他莫昔芬治疗乳腺癌与子宫内膜癌风险：一项病例对照研究。

Tamoxifen treatment for breast cancer and risk of endometrial cancer: a case-control study.

作者信息

Swerdlow Anthony J, Jones Michael E

机构信息

Section of Epidemiology, Brookes Lawley Building, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.

出版信息

J Natl Cancer Inst. 2005 Mar 2;97(5):375-84. doi: 10.1093/jnci/dji057.

DOI:10.1093/jnci/dji057

PMID:15741574

Abstract

BACKGROUND

Tamoxifen treatment of breast cancer is associated with an increased risk of endometrial cancer, but tamoxifen-related risks of endometrial cancer are unclear in premenopausal women, in long-term users of tamoxifen, and in women for whom several years have passed since ending treatment. We conducted a case-control study in Britain to investigate these risks.

METHODS

We compared treatment information on 813 case patients who had endometrial cancer after their diagnosis for breast cancer and 1067 control patients who had breast cancer but not subsequent endometrial cancer. We assessed risk by conditional logistic regression analysis. All statistical tests were two-sided.

RESULTS

Overall, tamoxifen treatment, compared with no treatment, was associated with an increased risk of endometrial cancer (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.8 to 3.0). Risk increased statistically significantly (P(trend)<.001) with duration of treatment (for > or =5 years of treatment compared with no treatment, OR = 3.6, 95% CI = 2.6 to 4.8). As an indication of background levels of treatment, 16% of control patients received 5 years or more of treatment. Risk of endometrial cancer adjusted for treatment duration did not diminish in follow-up to at least 5 years after the last treatment ended. Risk of endometrial cancer was not associated with the daily dose of tamoxifen and was comparable in pre- and postmenopausal women. Ever treatment with tamoxifen was associated with a much greater risk of Mullerian and mesodermal mixed endometrial tumors (OR = 13.5, 95% CI = 4.1 to 44.5) than of adenocarcinoma (OR = 2.1, 95% CI = 1.6 to 2.7) or clear cell and papillary serous tumors (OR = 3.1, 95% CI = 0.8 to 17.9).

CONCLUSIONS

There is an increasing risk of endometrial cancer associated with longer tamoxifen treatment, extending well beyond 5 years. The increased risk of endometrial cancer associated with tamoxifen treatment should be considered clinically for both premenopausal and postmenopausal women during treatment and for at least 5 years after the last treatment.

摘要

背景

他莫昔芬治疗乳腺癌会增加子宫内膜癌的风险，但在绝经前女性、长期使用他莫昔芬的女性以及停止治疗数年的女性中，与他莫昔芬相关的子宫内膜癌风险尚不清楚。我们在英国开展了一项病例对照研究以调查这些风险。

方法

我们比较了813例乳腺癌确诊后发生子宫内膜癌的病例患者与1067例患有乳腺癌但随后未发生子宫内膜癌的对照患者的治疗信息。我们通过条件逻辑回归分析评估风险。所有统计检验均为双侧检验。

结果

总体而言，与未接受治疗相比，他莫昔芬治疗与子宫内膜癌风险增加相关（比值比[OR]=2.4；95%置信区间[CI]=1.8至3.0）。风险随治疗持续时间呈统计学显著增加（P(趋势)<.001）（与未接受治疗相比，治疗≥5年，OR=3.6，95%CI=2.6至4.8）。作为治疗背景水平的一个指标，16%的对照患者接受了5年或更长时间的治疗。在最后一次治疗结束后至少随访5年期间，经治疗持续时间调整后的子宫内膜癌风险并未降低。子宫内膜癌风险与他莫昔芬的每日剂量无关，在绝经前和绝经后女性中相当。曾经使用他莫昔芬治疗与苗勒管和中胚层混合性子宫内膜肿瘤的风险（OR=13.5，95%CI=4.1至44.5）相比腺癌（OR=2.1，95%CI=1.6至2.7）或透明细胞和乳头状浆液性肿瘤（OR=3.1，95%CI=0.8至17.9）要高得多。