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High BMI in early adulthood may reduce risk for premenopausal breast cancer
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Increased adiposity, often assessed by BMI, in early adulthood appeared to decrease risk for premenopausal breast cancer, according to results of a prospective analysis.
“The results of our study suggest that increased BMI is inversely associated with the risk [for] breast cancer diagnosis before menopause, to a greater magnitude than suggested in previous analyses, and with the strongest associations for BMI at young ages,” Minouk J. Schoemaker, PhD, epidemiologist in the division of genetics and epidemiology at Institute of Cancer Research in London, and colleagues wrote.
Breast cancer accounts for 25% of all female cancer cases at any age, but a greater proportion of cancers among young women.
Previous studies showed increased BMI in childhood and prior to menopause is inversely associated with risk for breast cancer diagnosed at premenopausal and postmenopausal ages, whereas high BMI after menopause has been linked to increased risk.
However, incidence rates are lower among premenopausal women than postmenopausal women, studies have been limited to evaluate the association between BMI and risk for premenopausal breast cancer.
Schoemaker and colleagues sought to investigate the association of BMI with premenopausal breast cancer risk based on age at BMI assessment, attained age, risk factors for breast cancer and tumor characteristics.
Researchers evaluated pooled data from 758,592 premenopausal women (median age, 40.6 years) enrolled in 19 different prospective cohorts in North America, Europe, Asia and Australia between 1963 and 2013.
All women had no history of breast cancer at the beginning of enrollment.
Investigators used data from self-reported or multiple questionnaire rounds concerning weight at various ages prior to study enrollment to establish BMI within the following age ranges: 18 to 24 years, 25 to 34 years, 35 to 44 years, and 45 to 54 years.
Among all women, 13,082 in situ or invasive breast cancer cases occurred over 7.2 million premenopausal years of follow-up (median, 9.3 years; interquartile range [IQR], 4.9-13.5).
Obesity was more common among women aged 45 years or older (11.1%), who were nulliparous (12.4%), who had an early menarche (17%), who had a family history of breast cancer (12.8%) or who were black (26.8%).
Researchers observed a linear association between increased BMI and decreasing risk
of breast cancer via restricted cubic spline models; however, researchers observed a leveling of risk among some ages and tumor types associated with underweight (BMI < 18.5 mg/kg2) compared with normal weight (range of BMI, 18.5-24.9 mg/kg2).
As a result, researchers restricted linear modeling of BMI to values of 18.5 mg/kg2 or greater.
Analyses showed HRs for breast cancer decreased as BMI increased more at younger than older ages. Per 5-mg/kg2 difference in BMI, researchers observed a 23% risk reduction at 18 to 24 years (HR = 0.77; 95% CI, 0.73-0.8) and 12% reduction at 45 to 54 years (HR = 0.88; 95% CI, 0.86-0.91).
“The stronger inverse associations of risk with BMI at younger than older ages suggest that adiposity in young adulthood or earlier, if adiposity at approximately 20 years of age
is a proxy marker for adiposity in childhood, is the critical factor,” the researchers wrote.
Investigators observed a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI > 35 mg/kg2 vs. <1 7 mg/kg2) at ages 18 to 24 years (HR = 0.24; 95% CI, 0.14-0.4).
Researchers also observed significant differences in relative risk even within the normal range of BMI (23-24.9 mg/kg2 vs. 18.5-22.9 mg/kg2; HR = 0.8; 95% CI, 0.75-0.86).
HR did not appear to vary by attained age or between strata of other breast cancer risk factors.
Across every age group, linear associations appeared stronger among women with ER-positive and/or PR-positive breast cancer than hormone receptor-negative breast cancer. For example, the HR per 5-mg/kg2 difference in BMI at age 18 to 24 years was 0.76 (95% CI, 0.7-0.81) for ER-positive and/or PR-positive breast cancer and 0.85 (95% CI, 0.76-0.95) for hormone receptor–negative breast cancer.
BMI at age 25 to 54 years was not consistently associated with triple-negative or hormone receptor-negative breast cancer among the overall cohort, the researchers wrote.
The authors noted in a press release that they are not advocating for women to gain weight to reduce risk, but rather they are focused on the identification of potentially modifiable risk factors for this patient population.
“Understanding the biological mechanisms underlying these associations could have important preventive potential,” researchers wrote in the study. – by Melinda Stevens
Disclosures: The authors report no relevant financial disclosures.
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The Premenopausal Breast Cancer Collaborative Group. JAMA Oncol. 2018;doi:10.1001/jamaoncol.2018.1771.
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