Researchers Provide New Evidence for Role of FGFR1 Amplification in Tamoxifen Resistance

A group of scientists say they have demonstrated a pivotal role for FGFR1 gene amplification and overexpression in breast cancers with poor prognosis and resistance to tamoxifen therapy. They suggest the findings provide a strong rationale for investigating FGFR1-blocking drugs as potential new anticancer drugs, particularly in combination with endocrine therapies.

The studies, led by researchers at the Institute of Cancer Research’s (ICR) Breakthrough Breast Cancer Research Centre in London, are reported in Cancer Research in a paper titled “FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer.”

Scientists have known for some time that amplification of FGFR1 occurs in approximately 10% of breast cancers and is associated with poor prognosis, explains lead author Nick Turner, M.D., a Cancer Research UK clinician scientist at the ICR. However, it has been unclear whether overexpression of FGFR1 is causally linked to the poor prognosis of amplified cancers.

To try and address this, the ICR team identified cancer cell lines demonstrating FGFR1 gene amplification and overexpression. When they blocked FGFR1 in the cells, they became susceptible to tamoxifen again. The results also suggested that “amplification and overexpression of FGFR1 may be a major contributor to poor prognosis in luminal type breast cancers, driving anchorage-independent proliferation and endocrine therapy resistance,” the authors conclude. The work was carried out in collaboration with a team at the Royal Marsden Hospital Breast Unit and the Breast Cancer Research Unit at King's College London School of Medicine at Guy's Hospital.

“The next step is to set up a clinical trial to see whether a drug that blocks the action of this gene can counteract hormone-therapy resistance in breast cancer patients,” Dr. Turner suggests. “If these trials confirm our lab work, we could be on the verge of a potentially exciting new treatment for breast cancer.”