Predictive Significance of p53, Ki-67, and Bcl-2 Expression for Pathologic Complete Response after Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer

Abstract

PurposePatients with triple-negative breast cancer (TNBC) with pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) have superior survival outcomes compared to those with residual disease after NAC. This study investigated the value of three biomarkers, p53, Ki-67, and Bcl-2 for predicting pCR in NAC-treated patients with TNBC.MethodsBetween 2003 and 2012, 198 patients with pathologically confirmed primary TNBC were treated with two different taxane-based chemotherapeutic regimens prior to surgery. Before NAC, expression of p53 (cutoff 25%), Ki-67 (cutoff 10%), and Bcl-2 (cutoff 10%) was assessed immunohistochemically in core biopsy specimens. The incidence of pCR was correlated with the expression of these biomarkers.ResultsOverall, pCR occurred in 37 of the 198 patients (18.7%). A significant association was observed between the pCR rate and overexpression of the p53 and Ki-67 biomarkers. Multivariate analysis showed that only p53 expression was independently associated with pCR to NAC (odds ratio, 3.961; p=0.003). The sensitivity, specificity, positive predictive value, and negative predictive value of p53 expression for predicting pCR were 77.8%, 50.3%, 26.2%, and 90.9%, respectively. The pCR rate was the lowest (5.2%) in patients with low expression of both p53 and Ki-67, and it was the highest (25.8%) when both biomarkers showed high expression.ConclusionExpression of p53 was significantly associated with pCR after NAC in patients with TNBC, suggesting that this biomarker might be particularly valuable in identifying TNBC patients prone to have residual disease after NAC.

Correlation of BCL-2 and ERα mRNA Expression with the Clinical Chemotherapeutic Response in Breast Cancer

“…Other studies found that BCL-2 expression was not significantly associated with complete pathological response in patients with triple negative breast cancer and patients in the BCL-2-negative group tended to be more chemosensitive than those in the BCL-2-positive group 7 . This finding is in agreement with our results showing that BCL-2 could not predict the response to neoadjuvantchemotherapy.…”

“…The BCL-2 can inhibit apoptosis resulting from a variety of intracellular signals 19,20 . The BCL-2 has been shown into inhibiting apoptosis induced by chemotherapeutic drugs (including doxorubicin) in cancer cells 7 .…”

“…Overexpression of BCL-2 is commonly found in various types of cancers, including breast cancer 5,6 . The BCL-2 is an important clinical prognostic marker in breast cancer and patients positive for BCL-2 expression tend to relapse and have a shorter overall survival 7,8 . Studies revealed that analyzing BCL-2 might predict the patient response to selected endocrine-based and other chemotherapies [5][6][7]9 .…”

Preparation, characterization, and evaluation of antitumor effect of Brucea javanica oil cationic nanoemulsions

“…58,59 However, the prognostic significance of overexpression of Bcl-2 protein for cancer patients was not uniform. It was thought that the overexpression of Bcl-2 protein showed no significant correlation with patient prognosis in some studies, 60 but some other studies showed that it was related with good prognosis for cancer patients.…”

Prognostic Biomarkers in Triple Negative Breast Cancer as a Potential Target for Future Drug Discovery

“…Study conducted 2016, demonstrated that elevated p53 expression in TNBC patients, presented the worst prognosis [61]. Measurement of p53 expression may assist in making treatment decisions and in predicting response to treatment, when apply before starting neoadjuvant chemotherapy, as when p53 combines with ki67, gives great predictive accuracy [62]. The frequency of p53 mutations was found to be higher in basal breast cancer as compared to Luminal type tumors [63].…”