Aromatase inhibitors, tamoxifen, and endometrial cancer in breast cancer survivors

• Published in: Cancer Vol. 121; no. 13; pp. 2147 - 2155
• Main Authors: Chlebowski, Rowan T., Schottinger, Joanne E., Shi, Jiaxiao, Chung, Joanie, Haque, Reina
• Format: Journal Article
• Language: English
• Published: United States 01.07.2015
• Subjects: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal - administration & dosage; aromatase inhibitors; Aromatase Inhibitors - administration & dosage; breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; California - epidemiology; chemoprevention; Cohort Studies; endometrial cancer; Endometrial Neoplasms - epidemiology; Endometrial Neoplasms - prevention & control; Female; Humans; Incidence; Middle Aged; Survivors - statistics & numerical data; tamoxifen; Tamoxifen - administration & dosage; California; endometrial cancer; breast cancer; aromatase inhibitors; chemoprevention; tamoxifen
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.29332

BACKGROUND The risks of both endometrial cancer and postmenopausal breast cancer are increased by obesity and higher endogenous estrogen levels. Although aromatase inhibitors reduce breast cancer incidence, their influence on endometrial cancer is uncertain. METHODS The authors investigated this issue in a cohort of 17,064 women who were diagnosed with hormone receptor‐positive breast cancer in an integrated group practice health plan. Information on demographics, comorbidities, and the receipt of adjuvant endocrine therapy was available from electronic medical records and pharmacy records, respectively. Endometrial cancer information was obtained from the health plan's Surveillance, Epidemiology, and End Results‐affiliated tumor registry, and rates were compared across endocrine therapy groups (aromatase inhibitor, n = 5303; tamoxifen, n = 5155; switchers: both [n = 3787] or none [n = 2819]) using multivariable adjusted Cox proportional‐hazards models. RESULTS Endometrial cancer incidence was a statistically significant 48% lower in the aromatase inhibitor group versus the tamoxifen group (hazard ratio, 0.52; 95% confidence interval, 0.31‐0.87; P = .01). Endometrial cancer incidence was 29% lower in the aromatase inhibitor group versus the no endocrine therapy group (hazard ratio, 0.71; 95% confidence interval, 0.37‐1.35; P = .30) and 33% lower in the aromatase inhibitor group versus the tamoxifen group (hazard ratio, 0.67; 95% confidence interval, 0.42‐1.06; P = .08), but neither difference was statistically significant. Associations were stronger among those with good drug adherence. CONCLUSIONS In a community‐based, integrated health plan setting, endometrial cancer incidence was lower in women who were receiving an aromatase inhibitor compared with those who were receiving tamoxifen. In addition, aromatase inhibitors may mitigate the incidence of tamoxifen‐associated endometrial cancer. Although there were somewhat fewer endometrial cancers in the aromatase inhibitor group versus the no endocrine therapy group, further studies are needed for the definitive assessment of this potential association. Cancer 2015;121:2147–2155. © 2015 American Cancer Society. In a community‐based health plan, endometrial cancer incidence is lower among women who receive an aromatase inhibitor versus tamoxifen. In addition, aromatase inhibitors may mitigate the incidence of tamoxifen‐associated endometrial cancer.