Breast cancer risk factors in relation to estrogen receptor, progesterone receptor, insulin-like growth factor-1 receptor, and Ki67 expression in normal breast tissue

Hannah Oh,Rulla M Tamimi,Walter C Willett,Andrew H Beck,Stuart J Schnitt,Bernard Rosner,James L Connolly,Laleh Montaser-Kouhsari,A Heather Eliassen,Laura C Collins

doi:10.1038/s41523-017-0041-7

Abstract

Studies have suggested that hormone receptor and Ki67 expression in normal breast tissue are associated with subsequent breast cancer risk. We examined the associations of breast cancer risk factors with estrogen receptor (ER), progesterone receptor (PR), insulin-like growth factor-1 receptor (IGF-1R), and Ki67 expression in normal breast tissue. This analysis included 388 women with benign breast disease (ages 17–67 years) in the Nurses’ Health Studies. Immunohistochemical staining was performed on tissue microarrays constructed from benign biopsies containing normal breast epithelium and scored as the percentage of epithelial cells that were positively stained. Ordinal logistic regression (outcomes in tertiles), adjusting for age and potential confounders, was performed to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations with risk factors. Alcohol consumption was positively associated (≥2.5 vs.<0.4 drink/wk: OR = 2.69, 95% CI = 1.26–5.75, p-trend = 0.008) and breastfeeding was inversely associated (≥6 months vs. never: OR = 0.11, 95% CI = 0.04–0.35, p-trend = 0.0003) with ER expression. Height (≥66 vs.<64 inches: OR = 2.50, 95% CI = 1.34–4.67, p-trend = 0.005) and BMI at age 18 (≥22 vs.<20 kg/m2: OR = 2.33, 95% CI = 1.18–4.62, p-trend = 0.01) were positively associated with PR expression. Body size at age 5–10 years was inversely associated with Ki67 (Level ≥ 2.5 vs. 1: OR = 0.55, 95% CI = 0.30–1.01, p-trend = 0.03). Premenopausal BMI (≥25 vs.<20 kg/m2) was positively associated with cytoplasmic IGF-1R (OR = 5.06, 95% CI = 1.17–21.8, p-trend = 0.04). Our data suggest that anthropometrics, breastfeeding, and alcohol intake may influence the molecular characteristics of normal breast tissue, elucidating the mechanisms by which these risk factors operate. However, larger studies are required to confirm these results.

Highlights

IntroductionThe majority of breast cancer cases occur among the women of age 50 years or older.[2,3] Besides age, reproductive factors (e.g., nulliparity, older age at first birth),[4,5] exogenous hormone use,[6,7] height,[8] and family history of breast cancer[9] increase the risk
Breast cancer is the most common cancer in women worldwide[1].The majority of breast cancer cases occur among the women of age 50 years or older.[2,3] Besides age, reproductive factors,[4,5] exogenous hormone use,[6,7] height,[8] and family history of breast cancer[9] increase the risk
Anthropometric measures including height, body size at ages 5–10 years, and BMI at age 18 were associated with higher levels of progesterone receptor (PR) and lower levels of Ki67 expression

Summary

Introduction

The majority of breast cancer cases occur among the women of age 50 years or older.[2,3] Besides age, reproductive factors (e.g., nulliparity, older age at first birth),[4,5] exogenous hormone use,[6,7] height,[8] and family history of breast cancer[9] increase the risk. Lifestyle factors such as alcohol consumption,[10] lack of physical activity,[11] and postmenopausal obesity[12] are among the established risk factors for breast cancer. Prior studies[19,20,21,22] including ours[23,24] have suggested that expression levels of estrogen receptor (ER), progesterone receptor (PR), IGF-1 receptor (IGF-1R), and Ki67 in cancer-free breast tissue may be associated with subsequent breast cancer risk

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Conclusion