German researchers have identified an unexpected molecular marker that predicts how sensitive hard-to-treat triple-negative breast cancers are to chemotherapy.
Triple-negative breast cancers --which do not express the genes for estrogen receptor, or progesterone receptor and do not have Her2/neu overexpression or amplification-- are more aggressive than other forms of the disease and cannot be treated with endocrine or Her2 targeted therapies.
At the IMPAKT Breast Cancer Conference in Brussels, PhD student Carolin Huelsewig and Dr Cornelia Liedtke from Uniklinikum Muenster report that the molecule sFRP1 is much more highly expressed in these cancers, and that levels of the molecule in an individual tumor correlate with its sensitivity to chemotherapy.
The researchers undertook their study in three steps. First they conducted a gene expression analysis in breast cancer tissue samples, looking specifically for genes whose expression level differed between triple-negative cancers and non-triple negative cancers.
That analysis revealed that sFRP1 was the most highly overexpressed gene in triple-negative cancers relative to others. "The degree of difference was up to 4.7-fold in triple-negative vs. non-triple negative cancers," Ms Huelsewig said.
The results were a surprise, as sFRP1 is known to inhibit a signaling pathway within cells that is associated with the development of cancers. "The results of the differential gene expression analysis were initially astounding as sFRP1 has so far been understood as an antagonist within the wnt signaling cascade."
The researchers then tested genes for an association with relapse-free survival and response to neoadjuvant chemotherapy, finding that while sFRP1 expression was not associated with recurrence-free survival, it was significantly correlated with an increased sensitivity to chemotherapy.
Finally, the researchers conducted 'knockdown' experiments in cell
|Contact: Vanessa Pavinato|
European Society for Medical Oncology