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Journal of Clinical Oncology, Vol 23, No 12 (April 20), 2005: pp. 2870-2871 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.05.241
Time for Reappraisal of Progesterone-Receptor Testing in Breast Cancer ManagementInstitut Bergonié, Bordeaux, France To the Editor:
Banerjee et al1 published a report in the July 1, 2004, issue of the Journal of Clinical Oncology demonstrating the prognostic value of progesterone receptor (PR) status in a series of 1,055 patients with stage I-III breast cancer. Using recursive partitioning, a nonparametric statistical technique, they were able to determine four distinct prognostic groups defined by the number of positive nodes, tumor size, PR status, differentiation, race, and marital status. In the May 1, 2004, issue of the Journal, a letter to the editor by Olivotto et al2 advocated the interruption of PR testing in breast cancer patients on the basis of a study of 192 estrogen-receptor (ER) -negative breast cancer patients among which 191 were also PR-negative. PR status was determined by an immunohistochemical technique that used clone 1A6. In the opinion of Olivotto et al,2 routine PR testing is not warranted for its prognostic value, and may only serve to identify ER-negative patients who may respond to hormonal therapy. Given their results the authors were convinced that PR status determination did not give any additional information to ER determination. Following these publications, we would like to contribute to the debate on the utility of testing PR status for prognostication in early breast cancer. In 1996, we published a report concerning 942 patients with T1-3 breast cancer who had been surgically treated between 1980 and 1986 with a median follow-up period of 117.9 months.3 The purpose of this study was to validate the immunohistochemical detection of PR (IHC-PR) by comparing it with a standard dextran-coated charcoal (DCC) method, and to assess its prognostic significance in early breast cancer. Mean patient age in the series was 56 years, and there were 398 node-negative (42%) and 544 node-positive (58%) patients. IHC-PR tumor status was determined using the PgR-ICA Abbott monoclonal antibody. Five hundred and fifty tumors (58.4%) were IHC-PR positive. Concordance between the IHC and the DCC methods in the series was 83.2%. In the node-negative group of patients, IHC-PR status was the only independent prognostic factor for overall survival (OS; odds ratio [OR] = 3; 95% CI, 1.8 to 5.3; P < .0001) in a multivariate analysis, using a Cox proportional hazards model, including patients' age, menopausal status, tumor size, Scarff-Bloom-Richardson grade, and ER status. Furthermore, in the node-negative group of patients, IHC-PR status was an independent prognostic factor for disease-free survival (OR = 1.8; 95% CI, 1.2 to 2.8; P = .008) and metastasis-free survival (OR = 1.8; 95% CI, 1.1 to 3; P = .02), alongside with tumor size and Scarff-Bloom-Richardson grade. The five-year OS in the whole group (node-negative and node-positive patients) was 74% and 85% for patients with less than 10% and 10% to 49% IHC-PR–positive tumor cells (P = .0002), respectively, and 85% and 93% for patients with 10% to 49% and In our studies, PR status, as determined by accurate immunohistochemical methods, is a strong prognostic factor, and survival is correlated to the proportion of PR-positive cells in breast tumors. In contrast, ER status is of lesser prognostic significance. PR testing should be performed on patients with breast cancer, and the results should be used for correct determination of their prognosis and management. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. Acknowledgment The authors whish to acknowledge Dr Gabriel N. Hortobagyi for reviewing this letter. REFERENCES
1. Banerjee M, George J, Song EY, et al: Tree-based model for breast cancer prognostication. J Clin Oncol 22:2567-2575, 2004
2. Olivotto IA, Truong PT, Speers CH, et al: Time to stop progesterone receptor testing in breast cancer management. J Clin Oncol 22:1769-1770, 2004 3. MacGrogan G, Soubeyran I, de Mascarel I, et al: Immunohistochemical detection of progesterone receptors in breast invasive ductal carcinomas: A correlative study of 942 cases. Appl Immunohistochem 4:219-227, 1996
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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50% IHC-PR–positive tumor cells (P = .008), respectively. Subsequent to this publication, we performed the survival analysis again, using Dako PgR636, a different antibody specific for PR, in the same group of 398 node-negative patients with a longer median follow-up (170 months), and by adding peritumoral vascular emboli to the previous Cox proportional hazard model. PR status determined by PgR636 was again an independent prognostic factor for OS (relative risk [RR] = 2; 95% CI, 1.4 to 2.9); P = .0002), metastasis-free survival (RR = 1.9; 95% CI, 1.2 to 3; P = .001) and disease-free survival (RR = 1.5; 95% CI, 1.1 to 2.2; P = .02) alongside with peritumoral vascular emboli. 
