breast cancer dormancy · Molecular characterisation of a clinical model of estrogen receptor-positive breast cancer dormancy

Molecular characterisation of a clinical model of estrogen receptor-positive breast cancer dormancy

"Endocrine therapy has clearly improved outcomes for oestrogen receptor alpha-positive (ER+) breast cancer patients. However, the cumulative incidence of recurrence and death continues at a steady rate. The majority of ER+ breast tumours treated with neoadjuvant letrozole respond quickly and are generally excised after three months. A minority of tumours maintain a stable size by becoming dormant, these tumours continue to receive extended letrozole treatment and therefore represent the best currently available clinical model to investigate dormancy. In this project, for the first time, sequential samples from dormant and resistant tumours that have received extended (>4 months) neoadjuvant endocrine therapy were studied. We aimed to characterise ER+ breast cancer dormancy and letrozole resistance by combing expression profiling technologies with a unique series of patient-matched sequential samples collected in Edinburgh. Genome- and proteome-wide expression data after extended letrozole treatment was analysed and compared with data from the same patients at diagnosis according to clinical outcomes. Our study is the first to characterise extended growth suppression in letrozole-treated dormant-state breast cancer. Objectives of the study were 1) to determine genome- and proteome-wide expression profiles in ER+ breast cancer patients that received extended neoadjuvant endocrine therapy; and 2) to characterise ""predictive molecular signature"" of ER+ breast cancer dormancy and letrozole resistance through integrated analysis of genome- and proteome-wide expression data. Differentially expressed genes and enriched pathways in dormant and acquired resistant tumours under long-term neoadjuvant letrozole treatment were identified. In addition, a subset of the genes including histone genes significantly separating 12 (out of 20) acquired resistant from dormant tumours after long-term treatment were determined. The challenge in defining a clear separation between all resistant and dormant patients was mainly due to the heterogeneity amongst resistance patients as some of them share changes with dormant patients. In conclusion, these results will contribute to extending ER+ breast cancer patients' survival and quality of life by preventing metastasis and contribute to the economy and society by introducing an individualised therapy that is tailored in accordance with cancer patients’ expression profiles. This multidisciplinary project combined both clinical and academic aspects provided the fellow with great competence in cancer genomics through training in advanced integrative bioinformatics analysis of high-throughput data. "

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз