Value of epidermal growth factor receptor status compared with growth fraction and other factors for prognosis in early breast cancer

Abstract

Summary The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein whose expression is important in the regulation of breast cancer cell growth. The relationship between EGFR status (determined by an immunocytochemical assay) and various prognostic factors was investigated in 164 primary breast cancers. Overall 56% of tumours were EGFR-positive and the expression of EGFR was unrelated to axillary node status, tumour size and histological grade; and it was poorly associated with the tumour proliferative activity measured by Ki-67 immuno-cytochemistry. The relapse-free survival (RFS) probability at 3-years was significantly worse for patients with EGFR positive tumours (P = 0.003) and for those whose Ki-67 score was >7.5% (P = 0.0027), as well as in patients with axillary node involvement (P = 0.01) and with poorly differentiated tumours (P = 0.04). Immunocytochemical determination of EGFR and cell kinetics gave superimposable prognostic information for predicting RFS with odds ratios of 3.51, when evaluated singly. In our series of patients EGFR, Ki-67 and node status retain their prognostic value concerning RFS in multivariate analysis. The 3-year probability of overall survival (OS) was significantly better in node-negative patients (P = 0.04) and was similar in EGFR-positive and negative patients.In conclusion, EGFR status appears to be a significant and independent indicator of recurrence in human breast cancer and the concomitant measurement of the tumour proliferative activity seems to improve the selection of patients with different risks of recurrence.

Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients

“…HR associated with Ki-67 positivity in this case) from studies with inherent dissimilarities. The observed disparity among the conclusions of different studies, responsible for the observed heterogeneity, can be quantified by applying Bukholm et al (2003) 147 No Ceccarelli et al (2000) 217 Yes Galiegue et al (2004) 117 No Gasparini et al (1992) 164 Yes Haerslev et al (1996) 487 Yes Jalava et al (2000) 414 No Kroger et al (2006) 157 No Kronblad et al (2006) 377 Yes Lampe et al (1998) 142 Yes Liu et al (2000) 225 Yes Michels et al (2003) 104 No Molino et al (1997) 322 Yes Rudas et al (1994) 184 No Tsutsui et al (2005) 249 Yes Yang et al (2003) 147 No…”

Signal transduction in mammary tumorigenesis: a transgenic perspective

“…A number of genes are ampli®ed and/or overexpressed in human mammary tumors. These include growth factor like molecules (int2: Schuuring et al, 1992;Zhou et al, 1988), growth factor receptors (EGFR: Gasparini et al, 1992;Sainsbury et al, 1988, c-ErbB2: Slamon et al, 1987, 1989, other tyrosine kinases (Jacobs and Rubsamen, 1983;Ottenho -Kal et al, 1992;, signaling molecules (GRB7 Stein et al, 1994), transcription factors (c-myc: Berns et al, 1992) and cell cycle regulators (cyclin D1/PRAD-1: Bartkova et al, 1994;Buckley et al, 1993, CDC25B: Galaktionov, 1995. While several genes are ampli®ed in each amplicon (or at each locus), three candidates may be relevant to human disease (erbB-2, c-myc and cyclin D respectively).…”

Prospective evaluation of prognostic factors in operable breast cancer

“…Saez et al, 1983). The receptor for epidermal growth factor is a membrane protein (Mr 180 kDa), which has been reported to be a sign of bad prognosis, again in multiple studies (Sainsbury et al, 1987;Gasparini et al, 1992). The proteolytic enzyme, cathepsin D (Mr 52 kDa), has been suggested to be involved in metastasis formation and reported in several studies also to be a sign of bad prognosis when present in high levels (for a review see Rochefort, 1990).…”