Tamoxifen therapy for breast cancer and endometrial cancer risk.
BACKGROUND
Tamoxifen is effective in treating breast cancer, reduces breast cancer incidence among high-risk women, and is associated with increased endometrial cancer risk. This study was designed to examine the possible modifying effects of endometrial cancer risk factors on the tamoxifen-endometrial cancer association.


METHODS
We conducted a case-control study of endometrial cancer (324 case patients and 671 individually matched control subjects) nested within a population-based cohort of patients with breast cancer diagnosed from 1978 through 1992 within four regions of the United States. We obtained information on breast cancer treatment and endometrial cancer risk factors through interviews and reviews of medical records. All P values reported are two-sided.


RESULTS
Endometrial cancer risk was associated with tamoxifen therapy for breast cancer (odds ratio = 1.52; 95% confidence interval [CI] = 1. 07-2.17). Risk increased with duration of tamoxifen use (P for trend =.0002). Women with more than 5 years of exposure to tamoxifen had 4. 06-fold greater odds of developing endometrial cancer than nonusers (95% CI = 1.74-9.47). Prior use of estrogen replacement therapy (ERT) increased risk associated with tamoxifen use (P for homogeneity of trends <.0001). Risk associated with tamoxifen use was stronger among heavier women than among thinner women, although trends did not differ statistically (P =.10). Tamoxifen dose-response effects were more pronounced among women with both previous ERT exposure and higher body mass index than among women in other risk groups.


CONCLUSIONS
ERT use and obesity, both established endometrial cancer risk factors and markers of estrogen exposure, substantially modify the association between tamoxifen use and endometrial cancer risk among patients with breast cancer. Women with positive ERT histories and those who are obese, when prescribed tamoxifen, may warrant closer surveillance for endometrial cancer than women without such histories.
Bernstein
L
L
Department of Preventive Medicine, University of Southern California School of Medicine, USA. lbern@hsc.usc.edu
Deapen
D
D
Cerhan
J R
JR
Schwartz
S M
SM
Liff
J
J
McGann-Maloney
E
E
Perlman
J A
JA
Ford
L
L
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000627:therapeutic use; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000188:drug therapy*; D016022:Case-Control Studies; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects; D016889:Endometrial Neoplasms / Q000139:chemically induced* / Q000209:etiology; D020847:Estrogen Receptor Modulators / Q000009:adverse effects* / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D012306:Risk; D012307:Risk Factors; D018426:SEER Program; D013629:Tamoxifen / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors
D018931:Antineoplastic Agents, Hormonal; D003278:Contraceptives, Oral, Hormonal; D020847:Estrogen Receptor Modulators; D013629:Tamoxifen