Higher body mass index (BMI), especially in early adulthood, is associated with reduced risk for premenopausal breast cancer, say researchers from the Premenopausal Breast Cancer Collaborative Group.
In a multinational observational study using pooled data from 19 cohorts and involving 758,592 premenopausal women 18 to 54 years of age, an inverse linear association between breast cancer risk and BMI was observed across all age groups, even in women who were not overweight.
The median follow-up per participant was 9.3 years, and the median participant age was 40.6 years.
The inverse association was strongest in the youngest women between 18 and 24 years old, according to Minouk J. Schoemaker, PhD, from the Division of Genetics and Epidemiology at The Institute of Cancer Research in London, United Kingdom, and colleagues.
The report was published online June 21 in JAMA Oncology.
"The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI," the study authors write.
The inverse association was strongest for hormone receptor–positive breast cancer and did not vary by attained age or other characteristics.
Earlier studies have tied high BMI to a reduced risk for premenopausal breast cancer. The new report is "a more rigorous and systematic analysis" of that association, said Breast Cancer Now, a study funding partner, in a statement.
Obesity is a risk factor for breast cancer in older women. But the new study shows that the overweight–breast cancer link is more complicated than previously thought, said Schoemaker. "We now need follow-up research to understand why this effect seems to be reversed in younger women," she added
The analysis showed that in women 18 to 24 years of age, the hazard ratio (HR) per 5-kg/m2 (five-unit) difference in BMI was 0.77.
"We found that for every five-unit increase in BMI, which is equivalent to about 10 kg for someone of average height, the relative risk of breast cancer decreased by up to 23%," Schoemaker told Medscape Medical News.
This result was compared to an HR of 0.88 per five-unit difference in BMI in women 45 to 54 years of age.
Notably, the youngest women were 4.2 times less likely to develop early breast cancer if they were obese than if they were underweight (BMI ≥ 35.0 vs < 17.0; HR, 0.24).
In women older than 25 years, there was a 1.9- to 2.5-fold decreased risk for breast cancer in the same obese/underweight BMI categories. Significant reductions in relative risk were present even when BMI was within the range of normal (23.0 - 24.9 vs 18.5 - 22.9; HR, 0.80).
In every age group, the inverse associations between BMI and breast cancer risk were stronger for estrogen receptor–positive and/or progesterone receptor–positive than for hormone receptor–negative breast cancer. At age 18 to 24 years, the HR per five-unit difference in BMI for estrogen receptor–positive and progesterone receptor–positive tumors was 0.76 compared with 0.85 for hormone receptor–negative tumors.
Associations of BMI and breast cancer risk were not modified by risk factors for breast cancer later in life, with the possible exception of nulliparity and oral contraceptive use, the researchers say.
In women 25 to 54 years of age, BMI was not consistently associated with triple-negative or hormone receptor–negative breast cancer overall.
Not an Endorsement of Higher BMI
Schoemaker and colleagues emphasize that they are not advocating for weight gain as a preventive measure against premenopausal breast cancer.
When asked if she had any reservations about the clinical implications of these findings, Schoemaker said that understanding the mechanisms underlying this inverse association "helps us to try to understand what contributes to breast cancer risk in younger women, which will eventually aid prevention and accurate risk prediction."
For the study, the Premenopausal Breast Cancer Collaborative Group — which is facilitated by the National Cancer Institute Cohort Consortium — analyzed individual-level data from 19 prospective cohorts from North America, Europe, Asia, and Australia.
Participants who were premenopausal, had data for premenopausal BMI, and had no personal history of breast cancer were recruited from 1963 through 2013. The median follow-up per participant was 9.3 years, and the median participant age was 40.6 years.
Obesity, defined as a BMI of 30.0 or greater, was more common in women who were black (26.8%), had early menarche (17.0%), had a family history of breast cancer (12.8%), were nulliparous (12.4%), or were 45 years of age or older at study entry (11.1%).
There were 13,082 incident cases, including 10,836 invasive and 2138 in situ breast cancers. Data were analyzed from September 1, 2013, through December 31, 2017.
Although the reasons for lower breast cancer risk among heavier premenopausal women remain unclear, the fact that the inverse association was stronger in younger rather than older women suggests that "adiposity in young adulthood or earlier…is the critical factor," the researchers say.
The Premenopausal Breast Cancer Collaborative Group is now planning to examine patterns of breast cancer risk according to weight change in women, from early to mid-adulthood. The role of pregnancy and other factors potentially linked to breast cancer at a younger age will also be considered, Schoemaker said.
The study authors note that the use of BMI as a quantitative measure was somewhat limited because overall body fat percentage and distribution can differ among women with the same BMI. They also point out that the weight of many study participants was self-reported.
Funding was provided by breast cancer and health organizations in many different countries. Schoemaker and colleagues have disclosed no relevant financial relationships.
JAMA Oncol. Published online June 21, 2018.
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