Frequently increased epidermal growth factor receptor (EGFR) copy numbers and decreased BRCA1 mRNA expression in Japanese triple-negative breast cancers

We studied 969 consecutive Japanese patients diagnosed with invasive breast cancer from January 1981 to December 2003, and selected TNBCs based on the immunohistochemical data. Analyses of epidermal growth factor receptor (EGFR) gene mutations and amplification, and BRCA1 mRNA expression were performed on these samples using TaqMan PCR assays. The prognostic significance of TNBCs was also explored. Median follow-up was 8.3 years.A total of 110 (11.3%) patients had TNBCs in our series. Genotyping of the EGFR gene was performed to detect 14 known EGFR mutations, but none was identified. However, EGFR gene copy number was increased in 21% of TNBCs, while only 2% of ER- and PgR-positive, HER2-negative tumors showed slightly increased EGFR gene copy numbers. Thirty-one percent of TNBCs stained positive for EGFR protein by immunohistochemistry. BRCA1 mRNA expression was also decreased in TNBCs compared with controls. Triple negativity was significantly associated with grade 3 tumors, TP53 protein accumulation, and high Ki67 expression. TNBC patients had shorter disease-free survival than non-TNBC in node-negative breast cancers.TNBCs have an aggressive clinical course, and EGFR and BRCA1 might be candidate therapeutic targets in this disease.Although the overall mortality due to breast cancer in the United States has decreased, attributed in part to breast screening and early application of various treatments, overall mortality in Japan is still increasing [1]. Breast cancers represent a heterogeneous group of tumors that are diverse in behavior, outcome, and sensitivity to therapy. To reduce mortality from breast cancer, it would be desirable to identify and characterize tumors having a poor prognosis. Emerging data demonstrate that stratification of tumors by gene expression profiles divides breast cancer into four common subtypes which are associated with different clinical outcome [2]. Two of them are estrogen receptor (ER)-positive (luminal and luminal/HER2+) and two