Abstract
BackgroundAlthough it has been well-documented that obesity is associated with decreased risk of premenopausal breast cancer and increased risk of postmenopausal breast cancer, it is unclear whether these associations differ among breast cancer subtypes defined by the tumor protein expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).MethodsWe evaluated the associations of body mass index (BMI) at age 18 years and recent BMI in relation to risk of breast cancer overall and ER/PR/HER2-defined subtypes, in 6320 women (3934 case-patient participants, 2386 control participants) aged 35–64 years, who participated in one of three population-based case-control studies. We estimated multivariable-adjusted odd ratios (ORs) and corresponding 95% confidence intervals (CIs) using polychotomous unconditional logistic regression methods for case-control comparisons in premenopausal women and postmenopausal women.ResultsBMI at age 18 years was inversely associated with risk of breast cancer, particularly among premenopausal women (≥ 25 vs. < 20 kg/m2, OR = 0.72, 95% CI = 0.53–0.96; per 5 kg/m2 increase, OR = 0.83, 95% CI = 0.73–0.95). This inverse association did not differ across ER/PR/HER2-defined subtypes or by race (white women, African-American women). Recent BMI was not associated with risk of premenopausal breast cancer after adjustment for BMI at age 18 years; nevertheless, the analysis for the joint effects of BMI at age 18 years and recent BMI showed that premenopausal women in the highest categories of the two BMI measures (≥ 25 kg/m2 at age 18 years and ≥ 30 kg/m2 for recent BMI) had 46% lower risk of breast cancer than premenopausal women in the lowest categories of the two BMI measures (< 20 kg/m2 at age 18 years and < 25 kg/m2 for recent BMI; OR = 0.54, 95% CI = 0.38–0.78). Neither measure of BMI was statistically significantly associated with risk of postmenopausal breast cancer.ConclusionOur findings indicate that high BMI near the end of adolescence decreases risk of all ER/PR/HER2-defined subtypes of premenopausal breast cancer and also suggest that this benefit could be maximized among premenopausal women who consistently have high BMI during their premenopausal years.
Highlights
It has been well-documented that obesity is associated with decreased risk of premenopausal breast cancer and increased risk of postmenopausal breast cancer, it is unclear whether these associations differ among breast cancer subtypes defined by the tumor protein expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)
We present results from a pooled analysis of data from three population-based breast cancer case-control studies conducted among white women and AfricanAmerican women [6,7,8]; we examine the associations between body mass index (BMI) at age 18 years and BMI 5 years before case patients’ breast cancer diagnosis or control participants’ index date in relation to risk of breast cancer overall and risk of breast cancer subtypes defined by ER, PR, and HER2
In reporting the results of statistical tests determining whether the 5 kg/m2 increase in BMI differed from the null or whether slope coefficients differed across ER/PR/HER2-defined subtypes we considered a twosided P value less than 0.05 as statistically significant
Summary
It has been well-documented that obesity is associated with decreased risk of premenopausal breast cancer and increased risk of postmenopausal breast cancer, it is unclear whether these associations differ among breast cancer subtypes defined by the tumor protein expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Convincing epidemiologic evidence indicates that obesity is associated with decreased risk of premenopausal breast cancer and increased risk of postmenopausal breast cancer [2] It is unclear whether obesity impacts the tumorigenesis of all breast cancers or only certain breast cancer subtypes as defined by the tumor protein expression status of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Obesity was not associated with the risk of ER-negative (ER–)/PR– breast cancer in either premenopausal women or postmenopausal women
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