Metaplastic breast carcinomas are negative for Her-2 but frequently express EGFR (Her-1): potential relevance to adjuvant treatment with EGFR tyrosine kinase inhibitors?

Background: Metaplastic carcinomas (MCs) of the breast rarely express steroid receptors and Her-2, which minimises the options for adjuvant treatment in patients with advanced disease. Aims: To investigate the possible eligibility of patients with MCs for epidermal growth factor receptor ( EGFR) targeted treatment. Methods: Immunohistochemical assessment of the expression of steroid receptors and four members of the EGFR/Her family (EGFR/Her- 1 - 4) in 20 MCs ( eight with heterologous elements, seven spindle cell MCs, four carcinosarcomas, and one matrix producing carcinoma). Fourteen of the 20 MCs were positive for EGFR (Her-1). Among these cases, 1+, 2+, and 3+ reactivity were seen in two, four, and eight cases, respectively. Her-2 was only present in one MC with 1+ reactivity. Her-3 ( 1+ reactivity), Her-4 ( 2+ reactivity), and the androgen receptor ( 2+ reactivity) were also expressed by one tumour. Oestrogen and progesterone receptors ( 3+ reactivity each) were detected in the epithelial component only of two carcinosarcoma-type MCs. Conclusions: MCs express EGFR considerably more frequently than the types of breast carcinomas that have been investigated previously. Although molecular analyses for possible genetic alterations in the EGFR might be required, these results suggest that women suffering from this aggressive form of breast carcinoma might benefit from treatment with protein kinase inhibitors, such as gefitinib.