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In vitro effects of trastuzumab and vinorelbine in trastuzumab-resistant breast cancer cells

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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.

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Authors and Affiliations

  1. Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4095, USA

    Rita Nahta & Francisco J. Esteva

  2. Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA

    Francisco J. Esteva

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  1. Rita Nahta
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  2. Francisco J. Esteva
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Correspondence to Francisco J. Esteva.

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Nahta, R., Esteva, F.J. In vitro effects of trastuzumab and vinorelbine in trastuzumab-resistant breast cancer cells. Cancer Chemother Pharmacol 53, 186–190 (2004). https://doi.org/10.1007/s00280-003-0728-3

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  • DOI: https://doi.org/10.1007/s00280-003-0728-3

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