Hoogendoorn Wilhelmina E, Hollema Harry, van Boven Hester H, Bergman Elisabeth, de Leeuw-Mantel Geri, Platteel Inge, Fles Renske, Nederlof Petra M, Mourits Marian J E, van Leeuwen Flora E
Department of Epidemiology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Breast Cancer Res Treat. 2008 Nov;112(1):99-108. doi: 10.1007/s10549-007-9823-1. Epub 2007 Dec 7.
Tamoxifen increases the risk of uterine corpus cancer. Since only few, mostly small, studies have examined prognosis of uterine corpus cancer following tamoxifen, we conducted a large retrospective cohort study to further investigate this. We examined histopathologic and immunohistochemical characteristics of 332 patients with uterine corpus cancer following breast cancer, according to tamoxifen use. Survival was examined in the same patients combined with 309 patients from a previous study with updated follow-up. Histological review of all cancers was performed. Long-term tamoxifen users showed a higher proportion of non-endometrioid tumors than non-users (32.7% vs. 17.4%, P=0.004), especially serous adenocarcinomas and carcinosarcomas. An increased proportion of FIGO stage III and IV tumors was also observed (20.0% vs. 11.3%, P=0.049). Within FIGO stage I, both short-term and long-term tamoxifen users showed a higher proportion of tumors limited to the endometrium than non-users (35.7% vs. 22.9%, P=0.049 and 0.004 respectively). Uterine corpus cancers in long-term tamoxifen users were more often steroid receptor-negative (ERalpha, PRA and PRB, P<0.05) and P53-positive (P=0.015). Three-year uterine corpus cancer-specific survival was worse for long-term tamoxifen users than for non-users (82% vs. 93% P=0.0001). The survival difference remained after adjustment for histopathologic and immunohistochemical characteristics (hazard ratio (HR) for >or=2 years tamoxifen=2.4; 95% CI=1.2-4.6). In conclusion, this large study clearly shows that tamoxifen-associated tumors have less favorable histological features and a worse survival. Our results can be applied when weighing risks and benefits of tamoxifen versus other hormonal agents used in the prevention and treatment of breast cancer.
他莫昔芬会增加子宫体癌的风险。由于仅有少数（大多为小型）研究探讨过他莫昔芬治疗后子宫体癌的预后情况，我们开展了一项大型回顾性队列研究以进一步对此进行调查。我们根据他莫昔芬的使用情况，检查了332例乳腺癌后发生子宫体癌患者的组织病理学和免疫组化特征。对这些患者以及之前一项研究中的309例患者进行了更新随访，并检查了其生存率。对所有癌症进行了组织学复查。长期使用他莫昔芬的患者中，非子宫内膜样肿瘤的比例高于未使用者（32.7% 对 17.4%，P = 0.004），尤其是浆液性腺癌和癌肉瘤。FIGO III期和IV期肿瘤的比例也有所增加（20.0% 对 11.3%，P = 0.049）。在FIGO I期内，短期和长期使用他莫昔芬的患者中，局限于子宫内膜的肿瘤比例均高于未使用者（分别为35.7% 对 22.9%，P = 0.049和0.004）。长期使用他莫昔芬患者的子宫体癌更常出现类固醇受体阴性（雌激素受体α、孕激素受体A和孕激素受体B，P < 0.05）和P53阳性（P = 0.015）。长期使用他莫昔芬的患者三年子宫体癌特异性生存率低于未使用者（82% 对 93%，P = 0.0001）。在对组织病理学和免疫组化特征进行调整后，生存差异依然存在（使用他莫昔芬≥2年的风险比（HR）= 2.4；95%置信区间= 1.2 - 4.6）。总之，这项大型研究清楚地表明，与他莫昔芬相关的肿瘤具有不太有利的组织学特征和更差的生存率。在权衡他莫昔芬与用于预防和治疗乳腺癌的其他激素药物的风险和益处时，我们的结果可以作为参考。
