We continue the theme of progress in understanding the causes and potential for prevention of cancer. This understanding has advanced substantially over the 30 years since Doll and Peto published their landmark report. Today I return to obesity, hormones, and breast cancer.
Doll and Peto noted that obesity was related to increased risk of postmenopausal breast cancer and that excess death might in part be due to later diagnosis of breast cancer among obese women. At that time the data were limited and the assumption was that this relation of obesity to breast cancer was through higher circulating estrogen levels1. A new report from a collaborative reanalysis of 13 studies attests to how much data has been collected since that time. A detailed analysis of blood levels of hormones in over 6000 postmenopausal women reports the relations between obesity and numerous circulating sex hormones (see report). Among the obese women, compared to lean women, the largest difference was seen for free estradiol. The blood level of estradiol is strongly related to risk of breast cancer in postmenopausal women 2. Of note, women who reported bilateral removal of ovaries had lower testosterone levels than those who had natural menopause. This lower hormone level along with lower estrogen levels is consistent with the protective effect of surgery to remove ovaries on risk of breast cancer.
Overall these data show that circulating sex hormone concentrations in postmenopausal women are strongly associated with established risk factors for breast cancer and likely mediate the effects of obesity on breast cancer. Further evidence in support of the pathway from obesity to hormone levels and then risk of breast cancer comes from the reanalysis of cohort studies, which show that the major effect of obesity could be explained through the circulating estrogen levels 3.
The 2002 IARC prevention report on weight control and physical activity clearly documented the importance of obesity for cancer mortality in men and women. The evidence accumulated over the past 30 years now gives a pathway and improved understanding of how obesity causes breast cancer. Strategies to avoid weight gain and promote sustained weight loss are essential components of any cancer prevention program at both the local and national level.
1. Doll R, Peto R. Avoidable risks of cancer in the United States. J Natl Cancer Inst. 1981;66:1196-1265.
2. Missmer SA, Eliassen AH, Barbieri RL, Hankinson SE. Endogenous estrogen, androgen, and progesterone concentrations and breast cancer risk among postmenopausal women. J Natl Cancer Inst. Dec 15 2004;96(24):1856-1865.
3. Key T, Appleby P, Barnes I, Reeves G. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst. Apr 17 2002;94(8):606-616.