J Menopausal Med.  2021 Dec;27(3):s13-s14.

Breast cancer and menopausal hormone therapy: Health Insurance Database in South Korea (HISK)

• Kim TR
• Yuk JS
• Gwak 2 G

Abstract

Objective
The purpose of this study is to determine the risk of breast cancer on women at menopause from postmenopausal hormone therapy using Korea's national health checkup and insurance data. Method: Using the national health checkup and insurance data provided by the National Health Insurance Service (NHIS), we selected women who were over 40 years and confirmed to have menopause during the interview from 2003 to 2011. These women were followed up for breast cancer until December 31, 2019. The control group was defined as women who never used hormone drug during from 2003 to 2019, and the Menopausal Hormone Therapy (MHT) group was defined as women who used menopausal hormone drug for over 6 months. Menopausal hormone drugs were classified tibolone, combined estrogen plus progestin by manufacture (CEPM) (Estradiol Hemihydrate/Drospirenone, Estradiol Hemihydrate/Drospirenone, Estradiol Hemihydrate/Norethisterone Acetate, Cyproterone Acetate/Estradiol Valerate, Estradiol Hemihydrate/Norethisterone Acetate, Estradiol Valerate/Norethisterone Acetate), estrogen (Conjugated Estrogens, Estradiol Valerate, Estradiol Hemihydrate), combined estrogen plus progestin by physician (CEPP) (Estrogen + Progesterone Micronized, Medroxyprogesterone Acetate, Dydrogesterone), Topical estrogen (Estradiol Hemihydrate patch or gel). The variables that may affect breast cancer were adjusted, such as age, body mass index, socioeconomic status, region, Charlson Comorbidity Index, parity, age at menarche, age at menopause, smoking, alcohol, physical exercise, period from menopause to inclusion time.
Results
The control group, the tibolone group, CEPM group, the oral estrogen group, CEPP group, and the topical estrogen group were 920,783, 165,222, 107,088, 45,609, 5,633, and 1,729, respectively. In the Cox proportional hazard analysis with adjusted variables, the risk of breast cancer increased in CEPM group. {Hazard ratio [HR] 1.439, 95% confidence interval (CI) 1.374-1.507} However, there were no increase in the risk of breast cancer in the tibolone group, oral estrogen group, CEPP group and the topical estrogen group. (HR 0.968, 95% CI 0.925-1.012) (HR 1.002, 95% CI 0.929-1.081) (HR 0.929, 95% CI 0.75-1.15) (HR 1.139, 95% CI 0.809-1.603) There was no difference in the risk of breast cancer even with doubling the amount of tibolone used. (Over 5 mg: HR 1.306, 95% CI 0.326-5.226) The risk of breast cancer was lower in those in their 50s and 60s than in their 40s. (50s: HR 0.956, 95% CI 0.906-1.008) (60s: HR 0.846, 95% CI 0.776-0.922) As BMI increased, the risk of breast cancer increased. (25-29.9: HR 1.126, 95% CI 1.085-1.169) (30 or more: HR 1.356, 95% CI 1.258-1.462) There was an increased risk of breast cancer when menstrual age was 13 years or older. (HR 1.157, 95% CI 1.109-1.419) A history of smoking increased the risk of breast cancer (HR 1.254, 95% CI 1.109-1.419), and drinking history was not associated with breast cancer. Also, as the inclusion period from menopause increased, the risk of breast cancer decreased. (5-9 years: HR 0.918, 95% CI 0.879-0.959) (10 years or more: HR 0.846, 95% CI 0.791-0.904)
Conclusion
CEPM increased the risk of breast cancer. However, tibolone, oral estrogen, CEPP, and topical estrogen were not associated with breast cancer. The risk of breast cancer did not differ depending on the dose of tibolone.