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

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)

A Randomized, Placebo-Controlled, Phase II, Presurgical Biomarker Trial of Celecoxib Versus Exemestane in Postmenopausal Breast Cancer Patients

“…More recently, it has been shown that testosterone can be a biomarker of recurrence in postmenopausal women (39). Interestingly, in a case-control study nested to the WHEL trial, testosterone and SHBG levels were not associated with increased risk of recurrence, whereas higher serum estrogen concentrations were associated with recurrence risk (40). However, a more recent publication from the WHEL study showed a direct correlation between bioavailable testosterone levels and higher risk of recurrence in postmenopausal women with hot flashes (41).…”

Serum Adiponectin but not Leptin at Diagnosis as a Predictor of Breast Cancer Survival

“…For the Korean women, the hazard ratio of recurrence following diagnosis of primary breast cancer was increase less than 5 years survival period (Lee and Park, 2009). In postmenopausal women, BMI is significantly correlated with serum levels of estrone and estradiol (r=0.38, p<0.001 and r=0.41, p < 0.001 respectively) (Cauley et al, 1989); this is important as blood levels of estradiol, bioavailable estradiol and free estradiol have been associated with increased risk of breast cancer recurrence (Rock et al, 2008). This has raised concerns that aromatase inhibitors (AIs), which target the aromatase enzyme to lower blood estrogen levels, may be have reduced effectiveness in postmenopausal women who are overweight or obese.…”

Consumption of animal products, their nutrient components and postmenopausal circulating steroid hormone concentrations

“…High circulating concentrations of steroid hormones and low concentrations of sex hormone-binding globulin (SHBG) have been consistently associated with increased risk of postmenopausal breast cancer (Rock et al 2008). It is less clear which factors influence circulating steroid hormone concentrations and subsequent risk of breast cancer (Carruba et al, 2006), although dietary factors might affect metabolism and bioavailability of steroid hormones (Fung et al, 2007).…”