Tissue expression and serum levels of the oncoprotein HER-2/neu in 157 primary breast tumours.

BACKGROUND: We studied HER-2 expression in paired serum and tissue samples, in 157 selected cases from 701 consecutive primary breast cancer patients with pre-treatment HER-2 extracellular domain (ECD) > or = 10 ng/ml, or < 10 ng/ml but showing a HER-2 ECD lead time before first metastasis. PATIENTS AND METHODS: HER-2 ECD was measured by the Immuno 1 automated ELISA (Bayer). Tumour tissue was analysed by immunohistochemistry (IHC) with Dako A 0485 and CB 11 antibodies and scored with the Dako scoring system. RESULTS: Mean HER-2 ECD was 12.48+/-7.08 ng/ml and 21/157 (13.4%) sera were > or = 15 ng/ml (cut-off). Forty tumours (25.48%) showed both invasive and intraductal components, 3 (1.91%) were pure in situ carcinomas and 114 (72.61%) were pure invasive tumours. Elevated HER-2 ECD concentration was related only to pT (p=0.0008), histological grade (p=0.0465), presence of comedonecrosis (p=0.0123) or comedo-type carcinoma (p=0.041) and was unrelated to the presence of an intraductal component. HER-2 ECD was > or = 15 ng/ml in 48% of Dako 3+ and 60% of CB 11 2+ and 3+ tumours. By logistic regression analysis, the significant parameters associated with HER-2 ECD concentration were pT (p=0.0038) and Dako 3+ scores (p=0.0005). In Dako 3+ or CB 11 2+3+ tumours, elevated mean HER-2 ECD concentrations were observed only when pT exceeded 28-30 mm (p=0.0062 and p=0.0036, respectively). CONCLUSION: In breast tumours, a threshold in size and HER-2 overexpression is necessary to observe elevated concentrations of HER-2 ECD at diagnosis. This information may be useful when the primary tumour is not available for IHC.

Serum HER-2 extracellular domain: relationship with clinicobiological presentation and prognostic value before and after primary treatment in 701 breast cancer patients.

PURPOSE: To determine the clinical correlations and prognostic value of serum HER-2 (sHER-2) before and after primary breast cancer treatment. METHODS: sHER-2 from 701 consecutive patients with stage I-III tumors (median follow-up 7.7 years) was assayed by an enzyme-linked immunosorbent assay (Immuno 1, Bayer Diagnostics). RESULTS: The median pretreatment sHER-2 concentration was 8.30 ng/mL (range 3.15-82.00 ng/mL). Forty-seven patients (6.7%) had sHER-2 concentrations >12 ng/mL (cutoff level). Pretreatment sHER-2 correlated positively with CA 15.3 (p=0.0169), pathological tumor size (p=0.0082), number of invaded lymph nodes (pN, p=0.0160) and histological grading (p=0.0086). Kaplan-Meier analyses indicated that pretreatment sHER-2 was of prognostic value for contralateral breast cancer (p=0.0018), metastasis-free survival (MFS) (p=0.0008) - particularly lung (p=0.0082) and liver metastases (p=0.0035) - and overall disease-specific survival (DSS) (p=0.0020). According to pN status, pretreatment sHER-2 was of prognostic value only for pN-positive patients (p=0.0017). When combined with estradiol or progesterone receptor status, patients with elevated sHER-2 and receptor-negative tumors had a significantly shorter DSS (p<0.0001 for both receptors). Post-treatment sHER-2 also had individual prognostic value for MFS (p=0.0144) and DSS (p=0.0212). In multivariate analysis, only sHER-2 after primary treatment was an independent prognostic variable for MFS and DSS (p=0.0078 and p=0.0058, respectively). CONCLUSION: sHER-2 elevation in early breast cancer correlates with the principal criteria of tumor aggressiveness, thus permitting selection of patients with a high risk of visceral metastases and contralateral breast tumors. Post-treatment sHER-2 is an independent prognostic factor enabling to identify patients likely to benefit from aggressive adjuvant treatments.