S. Cabrero (Badalona, Spain)
Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP)Author Of 1 Presentation
- V. Quiroga Garcia (Badalona, Spain)
- S. Moran (Hospitalet, Spain)
- C. Queralt (Badalona, Spain)
- S. Cabrero (Badalona, Spain)
- A. Bernat (Badalona, Spain)
- A. Ferrando Diez (Badalona, Spain)
- L. Perez (Badalona, Spain)
- B. Cirauqui Cirauqui (Badalona, Ba, Spain)
- E. Felip (Badalona, Spain)
- I. Teruel-Garcia (Badalona, Spain)
- M. Romeo Marin (Badalona, Ba, Spain)
- A. Pous (Badalona, Spain)
- E. Castellà (Badalona, Spain)
- A. Martinez-Cardús (Badalona, Spain)
- M. Margeli (Badalona, Spain)
33P - Epigenetics biomarkers ID1, HOXB2 and ATOH8 could predict response to chemotherapy and prognosis in early breast cancer
Abstract
Background
Epigenetic alterations play an important role in the development of breast cancer and could differ between the different subtypes as well act as prognostic and/or predictive factor of response to chemotherapy. The potential reversibility of these alterations justifies the growing interest in their research as possible therapeutic targets in the context of precision medicine. Our aim is to perform a DNA methylation screening to identify potential biomarkers of prognosis and treatment response in breast cancer.
Methods
We retrospectively analyzed 138 breast cancer patients treated with neoadjuvant chemotherapy based on anthracyclines and taxanes. Patients were classified in breast cancer subtypes according to clinical and pathological characteristics. In the epigenetic analysis, a \"discovery\" cohort was selected from the BRCA cohort from TCGA. 28 cases with available methylation data were chosen, and 3 candidate genes (ID1, HOXB2 and ATOH8) were selected using bioinformatics tools. These biomarkers were validated in our \"validation cohort\" by pyrosequencing techniques. Results were correlated with clinical-pathological characteristics, response rate and survival.
Results
After pyrosequencing analyses, ID1 methylation was different (p< 0.001) among breast cancer subtypes; its hypomethylation was associated with triple negative subtype. Hypomethylation of HOXB2 was mostly detected in luminal tumors and was associated with a lower response rate (p=0.025) and worse survival. The combination of both hipermethylated ID1 and hypomethylated HOXB2, defined a subgroup of luminal patients with worse prognosis. Hypomethylation of ATOH8 was correlated with triple negative tumors (p=0.01), but it was related to a higher rate of pathological complete responses (p=0.016) and a trend to a greater disease-free survival in this subgroup.
Conclusions
Epigenetic platforms could be a useful tool to select predictive and prognostic markers in cancer. Although a validation in a larger and prospective cohort is required, ID1, HOXB2 and ATOH8 are suggested as epigenetic biomarkers for predicting response to chemotherapy and prognosis in breast cancer.
Legal entity responsible for the study
The authors.
Funding
Celgene.
Disclosure
V. Quiroga Garcia: Honoraria (self): Roche; Honoraria (self): Pfizer; Research grant/Funding (institution): Celgene; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Roche. B. Cirauqui Cirauqui: Advisory/Consultancy: BMS; Advisory/Consultancy: Roche; Advisory/Consultancy: Merck; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony: Roche; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: BMS; Travel/Accommodation/Expenses: Merck; Travel/Accommodation/Expenses: MSD. M. Romeo Marin: Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Clovis. All other authors have declared no conflicts of interest.