Risk of Endometrial Cancer and Frequencies of Invasive Endometrial Procedures in Young Breast Cancer Survivors Treated With Tamoxifen: A Nationwide Study

Abstract

BackgroundAlthough the guidelines recommend gynecological assessment and close monitoring for symptoms of endometrial cancer in postmenopausal breast cancer survivors taking tamoxifen (TAM), the risk of endometrial cancer in young breast cancer survivors has not yet been fully assessed. This study aimed to investigate the risk of developing endometrial cancer and the frequencies of gynecological examinations in young breast cancer survivors taking TAM in South Korea.MethodsA nationwide retrospective cohort study was conducted using the Health Insurance Review and Assessment Service claims data. Kaplan–Meier analyses and log-rank tests were used to assess the probability of endometrial cancer, benign endometrial conditions, and the probability of invasive endometrial procedure. To analyze the risk of endometrial cancer and benign endometrial conditions, we used a multivariable Cox proportional hazards regression model.ResultsBetween 2010 and 2015, 60,545 newly diagnosed female breast cancer survivors were included. The total person–years were 256,099 and 140 (0.23%) patients developed endometrial cancer during the study period. In breast cancer survivors aged ≥60 years [hazard ratio (HR), 5.037; 95% confidence interval (CI), 2.185–11.613], 50–59 years (HR, 4.343; 95% CI, 2.122–8.891), and 40–49 years (HR, 2.121; 95% CI, 1.068–4.213), TAM was associated with an increased risk of endometrial cancer. In subjects aged below 40 years, TAM did not significantly increase the risk of endometrial cancer. However, among the TAM subgroups, breast cancer survivors aged below 40 years [1.61 per 1,000 person–years (PY); HR, 12.460; 95% CI, 2.698–57.522] and aged 40–49 years (2.22 per 1,000 PY; HR, 9.667; 95% CI, 4.966–18.819) with TAM-related endometrial diseases showed significantly increased risks of endometrial cancer. Among the TAM subgroup with benign endometrial conditions, the ratios of the frequency of invasive diagnostic procedures to the incidence of endometrial cancer were higher in subjects under 40 than subjects aged 60 or more.ConclusionYoung breast cancer survivors with TAM-related benign endometrial diseases are at a higher risk of developing endometrial cancer. Gynecological surveillance should be tailored to the risk of endometrial cancer in young breast cancer survivors to improve the early detection of endometrial cancer and avoid unnecessary invasive procedures.

Risk of Endometrial Polyps, Hyperplasia, Carcinoma, and Uterine Cancer After Tamoxifen Treatment in Premenopausal Women With Breast Cancer

“…Tamoxifen use was associated with an approximately 4-fold higher risk of developing endometrial cancer, even after controlling for several confounding factors, including age, BMI, diabetes, hypertension, dyslipidemia, PCOS, and GnRH agonist treatment. In this study, the incidence of endometrial cancer was 2.01 cases per 1000 person-years in premenopausal women treated with tamoxifen and was comparable to that of tamoxifen-treated postmenopausal women with breast cancer (1.83/1000 person-years) observed in a previous multiethnic and multicenter cohort study in the US, 16 and the incidence was even higher than that in 17 A meta-analysis conducted 10 years earlier by the Early Breast Cancer…”

“…In this study, the incidence of endometrial cancer was 2.01 cases per 1000 person-years in premenopausal women treated with tamoxifen and was comparable to that of tamoxifen-treated postmenopausal women with breast cancer (1.83/1000 person-years) observed in a previous multiethnic and multicenter cohort study in the US, 16 and the incidence was even higher than that in various age groups (0.26-1.38 cases per 1000 person-years) observed in another population-based cohort study in South Korea. 17 A meta-analysis conducted 10 years earlier by the Early Breast Cancer Trialists’ Collaborative Group included 20 trials (21 457 participants) and reported that 5 years of tamoxifen use was associated with increased incidence of endometrial cancer only in women older than 55 years. 18 Another systematic review conducted around the same time also found that only women older than 50 years who received tamoxifen, and not younger patients, had a higher risk of endometrial cancer than those who did not use tamoxifen.…”

“…The study found that the use of tamoxifen was associated with an increased risk of endometrial cancer among women aged 40 to 49 years (HR, 2.12; 95% CI, 1.07-4.21). 17 However, these studies could not assess the menopausal status of women and did not control for some confounding factors in their analyses, such as BMI, although differences in baseline characteristics were observed between the tamoxifen and control groups. 19 , 20 …”

“…The study found that both older (aged Ն50 years) and younger (aged 40-49 years) patients treated with tamoxifen had a higher risk (HR, 3.74; 95% CI, 1.65-8.48) of endometrial cancer than those who did not use tamoxifen. 20 A recent retrospective cohort study 17 using Health Insurance…”

“…95% CI, 1.07-4.21). 17 However, these studies could not assess the menopausal status of women and did not control for some confounding factors in their analyses, such as BMI, although differences in baseline characteristics were observed between the tamoxifen and control groups. 19,20 Tamoxifen is also associated with endometrial hyperplasia and polyp formation.…”