Primary chemotherapy in breast invasive carcinoma: predictive value of the immunohistochemical detection of hormonal receptors, p53, c-erbB-2, MiB1, pS2 and GST pi

Abstract

Summary Primary chemotherapy in operable breast invasive carcinoma enables tumour reduction and conservative surgery. In order to search for one or more biological factors capable of predicting tumour behaviour under primary chemotherapy, and subsequent patient survival, an immunohistochemical study was performed with specific antibodies to p53, c-erbB-2 (Her-2/neu), Mibl (antiKi-67), pS2, GSTir, oestrogen receptors (ERs) and progesterone receptors (PRs). Core biopsies, obtained before primary chemotherapy, were available from a series of 128 breast invasive carcinomas treated between January 1985 and April 1989, with a median follow-up of 93.3 months. Univariate statistical analysis showed that negative ER detection by immunohistochemistry (IHC) was highly correlated with chemosensitivity (P=0.001). A high percentage of Mibl-positive tumour cells (>40%), as well as initial tumour size less than 4 cm, were also correlated with tumour responsiveness to chemotherapy (P=0.009 and P=0.03). By multivariate analysis IHC-ER, Mibl and initial tumour size were independent predictors, the last parameter being the most important. Concerning subsequent patient survival, c-erbB-2 overexpression, as detected by IHC, was significant with respect to overall survival (OS) (P=0.0006), disease-free interval (DFI) (P=0.03) and metastasis-free interval (MFI) (P=0.008) by univariate analysis. Furthermore, c-erbB-2 was the major independent prognostic factor for OS and MFI by multivariate analysis.

Oestrogen receptor status, pathological complete response and prognosis in patients receiving neoadjuvant chemotherapy for early breast cancer

“…Previous studies have shown that ER-negative tumours are likely to have better clinical (as opposed to pathological) responses than ER-positive tumours (Bonadonna et al, 1990;Mauriac et al, 1991;MacGrogan et al, 1996). Colleoni et al (2000b) found a significantly higher clinical response rate in patients receiving neoadjuvant chemotherapy, in whose tumours ER and PgR were absent, compared to those where ER and/or PgR were expressed (82 vs 57%; P ¼ 0.03).…”

DNA topoisomerase IIα expression and the response to primary chemotherapy in breast cancer

“…The predictive and prognostic value of the immunohistochemical detection of oestrogen and progesterone receptors, p53, Her-2/ neu, and Ki-67 (antibody: Mib-1), had been analysed previously on the same cohort (MacGrogan et al, 1996a) and served as reference data for the current study.…”

“…It also appears that Topo IIa expression is often correlated to Her-2/neu overexpression in breast carcinoma. This complex relationship between the two genes may explain the altered sensitivity to anthracyclines of Her-2/neu-amplified breast carcinomas (Bitran et al, 1996;MacGrogan et al, 1996a;Niskanen et al, 1997;Clahsen et al, 1998;Jarvinen et al, 1998;Paik et al, 1998;Thor et al, 1998;Vincent-Salomon et al, 2000). Most previous studies regarding the effect of Topo IIa poisons in relation to the cellular level of Topo IIa expression were either performed in vitro or on breast tumour fragments without analysis of the direct in vivo effect (Gudkov et al, 1993;Asano et al, 1996a, b;Vassetzky et al, 1996;Withoff et al, 1996a, b;Zhou et al, 1999;Stacey et al, 2000).…”

Increasing steroid hormone receptors expression defines breast cancer subtypes non responsive to preoperative chemotherapy

“…The early identification of features associated with response or resistance to primary therapy are important in the development of the most effective multimodal approaches, and identifying cohorts of patients most likely to benefit from preoperative chemotherapy (PCT) [1][2][3]. Features predictive of response and outcome include steroid hormone receptor expression.…”