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1.
Eur J Cancer ; 40(1): 28-32, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14687786

ABSTRACT

In animal models, acquired mutations of the p53 gene that result in increased p53 protein expression are associated with tumour recurrence following chemotherapy. The aim of this study was to test the hypothesis that breast cancer recurrences following adjuvant therapy exhibit aberrant p53 expression. We therefore evaluated p53 expression in paired primary and recurrent breast tumours: 48% of primary and 32% of recurrent tumours had abnormally increased p53 expression. Of the paired samples, 84% showed no change in p53 expression between the primary tumour and the metastasis. In fact, in no case was low (normal) p53 expression in the primary tumour followed by the development of high (aberrant) p53 expression in the recurrence. These results show that increased p53 expression is not selected for in the malignant cells emerging following adjuvant therapy, suggesting that p53 expression is unlikely to play a central role in breast cancer recurrences.


Subject(s)
Breast Neoplasms/metabolism , Tumor Suppressor Protein p53/metabolism , Adult , Aged , Cyclin-Dependent Kinase Inhibitor p21 , Cyclins/metabolism , Female , Humans , Immunohistochemistry/methods , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/metabolism
2.
Clin Cancer Res ; 6(10): 4043-8, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11051254

ABSTRACT

In laboratory studies, ectopic overexpression of the antiapoptotic protein Bcl-2 has been shown to result in resistance to the cytotoxic effects of many chemotherapeutic drugs. Furthermore, posttranslational modification of moderately expressed endogenous Bcl-2 has been correlated with susceptibility to paclitaxel treatment in vitro. To determine whether tumor expression of Bcl-2 protein correlates with response and ultimate outcome in vivo, we quantified Bcl-2 expression by immunohistochemical analysis of archived biopsy specimens from metastatic breast cancer patients treated with single-agent paclitaxel. The statistical association between the degree of Bcl-2 expression, objective tumor response, and clinical outcome was then determined. In patients (n = 39) whose tumors had low (< or = 10% cells positive) Bcl-2 levels by immunohistochemical analysis, the overall response (complete response + partial response) rate was 21% versus an overall response rate of 22% in patients (n = 36) with high (>10% cells positive) Bcl-2 expression (P = 0.92). In patients with low Bcl-2 expression, the median time to progression was 126 days [95% confidence interval (CI), 63-160 days]. This was not significantly different than the 105 days for patients with high tumor Bcl-2 expression (95% CI, 84-214 days). The median survival time from initiation of paclitaxel therapy for patients with low Bcl-2 expression was 663 days (95% CI, 456-1119 days) and was not significantly different than the 450 days (95% CI, 239-1058 days) observed for patients with high Bcl-2 expression. In conclusion, we found that in metastatic breast cancer, there is no significant association between tumor Bcl-2 expression and response to paclitaxel, median time to progression, or survival, suggesting that the main mechanism of paclitaxelinduced cytotoxicity in breast tumors is independent of Bcl-2 expression.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Drug Resistance, Neoplasm/genetics , Paclitaxel/therapeutic use , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Adult , Aged , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Disease-Free Survival , Female , Humans , Immunohistochemistry , Middle Aged , Time Factors
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