Marcadores moleculares de resistencia a quimioterapia en cáncer de mama

VARGAS ROIG L. M.; GAGO F. E.; CUELLO CARRIÓN F. D.; CIOCCA D. R.

ONCOLOGÍA CLÍNICA

SOCIEDAD ARGENTINA DE ONCOLOGÍA CLÍNICA

Lugar: Buenos Aires; Año: 2001 vol. 6 p. 553 - 558

1669-6336

Objectives: we have analyzed in breast cancer patients whether chemotherapy affects in vivo the expression of Hsp27, Hsp70, Hsc70, Hsp90, c-erbB-2, p53 and P 170, and whether these proteins may be determinants of tumor resistance to drug administration. Patients and methods: biopsies (n = 64) of locally advanced breast cancer patients treated with induction chemotherapy were examined by immunohistochemistry. Most patients (36/64) received relatively high doses of FAC or FEC (5-fIuorouracil, doxorubicin or epirubicin and cyclophosphamide), and 24 patients received relatively high doses of doxorubicin or epirubicin alone. The patients who received FAC/FEC treatment had a relatively long follow-up (mean: 34 months) and in this group we compared the molecular markers with disease-free survival (DFS) and overall survival (OS). Results: after chemotherapy, nuclear Hsp27 and Hsp70 expression was increased and Hsp70 and Hsc70 cytoplasmic expression was decreased. No significant changes were observed in the expression of c-erbB-2, p53, and P170 proteins after drug administration. A high nuclear proportion of Hsp70 in tumor cells (>10%) correlated significantly with drug resistance. c-erbB-2 was over-expressed in 50% of patients who developed distant metastases vs. 7% of the disease-free patients. We observed that patients whose tumors expressed nuclear or a high cytoplasmic proportion (>66%) of Hsp27 had shorter DFS. The combination of Hsp27 and Hsp70 levels showed a strong correlation with DFS. DFS curves between c-erbB-2- positive and c-erbB-2-negative patients were statistically significant. Conclusions: our results suggest that Hsp27, Hsp70, and c-erbB-2 are associated with development of distant metastases in breast cancer patients treated with induction chemotherapy with relatively high doses of anthracyclines.