Body measurements, estrogen availability and the risk of human breast cancer: a case-control study

Recent studies on lifestyle-related mechanisms involved in cardiovascular risk offer important clues for a better understanding of breast-cancer epidemiology. Central body-fat distribution promoted by an affluent dietary intake and a sedentary lifestyle over many years is related to elevated serum triglycerides and free fatty acids, with lower levels of sex-hormone-binding globulin (SHBG). The resulting greater availability of estradiol not bound to SHBG could help to explain the high breast-cancer incidence in Western industrialized countries. We conducted a case-control study comparing 225 women aged 38 to 75 years with operable (stage I or II) breast cancer and 441 women of the same age having no breast cancer who participated in a population-based breast-cancer screening program. Body fatness, as measured by body mass index (BMI), fat distribution as measured by waist-to-hip girth ratio (WHR), body height, serum lipids, SHBG and the available fraction of estradiol were analyzed in a conditional logistic regression, together with family history for breast cancer, reproductive history and smoking. Post-menopausal cases showed no difference in body fatness (BMI), but a significant preponderance of central adiposity (WHR). In contrast, pre-menopausal cases were significantly leaner, but had a similar body-fat distribution as compared with controls. In all women, WHR, and less strongly BMI, was positively correlated with serum levels of triglycerides and available estradiol fractions. An independent, positive linear correlation between body height and relative risk (RR) was observed. Moreover, a significant correlation between SHBG and menarcheal age was seen in cases, but not in controls. These data support our hypothesis that lifestyle relates to breast-cancer risk by metabolic-endocrine mechanisms which modulate the availability of individual sex-steroid concentrations in plasma. The findings of height as a risk factor and adult SHBG levels being correlated with menarcheal age suggest that lifestyle factors promoting breast-cancer development already act around puberty. The leanness of pre-menopausal cases awaits further explanation.