Surgical forum
Prognostic significance of p53, bcl-2, and Bax expression in early breast cancer☆

Abstract presented at the American College of Surgeons 85th Annual Clinical Congress, Surgical Forum, San Francisco, CA, October 1999.
https://doi.org/10.1016/j.jamcollsurg.2003.08.008Get rights and content

Abstract

Background

The use of adjuvant chemotherapy in early breast carcinoma is controversial, with most advocating its use in high-risk patients as defined by specific clinicopathologic parameters. Both bcl-2 and p53, which play a role in determining tumor growth by their effects on apoptosis and cell proliferation respectively, may serve to delineate this subset more accurately. The purpose of this study was to determine the prognostic value of bcl-2, Bax, and mutant p53 in stage I breast cancer.

Study design

A total of 75 patients with stage Ic breast carcinoma diagnosed from 1989 to 1992 were identified retrospectively and clinicopathologic parameters such as age, tumor size, estrogen receptor (ER) and progesterone receptor (PR) status, disease-free survival and overall survival obtained. Paraffin-embedded formalin-fixed tissues were immunostained with bcl-2, Bax and p53 monoclonal antibodies using a standard avidin biotin peroxidase reaction. Stained slides were evaluated by two independent pathologists for staining intensity and percentage of cells staining positively. Cox regression was used for multivariate survival analysis using the clinicopathologic parameters and molecular markers. Chi-square tests were used for frequency tables.

Results

Mean patient age was 58 years (range 29 to 79 years) with a median followup of 80 months from time of diagnosis. The most common histopathology was infiltrating ductal carcinoma. Neither bcl-2 nor Bax expression was associated statistically with disease-free or overall survival. Expression of mutant p53 was associated with a significant decrease in both 5-year disease-free survival (70% versus 98%, p ≤ 0.01 in multivariate analysis) and 5-year overall survival (74% versus 100%, p = 0.03). Expression of bcl-2 was associated with hormone receptor expression and tumor diploid status. Of tumors expressing bcl-2, 36 of 49 (73%) were ER+ (p = 0.017, versus tumors not expressing bcl-2, 6 of 15 [40%]), 22 of 49 (45%) PR+ (p = 0.027 versus tumors not expressing bcl-2, 2 of 15 [13%]) and 28 of 44 (64%) diploid (p = 0.004 versus tumors not expressing bcl-2, 1 of 9 [11%]).

Conclusions

These results indicate that bcl-2 expression is significantly associated with hormonal receptor status and that p53 is a significant prognostic marker for survival in early breast cancer.

Section snippets

Patients and specimens

Patients with stage Ic breast cancer diagnosed from 1989 to 1992 were identified from the Tumor Registry of the Royal Victoria Hospital. Patients with adequate longterm followup and good clinical pathologic specimens were chosen. Paraffin-embedded, formalin-fixed tissues were obtained from the Pathology Department. Samples were reviewed with a pathologist (FH) to ensure adequacy and that they were representative of the actual tumor. The charts of the patients were reviewed to obtain relevant

Clinicopathologic variables

Representative material was identified for 75 patients with stage Ic breast carcinomas. The mean (± SD) age of the patients was 58.3 (± 11.5) years and the mean tumor size was 1.52 (± 0.37) cm. The remaining parameters are summarized in Table 1. Receptor status was obtained in 64 of 75 patients; flow cytometry was performed in approximately two-thirds of the patients. Median followup was 2,400 (± 451) days. At the time of data analysis there were 10 recurrences and 6 deaths in the cohort of 75

Discussion

Identification of subsets of patients with early breast cancer with a worse outcome is imperative when deciding who should receive adjuvant therapy. This study specifically looked at patients with stage Ic breast cancers because it is in this group of patients that the decision either for or against adjuvant therapy is the most difficult. Looking at a number of clinicopathologic parameters we found that the presence of p53 mutations as detected by immunohistochemistry was the single most

Acknowledgements

We thank Ennia Mulfati for secretarial assistance and Manuela Das Neves for identifying the cases in the Tumor Registry.

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    ☆

    No competing interests declared.

    Supported in part by the Cedars Cancer Institute of the Royal Victoria Hospital.

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    Copyright © 2004 American College of Surgeons. Published by Elsevier Inc. All rights reserved.