Purpose: p63, a gene that shares structural and functional homologies with p53, codes for different isoforms, with (TA) and without (DeltaN) transactivating properties. The anti-apoptotic DeltaN isoform is often expressed in breast cancer (BC). DNA damaging drugs such as cisplatin (C) induce its degradation and stabilization of the TA, proapoptotic isoform. This supports the role of these drugs in the treatment of tumors expressing p63. The aim of the present study was to ascertain the predictive value of p63 immunoreactivity in patients treated preoperatively with regimens including cisplatin and/or anthracyclines.
Methods: We reviewed the pretreatment biopsies of 189 patients with large or locally advanced BC (cT1-4d, N0-2, M0) treated with preoperative chemotherapy, performing p63 immunohistochemistry. The rate of pathological complete remission (pCR) at final surgery was assessed with respect to cisplatin administration and p63 immunoreaction.
Results: pCR was identified in 20 patients (11%); 147 patients (78%) had an objective response, 39 (21%) stable disease, and 3 (1%) disease progression. One hundred forty seven patients (78%) received a cisplatin-containing regimen. Only regimens including cisplatin without anthracyclines yielded a higher rate of pCR in p63-positive compared with p63-negative tumors (23 vs. 0%, P=0.048). No significant difference in the pCR rate was observed for regimens containing anthracycline without cisplatin.
Conclusions: Administration of cisplatin without anthracyclines correlates with a high rate of pCR after primary chemotherapy in patients with p63-positive BC. The role of cisplatin-based chemotherapy should be further studied in these patients.