Whether body mass index (BMI) is associated with an increased risk of breast cancer is dependent on age and is not altered by menopausal status or by genetic factors, according to an analysis of 11,700 participants (5,400 families) already enrolled in the Breast Cancer Family Registry (in North America and Australia) and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (in Australia). The international group of researchers presented their findings on Friday, December 9, at the San Antonio Breast Cancer Symposium

Although clinicians are better able to identify women with increased genetic risk for breast cancer, it’s still unknown whether women with different genetic susceptibilities also have other risk factors. If differences do exist, that will play a role in prevention and screening measures, allowing them to be more targeted to separate groups of women. But if no differences exist, “advice to women regarding specific risk factors can be confidently given to women across the spectrum of genetic risk,” the researchers noted.

BMI is a potentially modifiable risk factor, but it remains complicated because the risk association depends on age and, some have suggested, menopausal status. In women who are 15 years or more post-menopause or aged 60 years or older, a higher BMI has been found to be associated with an increased risk of breast cancer. Conversely, a greater BMI in premenopausal women, young women, and even adolescent girls has been associated with a decreased risk of breast cancer.

The two cohort studies the researchers used included up to 20 years of follow-up (with a mean of about 10.5 years); they looked at 540 incident breast cancers with a mean age at diagnosis of 57.2 years.

The group found that the strength and direction of the association of BMI with risk depended on age at baseline (p = 0.004). This strong interaction was not changed after adjusting for menopausal status (p = 0.5). The change from decreased risk to increased risk was gradual over patients’ adult life, with no apparent perturbation attributed to menopausal status. However, a strong association occurred with genetic risk (p < 0.001), and this was unchanged after adjusting for the age-dependent association with BMI. Finally, the group found no evidence for an interaction between BMI as a function of age at baseline and genetic risk. 

The lack of interaction with genetic risk “is important because it supports, at least for BMI, current practice that assumes that breast cancer risk factors relevant to women in the general population also apply to women of higher genetic risk,” the researchers concluded. “In terms of potentially reducing absolute risk, increased BMI could be more important for women at higher genetic risk.”

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