A randomized placebo controlled phase II study with Metformin in metabolic-unbalanced breast cancer survivors at higher risk for recurrence

Metabolic imbalance such as metabolic syndrome, weight gein, obesity, elevated insulin and blood sugar, and insulin resistance are strongly associated with breast cancer recurrence and poorer prognosis. A recent pre-clinical study has demonstrated effect of 4 weeks of metformin to reduce Ki-67 (a standard surrogate biomarker to test the activity of candidate drugs) in BC cells specifically in metabolic unbalanced subjects. The hypothesis is that this commonly used and cheap oral anti-diabetic drug, given for 1 year, may decrease epithelial cells proliferation also in healthy, metabolic unbalanced BC survivors. Moreover it may favorably modulate various translational risk factors related to the target tissue and the host characteristics. Thus we hypothesize that these effects may induce a possible reduction of early and late BC recurrence/second primary. The joint effort of our research consortium will contribute to better elucidate the clinical and molecular effects of metformin and to confirm its role in tertiary prevention of high risk patients.

Prosjektet har hatt fokus på virkningen av legememiddelet metformin ved en ny problemstilling, forebygging av brystkreft hos kvinner. Studier har vist effekter av metformin på vekst av brystkreftceller, men vi har hatt lite kunnskap om forebygging. Siden brystkreft er en hyppig sykdom, og stadig flere kvinner lever med gjennomgått brystkreft, er mer kunnskap om forebygging av tilbakefall viktig. Prosjektet (ERA-NET, TRANSCAN) er basert på et samarbeid mellom Bergen og Milano, og har bidratt til økt internasjonalt samarbeid da vi har knyttet til oss en forskningsgruppe i Lyon som er eksperter på metabolomikk, og et nytt større senter i San Diego. Sistnevnte samarbeidspartner har bidratt til utvidelse av prosjektet med flere deltakere for derved å kunne øke statistisk styrke. Vi har gjennomført de alle analysene, og prosjektet vil resultere i en rekke vitenskapelige publikasjoner. Andre offentlige informasjonskanaler vil også bli benyttet for formidling av de viktigste resultatene.

Background: Metabolic unbalanced conditions, which can include the presence of metabolic syndrome, weight gain, central obesity, elevated serum insulin and glucose levels, and insulin resistance, have been strongly associated with breast cancer (BC) recurrence and worse outcomes after treatment. Preclinical and clinical studies have demonstrated the efficacy of metformin, the oral insulin-sensitizing drug most widely prescribed for the treatment of type 2 diabetes, to inhibit the growth of BC cells. In particular, a recent pre-surgical clinical study has shown the efficacy of 4 weeks of metformin to reduce Ki-67 (now fully considered a standard surrogate biomarker to test the activity of candidate drugs) in BC cells specifically in metabolic unbalanced subjects. Hypothesis: We think that this commonly used and cheap oral anti-diabetic drug, given for 1 year, may decrease epithelial cells proliferation also in healthy, metabolic unbalanced BC survivors. Moreover it may favorably modulate various translational risk factors related to the target tissue and the host characteristics. Thus we hypothesize that these effects may induce a possible reduction of early and late BC recurrence/second primary. The joint effort of our research consortium will contribute to better elucidate the clinical and molecular effects of metformin and to confirm its role in tertiary prevention of high risk patients.