Sung‑Chao Chua,b,c†, Chia‑Jung Hsiehd†, Tso‑Fu Wanga,c, Mun‑Kun Hongb,e, Tang‑Yuan Chub,e,f*
aDepartment of Hematology and Oncology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, bInstitute of Medical Sciences, Tzu Chi University, Hualien, Taiwan, cSchool of Medicine, College of Medicine, Tzu Chi University, Hualien, Taiwan, dDepartment of Public Health, Tzu Chi University, Hualien, Taiwan, eDepartment of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, fCenter for Prevention of Gynecological Cancer, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
†Both authors contributed equally to this work.
Open Access funded by Buddhist Compassion Relief Tzu Chi Foundation
Abstract
Objective: Previous Western studies reported that older (≥50 years) breast cancer survivors with tamoxifen treatment had higher risk of endometrial cancer. This study aims to disclose whether younger (<50 years) tamoxifen‑treated breast cancer patients also had higher risk of endometrial cancer and to examine whether sequenced aromatase inhibitor (AI) use could reduce the risk. Materials and Methods: A population‑based cohort of 39,216 newly diagnosed breast cancer patients was identified from Taiwan National Health Insurance Database from 1999 to 2012. The risk of endometrial cancer in nonusers (n = 14,588), tamoxifen‑only (n = 19,302), and sequenced AI (n = 5326) users was compared with Cox regression analysis and was adjusted with age, diabetes, hypertension,
and chemotherapy. Results: During the 14‑year study period, 133 patients were diagnosed with subsequent endometrial cancers. Compared with nonusers, tamoxifen‑only users had higher risk of endometrial cancer (14‑year incidence 1.7% vs. 0.3%; adjusted hazard ratio [HR] 3.90; 95% confidence interval [CI], 2.37–6.42). This was observed in both older (≥50 years) and younger (40–50 years) age groups. Adjusted HR (95% CI) for the latter was 3.74 (1.65–8.48). This risk persisted after cessation of tamoxifen use. The risk of endometrial cancer was lower in sequenced AI when compared with tamoxifen‑only users (adjusted HR 0.43; 95% CI, 0.25–0.72). Conclusions: Not only patients ≥50 years but also younger (40–49 years) patients with tamoxifen treatment had higher risk of subsequent endometrial cancer in this nation‑wide cohort. We suggest regular gynecologic monitoring not only during active use but also during follow‑up phase. Sequenced AI use may reduce the risk of endometrial cancer in tamoxifen‑treated breast cancer patients.
Keywords: Antiestrogen, Aromatase inhibitor, Breast cancer, Endometrial cancer, Tamoxifen
