Articles

PIK3CA in breast cancer: a Belgian practical testing guideline

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

SUMMARY

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)

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Genetic and molecular biology in pancreatobiliary cancers: Testing for pancreatobiliary cancer in the context of the Belgian NGS convention

BJMO - volume 15, issue 4, june 2021

Ir A. Hébrant PhD, H. Antoine-Poirel MD, PhD, K.B.M. Claes PhD, F. Dedeurwaerdere MD, J. Van der Meulen MD, F. Lambert MD, J. Van Huysse MD, G. Martens MD, PhD, N. D’Haene MD, PhD, K. Geboes MD, PhD, P. Pauwels MD, PhD, A. Jouret-Mourin MD, PhD, P. Peeters MD, M. van den Eynde MD, PhD, R. Salgado MD, PhD, P-J. Van Dam MD, P. Lefesvre MD, PhD, X. Sagaert MD, S. Metsu PhD, A. Demols MD, PhD, J-L. van Laethem MD, PhD

SUMMARY

Pancreatobiliary cancers (PBC) group pancreatic and biliary tract cancers and are among the cancers with the lowest survival rate. Emerging data suggest that novel biomarker-specific targeted therapies can be proposed for selected populations with survival benefit. This review summarises the scientific evidence to test for these biomarkers in order to optimise the management of pancreatobiliary cancers, within the context of the Belgian NGS convention.

(BELG J MED ONCOL 2021;15(4):170-6)

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Guidelines for the detection of NTRK fusions. A report from the Belgian Molecular Pathology Working Group

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, PhD, N. D’Haene MD, PhD

(BELG J MED ONCOL 2021;15(3):112-6)

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The Belgian next generation sequencing guidelines for haematological and solid tumours

BJMO - volume 11, issue 2, march 2017

Ir A. Hébrant PhD, G. Froyen PhD, B. Maes MD, PhD, R. Salgado MD, PhD, M. Le Mercier PhD, N. D’Haene MD, PhD, S. De Keersmaecker PhD, K. Claes PhD, J. Van der Meulen MD, P. Aftimos MD, J. Van Houdt PhD, K. Cuppens MD, K. Vanneste PhD, E. Dequeker PhD, S. Van Dooren PhD, J. Van Huysse MD, F. Nollet PhD, S. Van Laere PhD, B. Denys MD, V. Ghislain , C. Van Campenhout PhD, M. Van den Bulcke PhD

SUMMARY

Targeted next generation sequencing is a complex procedure including the ‘wet bench’ and ‘dry bench’ parts. Both parts are composed of many steps for which optimal assay conditions and settings must be determined.

The aim of these guidelines is to provide generic, platform independent, recommendations for targeted next generation sequencing tests to detect acquired somatic mutations in DNA, in (haemato)-oncology that are complementary to the ISO 15189 norm (medical laboratories) in order to:

  1. facilitate the implementation of the required quality metrics for the detection of somatic variants by next generation sequencing in oncology and haemato-oncology in the Belgian laboratories,
  2. harmonise test validation and verification,
  3. harmonise clinical interpretation and reporting of variants and,
  4. assure and maintain optimal test performance by establishing procedures and modalities for internal quality control and external quality assessments.

(BELG J MED ONCOL 2017;11(2):56–67)

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