在内分泌治疗中添加细胞周期蛋白依赖性激酶 4 和 6 抑制剂对分子降期的影响仍不确定。从高风险复发评分 (RS) 组切换到低风险复发评分 (RS) 组可以提供有用的信息来识别可能不需要化疗的患者。本研究的目的是评估来曲唑联合哌柏西利作为新辅助治疗对初始 Oncotype DX 的激素受体 (HR) 阳性/人表皮生长因子受体 2 (HER2) 阴性早期乳腺癌患者的生物学和临床活性RS ≥18。参与者是年龄≥18 岁、HR 阳性/HER2 阴性、Ki67 ≥ 20%、基线 RS ≥18 的 II-IIIB 期早期乳腺癌女性。符合条件的预治疗 RS 18-25（A 组）和 26-100（B 组）患者接受 6 个周期的 28 天来曲唑（每天 2.5 毫克；如果绝经前或围绝经期则加戈舍瑞林）加哌柏西利（每天 125 毫克） ; 3/1 时间表）手术前。两个队列的主要终点是手术时达到 RS ≤ 25 或病理完全缓解 (pCR) 的患者比例。总共入组 67 名患者，其中 65 名可评估主要终点（队列中 32 名患者A 组和 B 组中的 33 名）。手术时，队列 A 中的 22 名患者 (68.8%) 和队列 B 中的 18 名患者 (54.5%) 的 RS ≤ 25 或 pCR [队列 B 中只有 1 名患者 (3.0%)]，满足队列 B 中的主要终点（P < 0.01），但不在队列 A 中（P = 0.98）。未发现新的安全信号。对于 RS ≥ 18 的患者，来曲唑联合哌柏西利新辅助治疗的疗效似乎并不依赖于治疗前的 RS。然而，基线 RS 26-100 的 HR 阳性/HER2 阴性早期乳腺癌患者中约有一半通过此方案实现了分子降期。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

The effect of the addition of cyclin-dependent kinases 4 and 6 inhibitors to endocrine therapy in terms of molecular downstaging remains undetermined. Switching from a high-risk to a low risk Recurrence Score (RS) group could provide useful information to identify patients who might not require chemotherapy. The purpose of this study was to assess the biological and clinical activity of letrozole plus palbociclib as neoadjuvant treatment for patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with an initial Oncotype DX RS ≥18.Participants were women aged ≥18 years with HR-positive/HER2-negative, Ki67 ≥ 20%, stage II-IIIB early breast cancer with a baseline RS ≥18. Eligible patients with a pretreatment RS 18-25 (cohort A) and 26-100 (cohort B) received six 28-day cycles of letrozole (2.5 mg per day; plus goserelin if pre- or perimenopausal) plus palbociclib (125 mg per day; 3/1 schedule) before surgery. The primary endpoint for both cohorts was the proportion of patients who achieved an RS ≤25 at surgery or a pathological complete response (pCR).A total of 67 patients were enrolled, among which 65 were assessable for the primary endpoint (32 patients in cohort A and 33 in cohort B). At surgery, 22 (68.8%) patients in cohort A and 18 (54.5%) patients in cohort B had an RS ≤25 or a pCR [only 1 (3.0%) patient in cohort B], meeting the primary endpoint in cohort B (P < 0.01), but not in cohort A (P = 0.98). No new safety signals were identified.The efficacy of neoadjuvant treatment with letrozole plus palbociclib does not seem to depend on pretreatment RS for patients with RS ≥18. However, around half of patients with HR-positive/HER2-negative early breast cancer with an RS 26-100 at baseline achieved molecular downstaging with this regimen.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.