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乳腺癌新辅助全身治疗后残留病灶的异质性:综述

英文原题:Heterogeneity of Residual Disease After Neoadjuvant Systemic Therapy in Breast Cancer: A Review.

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Heterogeneity of Residual Disease After Neoadjuvant Systemic Therapy in Breast Cancer: A Review.

PubMed 2024/11/01(内容时间) JAMA Oncol Q1 · IF 23.9(JCR 2025)

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研究概要

对于新辅助治疗后仍有 RD 的乳腺癌患者,强化辅助治疗已带来有意义的生存改善。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治疗的精准性,超越 RD 与病理完全缓解的二元范式,转向辅助治疗中更有针对性的挽救策略。

研究思路结论见上方概要

在过去20年中,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。术前给予全身治疗可能改善手术结局,并允许评估对治疗的病理学反应。对于有残留病灶(RD)的患者,3种辅助策略已被证明可改善结局:(1)ERBB2阳性疾病使用辅助恩美曲妥珠单抗,(2)三阴性疾病使用辅助卡培他滨,(3)胚系BRCA变异患者使用辅助奥拉帕利。此外,研究正在新辅助后环境中测试新型药物。鉴于根据术前全身治疗反应来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与达到病理学完全缓解这一二元范式,正变得越来越必要。观察: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3期试验中作为新辅助治疗后RD患者的额外挽救选择进行评估。与此同时,随着残留癌症负荷的引入,RD的预后作用已被进一步细化。此外,已发现RD的基因组景观与长期预后相关,通过TIL(肿瘤浸润淋巴细胞)的存在所评估的疾病免疫背景也是如此。最后,循环肿瘤DNA的动态变化可能通过识别哪些患者存在可检测的微小RD,进一步改善预后判断。

展开英文摘要原文

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. OBSERVATIONS: 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.

论文信息

作者
Tarantino P、Hortobagyi G、Tolaney SM、Mittendorf EA
第一作者单位
Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.United States
通讯作者单位
Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, Massachusetts.United States
文献类型
综述
期刊
JAMA oncology2024 Nov 1
原文标识
PubMed 39264638 · DOI 10.1001/jamaoncol.2024.3679