A phase II trial of a neoadjuvant platinum regimen for locally advanced breast cancer: pathologic response, long-term follow-up, and correlation with biomarkers.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Yerushalmi
Rinat
R
Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada V5Z 4E6. ryerushalmi@bccancer.bc.ca
Hayes
Malcolm M
MM
Gelmon
Karen A
KA
Chia
Stephen
S
Bajdik
Chris
C
Norris
Brian
B
Speers
Caroline
C
Hassell
Patricia
P
O'Reilly
Susan E
SE
Allan
Sharon
S
Shenkier
Tamara N
TN
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000737:chemistry; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry; D010984:Platinum / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D010984:Platinum; D004317:Doxorubicin; D004250:DNA Topoisomerases, Type II; D017239:Paclitaxel; D002945:Cisplatin