Height and Body Size in Childhood, Adolescence, and Young Adulthood and Breast Cancer Risk According to Molecular Subtype in the Nurses' Health Studies

Abstract

Height and body size in childhood and young adulthood have been consistently associated with breast cancer risk; whether associations differ across molecular subtypes is unclear. In a pooled analysis of the Nurses’ Health Studies we prospectively examined the association of four exposures: height, body mass index (BMI) at age 18, childhood and adolescent somatotypes, with breast cancer risk according to molecular subtypes defined by immunohistochemical markers. We used multivariable-adjusted Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI).We identified 2983 luminal A, 1281 luminal B, 318 HER2-enriched, 408 basal-like and 128 unclassified tumors. Height was positively associated with all subtypes (p-heterogeneity=0.78). BMI at age 18 (p-heterogeneity=0.001), childhood (p-heterogeneity=0.51) and adolescent somatotype (p-heterogeneity=0.046) were inversely associated, but with differences in magnitude of association. BMI at age 18 of ≥25 kg/m2 (compared to 20-21.9 kg/m2) was associated with a 52% decreased risk of HER2-enriched (HR: 0.48, 95%CI: 0.26-0.91; p-trend <0.0001) and 39% reduced risk of basal-like tumors (HR: 0.61, 95% CI: 0.36-1.02; p-trend=0.008). Compared to the lowest category, women in the highest adolescent body size category were 71% less likely to develop HER2-enriched (HR: 0.29, 95%CI: 0.10-0.85; p-trend=0.0005) and 60% less likely to develop basal-like (HR: 0.40, 95%CI: 0.17-0.95; p-trend=0.0008). Height was positively associated with risk of all breast cancer molecular subtypes. BMI at age 18 and childhood and adolescent were inversely associated with risk of most breast cancer molecular subtypes with somewhat stronger associations with HER2-enriched and basal-like subtypes.

Menopausal hormone therapy and breast cancer risk: effect modification by body mass through life

“…Our results confirm that overweight at a young age, indicated by self-reported weight at 7 or 15 years of age, is associated with a relative reduction in breast cancer risk later in life. Similar findings have been reported by others [15,16,[18][19][20][21][22][23]51]. In addition, our findings suggest that HT use is associated with higher risk also in women who were overweight at a young age, but the association appears to be less pronounced than in HT users who either remained at normal weight through life or became overweight or obese as adults.…”

“…It is well established that HT use is more strongly associated with hormone receptor positive breast cancer [10], whereas overweight at a young age may confer a lower risk for all breast cancer subtypes [23]. Unfortunately, detailed information about breast cancer subtypes was not available to us, but we acknowledge that an effect modification of HT by life-course body mass patterns, may be more relevant for some than for other subtypes of breast cancer.…”

“…It is well known that overweight after menopause is positively associated with breast cancer risk [14][15][16], whereas overweight at younger ages is inversely associated with risk before menopause [15,17]. In addition, there is accumulating evidence that overweight in childhood and adolescence is inversely associated with risk, both before and after menopause [15,16,[18][19][20][21][22][23][24].…”

Obesity reversibly depletes the basal cell population and enhances mammary epithelial cell estrogen receptor alpha expression and progenitor activity

“…Although postmenopausal obesity is a significant risk factor for breast cancer, epidemiological studies suggest that obesity during puberty decreases life-long breast cancer risk [ 10 , 72 , 83 ], and decreases the risk of developing benign breast disease [ 84 ]. Puberty is an important stage of growth in the normal mammary gland, with the elongation of ducts and secondary branches forming from terminal end buds to fill the mammary fat pad.…”

Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women

“…Meta-analyses have aggregated studies that differed in age at BMI assessment, attained age of participants, and degree of adjustment for potential confounding, and results were not stratified by other risk factors. 2 , 3 , 4 , 5 , 15 , 16 , 17 , 18 Some studies suggest that the association of premenopausal adiposity with risk varies by tumor characteristics, 2 , 7 , 17 , 18 , 19 but larger studies are needed to provide stable estimates by hormone receptor status or intrinsic tumor subtype.…”