A multivariate analysis of tumour biological factors predicting response to cytotoxic treatment in advanced breast cancer

Abstract

Summary The study was designed to identify factors that could predict response to chemotherapy in breast cancer. A total of 173 patients with measurable or evaluable metastatic breast cancer were enrolled in a randomized trial between November 1987 and January 1991 to receive a monthly dose of 5-fluorouracil (500 mg m-2), epirubicin (60 mg m-2) and cyclophosphamide (500 mg m-2) either administered in four weekly doses or in an every-4-week dose as first-line cytotoxic treatment. In 103 evaluable patients we performed a multivariate analysis of the tumour biological factors, i.e. histological grade, oestrogen receptor (ER), progesterone receptor (PR), S-phase fraction (SPF), ploidy, p53, c-erbB-2, Bcl-2 and Bax expression, which showed significance in the univariate analysis according to treatment response, time to progression (TTP) or overall survival (OS). In the univariate analysis only SPF, grade and the proapoptotic protein Bax correlated with the response to cytotoxic treatment. In the multivariate analysis SPF had the strongest correlation, followed by grade and Bax. In the univariate analysis grade, PR, Bax and Bcl-2 correlated significantly with TTP, whereas in the multivariate analysis only PR showed a statistically significant correlation. In the univariate analysis PR and Bax correlated with OS and both retained its significance in the multivariate analysis. The factors that correlated significantly with the response to cytotoxic treatment in the univariate analysis, i.e. grade, SPF and Bax, seemed to predict independently the response to treatment in the multivariate analysis also. UTP and OS could be predicted partly by the same factors, although the association was quite weak. More studies and new tumour biological factors are needed to identify the group of breast cancer patients who get the most benefit from chemotherapy.

Prognostic Relevance of hMLH1, hMSH2, and BAX Protein Expression in Endometrial Carcinoma

“…Interestingly, in about one third of these cases, loss of hMLH1 was also revealed, and in one case, loss of hMSH2 expression, supporting that Bax is a target gene in tumors with MMR gene defects. In the present study, Bax immunostaining did not correlate with any clinicopathological factor (49,52) and did not provide prognostic information, which differs from observations in other tumor types (53)(54)(55)(56).…”

“…It functions as a tumor suppressor gene because it normally promotes apoptosis (51). The cellular distribution of Bax has been studied in a number of normal and neoplastic tissues with contradictory results (6,46,(52)(53)(54)(55)(56)(57).…”

Clinical studies of p53 in treatment and benefit of breast cancer patients.

“…A Finnish group has performed a multivariate analyses on 103 patients with inclusion of p53, c-erbB-2, bcl-2, bax, S-phase fraction, ploidy, receptors and histological grade with reference to time to progression and survival, once more with a negative result for p53 using immunohistochemistry (Sjöström et al 1998).…”

Gene expression profilers and conventional clinical markers to predict distant recurrences for premenopausal breast cancer patients after adjuvant chemotherapy

“…RNA quality was assessed with an Agilent 2100 Bioanalyzer RNA 6000 Lab.Chip kit (Agilent Technologies, Palo Alto, CA) and six samples were excluded due to poor RNA quality. The protocol for cDNA microarray has been reported previously (29). Briefly, the arrays were spotted with 27,648 sequence-verified cDNA clones (Unigene).…”

“…We then modified expression values according to an error model (29) where expression values x i , now representing the value merged on reporter, with large uncertainties u i were moved towards the weighted mean m across assays for that reporter. The modified expression value was given by x i '=w i (x i -m).…”