In vitro comparative evaluation of trastuzumab (Herceptin) combined with paclitaxel (Taxol) or docetaxel (Taxotere) in HER2-expressing human breast cancer cell lines.
BACKGROUND
Trastuzumab (Herceptin) has clinical indication in association with paclitaxel (Taxol) for the treatment of human epidermal growth factor receptor 2 (HER2)-expressing breast cancer. Synergistic interactions have been reported with taxane derivatives in HER2-expressing breast cancer cells. However, no direct comparison of the potential interest in combining trastuzumab with either paclitaxel or docetaxel (Taxotere) has been reported.


METHODS
The present study was designed to evaluate in a comparative way the interaction of trastuzumab with paclitaxel or docetaxel in HER2-overexpressing human breast cancer cell lines. HER2 expression was documented in MCF-7, MDA-MB453 and SK-BR3 cell lines using immunocytochemistry with purified mouse anti-human monoclonal antibody. Cytotoxicity assays were performed using the sulforhodamine B assay and in vitro interactions between trastuzumab and taxanes were analyzed using the median-effect principle.


RESULTS
Trastuzumab cytotoxicity was confirmed to be directly related to HER2 expression level. At the IC(50), the combination of trastuzumab with either paclitaxel or docetaxel led to synergism in all cell lines. However, considering mean values calculated in the IC(30)-IC(70) range of concentrations, trastuzumab interacted additively with docetaxel in SK-BR3 and MDA-MB453 cell lines while additive and synergistic interactions were achieved with paclitaxel in SK-BR3 and MDA-MB453, respectively. On the same basis, trastuzumab yielded synergistic interaction with both taxanes in the MCF-7 cell line.


CONCLUSIONS
The present study shows that at least additive interactions are observed when trastuzumab is combined with either paclitaxel or docetaxel in weak to moderate or more than moderate HER2-expressing cells. Some interesting results were achieved in cells displaying weak HER2 expression which could suggest some further potential interest in trastuzumab.
Merlin
J-L
JL
Centre Alexis Vautrin, Laboratoire de Recherche en Oncologie, Vandoeuvre-les-Nancy, France. jl.merlin@nancy.fnclcc.fr
Barberi-Heyob
M
M
Bachmann
N
N
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011336:Probability; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D043823:Taxoids; D000068878:Trastuzumab; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D000077143:Docetaxel; D000068878:Trastuzumab; D017239:Paclitaxel