F.P. Duhoux MD, PhD

The current treatment landscape for patients with HER2-low metastatic breast cancer

SUMMARY

HER2 overexpression has been a therapeutic target in breast cancer (BC) for many years and the development of anti-HER2 therapies has markedly improved the outcome of patients exhibiting high levels of HER2 expression. In this, the HER2 status of patients was traditionally defined in a binary fashion, in which patients with high levels of HER2 expression were classified as HER2-positive, while all the rest were denominated as HER2-negative. Despite being classified as HER2-negative; the majority of these BCs do express some level of HER2. Until recently, however, these low levels of HER2 expression did not have any therapeutic implications. This has changed with the publication of the DESTINY-Breast04 (DB-04) study in which trastuzumab deruxtecan (T-DXd) was shown to significantly improve the progression-free (PFS) and overall survival (OS) of patients with HER2-low metastatic BC. These findings require a recalibration of the treatment paradigm for patients with advanced BC. Furthermore, the increased interest in HER2-low BC led to questions on the biology, epidemiology, heterogeneity, and prognostic relevance of HER2-low disease and confronts physicians with the challenge of incorporating the treatment of HER2-low disease in the rapidly evolving treatment landscape for patients with hormone-receptor-positive (HR+) and triple-negative BC (TNBC).

(BELG J MED ONCOL 2024;18(4):141–51)

Belgian clinical practice guidelines for the treatment of patients with HER2-positive advanced breast cancer

SUMMARY

HER2-targeted agents are the central component of HER2-positive metastatic breast cancer (MBC) treatment. The combination of trastuzumab, pertuzumab and a taxane is the preferred first-line regimen in most settings. For patients with disease relapse after adjuvant therapy, treatment decisions in the first-line are influenced by the treatment-free interval and the regimens used in the (neo)adjuvant setting. T-DXd has been recently established as the preferred second-line therapy. T-DM1, or the combination of tucatinib, trastuzumab and capecitabine, are reasonable third-line options, although efficacy and safety data of these regimens after prior exposure to T-DXd are lacking. In fourth and later lines, trastuzumab duocarmazine, neratinib plus capecitabine, margetuximab plus chemotherapy, lapatinib-based combinations or the continuation of trastuzumab with different chemotherapy partners are valid alternatives.

(BELG J MED ONCOL 2022;16(6): 287–92)

PI3K inhibitors in medical oncology: Update on an emerging treatment Modality

SUMMARY

The phosphatidylinositol-3-kinases (PI3Ks) play a critical role in cellular metabolism and proliferation, as well as in the development of cancer. Several mutations in the genes coding for PI3Ks have been identified in a large proportion of tumours at different rates, depending on the tumour type. Therapies targeting PI3Ks have been developed in the last years and initially used in hematological malignancies. In medical oncology, a number of trials have tried to prove the efficacy of these compounds, but most of them have been confronted with very important toxicities and only a modest benefit in progression-free survival. Recent trials using more selective treatments have shown good efficacy with an acceptable toxicity profile. The aim of this article is to review the current knowledge about PI3K inhibitors, their potential use in medical oncology and their toxicities.

(BELG J MED ONCOL 2021;15(3):96-103)

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

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)

Molecular test algorithms for breast tumours

SUMMARY

In order to advise the Federal Government on all matters related to personalised medicine in oncology, including the reimbursement of molecular tests, the Commission of Personalized Medicine (ComPerMed) has applied, for the breast tumours, the same methodology as previously applied for the digestive tumours. Meaning, the different molecular tests, represented in the shape of algorithms, are annotated with test levels — which aim to reflect their relevance based on current available data and to define the reimbursement — and are documented with recent literature, guidelines and a brief technical description.

(BELG J MED ONCOL 2019;13(2):40–45)

Highlights in breast cancer

At ASCO 2018, the results of several anticipated studies were presented. While most of these studies were thought provoking, many results left practicing oncologists a little bit disoriented. How to translate these data in clinical practice?

Practice changing data from SABCS

In his presentation, professor François Duhoux (Cliniques Universitaires St. Luc, Brussels) gave an overview of the key messages from the 2017 San Antonio Breast Cancer Symposium. Four main topics were addressed: dose dense adjuvant chemotherapy, chemotherapy for patients with lobular disease, optimizing hormonal therapy for younger breast cancer patients and the optimal duration of endocrine therapy.