Topoisomerase-2alpha (T-2a), Ki67, Her-2 and response to neoadjuvant anthracycline-containing chemotherapy in breast cancer. A prospective, correlation study

• Published in: Journal of clinical oncology Vol. 25; no. 18_suppl; p. 21094
• Main Authors: Bari, M., Sartori, D., Zambenedetti, P., Tacchetti, G., Sicari, U., Rosetti, F., Iop, A., Pappagallo, G. L., Vinante, O.
• Format: Journal Article
• Language: English
• Published: 20.06.2007
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2007.25.18_suppl.21094

Abstract only 21094 Background: T-2a creates a reversible double-strand DNA break allowing DNA doubling. Anthracyclines (A) stabilize the DNA double-strand breaks, and T-2a is probably the primary molecular target of A. Due to the close location of T-2a and Her-2 genes on chromosome 17, T-2a gene aberrations are mainly associated with Her-2 gene amplification; while a correlation exists between Her-2 amplification and protein overexpression this is not true for T-2a. A linear correlation between T-2a and Ki67 labeling indices was found, suggesting that both essentially reflect cellular proliferation. The correlation between T-2a overexpression and both Her-2 and Ki67 was investigated in a series of consecutive patients undergone neoadjuvant A-containing chemotherapy for locally-advanced breast cancer. Material and Methods: T-2a expression was measured by means of monoclonal antibody Ki-S1; thresholds (ts) for immunopositivity were tested at 10%, 15% and 20%, respectively. Both the anti-c-erb-B2 primary antibody (clone CB11) and the Dako test were employed to recognize c-erb-B2 protein. Ki67 was measured using the MIB-1 antibody, with ts for positivity at 10%. Patients were required to have a cT>2cm breast cancer. The neoadjuvant chemotherapy included Adriamycin 60mg/m2 or Epirubicin 75mg/m2, in combination with Paclitaxel (175 mg/m2), every 3 weeks for 4 cycles. Bivariate correlations were performed according to Pearson. Results: 38 patients were enrolled until August, 2006. A significant correlation between T-2a and Ki67 was found (r=.598; P<.000); the T-2a positivity rate within Ki67 positive patients was of 90% (10% ts), 86% (15% ts), and 67% (20% ts). No correlation appeared between T-2a and Her-2 labeling indices (r=.150; P=.391); the T-2a positivity rate within Dako +++ patients was 75% (for both 10% and 15% ts) and 50% (for 20% ts). The overall response rate by T-2a overexpression was 61% (10% ts), 70% (15% ts), and 72% (20% ts). Conclusions: We provide a further evidence of the correlation between T-2a and Ki67. We can also generate the hypothesis that a 20% ts for T-2a correlate with a better prediction of response to A-containing chemotherapy; at the same ts, no correlation with Her-2 status was found. No significant financial relationships to disclose.