Purpose: The purpose of this study is to determine the response, tolerability, and long-term outcome of a neoadjuvant platinum-containing regimen for locally advanced breast cancer (LABC) and to search for a correlation between pathologic complete response (pCR) and predefined biomarkers in this cohort.
Patients and methods: Patients with LABC received 8 cycles of either sequence A or B. Sequence A was doxorubicin 60 mg/m(2) and paclitaxel 175 mg/m(2) (AT) every 3 weeks x 4 followed by cisplatin (C) 60 mg/m(2) and paclitaxel 90 mg/m(2) (CT) every 2 weeks x 4. Sequence B was CT x 4 (with paclitaxel dose escalation) followed by AT x 4. In addition to estrogen receptor (ER) and HER2, immunohistochemistry for MDR-1, MRP-1, topoisomerase IIalpha (topo IIalpha), and p53 was performed.
Results: A total of 88 patients were evaluable for response and toxicity. Median follow-up was 97 months. The overall pCR rate was 21.5%. For subgroups ER+/HER2-, HER2+ and double negative (ER-/HER2-) disease, the pCR rates were 5.9%, 23.3%, and 35%, respectively (P = .006). Five-year overall survival for the entire cohort was 71.1%. Five-year overall survival was 88.1% (95% CI, 77.1%-99.1%) for the ER+/HER2- group compared with 68.5% (95% CI, 51.3%-85.7%) and 49.5% (95% CI, 27.4%-71.6%) in the HER2+ and "double-negative" group, respectively (P = .0077). Overexpression of topo IIalpha was correlated with pCR (P < .001). There were no toxic deaths.
Conclusion: A platinum-containing neoadjuvant regimen was well tolerated and achieved a pCR comparable to other recent studies of multiagent chemotherapy. Further studies tailored for specific breast cancer subtypes are required.