乳腺癌新辅助系统治疗后残留疾病的异质性：综述
Heterogeneity of Residual Disease After Neoadjuvant Systemic Therapy in Breast Cancer: A Review
影响因子:20.10000
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
摘要
在过去的20年中，针对早期乳腺癌的全身疗法逐渐从辅助疗法转移到新辅助环境。手术前的全身疗法给药会导致手术结局的潜在改善，并可以评估对治疗的病理反应。对于残留疾病（RD）的患者，已证明3种辅助策略可以改善预后：（1）用于ERBB2阳性疾病的辅助曲妥珠单抗emtansine，（2）三型生殖疾病的辅助性capecitabine辅助性疾病；此外，研究正在测试神经辅助后环境中的新药物。 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新辅助治疗后针对RD患者的3阶段试验中的救援选择。同时，通过引入残留癌症负担来完善RD的预后作用。此外，已经发现RD的基因组景观与长期预后有关，该疾病的免疫背景也通过存在肿瘤浸润淋巴细胞进行了评估。最后，循环肿瘤DNA的动力学可以通过了解哪些患者具有可检测到的最小RD的患者，从而可以进一步改善预后。提高辅助治疗已导致新辅助治疗后乳腺癌和RD患者的有意义的生存改善。揭示RD的解剖学和生物学复杂性将使在神经辅助治疗后的精度提高，超越了RD与病理完全反应的二进制范式，朝着辅助环境中更量身定制的救援策略。
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.