Risk of malignant mixed mullerian tumors after tamoxifen therapy for breast cancer.
Recent studies have indicated that the tamoxifen-related risk of uterine corpus cancer may be especially high for some uncommon cell types, although the magnitude of risk has not been quantified. We evaluated data from 39 451 breast cancer patients diagnosed from 1980 through 2000 who were initially treated with tamoxifen and found that the overall risk of subsequent uterine corpus cancer was increased more than twofold (observed-to-expected ratio [O/E] = 2.17, 95% confidence interval [CI] = 1.95 to 2.41) relative to the general SEER population. The relative risk was substantially higher for malignant mixed mullerian tumors (MMMTs) (O/E = 4.62, O = 34, 95% CI = 3.20 to 6.46) than for endometrial adenocarcinomas (O/E = 2.07, O = 306, 95% CI = 1.85 to 2.32), although the excess absolute risk was smaller-an additional 1.4 versus 8.4 cancers per 10 000 women per year, respectively. Among those who survived for 5 years or longer, there was an eightfold relative risk for MMMTs and a 2.3-fold risk for endometrial adenocarcinomas, with patients developing MMMTs having a worse prognosis. These findings indicate that tamoxifen may have delayed effects, such as the increased risk of MMMTs, rare but aggressive tumors of unclear pathogenesis.
Curtis
Rochelle E
RE
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-7362, USA. rcurtis@mail.nih.gov
Freedman
D Michal
DM
Sherman
Mark E
ME
Fraumeni
Joseph F
JF
D000230:Adenocarcinoma / Q000139:chemically induced; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D044584:Carcinoma, Ductal / Q000188:drug therapy; D016001:Confidence Intervals; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D018200:Mixed Tumor, Mullerian / Q000139:chemically induced*; D016017:Odds Ratio; D018570:Risk Assessment; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors; D014594:Uterine Neoplasms / Q000139:chemically induced*
D018931:Antineoplastic Agents, Hormonal; D020847:Estrogen Receptor Modulators; D013629:Tamoxifen