Birthweight, childhood body size, and timing of puberty and risks of breast cancer by menopausal status and tumor receptor subtypes

BACKGROUND: Associations of birthweight, childhood body size and pubertal timing with breast cancer risks by menopausal status and tumor receptor subtypes are inconclusive. Thus, we investigated these associations in a population-based cohort of Danish women.

METHODS: We studied 162,419 women born between 1930 and 1996 from the Copenhagen School Health Records Register. The register includes information on birthweight, measured childhood weights and heights at the age of 7-13 years, and computed ages at the onset of the growth spurt (OGS) and at peak height velocity (PHV). The Danish Breast Cancer Cooperative Group database provided information on breast cancer (n = 7510), including estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2) and menopausal status. Hormone replacement therapy use came from the Danish National Prescription Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regression.

RESULTS: We found that birthweight was not associated with any breast cancer subtypes. While childhood BMI was not statistically significantly associated with ER+ tumors nor consistently with ER- tumors among pre-menopausal women, consistent inverse associations were found among postmenopausal women. At the age of 7 years, the HRs for postmenopausal ER+ and ER- tumors were 0.90 (95% CI 0.87-0.93) and 0.84 (95% CI 0.79-0.91) per BMI z-score, respectively. Similarly, childhood BMI was inversely associated with pre- and postmenopausal HER2- tumors, but not with HER2+ tumors. Childhood height was positively associated with both pre- and postmenopausal ER+ tumors, but not with ER- tumors. At the age of 7 years, the HRs for postmenopausal ER+ and ER- tumors were 1.09 (95% CI 1.06-1.12) and 1.02 (95% CI 0.96-1.09) per height z-score, respectively. In general, childhood height was positively associated with HER2+ and HER2- tumors among pre- and postmenopausal women. Ages at OGS and PHV were not associated with any breast cancer subtypes.

CONCLUSIONS: We showed that a high BMI and short stature in childhood are associated with reduced risks of certain breast cancer subtypes. Thus, childhood body composition may play a role in the development of breast cancer.