Neoadjuvant chemotherapy has been considered valuable beyond its role in facilitating conservative surgery and improving prognosis associated with pathologic complete response. Predictive factors of response would help to assess the expected individual benefit of this treatment. Bcl-2 and p53 have been mostly investigated predictive biomarker for the efficacy of chemotherapy in breast cancer, however, studies documenting predictive significance of biomarkers in triple negative breast cancer(TNBC) are limited by low n values of patients. Furthermore, studies did not provide consistent result to conclude about predictive value of biomarkers. There is no unique explanation to date to account for such inconsistencies across studies. In the present study, the two most studied inhibitors of apoptosis, the bcl-2 and p53, have been evaluated to assess whether they may play a role in modulating response to triple negative breast cancer to neoadjuvant chemotherapy. From January 2003 to December 2011, 187 patients presenting T1-4 N0-3 M0 primary TNBC were submitted to two different chemotherapeutic regimens before surgery. The first 154 received the doxetaxel/doxorubicin regimen, the remaining 33 were submitted to doxorubicin and cyclophosphamide followed by doxetaxel. The expression of p53, bcl-2 was evaluated in TNBC specimens obtained at diagnosis by core needle biopsy and at postchemotherapy surgery. Overall pathologic complete response(pCR) occurred in 43 of the 187 cases(23%). The pCR rate was superimposable in the patient subgroups with bcl-2-positive or –negative primary tumors. Conversely, p53 expression was significantly associated with higher pCR rate(19.5 vs 73.2%; p = 0.026; in patients with p53- and p53+ breast cancer). In a multivariate regression analysis, after adjusting for tumor and node status, treatment administered, p53 status maintained an independent predictive role for pCR.[relative risk(RR)=6.247, 95% confidence interval (CI)=0.9–39.1] In our homogeneous patient population, pCR was not associated with initial clinical stage, nodal status as well as other clinicopathologic factors. The status of the p53, which is mutated in a high percentage of breast tumors, is a predictive factor for cytotoxic drug activity. By contrast, bcl-2 failed to be related to chemotherapy activity.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-16.