Utility of C-erbB-2 in tissue and in serum in the early diagnosis of recurrence in breast cancer patients: comparison with carcinoembryonic antigen and CA 15.3

Abstract

Summary To evaluate the utility of c-erbB-2, carcinoembryonic antigen (CEA) and CA 15.3 in the early diagnosis of recurrence, serial serum determinations of these antigens were performed in 200 patients (followup 1-4 years, mean 2.2 years) with primary breast cancer and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). Eighty-nine patients developed metastases during follow-up. C-erbB-2, CEA and CA 15.3 were elevated (>20 U ml -, > 0 ng ml-or >60 U ml-1 respectively) before diagnosis in 28%, 30% and 47% of the 89 patients with recurrence, with a lead time of 4.5 + 2.4, 4.9+2.4 and 4.8 + 2.4 months respectively. Tumour marker sensitivity was clearly related to the site of recurrence, with the lowest sensitivity found in locoregional relapse and the highest in patients with liver metastases. When patients with locoregional recurrences were excluded, sensitivity improved: 31 % (cerbB-2), 33% (CEA) and 56% (CA 15.3), with 76% having at least one of the three tumour markers. C-erbB-2 sensitivity in early diagnosis was significantly higher in patients with c-erbB-2 overexpression in tissue (8/10, 80%) than in those without overexpression (1/30, 3.3%) (P=0.0001). Likewise, higher levels of both, c-erbB-2 and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse and a higher lead time were found in PR+ patients (CA 15.3, P<0.0001) or in PR-patients (c-erbB-2, P=0.009). Specificity of the tumour markers was 100% for all three markers (111 NED patients). In conclusion, c-erbB-2 is a useful tool for early diagnosis of metastases, mainly in those patients with c-erbB-2 overexpression in tissue. Using all three markers simultaneously it is possible to increase the sensitivity in the early diagnosis of recurrence by 11.2%.

Expression of C-erbB-2/HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous blood stem cell support

“…This is consistent with that found in the few studies that have examined overexpression in MBC; ie 20-57% of patients with MBC have elevated HER-2 plasma concentrations. [14][15][16][17][18][19][20][22][23][24][25] The HER-2 positive patients in this study had a significantly decreased OS and PFS following HDCT and ABSC transplantation ( Table 2 and Figures 1 and 2). Therefore, the presence of elevated plasma HER-2 may be an important prognostic factor that could be used to select more effective and additional therapies for these patients (eg directly targeted treatments using immunologic therapy).…”

“…[7][8][9][10][11][12][13][14] Although HER-2 oncoprotein overexpression correlates with reduced patient survival, few studies have evaluated the incidence of HER-2 overexpression in patients with metastatic breast cancer (MBC) and examined whether increased levels of this protein indicate a poorer prognosis and/or reduced responsiveness to systemic treatment. [14][15][16][17][18][19][20][21][22][23][24] In these studies, 30-50% of patients with MBC had elevated levels of circulating (plasma, serum) extracellular domain of HER-2. [14][15][16][17][18][19] Overexpression correlates with an increased tumour burden and reduced survival.…”

“…[14][15][16][17][18][19] Overexpression correlates with an increased tumour burden and reduced survival. [14][15][16]18,[22][23][24][25] Since EIA (enzyme immunoassay) is a relatively simple assay commonly used in clinical medicine, the possibility that elevated levels of extracellular HER-2 could indicate poor prognosis in patients with MBC is of particular interest.…”

ADVIA Centaur® Her-2/Neu Shows Value in Monitoring Patients with Metastatic Breast Cancer

“…Since 1989, many reports have been published demonstrating the importance of quantifying the HER-2/neu ECD in serum or plasma of women with metastatic breast cancer (19)(20)(21)(22)(23)(24). Many of these studies have shown that breast cancer patients with elevated levels of serum HER-2/neu have a poor prognosis and shorter overall survival.…”

Relationships among Serum CA15-3 Tumor Marker, TNM Staging, and Estrogen and Progesterone Receptor Expression in Benign and Malignant Breast Lesions

“…Increased levels were observed in patients with breast cancer (Kobayashi et al, 1989). Clinical uses of this marker include monitoring of patients with breast cancer (Duffy, 1999;Duffy et al, 2006), prognosis (McLaughlin et al, 2000), recurrence (Busetto et al, 1995;Molina et al, 1996;Molina et al, 1999) and metastasis (Elston et al, 1999;Thompson et al, 1991). CA15-3 level correlate exclusively with tumor size; higher CA15-3 serum level was found in advanced cancer stages, higher grades and metastasis (Berruti et al, 1994;Gang et al, 1985;Kikuchi et al, 1987;Theriault et al, 1989Theriault et al, :2007Tampellini et al, 1997;Gion et al, 2002).…”