Sydney Medical School - Westmead, The University of Sydney, Sydney, Australia.
Present Address: South Eastern Sydney Local Health District, and St. George and Sutherland Clinical Schools, UNSW Medicine, Sydney, Australia.
Breast Cancer Res. 2020 Jul 20;22(1):77. doi: 10.1186/s13058-020-01314-6.
For patients with locally advanced estrogen receptor or progesterone receptor-positive breast cancer, neoadjuvant endocrine therapy (NET) facilitates down-staging of the tumor and increased rates of breast-conserving surgery. However, NET remains under-utilized, and there are very limited clinical guidelines governing which therapeutic agent to use, or the optimal duration of treatment in postmenopausal women. This literature review aims to discuss the evidence surrounding (1) biomarkers for patient selection for NET, (2) the optimal neoadjuvant endocrine agent for postmenopausal women with locally advanced breast cancer, and (3) the optimal duration of NET. In addition, we make initial recommendations towards developing a clinical guideline for the prescribing of NET.
A wide-ranging search of online electronic databases was conducted using a truncated PIC search strategy to identify articles that were relevant to these aims and revealed a number of key findings.
Randomized trials have consistently demonstrated that aromatase inhibitors are more effective than tamoxifen, in terms of objective response rate and rate of BCS, and should be used as first-line NET. The three available aromatase inhibitors have so far been demonstrated to be biologically equivalent, with the choice of aromatase inhibitor not having been shown to affect clinical outcomes. There is increasing evidence for extending the duration of NET beyond 3 to 4 months, to at least 6 months or until maximal clinical response is achieved. While on-treatment levels of the proliferation marker Ki67 are predictive of long-term outcome, the choice of adjuvant therapy in patients who have received NET and then surgery is best guided by the preoperative endocrine prognostic index, or PEPI, which incorporates Ki67 with other clinical parameters.
This study reveals that in appropriately selected patients, NET can provide equivalent clinical benefit to neoadjuvant chemotherapy in the same cohort, if suitable treatments and durations are chosen. Our findings highlight the need for better defined biomarkers both for guiding patient selection and for measuring outcomes. Development of standard guidelines for the prescribing of NET has the potential to improve both clinical outcomes and quality of life in this patient cohort.
对于局部晚期雌激素受体或孕激素受体阳性的乳腺癌患者，新辅助内分泌治疗（NET）可使肿瘤降级，并提高保乳手术的比例。然而，NET 的应用仍然不足，而且关于治疗药物的选择，以及绝经后妇女的最佳治疗时间，几乎没有临床指南。本文献综述旨在讨论以下方面的证据：（1）NET 患者选择的生物标志物；（2）局部晚期乳腺癌绝经后妇女最佳的新辅助内分泌药物；（3）NET 的最佳时间。此外，我们对制定 NET 处方临床指南提出了初步建议。
采用截断 PIC 搜索策略，对在线电子数据库进行广泛搜索，以确定与这些目标相关的文章，并揭示了一些关键发现。
随机试验一致表明，在客观缓解率和保乳率方面，芳香化酶抑制剂比他莫昔芬更有效，应作为 NET 的一线药物。目前已证明三种可用的芳香化酶抑制剂在生物学上等效，选择哪种芳香化酶抑制剂不会影响临床结果。越来越多的证据表明，NET 的持续时间应延长至 3 至 4 个月以上，至少 6 个月或直到达到最大临床反应。尽管治疗期间的增殖标志物 Ki67 水平可预测长期预后，但接受 NET 治疗后再手术的患者的辅助治疗选择最好由术前内分泌预后指数（PEPI）指导，该指数将 Ki67 与其他临床参数结合在一起。
本研究表明，在适当选择的患者中，如果选择合适的治疗药物和持续时间，NET 可以与同一队列中的新辅助化疗提供等效的临床获益。我们的研究结果强调了需要更好地定义生物标志物，以指导患者选择和衡量结果。制定 NET 处方的标准指南有可能改善该患者群体的临床结果和生活质量。
