IN14 IS OVARIAN ABLATION MANDATORY IN PRE-MENOPAUSAL ER+ ABC PATIENTS?

Abstract

and confer sensibility to neratinib, an irreversible HER tyrosine kinase inhibitor while lapatinib was not active. Currently a clinical trial is examining the activity of neratinib in patients with HER2 mutated breast cancer. Targeting the fibroblast growth pathway appear to be relevant as FGFR1 amplification occurs in 10% of all breast cancers, and enriched in luminal B subtype and associated with resistance to ET. Clinical trials have explored the potential to target FGFR signalling in breast cancer with multitargeting inhibitors as dovitinib and lucitanib, and further studies with other agents and in combination with endocrine therapy are ongoing. Other rare genetic events can been found also in breast cancer such as mutation/amplification KIT, MET, PDGFRA and may represent therapeutic target. Due to the very low frequency of such molecular alterations, it is important to consider a new approach for clinical trials as AURORA or SAFIR02 programs. ER signalling remains an important therapeutic target even in the resistance setting. These new data in molecular characterization provide strong rational for new strategies to either manage or impede resistance to ET. In addition, there is a need for biologically driven criteria to guide treatment choice, identification of the optimal combinations or sequences of targeted agents and integration of new agents into current regimens. [1] Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012; 490:61-70. [2] Goncalves R, Warner WA, Luo J and Ellis MJ New concepts in breast genomics and genetics. Breast Cancer Research 2014, 16:460. [3] Segal CV, Dowsett M Estrogen receptor mutations in Breast cancer – New focus on an old target. Clin Cancer Res 2014, 20(7) 1724-26. [4] Zardavas D, Maetens M, Irrthum A et al: The AURORA initiative for metastatic breast cancer BJC (2014) 111, 1881-87