Abstract

BackgroundObesity and elevated breast density are common risk factors for breast cancer, and their effects may vary by estrogen receptor (ER) subtype. However, their joint effects on ER subtype-specific risk are unknown. Understanding this relationship could enhance risk stratification for screening and prevention. Thus, we assessed the association between breast density and ER subtype according to body mass index (BMI) and menopausal status.MethodsWe conducted a case-control study nested within two mammography screening cohorts, the Mayo Mammography Health Study and the San Francisco Bay Area Breast Cancer SPORE/San Francisco Mammography Registry. Our pooled analysis contained 1538 ER-positive and 285 ER-negative invasive breast cancer cases and 4720 controls matched on age, menopausal status at time of mammogram, and year of mammogram. Percent density was measured on digitized film mammograms using computer-assisted techniques. We used polytomous logistic regression to evaluate the association between percent density and ER subtype by BMI subgroup (normal/underweight, < 25 kg/m2 versus overweight/obese, ≥ 25 kg/m2). We used Wald chi-squared tests to assess for interactions between percent density and BMI. Our analysis was stratified by menopausal status and hormone therapy usage at the time of index mammogram.ResultsPercent density was associated with increased risk of overall breast cancer regardless of menopausal status or BMI. However, when analyzing breast cancer across ER subtype, we found a statistically significant (p = 0.008) interaction between percent density and BMI in premenopausal women only. Specifically, elevated percent density was associated with a higher risk of ER-negative than ER-positive cancer in overweight/obese premenopausal women [OR per standard deviation increment 2.17 (95% CI 1.50–3.16) vs 1.33 (95% CI 1.11–1.61) respectively, Pheterogeneity = 0.01]. In postmenopausal women, elevated percent density was associated with similar risk of ER-positive and ER-negative cancers, and no substantive differences were seen after accounting for BMI or hormone therapy usage.ConclusionsThe combination of overweight/obesity and elevated breast density in premenopausal women is associated with a higher risk of ER-negative compared with ER-positive cancer. Eighteen percent of premenopausal women in the USA have elevated BMI and breast density and may benefit from lifestyle modifications involving weight loss and exercise.

Highlights

  • Breast cancer risk is multifactorial, with > 40% of women having multiple risk factors [1]

  • We evaluated the associations between overweight/obese body mass index (BMI) and breast cancer by estrogen receptor (ER) subtype, across menopausal status (Table 2)

  • After adjustment for percent density, premenopausal women who were overweight/obese had increased risk of ER-negative cancer [odds ratio (OR) 2.51] and ER-positive cancer [OR 1.53] relative to their normal/underweight counterparts

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Summary

Introduction

Breast cancer risk is multifactorial, with > 40% of women having multiple risk factors [1]. Premenopausal overweight/obesity is associated with higher risk of ER-negative than ER-positive cancers, whereas postmenopausal overweight/obesity is associated with similar risk of both ER subtypes [10, 11]. The latter relationships are modified by postmenopausal hormone therapy (HT) use [10, 11]. Obesity and elevated breast density are common risk factors for breast cancer, and their effects may vary by estrogen receptor (ER) subtype. Their joint effects on ER subtype-specific risk are unknown. We assessed the association between breast density and ER subtype according to body mass index (BMI) and menopausal status

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