Serum epidermal growth factor receptor and HER2 expression in primary and metastatic breast cancer patients.
BACKGROUND
Breast tissue expression of the ERBB proto-oncogene family has been extensively studied. It was recently shown that expression of epidermal growth factor receptor (EGFR; c-erbB-1) and epidermal growth factor receptor (HER)2 (c-erbB-2) can be detected in the serum of breast cancer patients. The clinical relevance of this has not been fully established.


METHODS
EGFR and HER2 immunoassays were conducted in blood from 57 patients in whom paired serum samples were available (from the times of primary and metastatic diagnoses), from 96 primary breast cancer patients and from 49 normal individuals. Of the 57 patients with paired serum samples, paired tissue samples for HER2 expression were available for eight.


RESULTS
Serum levels of EGFR serum levels were significantly higher in normal individuals (median 75.3 ng/ml, range 43.2 to 114.2 ng/ml) than in patients with primary breast cancer (median 59.3 ng/ml, range 21.3 to 94.1 ng/ml; P < 0.001). In the paired serum samples, EGFR levels decreased significantly between the time of primary diagnosis (median 56.3 ng/ml, range 29.1 to 142.7 ng/ml) and metastatic diagnosis (median 30.9 ng/ml, range 10.9 to 106.4 ng/ml; P < 0.001). In six (11%) a change occurred from over-expression (>78 ng/ml) to normal expression. In contrast, no significant difference was seen in HER2 serum levels in normal individuals (median 12.2 ng/ml, range 7.8 to 20.9 ng/ml) and primary breast cancer patients (median 12.5 ng/ml, range 6.9 to 122.2 ng/ml; P = 0.511). However, in the paired serum samples, HER2 levels increased significantly between the time of primary (median 12.2 ng/ml, range 5.7 to 85.0 ng/ml) and metastasis (median 17.7 ng/ml, range 6.3 to 3,337.4 ng/ml; P < 0.001). HER2 over-expression (>15 ng/ml) was observed in 16 out of 57 patients (28%) at primary breast cancer diagnosis and in 31 out of 57 (54%) at metastasis. In 18 patients (32%) HER2 expression changed from normal to over-expression.


CONCLUSIONS
Decisions regarding the use of targeted therapies in the metastatic setting are often based on the oncogene expression of the primary tumour. Our results suggest that serum oncogene assessments may be complementary to this and could potentially widen the indications for these beneficial therapies.
Asgeirsson
Kristjan S
KS
Division of Breast Surgery, University of Nottingham, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, UK. kriskuli@landspitali.is
Agrawal
Amit
A
Allen
Claire
C
Hitch
Anthony
A
Ellis
Ian O
IO
Chapman
Caroline
C
Cheung
Kwok L
KL
Robertson
John F R
JF
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D002272:Carcinoembryonic Antigen / Q000097:blood; D017024:Chemotherapy, Adjuvant; D066246:ErbB Receptors / Q000097:blood*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007118:Immunoassay; D016555:Matched-Pair Analysis; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood; D011237:Predictive Value of Tests; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D015854:Up-Regulation
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D066246:ErbB Receptors; D018396:Mucin-1; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human