IGF1 and Insulin Receptor Single Nucleotide Variants Associated with Response in HER2-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy with or without a Fasting Mimicking Diet (BOOG 2013-04 DIRECT Trial)

The authors tested germline DNA from 113 patients in the DIRECT trial, in which patients with HER2-negative breast cancer received neoadjuvant chemotherapy with or without a Fasting Mimicking Diet (FMD). Seventeen systematically selected single nucleotide variants in the IGF1R and INSR genes were tested for association with pathological and radiological response. The subject under study is the gene variants, not the effect of the diet.

The authors reported that two IGF1R variants were associated with worse pathological response than the reference alleles. They reported that one INSR variant may be associated with worse radiological response, while noting that this result was not significant after Bonferroni correction. They reported that an exploratory analysis suggested two further IGF1R variants interact negatively with the diet group for radiological response. They describe the main result as suggesting potential relevance as a predictive biomarker and say further research is needed to validate the findings and the mechanisms.

This is an exploratory genetic association study in 113 patients, and associations of this kind do not establish cause. One reported result lost significance once the authors corrected for multiple testing, and the interaction findings are labelled exploratory by the authors themselves. The study examines gene variants and response to chemotherapy; it does not measure what the diet does, and it does not evaluate Prolon directly. The population is breast cancer patients receiving neoadjuvant chemotherapy, not a general wellness population.