BJMO - volume 15, issue 6, october 2021
G. Broeckx MD, Ir A. Hébrant PhD, N. D’Haene MD, PhD, K. Van de Vijver MD, PhD, J. Van Huysse MD, I. Vanden Bempt PhD, P. Aftimos MD, P. Neven MD, PhD, P. Pauwels MD, PhD
The PI3K/AKT pathway plays an important role in the oncogenesis of breast cancer. Activating mutations in PI3K, more specifically in the p110α catalytic unit of the class IA PI3K isoform (encoded by the PIK3CA gene), lead to an increased conversion of phosphatidylinositol-4,5-biphosphate (PIP2) to phosphatidylinositol-3,4,5-triphosphate (PIP3) inducing a cell signalling cascade for cell proliferation and cell survival. PIK3CA mutations are found in 20–32% of all breast cancers (BC), particularly in hormone sensitive (HR+) BC. In breast cancer, activation of the PI3K pathway coexists with the activation of the oestrogen receptor pathway. Inhibition of one of these pathways may lead to compensatory activation of the other pathway. Therefore, mono-therapy with PI3K inhibitors has limited activity in HR+ BC. On the other hand, this explains the efficacy of a PI3K/ER dual blockade. This dual blockade is researched in the phase III SOLAR-1 trial. In the PIK3CA-mutated cohort of this study, there is an improved outcome for patients with advanced or metastatic HR+ HER2- BC, harbouring activating hotspot mutations in PIK3CA and previously treated with an aromatase inhibitor and no more than one line of endocrine therapy for MBC, who received fulvestrant (a selective oestrogen receptor degrader) and alpelisib (a p110α-isoform specific inhibitor) in comparison to the patients that received fulvestrant and placebo. Based on these results, a medical need program for alpelisib in a heavily pre-treated setting and an amendment were approved by the EMA and the Belgian FAMHP. Supporting this data, we propose the mutational analysis of PIK3CA, preferably by next generation sequencing on FFPE tumour material, in advanced or metastatic HR+ HER2- BC, previously treated with three lines of systemic therapy.
(BELG J MED ONCOL 2021;15(6):304-14)Read more
BJMO - volume 15, issue 3, may 2021
P. Pauwels MD, PhD, G. Broeckx MD, F. Dedeurwaerdere MD, C. Galant MD, Ir A. Hébrant PhD, I. Vanden Bempt PhD, K. Van de Vijver MD, PhD, J. Van Huysse MD, B. Weynand MD, N. D’Haene MD, PhD
(BELG J MED ONCOL 2021;15(3):112-6)Read more