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.


OBJECTIVE
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.
Department of Pathology, Medical University of Graz, Auenbruggerplatz 25, A-8036 Graz, Austria. sebastian.leibl@klinikum-graz.at
S
S
Leibl
F
F
Moinfar
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000627:therapeutic use*; D008679:Metaplasia / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
D000970:Antineoplastic Agents; D066246:ErbB Receptors; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C015482:protein kinase modulator