HER2 Support Group Forums - View Single Post - are her2+ (and/or EGFR+) tumors more radioresistant (ie radiation therapy doesn't

Lani · 10-31-2006, 05:11 PM

DISCUSSION Go to:
The oncogene HER-2, a member of a family of protein kinases that includes the EGFRs, is an important molecular marker in breast cancer that is overexpressed in 20–30% of all breast cancers. Amplification of the gene has been associated with a poorer prognosis (2,3) and with resistance to chemotherapy and hormonal therapy (18,19). EGFR family members' overexpression has been implicated in radioresistance pathways. Very limited data exist with respect to the clinical interaction of HER-2 overexpression and breast irradiation.

Several studies have shown that overexpression of HER-2 and other EGFR family members is associated with radioresistance in laboratory systems. In a study using MCF-7 breast cancer cells, epidermal growth factor (EGF) stimulated growth and increased radioresistance in vitro (20). A study in a murine model including four breast carcinomas found that tumor radioresponsiveness was highly correlated with EGFR expression and that high levels of EGFR expression required a higher radiation dose to achieve 50% tumor control (TCD50) (21). A causal relationship between EGFR expression and radioresponse was suggested by a study in which EGFR (HER-1) was transfected into ovarian carcinoma cells, which showed an EGFR level dependent increase in radioresistance by a factor of 1.60 for high levels of expression, and by lesser factors for lower levels of expression (22). This effect was reversed by treatment of the transfected cells with C225, a monoclonal antibody that blocks EGFR.

10-31-2006, 05:11 PM	#2
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	more... DISCUSSION Go to: The oncogene HER-2, a member of a family of protein kinases that includes the EGFRs, is an important molecular marker in breast cancer that is overexpressed in 20–30% of all breast cancers. Amplification of the gene has been associated with a poorer prognosis (2,3) and with resistance to chemotherapy and hormonal therapy (18,19). EGFR family members' overexpression has been implicated in radioresistance pathways. Very limited data exist with respect to the clinical interaction of HER-2 overexpression and breast irradiation. Several studies have shown that overexpression of HER-2 and other EGFR family members is associated with radioresistance in laboratory systems. In a study using MCF-7 breast cancer cells, epidermal growth factor (EGF) stimulated growth and increased radioresistance in vitro (20). A study in a murine model including four breast carcinomas found that tumor radioresponsiveness was highly correlated with EGFR expression and that high levels of EGFR expression required a higher radiation dose to achieve 50% tumor control (TCD50) (21). A causal relationship between EGFR expression and radioresponse was suggested by a study in which EGFR (HER-1) was transfected into ovarian carcinoma cells, which showed an EGFR level dependent increase in radioresistance by a factor of 1.60 for high levels of expression, and by lesser factors for lower levels of expression (22). This effect was reversed by treatment of the transfected cells with C225, a monoclonal antibody that blocks EGFR.