Western studies reveal older ( >50 years) breast cancer survivors with tamoxifen treatment had higher risk of endometrial cancer. The purpose of the study is to disclose whether sequenced aromatase inhibitor (AI) use could reduce the incidence of endometrial cancer in tamoxifen-treated breast cancer patients.
A population-based cohort of 40740 newly diagnosed breast cancer patients with and without antiestrogen therapy were identified from the Taiwan National Health Insurance Database from 1999 to 2012. Endometrial cancer risk was compared with Cox regression analysis with competing risk analysis by the Fine and Gray method, and adjusted for antiestrogen use, age, diabetes, hypertension and chemotherapy.
During the 14-year study period, 135 patients were diagnosed with subsequent endometrial cancers and the incidence per 105 person-years patients were 24.8, 91.9 and 46.7 in nonuser (n = 14588), tamoxifen (n = 19302) and AI-included group (n = 6850), respectively. When compared with nonuser, tamoxifen had a higher risk of endometrial cancer (14-year incidence 1.4% vs 0.3%; HR 3.92; 95% CI, 2.38 to 6.46; p 50 years) tamoxifen-treated patients had higher risk of endometrial cancer. But our younger (40-50 years) tamoxifen-treated patients also had higher risk of endometrial cancer (HR 3.74; 95% CI, 1.65 to 8.48; p = 0.0015). The 4004 tamoxifen-treated patients taking sequenced AI were matched with 8008 tamoxifen-only patients after adjusting for age, cumulative dose of tamoxifen and year of breast cancer diagnosis. The risk of endometrial cancer was lower in patients with sequenced AI (14-year incidence 0.6% vs 1.4%; HR 0.4; 95% CI, 0.22 to 0.73; p = 0.0028).
In Taiwan, not only older( >50 years) but younger (40-50 years) patients with tamoxifen treatment had higher risk of subsequent endometrial cancer. The risk of endometrial cancer still increased after patients had discontinued tamoxifen for several years. Sequenced AI use may reverse endometrial cancer risk in tamoxifen-treated breast cancer patients.
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Legal entity responsible for the study
This study was approved by the Research Ethics Committee of Buddhist Tzu Chi General Hospital, Hualien, Taiwan (IRB101-98).
The National Science Council of the Republic of China, and Buddhist Tzu Chi General Hospital Taiwan were appreciated for supporting this research under Contract No. NSC 101-2314-B-303-020 and TCRD102-52.
All authors have declared no conflicts of interest.