Originally published as JCO Early Release 10.1200/JCO.2007.14.5565 on February 19 2008

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Estrogen Receptor, Progesterone Receptor, HER-2, and Response to Postmastectomy Radiotherapy in High-Risk Breast Cancer: The Danish Breast Cancer Cooperative Group

Marianne Kyndi, Flemming B. Sørensen, Helle Knudsen, Marie Overgaard, Hanne Melgaard Nielsen, Jens Overgaard

From the Departments of Experimental Clinical Oncology, Oncology, and Pathology, Aarhus University Hospital, Århus; and the Department of Pathology, Herlev Hospital, Herlev, Denmark

Corresponding author: Marianne Kyndi, MD, Department of Experimental Clinical Oncology, Aarhus University Hospital, Århus Sygehus, Noerrebrogade 44, Building 5, 2, DK-8000 Aarhus C, Denmark; e-mail: kyndi{at}oncology.dk

Purpose To examine the importance of estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER-2), and constructed subtypes in a large study randomly assigning patients to receive or not receive postmastectomy radiotherapy (PMRT).

Patients and Methods The present analysis included 1,000 of the 3,083 high-risk breast cancer patients randomly assigned to PMRT in the Danish Breast Cancer Cooperative Group (DBCG) protocol 82 trials b and c. Tissue microarray sections were stained for ER, PgR, and HER-2. Median follow-up time for patients alive was 17 years. End points were locoregional recurrence as isolated first event, distant metastases, and overall survival. For statistical analyses four subgroups were constructed from hormonal receptors (Rec). Rec+ was defined as ER+ and/or PgR+. Rec–as both ER–and PgR–. The four subgroups were Rec+/HER-2–, Rec+/HER-2+, Rec–/HER-2–(triple negative), and Rec–/HER-2+.

Results A significantly improved overall survival after PMRT was seen only among patients characterized by good prognostic markers such as hormonal receptor–positive and HER-2– patients (including the two Rec+ subtypes). No significant overall survival improvement after PMRT was found among patients with an a priori poor prognosis, the hormonal receptor–negative and HER-2+ patients, and in particular the Rec–/HER-2+ subtype. Furthermore, comparing hazard ratios and 95% CIs, significantly smaller improvements in locoregional recurrence control after PMRT were found for ER–and PgR–tumors compared with the ER+ and PgR+ tumors (P = .003 and .04, respectively), and for the triple-negative (P = .02), and the Rec–/HER-2+ subtypes (P = .003) compared with the Rec+/HER-2–subtype.

Conclusion Hormonal receptor status, HER-2, and the constructed subtypes may be predictive of locoregional recurrence and survival after postmastectomy radiotherapy.

published online ahead of print at www.jco.org on February 19, 2008.

Supported by grants from the Danish Cancer Society, the University of Aarhus, the Danish Medical Research council, Danish Ministry of Health, and M.L. Jørgensen and Gunnar Hansen's foundation.

Presented in part at the 5th European Breast Cancer Conference, March 21-25, 2006, Nice, France.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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