E. de Azambuja MD, PhD

Extended adjuvant endocrine therapy: The impact of recent insights on clinical practice

SUMMARY

Five years used to be the standard duration for adjuvant endocrine therapy (ET) for hormone receptor-positive early breast cancers, but the benefit of extending treatment duration beyond this period to reduce the risk of disease recurrence has been investigated in several randomised trials, mostly including postmenopausal patients and investigating the extension of aromatase inhibitors as part of the ET. Premenopausal patients represent, to date, a small proportion of the population in a few trials, and the options for extending adjuvant ET, especially in those patients receiving ovarian function suppression (OFS), are underexplored yet. For post-menopausal women, numerous sequences and durations have been proposed, but the optimal duration of extended adjuvant ET remains controversial. Distinct aspects influence this choice, such as the patient’s menopausal status, risk of recurrence, toxicity profile and patient’s preference. Furthermore, the introduction of new targeted agents into the adjuvant setting has brought new uncertainty regarding the ideal length of ET.

(BELG J MED ONCOL 2024;18(4):124–31)

Tailoring systemic treatment after neoadjuvant chemotherapy in patients with early breast cancer

SUMMARY

Neoadjuvant treatments in patients with breast cancer provide the opportunity for a direct evaluation of treatment effect on tumour size, allow higher rates of conservative surgery and give the chance to tailor systemic treatments after surgery. Patients who achieve a pathological complete response experience better long-term survival, compared to those with residual disease after the completion of neoadjuvant therapy, and those with residual invasive disease at surgery may benefit from additional post-neoadjuvant treatment strategies. Some systemic post-neoadjuvant treatments for patients with residual disease at surgery are already approved in clinical practice (i.e., capecitabine for patients with triple-negative breast cancer, or T-DM1 for patients with HER2-positive disease), and several new strategies are currently under evaluation. The present review discusses the available evidence for the implementation of systemic post-neoadjuvant treatment strategies into clinical practice for patients with early breast cancer, shading light on the pitfalls and limitations of different studies, and summarising data on novel promising treatment strategies that are being explored in clinical trials.

(BELG J MED ONCOL 2022;16(6):262–73)

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)

Escalation and de-escalation strategies in early breast cancer

SUMMARY

Early breast cancer is the most frequently diagnosed cancer among women worldwide. Different subtypes have been identified, and with them, new treatment strategies have emerged. In order to elaborate a personalised treatment, clinicians need reliable pathological and molecular disease subtyping, refined assessments of the risk of relapse, and predictive markers to estimate treatment benefit. Combining these elements allows for de-escalation in some patients and, on the contrary, identifies those who should receive more intensive therapy and serve as candidates for escalation strategies in standard practice or clinical trials. This article reviews the de-escalation and escalation strategies currently available and will explore future treatment perspectives in early breast cancer.

(BELG J MED ONCOL 2022;16(3):102–13)

Cardiotoxicity of immune-checkpoint inhibitors: A rare, yet possibly fatal complication

SUMMARY

Immune checkpoint inhibitors (ICI) represent a class of drugs that has dramatically improved survival outcomes of patients with several solid and haematological malignancies. Due to their mechanism of action, treatment-related adverse events (AEs) induced by ICI are mostly immune-related AEs, which can affect any organ, including the cardiovascular system. Immune-related cardiac AEs are rare, occurring in less than 1% of patients receiving ICI. However, they are associated with a high fatality rate compared to other AEs. Together with an increasing awareness among physicians, cardiotoxicity of ICI requires further investigation to better understand the pathophysiology of this rare but possibly fatal complication, and to improve its diagnosis and treatment. The present narrative review aimed to describe the incidence and the underlying mechanism of ICIs’ cardiotoxicity, providing key messages for clinical practice for oncologists and cardiologists on their clinical manifestations and management.

Neoadjuvant treatment considerations in HER2-positive breast cancer patients

SUMMARY

HER2-positive breast cancer was considered an aggressive subtype with a worse prognosis, but the development of anti-HER2 agents changed this paradigm. In the last years, the treatment of early HER2 breast cancer patients faced several improvements. Different anti-HER2 targeted drugs, like trastuzumab, pertuzumab, lapatinib, and TDM-1 used in advanced disease started to be included in multimodal curative strategies. Further, the presence of complete pathological response to neoadjuvant treatments started to be used as a surrogate outcome and led to the development of post-neoadjuvant strategies. Here, we summarise the neoadjuvant and post-neoadjuvant treatments of HER2-positive breast cancer according to the best evidence, reviewing the pharmacological aspects of HER2 targeted agents.

(BELG J MED ONCOL 2021;15(1):4-10)

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

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)