Latest findings presented at Europe’s leading breast cancer translational research conference shed new light on the biological features that make tumours more or less sensitive to important therapies. Breast cancers that express low levels of the protein mucin-1 (MUC1) tend to respond better to neoadjuvant chemotherapy with anthracyclines and taxanes, German researchers reported at the 4th IMPAKT Breast Cancer Conference (3-5 May 2012), in Brussels, Belgium.
MUC1 is expressed in normal breast epithelium and invasive breast cancer. It has pleiotropic effects on tumour biology, e.g. regulation of cell polarity, crosstalk with cellular signalling and regulation of immune response. Tumour vaccines targeting MUC1 are currently tested in clinical trials. The aim of this study was to evaluate the frequency of MUC1 expression and its predictive value for response and survival after neoadjuvant anthracycline/taxane-based chemotherapy.
Frequency of MUC1 expression
Dr Bruno Sinn from Charité Universitätsmedizin Berlin and colleagues from the German Breast Group studied tumour biopsy samples from a previous clinical trial of the German Breast Group. In 691 samples, they tested for the presence of MUC1 protein, and in 268 they explored expression of messenger RNA for the gene. They could detect MUC1 protein in 656 (95%) cases, and the level of mRNA for the gene varied 1000-fold between tumours.
High MUC1 protein and mRNA expression were seen more frequently in hormone-receptor positive tumours. On the other hand, tumours that were hormone receptor negative and HER2 negative had lower MUC1 protein and mRNA expression compared to other subtypes.
When the researchers correlated the expression of the protein and mRNA with the patient’s response to chemotherapy, they found that low levels of expression were predictive for pathological complete response. This correlation held true for the overall population and in the subgroups of hormone receptor positive, hormone receptor negative, HER2-, and hormone receptor positive/HER2- tumours.
The researchers observed that MUC1 is frequently expressed in a large cohort of breast cancers, especially in hormone receptor positive tumours. Evaluation of this gene is feasible by immunohistochemistry and quantitative reverse transcriptase PCR and may provide information on therapy response and survival following neoadjuvant chemotherapy. The researchers put their data into clinical perspective and concluded that MUC1 expression may serve as a predictive marker in clinical immunotherapy trials.