Classical markers like ER and ki-67, but also survivin and pERK, could be involved in the pathological response to gemcitabine, adriamycin and paclitaxel (GAT) in locally advanced breast cancer patients: results from the GEICAM/2002-01 phase II study.
BACKGROUND
The identification and validation of biomarkers of chemotherapy sensitivity is critical in order to individualise therapy in breast cancer. We evaluated pathological complete response (pCR) to GAT, and its correlation with tumour biomarkers before and after neoadjuvant chemotherapy.


METHODS
Stage III (and stage II with T≥5 cm) breast cancer patients were included. Treatment consisted of adriamycin (40 mg/m(2)) day 1, and paclitaxel (150 mg/ m(2)) followed by gemcitabine (2000 mg/m(2)) day 2, every 14 days for six cycles. Tissue from pre-treatment biopsy and surgery was evaluated for biologic markers by immunohistochemistry. Two XPD single nucleotide polymorphisms (SNP) were also analysed.


RESULTS
Forty-six patients entered the trial. Median age was 49.5 years (range 31-72); 25 patients (54%) were pre-menopausal; 12 (26%) were ER-PgR-negative; pCR was observed in 17% (95% CI: 6.4-28.4) of patients. Significant differences in marker expression (mean±SD) in correlation to pathological response were only found in Ki- 67. After treatment, tumours showed lower Ki-67-, surviving- and pERK-positive cells. No correlation between XPD polymorphisms and pCR was found. The overall response rate was 89% (95% CI: 80.1-98.1). Fifteen patients (33%) underwent breast-conserving surgery. The most frequent grade 3 or 4 toxicities were neutropenia (with one febrile neutropenia) and asthenia.


CONCLUSIONS
These results show an effective regimen with acceptable tolerability. Our data suggest that not only classical markers (ER, Ki-67), but also survivin and pERK could be involved in the response to GAT, which may contribute to therapy individualisation in future study designs.
Medical Oncology Department, Jaén Hospital Complex, Avda. del Ejército Español, 10, ES-23007 Jaén, Spain. pedro.sanchez.rovira.sspa@juntadeandalucia.es
Pedro
P
Sánchez-Rovira
Antonio
A
Antón
Agustí
A
Barnadas
Amalia
A
Velasco
María
M
Lomas
María
M
Rodríguez-Pinilla
José Luis
JL
Ramírez
César
C
Ramírez
María José
MJ
Ríos
Eva
E
Castellá
Carmen
C
García-Andrade
Belén
B
San Antonio
Eva
E
Carrasco
José Luis
JL
Palacios
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004317:Doxorubicin / Q000008:administration & dosage; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000378:metabolism*; D000077022:Survivin; D000093542:Gemcitabine
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D000077022:Survivin; D003841:Deoxycytidine; D004317:Doxorubicin; D048049:Extracellular Signal-Regulated MAP Kinases; D017239:Paclitaxel; D000093542:Gemcitabine