Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer........

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J Clin Oncol. 2008 Mar 20;26(9):1419-26. Epub 2008 Feb 19.
receptor, progesterone receptor, HER-2, and response to postmastectomy
radiotherapy in high-risk breast cancer: the Danish Breast Cancer
Cooperative Group.

Kyndi M, Sørensen FB, Knudsen H, Overgaard M, Nielsen HM, Overgaard J; Danish Breast Cancer Cooperative Group.
of Experimental Clinical Oncology, Aarhus University Hospital, Arhus
Sygehus, Noerrebrogade 44, Building 5, 2, DK-8000 Aarhus C, Denmark.

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
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.