Document Type
Article
Abstract
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 (P trend = 0.0003) and the ER H-score (P trend = 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 (P trend = 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 P trend ≤ 0.01) while the ER/PR/HER2 score provided additional discrimination for both white women (P trend = 0.01) and black women (P trend = 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.
Disciplines
Hormones, Hormone Substitutes, and Hormone Antagonists | Oncology | Women's Health
Recommended Citation
Ma et al.: Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women. Breast Cancer Research 2013 15:R90. 17. Press MF, Sauter G, Bernstein L, Villalobos IE, Mirlacher M, Zhou J-Y, Wardeh R, Li Y-T, Guzman R, Ma Y, Sullivan-Halley J, Santiago A, Park JM, Riva A, Slamon DJ: Diagnostic evaluation of HER-2 as a molecular target: an assessment of accuracy and reproducibility of laboratory testing in large, prospective, randomized clinical trials. Clin Cancer Res 2005, 11:6598–6607. 18. Ma H, Wang Y, Sullivan-Halley J, Weiss L, Burkman RT, Simon MS, Malone KE, Strom BL, Ursin G, Marchbanks PA, McDonald JA, Spirtas R, Press MF, Bernstein L: Breast cancer receptor status: do results from a centralized pathology laboratory agree with SEER registry reports? Cancer Epidemiol Biomarkers Prev 2009, 18:2214–2220. 19. Cox D, Oakes D: Analysis of Survival Data. London: Chapman & Hall; 1984. 20. Ma H, Lu Y, Malone KE, Marchbanks PA, Deapen DM, Spirtas R, Burkman RT, Strom BL, McDonald JA, Folger SG, Simon MS, Sullivan-Halley J, Press MF, Bernstein L: Mortality risk of black women and white women with invasive breast cancer by hormone receptors, HER2, and p53 status. BMC Cancer 2013, 13:225. 21. Morgan DA, Refalo NA, Cheung KL: Strength of ER-positivity in relation to survival in ER-positive breast cancer treated by adjuvant tamoxifen as sole systemic therapy. Breast 2011, 20:215–219. Kleinbaum G, Kupper L, Morgestern H: Epidemiologic Research: Principles and Quantitative Methods. New York: Van Nostrand Reinhold; 1982. 22. 23. Howat JM, Harris M, Swindell R, Barnes DM: The effect of oestrogen and progesterone receptors on recurrence and survival in patients with carcinoma of the breast. Br J Cancer 1985, 51:263–270. 25. 26. 24. Vollenweider-Zerargui L, Barrelet L, Wong Y, Lemarchand-Beraud T, Gomez F: The predictive value of estrogen and progesterone receptors’ concentrations on the clinical behavior of breast cancer in women. Clinical correlation on 547 patients. Cancer 1986, 57:1171–1180. Shek LL, Godolphin W: Survival with breast cancer: the importance of estrogen receptor quantity. Eur J Cancer Clin Oncol 1989, 25:243–250. Lockwood CA, Ricciardelli C, Raymond WA, Seshadri R, McCaul K, Horsfall DJ: A simple index using video image analysis to predict disease outcome in primary breast cancer. Int J Cancer 1999, 84:203–208. Elledge RM, Green S, Pugh R, Allred DC, Clark GM, Hill J, Ravdin P, Martino S, Osborne CK: Estrogen receptor (ER) and progesterone receptor (PgR), by ligand-binding assay compared with ER, PgR and pS2, by immuno-histochemistry in predicting response to tamoxifen in metastatic breast cancer: a Southwest Oncology Group Study. Int J Cancer 2000, 89:111–117. 27. 28. Byar DP, Sears ME, McGuire WL: Relationship between estrogen receptor values and clinical data in predicting the response to endocrine therapy for patients with advanced breast cancer. Eur J Cancer 1979, 15:299–310. 29. Bartlett JM, Brookes CL, Robson T, van de Velde CJ, Billingham LJ, Campbell FM, Grant M, Hasenburg A, Hille ET, Kay C, Kieback DG, Putter H, Markopoulos C, Kranenbarg EM, Mallon EA, Dirix L, Seynaeve C, Rea D: Estrogen receptor and progesterone receptor as predictive biomarkers of response to endocrine therapy: a prospectively powered pathology study in the Tamoxifen and Exemestane Adjuvant Multinational trial. J Clin Oncol 2011, 29:1531–1538. 30. Dowsett M, Allred C, Knox J, Quinn E, Salter J, Wale C, Cuzick J, Houghton J, Williams N, Mallon E, Bishop H, Ellis I, Larsimont D, Sasano H, Carder P, Cussac AL, Knox F, Speirs V, Forbes J, Buzdar A: Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the Arimidex, Tamoxifen, Alone or in Combination trial. J Clin Oncol 2008, 26:1059–1065. Silverstrini R, Daidone MG, Di Fronzo G: Relationship between proliferative activity and estrogen receptors in breast cancer. Cancer 1979, 44:665–670. 31. 32. Raber MN, Barlogie B, Latreille J, Bedrossian C, Fritsche H, Blumenschein G: Ploidy, proliferative activity and estrogen receptor content in human breast cancer. Cytometry 1982, 3:36–41. 33. Meyer JS, Lee JY: Relationships of S-phase fraction of breast carcinoma in relapse to duration of remission, estrogen receptor content, therapeutic responsiveness, and duration of survival. Cancer Res 1980, 40:1890–1896. 34. Gorin SS, Heck JE, Cheng B, Smith SJ: Delays in breast cancer diagnosis and treatment by racial/ethnic group. Arch Intern Med 2006, 166:2244–2252. 35. Griggs JJ, Sorbero ME, Stark AT, Heininger SE, Dick AW: Racial disparity in the dose and dose intensity of breast cancer adjuvant chemotherapy. Breast Cancer Res Treat 2003, 81:21–31.
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