新辅助系统治疗后乳腺癌残余病灶的异质性综述
Heterogeneity of Residual Disease After Neoadjuvant Systemic Therapy in Breast Cancer: A Review
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影响因子:20.1
分区:医学1区 Top / 肿瘤学1区
发表日期:2024 Nov 01
作者:
Paolo Tarantino, Gabriel Hortobagyi, Sara M Tolaney, Elizabeth A Mittendorf
DOI:
10.1001/jamaoncol.2024.3679
keywords:
摘要
在过去20年中，早期乳腺癌的系统治疗逐渐从辅助治疗转向新辅助治疗。术前进行系统治疗有望改善手术效果，并可评估治疗的病理反应。对于残余病灶（RD）患者，有三种辅助策略已被证明能改善预后：(1) ERBB2阳性疾病的辅助曲妥珠单抗酰胺（trastuzumab emtansine），(2) 三阴性疾病的辅助卡培他滨（capecitabine），以及(3) 有生殖系BRCA突变的患者的辅助奥拉帕尼（olaparib）。此外，也有研究在新辅助后期探索新药物。鉴于根据术前系统治疗反应定制辅助治疗的潜力，认识新辅助治疗反应的复杂性并超越RD与完全缓解（pCR）二分范式变得愈发重要。三期试验正在评估新抗体药物偶联物、抗ERBB2酪氨酸激酶抑制剂和免疫检查点抑制剂作为RD患者的救援新方案。同时，残余癌症负荷的引入细化了RD的预后作用。RD的基因组特征与长期预后有关，免疫背景（如肿瘤浸润淋巴细胞的存在）也具有预测价值。最后，循环肿瘤DNA（ctDNA）的动态变化可能有助于通过检测微量残余病灶，进一步改善预后评估。提升的辅助治疗已带来乳腺癌伴RD患者的显著存活改善。揭示RD的解剖学和生物学复杂性将促使新辅助后治疗的精准化，超越RD与病理完全缓解的二元范式，推动更个性化的救援策略。
Abstract
Over 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.Novel 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.Escalating 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.