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C-erbB-2 expression does not predict response to docetaxel or sequential methotrexate and 5-fluorouracil in advanced
J Sjöström1, J Collan, K von Boguslawski
1Department of Oncology, Helsinki University Hospital, Haartmaninkatu 4, FIN-00290, Helsinki, Finland. johanna.sjostrom@hus.fi
Abstract:
Breast cancer patients with c-erbB-2-positive tumours seem to benefit from anthracycline-based adjuvant chemotherapy. The predictive value of c-erbB-2 for taxane sensitivity is not yet clear. The purpose of this study was to assess whether c-erbB-2 expression is associated with clinical sensitivity to docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). A total of 283 patients with metastatic breast cancer were initially enrolled in a randomised multicentre trial comparing docetaxel with sequential MF in advanced breast cancer. Paraffin-embedded blocks of the primary tumour were available for 131 patients (46%). c-erbB-2 status was determined by immunohistochemistry using a polyclonal antibody to the c-erbB-2 protein. C-erbB-2 expression was scored in a semi-quantitative fashion using a 0 to 3+ scale. Staining scores 2+ or greater were considered positive. Response evaluation was performed according to World Health Organization (WHO) recommendations. Overall 54 (42%) patients had c-erbB-2-positive tumours. There was no association between treatment outcome and c-erbB-2 overexpression. The overall response rates (RR) (n=128) among c-erbB-2-negative and -positive patients were 35 and 44%, respectively (P=0.359). In the MF arm (n=62), the RR was somewhat higher in the c-erbB-2 overexpressors (33% versus 18%, P=0.18). In the docetaxel arm the RRs were very similar, regardless of the c-erbB-2 expression (53% versus 53%). While several studies have suggested a prognostic and putative predictive significance of c-erbB-2 overexpression in early breast cancer, the significance of c-erbB-2 expression as a predictive factor for response to various cytotoxic treatments in advanced breast cancer is still controversial. In this study, c-erbB-2 expression could not predict response to either MF or T. Thus, tumours over-expressing c-erbB-2 are not uniformly more sensitive to taxanes and c-erbB-2 expression cannot yet be applied clinically as a predictive factor for response in advanced breast cancer.
Insights
c-erbB-2 overexpression in breast cancer does not predict response to docetaxel or methotrexate/5-fluorouracil chemotherapy. This finding suggests c-erbB-2 status is not a reliable clinical predictor for these advanced breast cancer treatments.
Area of Science:
- Oncology
- Molecular Biology
- Clinical Trials
Background:
- c-erbB-2 (also known as HER2) positive tumors are often associated with improved outcomes with anthracycline-based chemotherapy.
- The role of c-erbB-2 expression in predicting sensitivity to taxanes, like docetaxel, in breast cancer remains unclear.
- Understanding predictive biomarkers is crucial for tailoring treatment strategies in advanced breast cancer.
Purpose of the Study:
- To evaluate the association between c-erbB-2 expression and clinical response to docetaxel (T) versus sequential methotrexate and 5-fluorouracil (MF) in metastatic breast cancer patients.
- To determine if c-erbB-2 overexpression can serve as a predictive biomarker for taxane-based chemotherapy in advanced breast cancer.
Main Methods:
- A randomized multicenter trial comparing docetaxel (T) with sequential methotrexate and 5-fluorouracil (MF) in 283 patients with advanced breast cancer.
- Immunohistochemistry was used to determine c-erbB-2 expression status (scored 0-3+; 2+ or greater considered positive) on primary tumor samples from 131 patients.
- Response evaluation followed World Health Organization (WHO) guidelines.
Main Results:
- Overall, 42% of patients had c-erbB-2 positive tumors; no significant association was found between c-erbB-2 status and overall treatment outcome.
- Overall response rates (RR) were similar between c-erbB-2 negative (35%) and positive (44%) patients (P=0.359).
- In the docetaxel arm, RR was identical (53%) for both c-erbB-2 negative and positive groups. In the MF arm, RR was slightly higher in c-erbB-2 overexpressors (33% vs 18%).
Conclusions:
- c-erbB-2 expression does not appear to predict response to either docetaxel or sequential methotrexate/5-fluorouracil in advanced breast cancer.
- Tumors overexpressing c-erbB-2 are not uniformly more sensitive to taxanes.
- c-erbB-2 status cannot currently be used as a clinical predictive factor for treatment response in advanced breast cancer.