Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer
- PMID: 23233704
- PMCID: PMC3532392
- DOI: 10.1200/JCO.2012.43.4134
Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer
Abstract
Purpose: Current immunohistochemical (IHC)-based definitions of luminal A and B breast cancers are imperfect when compared with multigene expression-based assays. In this study, we sought to improve the IHC subtyping by examining the pathologic and gene expression characteristics of genomically defined luminal A and B subtypes.
Patients and methods: Gene expression and pathologic features were collected from primary tumors across five independent cohorts: British Columbia Cancer Agency (BCCA) tamoxifen-treated only, Grupo Español de Investigación en Cáncer de Mama 9906 trial, BCCA no systemic treatment cohort, PAM50 microarray training data set, and a combined publicly available microarray data set. Optimal cutoffs of percentage of progesterone receptor (PR) -positive tumor cells to predict survival were derived and independently tested. Multivariable Cox models were used to test the prognostic significance.
Results: Clinicopathologic comparisons among luminal A and B subtypes consistently identified higher rates of PR positivity, human epidermal growth factor receptor 2 (HER2) negativity, and histologic grade 1 in luminal A tumors. Quantitative PR gene and protein expression were also found to be significantly higher in luminal A tumors. An empiric cutoff of more than 20% of PR-positive tumor cells was statistically chosen and proved significant for predicting survival differences within IHC-defined luminal A tumors independently of endocrine therapy administration. Finally, no additional prognostic value within hormonal receptor (HR) -positive/HER2-negative disease was observed with the use of the IHC4 score when intrinsic IHC-based subtypes were used that included the more than 20% PR-positive tumor cells and vice versa.
Conclusion: Semiquantitative IHC expression of PR adds prognostic value within the current IHC-based luminal A definition by improving the identification of good outcome breast cancers. The new proposed IHC-based definition of luminal A tumors is HR positive/HER2 negative/Ki-67 less than 14%, and PR more than 20%.
Conflict of interest statement
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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Comment in
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Menopausal status should be taken into consideration for patients with luminal a breast cancer in terms of the effect of differential biology on prognosis.J Clin Oncol. 2013 Jul 1;31(19):2516. doi: 10.1200/JCO.2013.49.4062. Epub 2013 May 20. J Clin Oncol. 2013. PMID: 23690409 No abstract available.
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Reply to Y.Yamamoto et al.J Clin Oncol. 2013 Jul 1;31(19):2517-8. doi: 10.1200/JCO.2013.49.9061. J Clin Oncol. 2013. PMID: 23967491 No abstract available.
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