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

• Autores: Pedro Sánchez Rovira, A. Antón Torres, Agustí Barnadas i Molins, Amalia Velasco, María Lomas Garrido, María Rodríguez-Pinilla, José Luis Ramírez, César Ramírez, María José Ríos, Eva Castellà Fernández, Carmen García-Andrade, Belén San Antonio, Eva Carrasco, José Luis Palacios
• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 14, Nº. 6, 2012, págs. 430-436
• Idioma: inglés
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• Resumen

  • Introduction 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.

    Materials and methods Stage III (and stage II with T=5 cm) breast cancer patients were included. Treatment consisted of adriamycin (40 mg/m2) day 1, and paclitaxel (150 mg/m2) followed by gemcitabine (2000 mg/m2) 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.

    Conclusion 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.