperative systemic therapy, recognizing the complexities of response to neoadjuvant therapy and moving beyond the binary paradigm of RD vs experiencing a pathologic complete response is becoming increasingly necessary.ObservationsNovel antibody-drug conjugates, anti-ERBB2 tyrosine kinase inhibitors, and immune checkpoint inhibitors are being evaluated as additional rescue options in phase 3 trials for patients with RD after neoadjuvant treatment. Concomitantly, the prognostic role of RD has been refined by the introduction of the residual cancer burden. In addition, the genomic landscape of RD has been found to be associated with long-term prognosis, as has the immune background of the disease evaluated via the presence of tumor-infiltrating lymphocytes. Lastly, the dynamics of circulating tumor DNA may allow for further improvement in prognostication by understanding which patients harbor detectable minimal RD.Conclusions and RelevanceEscalating adjuvant treatment has led to meaningful survival improvements among patients with breast cancer and RD after neoadjuvant therapy. Uncovering the anatomic and biological intricacies of RD will allow for increased precision in postneoadjuvant treatments, moving beyond the binary paradigm of RD vs pathologic complete response, toward more tailored rescue strategies in the adjuvant setting.

中文翻译：

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乳腺癌新辅助全身治疗后残留病灶的异质性


重要性在过去的 2 年里，早期乳腺癌的全身治疗逐渐从辅助治疗转向新辅助治疗。手术前进行全身治疗可导致手术结局的潜在改善，并允许评估对治疗的病理反应。对于残留病灶 （RD） 患者，3 种辅助策略已被证明可以改善结局：（1） 曲妥珠单抗 emtansine 辅助治疗 ERBB2 阳性疾病，（2） 卡培他滨辅助治疗三阴性疾病，以及 （3） 奥拉帕尼辅助治疗种系 BRCA 变异患者。此外，研究正在新辅助治疗后测试新药。鉴于有可能根据对术前全身治疗的反应来定制辅助治疗，认识到对新辅助治疗反应的复杂性并超越 RD 与经历病理完全反应的二元范式变得越来越必要。观察结果新型抗体-药物偶联物、抗 ERBB2 酪氨酸激酶抑制剂和免疫检查点抑制剂正在新辅助治疗后 RD 患者的 3 期试验中作为额外的拯救选择进行评估。同时，RD 的预后作用也通过引入残余癌症负担而得到完善。此外，已发现 RD 的基因组景观与长期预后相关，通过肿瘤浸润淋巴细胞的存在评估疾病的免疫背景也是如此。最后，循环肿瘤 DNA 的动力学可能通过了解哪些患者携带可检测到的轻微 RD 来进一步改善预后。结论和相关性不断升级的辅助治疗导致新辅助治疗后乳腺癌和 RD 患者的生存率显著改善。揭示 RD 的解剖学和生物学复杂性将提高新辅助治疗的精确性，超越 RD 与病理完全反应的二元范式，在辅助治疗中转向更有针对性的挽救策略。