Potkul Ronald K, Unger Joseph M, Livingston Robert B, Crew Katherine D, Wilczynski Sharon P, Salomon Caryl G, Smith Barbara L, Wong Lucas, Campbell David L, Einspahr David E, Anderson Garnet L, Hershman Dawn, Goodman Gary E, Brown Powel H, Meyskens Frank L, Albain Kathy S
Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, IL, USA.
SWOG Statistical Center, Seattle, WA, USA.
NPJ Breast Cancer. 2016 Aug 10;2:16024. doi: 10.1038/npjbcancer.2016.24. eCollection 2016.
The proliferative effect of adjuvant tamoxifen on the endometrium can potentially result in endometrial abnormalities, including cancer in postmenopausal women. We conducted a randomized, controlled trial to assess endometrial pathological diagnoses in postmenopausal women with early stage, ER-positive breast cancer without endometrial pathology at baseline. They were assigned to tamoxifen alone versus tamoxifen plus cyclical medroxyprogesterone acetate (MPA 10 mg for 14 days every 3 months) for 5 years. Endovaginal sonograms (EVS) +/- endometrial biopsies (EMB) were required at baseline, 2 and 5 years. Of 313 patients registered, 296 were eligible and 169 (57%; 89, tamoxifen; 80, tamoxifen+MPA) were evaluable (completed year-2 EVS, with an EMB if stripe width was ⩾5 mm). Sixty (67%) of these in the tamoxifen arm had an endometrial stripe width ⩾5 mm (and underwent subsequent EMB) compared with 48 (60%) in the tamoxifen+MPA arm (=0.40). There were four cases of proliferative endometrium and one simple hyperplasia on the tamoxifen arm (6% (95% confidence interval (CI): 2-13%) among evaluable patients and one proliferative endometrium on the tamoxifen+MPA arm (=0.11). The overall fraction with benign endometrial abnormalities at year 2 was 3.6% (6/169; 95% CI: 1.3-7.6%), with only 1 (of 102) new benign proliferative event at year 5. The event rate in both arms was much lower than projected, making treatment arm comparisons less informative. A normal endometrium prior to tamoxifen may provide reassurance regarding future endometrial events. However, validation in a larger trial is needed before changing practice in asymptomatic, postmenopausal women.
辅助性他莫昔芬对子宫内膜的增殖作用可能会导致子宫内膜异常，包括绝经后女性患癌。我们开展了一项随机对照试验，以评估基线时无子宫内膜病变的绝经后早期雌激素受体（ER）阳性乳腺癌女性的子宫内膜病理诊断情况。她们被分为两组，一组单独使用他莫昔芬，另一组使用他莫昔芬加周期性醋酸甲羟孕酮（每3个月服用10毫克醋酸甲羟孕酮，共14天），为期5年。在基线、第2年和第5年时需要进行经阴道超声检查（EVS）和/或子宫内膜活检（EMB）。在登记的313例患者中，296例符合条件，169例（57%；单独使用他莫昔芬组89例，他莫昔芬加醋酸甲羟孕酮组80例）可进行评估（完成了第2年的EVS检查，若内膜条纹宽度≥5毫米则进行EMB）。单独使用他莫昔芬组中有60例（67%）内膜条纹宽度≥5毫米（随后进行了EMB），而他莫昔芬加醋酸甲羟孕酮组有48例（60%）（P=0.40）。单独使用他莫昔芬组有4例增殖期子宫内膜和1例单纯性增生（在可评估患者中占6%（95%置信区间（CI）：2%-13%）），他莫昔芬加醋酸甲羟孕酮组有1例增殖期子宫内膜（P=0.11）。第2年时良性子宫内膜异常的总体比例为3.6%（169例中有6例；95%CI：1.3%-7.6%），第5年时只有1例（102例中的）新的良性增殖事件。两组的事件发生率均远低于预期，使得治疗组间比较的信息量减少。他莫昔芬治疗前子宫内膜正常可能会让人对未来的子宫内膜事件放心。然而，在改变无症状绝经后女性的治疗方案之前，需要在更大规模的试验中进行验证。
