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疾病的异质性


重要性在过去的20年里，早期乳腺癌的全身治疗已逐渐从辅助治疗转向新辅助治疗。手术前进行全身治疗可能会改善手术结果，并可以评估对治疗的病理反应。对于残留病灶 (RD) 的患者，3 种辅助策略已被证明可以改善预后：(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，(3) 奥拉帕尼辅助治疗患者具有种系 BRCA 变异。此外，研究正在新辅助治疗后测试新药。鉴于根据对术前全身治疗的反应定制辅助治疗的潜力，认识到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有必要。 -ERBB2酪氨酸激酶抑制剂和免疫检查点抑制剂正在3期试验中作为新辅助治疗后RD患者的额外救援选择进行评估。与此同时，通过引入残余癌症负担，RD 的预后作用得到了改善。此外，RD 的基因组景观被发现与长期预后相关，通过肿瘤浸润淋巴细胞的存在评估该疾病的免疫背景也是如此。最后，循环肿瘤 DNA 的动态可以通过了解哪些患者具有可检测到的最小 RD 来进一步改善预后。结论和相关性在新辅助治疗后，逐步升级的辅助治疗可以显着改善乳腺癌和 RD 患者的生存率。揭示 RD 的解剖学和生物学复杂性将有助于提高新辅助治疗后的精确度，超越 RD 与病理完全反应的二元范式，在辅助环境中采取更有针对性的救援策略。