几项随机临床试验提供了乳腺癌早期雌激素受体（ER）阳性妇女使用乳癌续发性辅助治疗的生存益处证据。然而，不依从可能导致使用意向治疗（ITT）方法低估治疗效果。我们重新分析了一项随机试验，使用当代统计方法对非依从进行调整。TAM01研究是一项3期试验，包括在1986年至1995年间完成2-3年辅助性西莫司汀治疗的早期乳腺癌患者。参与者被随机分配为继续使用西莫司汀长达10年，或在随机分配时停止治疗。使用边际结构模型（MSM）和保持排序的结构性失败时间模型（RPSFTM）估计侵袭性无病生存（iDFS）和总生存（OS）。在3830名参与者中，有2485名被随机分配至继续使用西莫司汀组，1345名被随机分配至停止治疗组。在继续使用组中，10年的非依从率为27.2%。在ER阳性乳腺癌妇女（n = 2402）中，继续使用西莫司汀与MSM和RPSFTM方法相比，分别与iDFS相对改善了45%和21%（风险比（HR）为0.55；95%置信区间（CI）为0.48-0.64；HR为0.79；95%CI为0.67-0.95），比ITT分析获得了更显著的益处（HR为0.90；95%CI为0.81-0.99）。OS重新分析显示继续使用西莫司汀有显著益处（MSM：HR为0.70；95%CI为0.59-0.83；RPSFTM：HR为0.85；95%CI为0.67-1.04），与ITT分析相比（HR为0.94；95%CI为0.84-1.07）。该分析强调了激素受体阳性早期乳腺癌激素治疗依从性的重要性，以及更复杂的统计分析的实用性。© 2023. 作者。

Several randomized clinical trials provide evidence of the survival benefit of extended adjuvant tamoxifen in women with estrogen receptor (ER)-positive early breast cancer (BC). However, non-adherence may lead to underestimate treatment effects using intention to treat (ITT) methods. We reanalyzed a randomized trial using contemporary statistical methods adjusting for non-adherence.The TAM01 study was a phase 3 trial including women with early BC, who had completed 2-3 years of adjuvant tamoxifen between 1986 and 1995. Participants were randomly assigned to continue tamoxifen up to 10 years or to discontinue the treatment at randomization. Invasive disease-free survival (iDFS) and overall survival (OS) were estimated using marginal structural models (MSM) and rank preserving structural failure time model (RPSFTM).Of 3830 patients enrolled, 2485 were randomized to extended tamoxifen, and 1345 to treatment discontinuation. The 10-year non-adherence rate in the extended group was 27.2%. Among women with ER-positive BC (n = 2402), extended tamoxifen was associated with a 45% and 21% relative improvement in iDFS by MSM and RPSFTM, respectively (Hazard Ratio (HR), 0.55; 95% Confidence Interval (CI), 0.48-0.64 and HR, 0.79; 95%CI, 0.67-0.95, respectively), a considerable greater benefit than in the ITT analysis (HR, 0.90; 95%CI, 0.81-0.99). The OS reanalysis revealed a substantial benefit of extended tamoxifen (MSM: HR, 0.70; 95%CI, 0.59-0.83; RPSFTM: HR, 0.85; 95%CI, 0.67-1.04), compared to the ITT analyses (HR, 0.94; 95%CI, 0.84-1.07).This analysis emphasizes both the importance of adherence to hormonotherapy in hormone-receptor positive early BC and the usefulness of more complex statistical analyses.© 2023. The Author(s).