Abstract
IntroductionPrevious studies showed that higher testosterone levels are associated with greater risk of breast cancer in premenopausal women, but the literature is scant and inconsistent.MethodsIn a prospective nested case-control study of 104 premenopausal women with incident breast cancer and 225 matched controls, all characterized by regular menstrual cycles throughout their lifetime, we measured the concentration of estradiol, total and free testosterone (FT), progesterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in blood samples collected on days 20 through 24 of their cycles.ResultsIn logistic regression models, the multivariate odds ratios (ORs) of invasive breast cancer for women in the highest tertile of circulating FT compared with the lowest was 2.43 (95% confidence interval (95% CI), 1.15 to 5.10; Ptrend = 0.03), whereas for total testosterone, the association had the same direction but was not statistically significant (OR, 1.27; 95% CI, 0.62 to 2.61; Ptrend = 0.51). Endogenous progesterone was not statistically associated with breast cancer (OR, 1.16; 95% CI, 0.60 to 2.27; Ptrend = 0.75), nor were the other considered hormones.ConclusionsConsistent with previous prospective studies in premenopausal women and our own earlier investigation, we observed that higher levels of FT are positively associated with breast cancer risk in women with regular menstrual cycles throughout their lifetimes. No evidence of risk was found associated with the other endogenous sex steroids.
Highlights
Previous studies showed that higher testosterone levels are associated with greater risk of breast cancer in premenopausal women, but the literature is scant and inconsistent
BMI, body mass index; 95% CI, 95% confidence interval; FSH, follicle-stimulating hormone; LH, luteinizing hormone; OR, odds ratio; SHBG, sex hormone-binding globulin
Of the prospective studies published to date [4,5,6,7,8,9,10,11,12,13,14,15,16], the two largest ones, based in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Nurses’ Health Study II (NHS2) cohorts, reported for circulating estradiol either no overall association [4] or only if estradiol levels were measured in the follicular phase of the menstrual cycle [11]
Summary
Previous studies showed that higher testosterone levels are associated with greater risk of breast cancer in premenopausal women, but the literature is scant and inconsistent. Few previous studies have evaluated the association between circulating sex steroids and breast cancer risk in premenopausal on lifestyle, reproductive history, and standardized anthropometric measurements, together with a median cohort follow-up of 20 years and the identification of all breast cancer cases assured by the local Varese Cancer Registry, render the Hormones and Diet in the Etiology of Breast Cancer Risk (ORDET) study an ideal setting for better clarification of hormonal risk factors in relation to breast cancer development [17,18,19]. We considered in the analysis follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
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