Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women

Abstract

Introduction: The association of breast cancer patients’ mortality with estrogen receptor (ER) status (ER + versus ER-) has been well studied. However, little attention has been paid to the relationship between the quantitative measures of ER expression and mortality.

Methods: We evaluated the association between semi-quantitative, immunohistochemical staining of ER in formalin-fixed paraffin-embedded breast carcinomas and breast cancer-specific mortality risk in an observational cohort of invasive breast cancer in 681 white women and 523 black women ages 35-64 years at first diagnosis of invasive breast cancer, who were followed for a median of 10 years. The quantitative measures of ER examined here included the percentage of tumor cell nuclei positively stained for ER, ER Histo (H)-score, and a score based on an adaptation of an equation presented by Cuzick and colleagues, which combines weighted values of ER H-score, percentage of tumor cell nuclei positively stained for the progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) results. This is referred to as the ER/PR/HER2 score.

Results: After controlling for age at diagnosis, race, study site, tumor stage, and histologic grade in multivariable Cox proportional hazards regression models, both percentage of tumor cell nuclei positively stained for ER (Ptrend = 0.0003) and the ER H-score (Ptrend = 0.0004) were inversely associated with breast cancer-specific mortality risk. The ER/PR/HER2 score was positively associated with breast cancer-specific mortality risk in women with ER + tumor (Ptrend = 0.001). Analyses by race revealed that ER positivity was associated with reduced risk of breast cancer-specific mortality in white women and black women. The two quantitative measures for ER alone provided additional discrimination in breast cancer-specific mortality risk only among white women with ER + tumors (both Ptrend ≤ 0.01) while the ER/PR/HER2 score provided additional discrimination for both white women (Ptrend = 0.01) and black women (Ptrend = 0.03) with ER + tumors.

Conclusions: Our data support quantitative immunohistochemical measures of ER, especially the ER/PR/HER2 score, as a more precise predictor for breast cancer-specific mortality risk than a simple determination of ER positivity.

Figure 1

Frequency distribution of estrogen receptor expression. Percentage of tumor cell nuclei positively stained for estrogen receptor (ER) (A) and ER Histo (H)-score (B) in 1,204 white women and black women diagnosed with invasive breast cancer.

Figure 2

Percentage of tumor cell nuclei positively stained for estrogen receptor and breast cancer-specific mortality risk. Adjusted hazard ratio (HR) estimates (95% confidence intervals (CIs)) of breast cancer-specific mortality associated with the percentage of tumor cell nuclei positively stained for estrogen receptor (ER) in all women (A), in white women (B), and in black women (C) with invasive breast cancer.

Figure 3

Estrogen receptor Histo-score and breast cancer-specific mortality risk. Adjusted hazard ratio (HR) estimates (95% confidence intervals (CIs)) of breast cancer-specific mortality associated with the estrogen receptor (ER) Histo (H)-score in all women (A), in white women (B), and in black women (C) with invasive breast cancer.

Figure 4

ER/PR/HER2 score and breast cancer-specific mortality risk in women diagnosed with estrogen receptor-positive breast cancer. Adjusted hazard ratio (HR) estimates (95% confidence intervals (CIs)) of breast cancer-specific mortality associated with the estrogen receptor/progesterone receptor/ human epidermal growth factor receptor 2 (ER/PR/HER2) score in all women (A), in white women (B), and in black women (C) with ER-positive invasive breast cancer.