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C Singer, Special Gynecology, Medical University of Vienna, Vienna, 1090, Austria
G Hudelist, Villach, Austria
E Fuchs, Oncology, MUW, vienna, Austria
W Koestler, vienna, Austria
A Fink-Retter, vienna, Austria
D Gschwantler-Kaulich, special gynaecology, Medical University of vienna, Vienna, Austria
M Gnant, Surgery, MUV, vienna, Austria
W Lamm, Division of Special gynaecology, MUV, vienna, Austria
M Rudas, pathology, muv, austria, Austria
K Czerwenka, vienna, Austria
E Kubista, vienna, Austria

Correspondence: Christian Singer, Email: christian.singer{at}meduniwien.ac.at

Abstract

HER-2 amplification and consecutive overexpression is a predictor for poor prognosis in breast cancer patients. In addition, incomplete resection of HER2 overexpressing tumors leads to increased proliferation of residual breast cancer cells. While the local release of cytokines is thought to be responsible for the malignant behaviour of remaining tumor tissue, the exact mechanism is still unknown. We have analyzed EGFR, activated (p)EGFR, and activated (p)HER2 protein expression in HER2 overexpressing and in non-HER2 overexpressing tumors from patients who underwent breast surgery and consecutive reexcision for involved margins, and compared expression levels by IHC. While overall HER2 protein expression in the initial and the reexcised sample were comparable, we observed an increase in pHER2 in DCIS in both, HER2 overexpressing (16/21 vs 24/24; P=0.018, Chi Square test) and non-HER2 overexpressing tumors (3/28 vs 5/12; P=0.025, Chi Square test). pHER2 was not increased in invasive tumors, regardless on whether the samples had been taken from a HER2 overexpressing (9/25 vs 6/17; P=0.261, Chi Square test), or a non-HER2 overexpressing tumor (1/27 vs 0/8; P=0.581, Chi Square test). EGFR expression was only detected in 1/47 HER2 overexpressing primary tumors and 2/48 non-HER2 overexpressing tumors, and was undetectable in reexcised specimen. Taken together, we have demonstrated an increase in HER2 receptor activation in incompletely resected preinvasive breast cancer. We hypothesize that receptor phosphorylation is caused by growth factor stimulation in response to intraoperative tissue damage, and perioperative inhibition of specific cytokines could become a promising therapeutic strategy.