Direction of associations between body mass index (BMI, kg/m2) and breast cancer risk depends on menopausal status [1]. A wide body of evidence supports an inverse association between BMI and breast cancer risk before menopause [2], [3], [4], [5], [6], [7]. Higher young adult BMI is a protective factor for breast cancer incidence [6], [8] and may have the potential to modify patterns in estimated BMI HRs later in life. Following menopause, this inverse association changes to a positive association [5], [9], [10], [11], [12]. With this evidence prior to and after menopause, along this continuum on an age scale, it is clear that the association between BMI and breast cancer risk changes from a protective to a deleterious association. Although potential biological mechanisms have been proposed to explain the difference in associations between BMI and breast cancer by menopausal status [1], the time-course for this reversal has not been well described, particularly in relation to type of menopause.

Including menopausal status as an effect measure modifier of the association between BMI and breast cancer risk is one analytic approach to model associations between BMI and breast cancer risk dependent on menopause. Evaluation of these associations can entail inclusion of a product term between a continuous constant BMI variable and a binary menopause variable in a regression model [13]. These types of analyses assume a constant hazard ratio (HR) over time allowing for an abrupt shift at menopause, but age-time dependent changes in these associations remain unknown and may be more gradual or vary by type of menopause. Describing changes in associations between BMI and breast cancer risk around the typical age at menopausal transition may provide a better understanding of these temporal patterns.

Given the lack of evidence assessing changes in the associations between BMI and breast cancer risk around ages of menopausal transition, our primary aim was to describe patterns of change over age-time in the association between BMI and breast cancer risk from 45 to 55 years. We examined the change in the associations between BMI and breast cancer risk across the age-time scale by menopausal status using a large consortium-based pooled sample from 16 cohorts.