Breast Cancer Risk Factors Defined by Estrogen and Progesterone Receptor Status: The Multiethnic Cohort Study

V W Setiawan,M C Pike,K R Monroe,L R Wilkens,L N Kolonel,B E Henderson

doi:10.1093/aje/kwp036

Abstract

Prospective data on ethnic differences in hormone receptor-defined subtypes of breast cancer and their risk factor profiles are scarce. The authors examined the joint distributions of estrogen receptor (ER) and progesterone receptor (PR) status across 5 ethnic groups and the associations of established risk factors with ER/PR status in the Multiethnic Cohort Study (Hawaii and Los Angeles, California). During an average of 10.4 years of follow-up of 84,427 women between 1993-1996 and 2004/2005, 2,543 breast cancer cases with data on ER/PR status were identified: 1,672 estrogen receptor-positive (ER+)/progesterone receptor-positive (PR+); 303 ER+/progesterone receptor-negative (PR-); 77 estrogen receptor-negative (ER-)/PR+; and 491 ER-/PR-. ER/PR status varied significantly across racial/ethnic groups even within the same tumor stage (for localized tumors, P < 0.0001; for advanced tumors, P = 0.01). The highest fraction of ER-/PR- tumors was observed in African Americans (31%), followed by Latinas (25%), Whites (18%), Japanese (14%), and Native Hawaiians (14%). Associations differed between ER+/PR+ and ER-/PR- cases for postmenopausal obesity (P = 0.02), age at menarche (P = 0.05), age at first birth (P = 0.04), and postmenopausal hormone use (P < 0.0001). African Americans are more likely to be diagnosed with ER-/PR- tumors independently of stage at diagnosis, and there are disparate risk factor profiles across the ER/PR subtypes of breast cancer.

Highlights

Prospective data on ethnic differences in hormone receptor-defined subtypes of breast cancer and their risk factor profiles are scarce
Women diagnosed with estrogen receptor-positive (ERþ)/progesterone receptor-positive (PRþ) tumors are more responsive to hormonal treatment and have a better prognosis than those diagnosed with estrogen receptor-negative (ERÀ)/progesterone receptornegative (PRÀ) tumors
Using data from the Multiethnic Cohort Study, we have shown that 1) ER/PR status in breast cancer cases varies across racial/ethnic groups, 2) ERÀ/PRÀ tumors are most common in African-American women, and 3) risk factor profiles differ across the ER/PR subtypes

Summary

Introduction

Prospective data on ethnic differences in hormone receptor-defined subtypes of breast cancer and their risk factor profiles are scarce. During an average of 10.4 years of follow-up of 84,427 women between 1993–1996 and 2004/2005, 2,543 breast cancer cases with data on ER/PR status were identified: 1,672 estrogen receptor-positive (ERþ)/progesterone receptor-positive (PRþ); 303 ERþ/progesterone receptor-negative (PRÀ); 77 estrogen receptor-negative (ERÀ)/PRþ; and 491 ERÀ/PRÀ. African Americans are more likely to be diagnosed with ERÀ/PRÀ tumors independently of stage at diagnosis, and there are disparate risk factor profiles across the ER/PR subtypes of breast cancer. The basal-like subtypes and the subtypes expressing human epidermal growth factor receptor 2, which both are ERÀ/PRÀ, are more common among younger African Americans, and they have the poorest prognosis [1, 4]. Racial/ ethnic distributions differ by hormone receptor status; ERÀ/PRÀ tumors account for approximately 15%–20% of A recent large genetic association study showed differential associations between susceptibility loci identified from genome-wide scans and tumor subtypes defined by ER status [9], suggesting that hormone receptor-defined tumors are probably distinct at the germline level as well

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Conclusion