Rita Nahta1, Francisco J Esteva. 1. Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4095, USA.
Abstract
PURPOSE: The majority of patients who initially respond to trastuzumab will progress within 1 year. Currently, patients who progress after trastuzumab-based therapy are often maintained on trastuzumab combined with a different chemotherapeutic agent, such as vinorelbine. However, evidence supporting the continued use of trastuzumab in these breast cancers is lacking. METHODS: We created a preclinical model of trastuzumab resistance using the SKBR3 HER-2-overexpressing breast cancer cell line. Dose-response and cell cycle alterations in response to trastuzumab and/or vinorelbine were assessed. RESULTS: In contrast to the parental SKBR3 cells, vinorelbine-mediated growth inhibition and apoptosis were not significantly enhanced by the addition of trastuzumab in the trastuzumab-resistant pools. CONCLUSIONS: These results suggest that the continued treatment of trastuzumab-resistant breast cancers with trastuzumab-containing regimens may not be effective. A randomized clinical trial of trastuzumab plus vinorelbine versus vinorelbine alone should be conducted in patients with HER-2-overexpressing breast cancer to determine the optimal duration of trastuzumab therapy upon progression.
PURPOSE: The majority of patients who initially respond to trastuzumab will progress within 1 year. Currently, patients who progress after trastuzumab-based therapy are often maintained on trastuzumab combined with a different chemotherapeutic agent, such as vinorelbine. However, evidence supporting the continued use of trastuzumab in these breast cancers is lacking. METHODS: We created a preclinical model of trastuzumab resistance using the SKBR3 HER-2-overexpressing breast cancer cell line. Dose-response and cell cycle alterations in response to trastuzumab and/or vinorelbine were assessed. RESULTS: In contrast to the parental SKBR3 cells, vinorelbine-mediated growth inhibition and apoptosis were not significantly enhanced by the addition of trastuzumab in the trastuzumab-resistant pools. CONCLUSIONS: These results suggest that the continued treatment of trastuzumab-resistant breast cancers with trastuzumab-containing regimens may not be effective. A randomized clinical trial of trastuzumab plus vinorelbine versus vinorelbine alone should be conducted in patients with HER-2-overexpressing breast cancer to determine the optimal duration of trastuzumab therapy upon progression.
Authors: Francisco J Esteva; Carol D Cheli; Herbert Fritsche; Monica Fornier; Dennis Slamon; Robert P Thiel; Diana Luftner; Farooq Ghani Journal: Breast Cancer Res Date: 2005-04-08 Impact factor: 6.466
Authors: Giuseppe Cancello; Emilia Montagna; Diego D'Agostino; Mario Giuliano; Antonio Giordano; Giuseppe Di Lorenzo; Monica Plaitano; Sabino De Placido; Michele De Laurentiis Journal: Breast Cancer Res Date: 2008-07-16 Impact factor: 6.466