Reproductive Steroid Hormones and Recurrence-Free Survival in Women with a History of Breast Cancer

^{1 1}Moores UCSD Cancer Center, University of California-San Diego, La Jolla, California; ²Department of Public Health Sciences, University of California-Davis, Davis, California; ³Arizona Cancer Center, University of Arizona, Tucson, Arizona; ⁴University of Texas M. D. Anderson Cancer Center, Houston, Texas; ⁵Division of Research, Kaiser Permanente Northern California, Oakland, California; ⁶Stanford Comprehensive Cancer Center, Stanford University, Stanford, California; and ⁷Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, California

^* To whom correspondence should be addressed. E-mail: clrock{at}ucsd.edu.

	Abstract

Epidemiologic studies fairly consistently show in postmenopausal women that reproductive steroid hormones contribute to primary breast cancer risk, and this association is strongly supported by experimental studies using laboratory animals and model systems. Evidence linking sex hormone concentrations with risk for recurrence in women diagnosed with breast cancer is limited; however, beneficial effects of antiestrogenic therapy on recurrence-free survival suggest that these hormones affect progression and risk for recurrence. This study examined whether baseline serum concentrations of estradiol, testosterone, and sex hormone binding globulin were associated with recurrence-free survival in a nested case-control cohort of women from a randomized diet trial (Women's Healthy Eating and Living Study) who were followed for >7 years after diagnosis. In 153 case-control pairs of perimenopausal and postmenopausal women in this analysis, total estradiol [hazard ratio (HR), 1.41 per unit increase in log concentration; 95% confidence interval (95% CI), 1.01-1.97], bioavailable estradiol (HR, 1.26; 95% CI, 1.03-1.53), and free estradiol (HR, 1.31; 95% CI, 1.03-1.65) concentrations were significantly associated with risk for recurrence. Recurred women had an average total estradiol concentration that was double that of nonrecurred women (22.7 versus 10.8 pg/mL; P = 0.05). Testosterone and sex hormone binding globulin concentrations did not differ between cases and controls and were not associated with risk for recurrence. Although genetic and metabolic factors likely modulate the relationship between circulating sex hormones and risk, results from this study provide evidence that higher serum estrogen concentration contributes to risk for recurrence in women diagnosed with early stage breast cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(3):614–20)

Key Words: Breast cancer, Steroid hormones and receptors, Reproductive, hormonal, and related risk factors