Lifetime Body Size and Estrogen-receptor-positive Breast Cancer Risk in the California Teachers Study Cohort

Background: Obesity is a public health epidemic and an important breast cancer risk factor. The relationship between interrelated body measurements is complex and most studies fail to account for this complexity. We identified key aspects of body size which jointly, over the life-course (since adolescence), are associated with estrogen-receptor-positive (ER+) breast cancer risk.

Methods: Among 109,862 women participating in the California Teachers Study cohort, 3844 were diagnosed with invasive ER+ breast cancer between 1997-1998 and December 2011. Based on validated self-reported height and weight at age 18, baseline, and 10-year follow up and waist circumference at 2-year and 10-year follow up, we identified 16 a priori body-size phenotypes. Multivariable Cox proportional hazards models provided estimates of hazard rate ratios (HR) and 95% confidence intervals (CI).

Results: Premenopausal breast cancer was influenced by adolescent, but not adult, body size (HR = 0.51, 95% CI 0.31-0.86 for body mass index (BMI; kg/m) ≥25 vs <20 at age 18). Among postmenopausal women currently using hormone therapy, only those with the greatest body size had increased breast cancer risk (HR = 1.36, 95% CI 1.13-1.64 for height ≥67 inches and adult BMI ≥25 vs height <67). Among postmenopausal women not currently using hormone therapy, the relationship between body size and risk was complex, with the largest effects of adiposity among short women. Among short women, those with gluteal adiposity (HR = 2.70, 95% CI 1.77-4.10) and those who continued to gain weight throughout adulthood (HR = 2.57, 95% CI 1.60-4.12) were at greatest risk, whereas those who had been overweight/obese since adolescence were not at increased risk (HR = 1.33, 95% CI 0.84-2.10). Height was associated with a small increased risk, with borderline statistical significance.

Conclusions: Considering absolute body mass in adolescence and at two points in adulthood, dynamic changes in adiposity over time, and body fat distribution, we identified obesity phenotypes associated with ER+ breast cancer risk. Our approach more clearly identifies specific risk groups than do analyses that evaluate similar measures separately. These findings may aid in improving risk prediction models and developing targeted interventions, and may clarify inconsistent findings across studies.