BACKGROUND: The predictive role of HER-2 in node-positive breast cancer patients receiving CMF or ananthracycline-based adjuvant therapy remains unclear. In addition, topo-isomerase II alpha (topo IIalpha), as the cellular target of anthracyclines, might have value as a predictive marker. PATIENTS AND METHODS: Four hundred eighty-one archival primary tumor samples were collected among 777 patients entered into a multicenter phase III trial comparingclassical CMF with epirubicin cyclophosphamide (HEC) as adjuvant therapy of node-positive breast cancer. HER-2 was evaluated by immunohistochemistry (IHC) using different antibodies (Abs). Topo IIalpha was evaluated by IHC using the Ab KiS 1. In each subgroup of patients identified by HER-2 and topo IIalpha, adjusted hazard ratios for event-free survival (EFS) and the corresponding 95% confidence intervals have been calculated for the different study comparisons. An interaction test has been performed to investigate the role of HER-2 and topo IIalpha as predictive markers. RESULTS: When HER-2 was evaluated by CB-11 and 4D5 mAbs, the EFS adjusted hazard ratios (HR) for the main study comparison HEC vs. CMF were: HER-2 positive: 0.33 (95% confidence interval (95% CI): 0.09 1.27, P = 0.08), HER-2 negative: 1.16 (95%, CI: 0.71-1.90, P = 0.56); the P-value for the interaction test was 0.10. When HER-2 was evaluated by TAB-250 + pAbl Abs, the adjusted HR for the same comparison were: HER-2 positive: 1.06 (95% CI: 0.45-2.52, P = 0.90), HER-2 negative: 0.99 (95% CI: 0.58-1.68, P = 0.97); the P-value for the interaction test was 0.84. With regard to topo IIalpha, the adjusted HR for the EFS comparison HEC vs. CMF were: topo IIalpha positive: 0.66 (95% CI: 0.32-1.36, P = 0.25), topo IIalpha negative: 1.26 (95% CI: 0.63-2.50, P = 0.51); the P-value for the interaction test was 0.13. CONCLUSIONS: This study suggests that in node-positive breast cancer patients randomly treated withCMF or an epirubicin-based regimen, the predictive value of HER-2 may vary according to the Abs used in the immunohistochemistry assay. In addition, the study supports the concept that topo IIalpha might be involved in the determination of tumor responsiveness to an anthracycline-based adjuvant therapy.
RCT Entities:
BACKGROUND: The predictive role of HER-2 in node-positive breast cancerpatients receiving CMF or an anthracycline-based adjuvant therapy remains unclear. In addition, topo-isomerase II alpha (topo IIalpha), as the cellular target of anthracyclines, might have value as a predictive marker. PATIENTS AND METHODS: Four hundred eighty-one archival primary tumor samples were collected among 777 patients entered into a multicenter phase III trial comparing classical CMF with epirubicin cyclophosphamide (HEC) as adjuvant therapy of node-positive breast cancer. HER-2 was evaluated by immunohistochemistry (IHC) using different antibodies (Abs). Topo IIalpha was evaluated by IHC using the Ab KiS 1. In each subgroup of patients identified by HER-2 and topo IIalpha, adjusted hazard ratios for event-free survival (EFS) and the corresponding 95% confidence intervals have been calculated for the different study comparisons. An interaction test has been performed to investigate the role of HER-2 and topo IIalpha as predictive markers. RESULTS: When HER-2 was evaluated by CB-11 and 4D5 mAbs, the EFS adjusted hazard ratios (HR) for the main study comparison HEC vs. CMF were: HER-2 positive: 0.33 (95% confidence interval (95% CI): 0.09 1.27, P = 0.08), HER-2 negative: 1.16 (95%, CI: 0.71-1.90, P = 0.56); the P-value for the interaction test was 0.10. When HER-2 was evaluated by TAB-250 + pAbl Abs, the adjusted HR for the same comparison were: HER-2 positive: 1.06 (95% CI: 0.45-2.52, P = 0.90), HER-2 negative: 0.99 (95% CI: 0.58-1.68, P = 0.97); the P-value for the interaction test was 0.84. With regard to topo IIalpha, the adjusted HR for the EFS comparison HEC vs. CMF were: topo IIalpha positive: 0.66 (95% CI: 0.32-1.36, P = 0.25), topo IIalpha negative: 1.26 (95% CI: 0.63-2.50, P = 0.51); the P-value for the interaction test was 0.13. CONCLUSIONS: This study suggests that in node-positive breast cancerpatients randomly treated with CMF or an epirubicin-based regimen, the predictive value of HER-2 may vary according to the Abs used in the immunohistochemistry assay. In addition, the study supports the concept that topo IIalpha might be involved in the determination of tumor responsiveness to an anthracycline-based adjuvant therapy.
Authors: Michael F Press; Guido Sauter; Marc Buyse; Leslie Bernstein; Roberta Guzman; Angela Santiago; Ivonne E Villalobos; Wolfgang Eiermann; Tadeusz Pienkowski; Miguel Martin; Nicholas Robert; John Crown; Valerie Bee; Henry Taupin; Kerry J Flom; Isabelle Tabah-Fisch; Giovanni Pauletti; Mary-Ann Lindsay; Alessandro Riva; Dennis J Slamon Journal: J Clin Oncol Date: 2010-12-28 Impact factor: 44.544
Authors: Anna J Zaczek; Aleksandra Markiewicz; Barbara Seroczynska; Jaroslaw Skokowski; Janusz Jaskiewicz; Tadeusz Pienkowski; Wojciech P Olszewski; Jolanta Szade; Piotr Rhone; Marzena Welnicka-Jaskiewicz; Jacek Jassem Journal: Oncologist Date: 2012-08-07
Authors: Mehmet Salih Iyikesici; Gul Basaran; Faysal Dane; Meltem Ekenel; P Fulden Yumuk; Devrim Cabuk; Mehmet Teomete; N Serdar Turhal Journal: Int J Clin Exp Med Date: 2014-05-15
Authors: Raymond Tubbs; William E Barlow; G Thomas Budd; Eric Swain; Peggy Porter; Allen Gown; I-Ten Yeh; George Sledge; Charles Shapiro; James Ingle; Charles Haskell; Kathy S Albain; Robert Livingston; Daniel F Hayes Journal: J Clin Oncol Date: 2009-07-20 Impact factor: 44.544