In vitro effects of trastuzumab and vinorelbine in trastuzumab-resistant breast cancer cells.
OBJECTIVE
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.
Nahta
Rita
R
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4095, USA.
Esteva
Francisco J
FJ
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000068878:Trastuzumab; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000077235:Vinorelbine
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D000068878:Trastuzumab; D000077235:Vinorelbine