A statistically significant association between obesity and recurrence or survival was reported in 23 studies (total N=27,077 women) while no association was reported in 7 studies (total N=4,155 women).7
The negative effect of body weight and BMI on breast cancer recurrence and survival has been observed in both premenopausal and postmenopausal women.7,12–16
However, potential interactions among adjuvant therapy, obesity, and clinical outcome have not been systematically addressed.
In a meta-analysis, the hazard ratio for recurrence at five years by body weight (highest vs. lowest category) was 1.91 (1.52–2.40) and for death at ten years was 1.6 (1.38–1.76), suggesting women with excess weight at diagnosis were significantly more likely to develop recurrence and less likely to survive.1
Goodwin et al. found that after three to nine years of follow-up, women with newly diagnosed breast cancer (N=535, median age 50 years) with BMI ≥ 27.8 had a 70% increased risk of recurrence (90% confidence interval 1.3–2.3) and an 80% increased risk of death (95% confidence interval 1.3–2.5) compared with lighter-weight women.15
In several studies, overweight and obese postmenopausal women without breast cancer have been observed to have higher estrogen and androgen concentrations, and lower SHBG concentrations, compared with lighter-weight women.2–4, 17–22
High concentrations of estrogens and androgens have been associated with increased risk for incident breast cancer in several cohort studies,23
suggesting that these hormones may be breast tumor promoters.7
One study examined the association between BMI and sex hormone concentrations in 36 women with breast cancer and 36 controls, and found that testosterone increased with increasing BMI (p=.08).24
Furthermore, SHBG level was positively associated with increased upper body fat distribution as measured by skin folds. No association between BMI and estrone was observed. However, the sample included both premenopausal and postmenopausal women, and data for cases and controls were combined in the analysis. Therefore, ours is the first study to report on the association between adiposity and sex hormones in a relatively large cohort of breast cancer survivors limited to postmenopausal women.
We found statistically significant trends toward increasing estrone, estradiol, testosterone, free estradiol, and free testosterone with increasing BMI, body fat mass, percent body fat, and waist circumference. SHBG significantly decreased with increasing levels of all measures of adiposity.
Our consistent findings among several measures of adiposity (BMI, body fat mass, percent body fat, and waist circumference) and the finding that waist-to-hip was not associated with hormone concentrations at either clinical site suggest that overall amount of body fat may be more important than distribution of body fat in determining sex hormone concentrations in postmenopausal women with breast cancer. On the other hand, numerous studies have reported that hyperandrogenism is more strongly associated with centralized or visceral obesity than generalized obesity in post-menopausal women, and is associated with increased cortisol and insulin levels in this obesity phenotype.25
Some investigators have suggested that waist-to-hip circumference ratio may be an inadequate index of body fat distribution, particularly in post-menopausal women, for a variety of reasons including the influence of age-related variation in muscle mass and tone.26
There are several limitations to these data. While the study was population-based, only 41% of age- and stage- eligible incident cases were enrolled into the cohort. Although our analyses were limited to within-cohort comparisons, we cannot be sure that these associations pertain to all breast cancer survivors. Certain race/ethnic groups were under-represented in theses analyses, namely African-American and Asian-American women. Since an additional HEAL site in Los Angeles County has enrolled 273 African-American women with breast cancer (blood not available at baseline), we will be able to assess body mass-hormone associations in blood collected during the follow-up stage of the study for that racial group.
The methods of data collection were not identical between the sites for several measures, namely the type of DXA scanner, method of waist circumference measurement, and fasting status at blood draw. We assessed all associations first within each clinical site, and only combined data when associations were the same between the two sites, and we adjusted for clinical site in all analyses to compensate for these differences.
The CVs for some hormones, particularly estradiol, were large although consistent with published CVs for these hormones and reflect the difficulty with measuring estrogens at the low levels present in postmenopausal women. We did not collect information on whether women were currently undergoing chemotherapy or radiation treatment at the time of their blood draw, and thus the results could be confounded by current treatment status. However, we did not see a difference in association between serum hormones and adiposity by stage, which suggests that current treatment is unlikely to have been a major confounder since few women with in situ disease underwent radiation or chemotherapy.
These data were cross-sectional only, and do not imply cause and effect. Specifically, we did not measure the effect of gain or loss of body mass or body fat on sex hormones. Similarly, although we adjusted our analyses for variables that might be associated with both body mass and hormone levels, there could be other confounding factors that we did not take into account.
Differential variation in sex hormones by body mass and body fat may be one explanation for the poorer survival experienced by overweight women with breast cancer and the poorer response to tamoxifen therapy in overweight or obese women.7
In the HEAL population-based cohort of breast cancer survivors, 30 percent were overweight (body mass index 25.0–29.9) and 23% were obese (body mass index ≥ 30.0). Thus, if reduction of body fat can improve prognosis and survival, a large number of breast cancer survivors might be expected to benefit from weight-loss interventions.