Department of Obstetrics and Gynecology, Korea University Anam Hospital, Korea University College of Medicine, Seongbuk-gu, Seoul, Republic of Korea.
Department of Biostatistics, Korea University Anam Hospital, Korea University College of Medicine, Seongbuk-gu, Seoul, Republic of Korea.
JAMA Netw Open. 2022 Nov 1;5(11):e2243951. doi: 10.1001/jamanetworkopen.2022.43951.
The association of tamoxifen use with the risk of uterine diseases, such as endometrial cancer, in premenopausal women with breast cancer remains controversial. However, many studies have reported an increased risk of uterine disease among postmenopausal tamoxifen users.
To investigate the association of tamoxifen use with the risk of endometrial cancer and other uterine diseases in premenopausal women with breast cancer.
DESIGN, SETTING, AND PARTICIPANTS: A nationwide, population-based, retrospective longitudinal cohort study with an 18-year study period was conducted using data obtained from the Korean National Health Insurance Service. Participants included premenopausal women aged 20 to 50 years with breast cancer diagnoses between January 2003 and December 2018. Data were analyzed from April to December 2021.
Tamoxifen treatment.
The incidence of uterine diseases, including endometrial cancer, hyperplasia, polyps, and other uterine cancers, was identified in the study cohort using insurance claim codes. The incidence of uterine diseases per 1000 person-years was compared between women receiving tamoxifen and those not treated with adjuvant hormone therapy. Multivariable Cox proportional hazard regression analysis was performed to determine the risk of each uterine disease.
Among 78 320 female participants with a mean (SD) age of 42.1 (6.1) years, 34 637 (44.2%) were categorized into the tamoxifen group and 43 683 (55.8%) were categorized into the control group. Among tamoxifen users, during the mean (SD) follow-up duration of 6.13 (4.15) years, the incidence of newly diagnosed endometrial polyps was 20.13 cases per 1000 person-years, that of endometrial hyperplasia was 13.49 cases per 1000 person-years, that of endometrial cancer was 2.01 cases per 1000 person-years, and that of other uterine cancers was 0.45 cases per 1000 person-years. The risk of endometrial cancer was higher in the tamoxifen group than in the control group (hazard ratio, 3.77; 95% CI, 3.04-4.66) after adjusting for age, body mass index, history of diabetes, hypertension, dyslipidemia, polycystic ovary syndrome, gonadotropin-releasing hormone agonist treatment, and trastuzumab treatment.
In this longitudinal cohort study, premenopausal Korean women with breast cancer who received tamoxifen as adjuvant hormone therapy had a significantly increased risk of endometrial hyperplasia, polyps, carcinoma, and other uterine cancers compared with those who were not treated with adjuvant hormone therapy. These findings suggest that clinicians should consider the risk of uterine disease among tamoxifen users, including premenopausal women.
在患有乳腺癌的绝经前妇女中，他莫昔芬的使用与子宫疾病（如子宫内膜癌）的风险之间的关联仍存在争议。然而，许多研究报告称，绝经后使用他莫昔芬的妇女患子宫疾病的风险增加。
研究他莫昔芬的使用与患有乳腺癌的绝经前妇女的子宫内膜癌和其他子宫疾病的风险之间的关联。
设计、地点和参与者：这是一项全国性的、基于人群的、回顾性的纵向队列研究，使用韩国国家健康保险服务的数据，研究期间为 18 年。参与者包括年龄在 20 岁至 50 岁之间、2003 年 1 月至 2018 年 12 月期间诊断患有乳腺癌的绝经前妇女。数据于 2021 年 4 月至 12 月进行分析。
他莫昔芬治疗。
使用保险索赔代码在研究队列中确定了子宫疾病（包括子宫内膜癌、增生、息肉和其他子宫癌）的发病率。比较了接受他莫昔芬治疗和未接受辅助激素治疗的女性每 1000 人年的子宫疾病发病率。采用多变量 Cox 比例风险回归分析确定每种子宫疾病的风险。
在 78320 名平均（标准差）年龄为 42.1（6.1）岁的女性参与者中，34637 名（44.2%）被归入他莫昔芬组，43683 名（55.8%）被归入对照组。在他莫昔芬使用者中，在平均（标准差）6.13（4.15）年的随访期间，新诊断的子宫内膜息肉的发病率为每 1000 人年 20.13 例，子宫内膜增生的发病率为每 1000 人年 13.49 例，子宫内膜癌的发病率为每 1000 人年 2.01 例，其他子宫癌的发病率为每 1000 人年 0.45 例。调整年龄、体重指数、糖尿病、高血压、血脂异常、多囊卵巢综合征、促性腺激素释放激素激动剂治疗和曲妥珠单抗治疗后，他莫昔芬组子宫内膜癌的风险高于对照组（风险比，3.77；95%CI，3.04-4.66）。
在这项纵向队列研究中，与未接受辅助激素治疗的患者相比，接受他莫昔芬作为辅助激素治疗的患有乳腺癌的绝经前韩国女性发生子宫内膜增生、息肉、癌和其他子宫癌的风险显著增加。这些发现表明，临床医生应考虑到包括绝经前妇女在内的他莫昔芬使用者的子宫疾病风险。
