Kawamura Chitose, Bhaskaran Krishnan, Konishi Takaaki, Sagara Yasuaki, Bando Hiroko, Shinozaki Tomohiro, Nojiri Shuko, Adomi Motohiko, Wong Angel Y S, Tamiya Nanako, Iwagami Masao
Department of Health Services Research, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
Department of Digital Health, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.
Breast Cancer. 2025 Aug 27. doi: 10.1007/s12282-025-01769-5.
Breast cancer (BC) survivors may have an increased risk of endometrial cancer due to shared risk factors and tamoxifen use. However, the risk among women in Japan and that for each endocrine therapy regimen remains unknown when comparing BC survivors to women without BC.
We conducted a matched-cohort study using the JMDC claims database, covering company employees and their family members in Japan. Between January 2005 and December 2019, women aged 18-74 years with BC were matched to women without BC in a 1:4 ratio by age and database entry timing. Endometrial cancer risk was compared using stratified Cox regression. In addition, starting the follow-up at one year after matching, we assessed risk by endocrine treatment (tamoxifen, aromatase inhibitor [AI], and no endocrine therapy) using unstratified Cox regression.
Among 23,729 BC survivors and 95,659 matched women (median age, 49.5 years), there were 56 vs 40 endometrial cancer cases (0.73 vs 0.13 cases/1,000 person-years, respectively), with adjusted hazard ratios of 7.71 (95% confidence interval 4.56-13.0). In the analysis by endocrine treatment, tamoxifen (n = 9,183; median 46.3 years), AI (n = 4,582; 58.1 years), and no endocrine therapy (n = 5,763; 49.4 years) cases were 26, 5, and 10 (0.92, 0.43, and 0.61 cases/1,000 person-years, respectively), and the adjusted hazard ratios were 5.67 (3.20-10.0), 2.17 (0.79-5.95), and 3.56 (1.66-7.65), respectively, compared to women without BC.
BC survivors in Japan had an increased risk of endometrial cancer compared to women without BC. The risk was higher in women prescribed tamoxifen and those with no endocrine therapy.
由于存在共同的风险因素以及使用他莫昔芬，乳腺癌（BC）幸存者患子宫内膜癌的风险可能会增加。然而，在将BC幸存者与未患BC的女性进行比较时，日本女性的风险以及每种内分泌治疗方案的风险仍然未知。
我们使用JMDC理赔数据库进行了一项匹配队列研究，该数据库涵盖了日本的公司员工及其家庭成员。在2005年1月至2019年12月期间，将年龄在18 - 74岁的BC女性与未患BC的女性按年龄和数据库录入时间以1:4的比例进行匹配。使用分层Cox回归比较子宫内膜癌风险。此外，在匹配后一年开始随访，我们使用非分层Cox回归按内分泌治疗（他莫昔芬、芳香化酶抑制剂[AI]和无内分泌治疗）评估风险。
在23,729名BC幸存者和95,659名匹配女性（中位年龄49.5岁）中，子宫内膜癌病例分别为56例和40例（分别为0.73例/1000人年和0.13例/1000人年），调整后的风险比为7.71（95%置信区间4.56 - 13.0）。在内分泌治疗分析中，他莫昔芬组（n = 9183；中位年龄46.3岁）、AI组（n = 4582；58.1岁）和无内分泌治疗组（n = 5763；49.4岁）的病例数分别为26例、5例和10例（分别为0.92例/1000人年、0.43例/1000人年和0.61例/1000人年），与未患BC的女性相比，调整后的风险比分别为5.67（3.20 - 10.0）、2.17（0.79 - 5.95）和3.56（1.66 - 7.65）。
与未患BC的女性相比，日本的BC幸存者患子宫内膜癌的风险增加。接受他莫昔芬治疗的女性和未接受内分泌治疗的女性风险更高。
