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

Abstract

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.

Breast Carcinosarcomas

“…The detection of EGFR (epidermal growth factor receptor) positivity in 14 of 20 patients with metaplastic carcinoma revealed the importance of developing strategies targeting these receptors (38). With the development of drugs such as gefitinib and cetuximab that target EGFR receptors, new treatment options will be available.…”

Spindle Cell Metaplastic Breast Carcinoma with Leiomyoid Differentiation: A Case Report

“…The role of ifosfamide should also be considered as an alternative approach to treatment. Other recommendations include wide local excision or mastectomy without axillary dissection [15], protein kinase inhibitors [14], anti-epidermal growth factor receptor drugs [16], or adjuvant radiotherapy [11], however, literature on current treatment guidelines is sparse due to the rarity of this disease.…”

“…However, although these markers clearly lend themselves to narrowing the diagnosis, they are not diagnostic for metaplastic carcinoma. HER2/neu and estrogen receptor status should also be evaluated for treatment options, however, spindle cell carcinomas rarely express these hormone receptors [14]. Mammography is not useful in the diagnosis of spindle cell carcinoma of the breast but is useful for the detection of a breast mass.…”

Clinicopathological and therapeutic features of metaplastic carcinoma of the breast: a study of 15 cases

“…Leibl and Moinfar found that targeted protein kinase such as gefitinib might be effective for some patients with MBC. 23 Although molecular analysis for possible genetic alterations in the EGFR might be required, there is a good possibility that women fighting MBC might benefit from treatment with protein kinase inhibitors, such as gefitinib and cetuximab. The prognosis of MBC, with respect to 'triple negative' status, is contrary to the norm.…”