Markers of insulin resistance and sex steroid hormone activity in relationto breast cancer risk: a prospective analysis of abdominal adiposity, sebum production, and hirsutism (Italy)

Objective: Insulin resistance and increased levels of serum steroids have b een hypothesized to be relevant etiological factors for breast cancer. Meas urements of markers of insulin resistance and elevated serum steroids may i dentify women at high risk for breast cancer. The present study analyzed th e association of breast cancer with markers of insulin resistance and eleva ted serum sex steroids, abdominal adiposity, increase in sebum production a nd hirsutism in a case-control study nested in a prospective cohort study. Methods: Between 1987 and 1992, 10,786 women (aged 35-69) were recruited in a prospective study on breast cancer in Italy, the ORDET study. Women with a history of cancer and on hormone therapy were excluded at baseline. At r ecruitment, abdominal adiposity was calculated from the ratio of waist-to-h ip circumferences. Sebum production was measured on the forehead under stan dardized conditions using a sebumeter. Nine androgen-sensitive body areas w ere evaluated for hirsutism and a total hirsutism score was computed. After an average of 5.5 years of follow-up, 144 breast cancer cases were identif ied among the participants of the cohort. For each breast cancer case, four matched controls were randomly chosen from members of the cohort who did n ot develop breast cancer during the follow-up period. Results: Waist-to-hip ratio was associated with breast cancer in premenopau sal women: age and body mass index (BMI) adjusted relative risk (RR) for th e highest tertile of waist-to-hip ratio was 2.2 [95% confidence interval (C I) 1.04-4.75], p for trend 0.03. In the analysis conducted within strata of BMI, the effect of waist-to-hip ratio was confined to the group of thinner women: RR for the highest tertile of waist-to-hip ratio was 3.4 (95% CI 1. 2-9.5). Sebum production and hirsutism were associated with breast cancer a mong postmenopausal women. Age and BMI adjusted RRs for the upper tertiles were 2.2 (95% CI 1.1-4.6), p for trend 0.01, and 2.3 (95% CI 1.1-4.9), p fo r trend 0.03, for sebum and hirsutism, respectively. Conclusion: These results add evidence for a role of hormones and metabolic alterations in breast cancer etiology and for different relations of these risk factors with breast cancer in premenopausal and postmenopausal women.