According to recently published findings in JAMA Oncology, higher body mass index (BMI) is linked to lower risk of breast cancer in premenopausal women. While obesity has been shown to have a strong correlation with an increased risk of breast cancer in postmenopausal women, the results from this large-scale, multicenter analysis show that the inverse may actually be true for younger women.
The researchers collected data from 19 prospective cohorts in North America (n=9), Europe (n=7), Asia (n=2), and Australia (n=1). Participants in these cohorts were recruited from January 1, 1963 through December 31, 2013. Data from each study were standardized to a common template for 1 to 16 questionnaire rounds per study. The researchers also took self-reported or measured information on current weight and height to construct BMI within the age ranges of 18 to 24, 25 to 34, 35 to 44, and 45 to 55. All of the breast cancers included in the study were diagnosed before menopause and the main analytic endpoint was invasive or in situ premenopausal breast cancer.
The analyses included 758,592 women (median age, 40.6 years; interquartile range, 35.2-45.5 years). Among these women, 13,082 in situ or invasive breast cancer cases occurred during 7.2 million premenopausal years of follow-up (median, 9.3 years; interquartile range, 4.9-13.5 years). Depending on age, 88.9% to 99.6% of weights were self-reported. Weight at ages 18 to 24 was retrospectively reported for 96.9% of women, but that was the case for fewer than 10% of women who were older. The researchers noted that obesity was more common in women who were aged 45 and older (11.1%), nulliparous (12.4%), had a family history of breast cancer (12.8%), had an early menarche (17.0%), or were black (26.8%).
The researchers found a linear association between increasing BMI and decreasing risk of breast cancer, but there appeared to be a leveling of risk for underweight women (BMI < 18.5) for some ages and tumor types when compared to women in the normal weight range (BMI 18.5-24.9). As a result, the authors restricted the linear modeling of BMI to values ≥ 18.5. Hazard ratios for breast cancer decreased as BMI increased, more so with younger than older women. The researchers saw a risk reduction of 23% per each 5 kg/m2increase in BMI (HR, 0.77; 95% CI, 0.73-0.80) at ages 18 to 24 and 12% (HR, 0.88; 95% CI, 0.86-0.91) for BMI increases at 45 to 54 years. Between the highest and lowest BMI categories (BMI ≥ 35.0 vs < 17.0) at ages 18 to 24 years, the risk gradient was 4.2-fold (HR, 0.24; 95% CI, 0.14-0.40). Even within the normal range for BMI, significant differences in relative risk were observed (23.0-24.9 vs 18.5-22.9: HR, 0.80; 95% CI,0.75-0.86). HRs for BMI at 18 to 24 years stayed significantly significant even after additional adjustment for the woman’s most recent BMI measurement (HR per 5kg/m2increase, 0.80; 95% CI, 0.76-0.84).
Among the 2138 incident cases of in situ breast cancer, associations with risk per 5 kg/m2difference in BMI were significantly larger (HR, 0.76; 95% CI, 0.69-0.85) compared to the 10,836 incident cases of invasive breast cancer (HR, 0.88; 95% CI, 0.84-0.92) (P = .02 for interaction), at ages 25 to 34. At ages 35 to 44 years, difference in associations were also found for in situ (HR, 0.81; 95% CI 0.76-0.86) and invasive breast cancer (HR, 0.88; 95% CI 0.86-0.90) (P = .01).
The authors noted a few strengths and limitations to their study. Among the noted strengths were the large number of cases and the precise estimates of relative risk they provided. Some limitations were use of BMI since women can have different body fat distributions and levels but still have the same BMI. Participants were also asked to retrospectively come up with their height and weight at age 18. In addition, one of the included studies asked participants to self-report their current weight and overweight women tend to underreport while underweight women tend to overreport. Ultimately, the researchers believe the results of their study suggest that increased BMI has a more significant association with reduced breast cancer risk in premenopausal women than previous analyses. However, more research is necessary to better understand the biological mechanism causing this association.