PRACTICE GUIDELINES

PIK3CA in breast cancer: a Belgian practical testing guideline

BJMO - volume 15, issue 6, october 2021

Ir A. Hébrant PhD, G. Broeckx MD, I. Vanden Bempt PhD, J. Van Huysse MD, K. Van de Vijver MD, PhD, N. D’Haene MD, 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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Guidelines for the detection of NTRK fusions. A report from the Belgian Molecular Pathology Working Group

BJMO - volume 15, issue 3, may 2021

Ir A. Hébrant PhD, B. Weynand MD, C. Galant MD, F. Dedeurwaerdere MD, G. Broeckx MD, I. Vanden Bempt PhD, J. Van Huysse MD, K. Van de Vijver MD, PhD, N. D’Haene MD, PhD, P. Pauwels MD, PhD

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

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Practical guidelines in axillary management after neo-adjuvant chemotherapy in breast cancer patients

BJMO - volume 15, issue 2, march 2021

A.-S. Vliegen MD, C. Thywissen MD, G. Orye MD, J. Mebis MD, PhD, K. Van Baelen MD, L. Noé MD, L. Vansteelant MD, M. Drijkoningen MD, PhD, N. Van den Rul MD, S. Marquette MD

SUMMARY

In clinical practice, the diversity in the surgical management of the axilla after neo-adjuvant chemotherapy (NACT) for node positive patients is huge. Given the morbidity of axillary lymph node dissection (ALND), a trend to perform a less invasive technique is seen in both literature and clinical practice. There are three major techniques: 1) sentinel lymph node biopsy (SLNB), 2) guided removal of lymph nodes that were positive prior to NACT, and 3) Targeted Axillary Dissection (TAD) which is a combination of the previous two techniques. Criteria for patients eligible for these techniques vary widely and oncological safety cannot always be guaranteed. With this report, we aim to introduce TAD in a safe way into the clinical practice.

(BELG J MED ONCOL 2021;15(2):69-74)

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Systemic treatment landscape and algorithm for hormone-receptor positive, HER2 negative advanced breast cancer

BJMO - volume 15, issue 1, january 2021

F. Derouane MD, F.P. Duhoux MD, PhD, K. Punie MD

SUMMARY

Hormone-receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer accounts for 65% of all metastatic breast cancer (MBC) cases. With the advent of CDK4/6 inhibitors, single-agent endocrine therapy (ET) is no longer the only first-line systemic treatment option for the vast majority of patients presenting without visceral crisis. Other endocrine-based treatment options are emerging in further lines, with the goal to delay the administration of chemotherapy as long as possible. The optimal sequence of treatment is unknown. We here present a review of the available treatments and propose a treatment algorithm taking into account the latest therapeutic developments.

(BELG J MED ONCOL 2021;15(1):20-33)

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Clinical management of first-line advanced triple-negative breast cancer patients

BJMO - volume 14, issue 7, november 2020

A. Awada MD, PhD, D. Taylor MD, E. de Azambuja MD, PhD, E. Naert MD, FP. Duhoux MD, PhD, H. Denys MD, PhD, H. Wildiers MD, PhD, K. Punie MD, M. Ignatiadis MD, PhD, M. Rediti MD

SUMMARY

Chemotherapy has represented the main treatment option for patients with advanced triple-negative breast cancer for a long time. However, due to our better understanding of tumour biology, recent clinical trials led to a change in the treatment paradigm of this disease, identifying clinically relevant subgroups with different therapeutic options. Both clinical and biological factors have become relevant and need to be considered in the treatment decision algorithm of this heterogeneous disease.

(BELG J MED ONCOL 2020;14(7):333-38)

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An update on the management of metastatic clear-cell renal cell carcinoma: the BSMO expert panel recommendations

BJMO - volume 14, issue 2, march 2020

A. Verbiest MD, B. Beuselinck MD, PhD, B. Delafontaine MD, C. De Backer MD, C. Gennigens MD, PhD, C. Vulsteke MD, PhD, G. Pelgrims MD, G. Van Lancker MD, L. D’Hondt MD, PhD, M. Strijbos MD, PhD, N. Martínez Chanzá MD, On behalf of the BSMO Uro-Oncology Task Force Group , P. Debruyne MD, PhD, S. Rottey MD, PhD, T. Gil MD

SUMMARY

The management of recurrent or metastatic renal cell carcinoma is evolving fast, with new therapeutic options becoming available that may improve the outcome of patients. In this paper, recent evolutions are discussed and recommendations are made regarding the management of renal cell carcinoma in a Belgian context.

(BELG J MED ONCOL 2020;14(2):56–70)

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Algorithms for molecular testing in solid tumours

BJMO - volume 13, issue 7, november 2019

A. Dendooven MD, PhD, Ir A. Hébrant PhD, A. Van den Bruel MD, A. Vanderstichele MD, PhD, B. Decallonne MD, PhD, B. Maes MD, PhD, B. Weynand MD, C. Dooms MD, PhD, C. Van den Broecke MD, D. Creytens MD, PhD, E. Govaerts MD, E. Hauben MD, PhD, E. Van Valckenborgh PhD, E. Wauters MD, PhD, F. Dedeurwaerdere MD, G. Costante MD, G. Floris MD, PhD, G. Martens MD, PhD, G. Raicevic PhD, H. Denys MD, PhD, HA. Poirel MD, PhD, I. Salmon MD, PhD, I. Van den Berghe MD, J. De Grève MD, PhD, J. Kerger MD, J. Van den Oord MD, PhD, J. Van der Meulen PhD, J.P. Machiels MD, PhD, K. Punie MD, K. Van de Vijver MD, PhD, K. Vandecasteele MD, PhD, K. Vermaelen MD, PhD, L. Brochez MD, PhD, L. Ferdinande MD, PhD, L. Lapeire MD, PhD, L. Van de Voorde MD, L. Vanwalleghem MD, M. Garmyn MD, PhD, M. Lammens MD, PhD, M. Remmelink MD, PhD, M. Van den Bulcke PhD, M.C. Burlacu MD, N. D’Haene MD, PhD, O. Kholmanskikh Van Criekingen MD, PhD, P. De Paepe MD, PhD, P. Lefesvre MD, PhD, P. Neven MD, PhD, P. Pauwels MD, PhD, R. De Pauwn MD, R. Forsyth MD, PhD, R. Salgado MD, PhD, R. Sciot MD, PhD, S. Rottey MD, PhD, S. Tejpar MD, PhD, T. Boterberg MD, PhD, T. Gevaert MD, PhD, V. Kruse MD, PhD, Y. Lalami MD

SUMMARY

In order to advise the Federal Government on the reimbursement of molecular tests related to Personalised Medicine in Oncology, the Commission of Personalised Medicine (ComPerMed), represented by Belgian experts, has developed a methodology to classify molecular testing in oncology. The different molecular tests per cancer type are represented in algorithms and are annotated with a test level reflecting their relevance based on current guidelines, drug approvals and clinical data. The molecular tests are documented with recent literature, guidelines and a brief technical description. This methodology was applied on different solid tumours for which molecular testing is a clear clinical need.

(BELG J MED ONCOL 2019;13(7):286–95)

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