P. Neven MD, PhD

How to use and sequence systemic therapy in stage III luminal breast cancer?

SUMMARY

Luminal (HR+/HER2-) breast cancer (BC) is the most frequent BC subtype and is highly heterogenous. Stage III is associated with a high risk of relapse. Clinical benefit can be expected from the (neo-)adjuvant use of various systemic therapies (chemotherapy, endocrine therapy, CDK4/6 inhibitors, and PARP inhibitors). No trials are available specifically for patients with stage III. In this narrative review, we summarise the available evidence and provide recommendations on the use and timing of different neoadjuvant systemic therapies in this high-risk population. Neoadjuvant systemic treatment is the most used approach in this setting. Alternatively, upfront surgery followed by adjuvant systemic treatment can be an appropriate initial choice for selected patients, such as elderly patients with low-grade BC and high endocrine sensitivity. In premenopausal patients, neoadjuvant chemotherapy (NAC) is often preferred, as small studies have shown it to be superior to endocrine therapy (ET). The most used regimen is dose-dense anthracycline-cyclophosphamide followed by taxanes. Docetaxel with cyclophosphamide could be an alternative if the use of anthracycline is contraindicated, but limited data exist. For postmenopausal patients, neoadjuvant endocrine therapy (NET) has demonstrated similar pathological and clinical response rates compared to both NAC and ET combined with CDK4/6 inhibitors. NET can be recommended as the first-line treatment, particularly for elderly or frail patients. Pathological complete response is not an optimal surrogate endpoint for survival in luminal BC. Alternative endpoints, such as residual cancer burden, should be further explored. Despite not being investigated specifically in stage III, gene expression profiling (GEP) determination at diagnosis or dynamic KI67 evolution after two to four weeks of NET could help clinicians and patients to guide the need for chemotherapy. Many treatment options are available for stage III luminal BC; in this review we provide evidence and guidance for optimal use and sequencing of (neo) adjuvant therapies for these patients.

(BELG J MED ONCOL 2025;19(6):266–280)

SABCS 2024: Highlights of new data on systemic therapy for breast cancer

SUMMARY

As a yearly tradition, the annual San Antonio Breast Cancer Symposium provided us with important updates regarding the systemic treatment approaches of breast cancer. In the early breast cancer landscape, probably the most awaited data release at SABCS 2024 was the primary analysis of GeparDouze investigating atezolizumab in early triple-negative breast cancer. In the advanced breast cancer, results from EMBER-3 investigating imlunestrant as a single agent and in combination with abemaciclib were eagerly awaited. In addition, the PATINA trial provided an unexpected late-breaking abstract reporting on the addition of palbociclib to maintenance treatment with endocrine and anti-HER2 therapy in advanced hormone receptor positive/HER2-positive breast cancer. Next to many systemic therapy updates, important data has been presented on local therapy for breast cancer and will be discussed in another issue, mostly focusing on de-escalation concepts such as surgery deferral for ductal carcinoma in situ, abstinence of sentinel lymph node procedure in low-risk disease or postmastectomy radiotherapy in pN0/pN1 disease. On the intersection between radiotherapy and systemic therapy, the innovative EUROPA trial reported an early interim analysis of a study investigating either radiotherapy or endocrine therapy as a single modality for stage 1 hormone receptor positive, HER2-negative breast cancer in patients aged ≥70 years.² Without ipsilateral breast tumour recurrences (IBTR) at the data cut-off, further follow-up is required for comparative efficacy analysis as defined by five-year IBTR. However, the presented co-primary endpoint of health-related quality-of-life at two years showed a significant reduction in quality-of-life associated with endocrine therapy compared to baseline and to patients receiving only radiation therapy during the first two years of treatment, with at least 22.5% of patients requiring a switch of endocrine therapy and 12.4% discontinuing endocrine therapy during the follow-up. These data are very encouraging and can gradually be implemented in clinical practice in selection based on life expectancy, patient preference and further study follow-up. Below, we summarise the most important data releases regarding systemic breast cancer treatment presented at SABCS 2024.

(BELG J MED ONCOL 2025;19(3):129–136)

Highlights in Breast Cancer

SUMMARY

ASCO 2025 was an outstanding year for breast cancer research, particularly in the metastatic setting, bringing forward practice-changing data and challenging existing therapeutic algorithms. These advancements offer hope that breakthroughs in advanced disease will eventually translate into improved cure rates when applied earlier, at a stage where the disease is still at a subclinical, micro-metastatic level. These new findings raise the hope that every progress made in this life-threatening disease will be translated later into an improved cure when used in the early setting when these therapeutic innovations are and will be investigated at the time the disease is still at the subclinical micro-metastatic level.

Although most progress was reported in the field of luminal (HR+/HER2-) metastatic breast cancer, important breakthroughs were also seen in the first-line treatment of HER2-amplified and triple-negative metastatic breast cancer. In addition, important findings have been reported in the early disease setting. Translational studies from pivotal trials are helping to individualise therapeutic approaches and the emergence of therapeutic concepts of great interest are paving the way to a new era in the management of this particular and unique solid tumour. In this paper, we summarised the key clinical data and their clinical relevance for everyday practice in several tables. We also attempted to adapt current therapeutic algorithms in the metastatic setting to reflect the evolving landscape of new agents and strategies. Given the broad plethora of interesting studies presented at ASCO 2025, not all studies could be discussed in the text. Therefore, a selection of additional key messages and tables are provided at the end of the article.

The statements and interpretation of reported data reflect the opinion of the authors. However, we aim to use these new data and adapted therapeutic algorithms as a starting point for further discussion in following papers and meetings. In this summary, we proceed by describing new data for each molecular subgroup from the metastatic to the early setting, followed by a proposal of a new therapeutic algorithm. In addition, a selection of key data from local and regional therapeutic approaches will be reported and analysed. The paper will close with an overview of clinically meaningful supportive care data.

(BELG J MED ONCOL 2025;19(4):235–244)

Highlights in HR-positive breast cancer

With respect to hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer, a post hoc analysis of the TAILORx trial was presented during SABCS 2024, in which the potential benefit of adding adjuvant anthracyclines to a taxane-containing regimen was evaluated according to genomic risk using Oncotype DX. In addition, in early breast cancer (EBC), nab-paclitaxel was compared to solvent-based (sb)-paclitaxel in the chemotherapy cohort of the WSG-ADAPT HR+/HER2- trial. Also, additional analyses related to the NATALEE trial were presented, including the effect of adjuvant ribociclib dose reduction on efficacy, and assessment of the benefit of ribociclib plus non-steroidal aromatase inhibitors (NSAIs) on distant disease-free survival (dDFS) across several subgroups. In the metastatic setting, SABCS 2024 featured the results of the phase III EMBER trial, which evaluated the efficacy and safety of imlunestrant as monotherapy or combined with abemaciclib in patients with endocrine-resistant oestrogen receptor (ER)-positive, HER2-negative metastatic breast cancer (MBC); they either progressed during adjuvant or first-line endocrine therapy (ET) and prior cyclin dependent kinase 4 or 6 inhibitor (CDK4/6i) was allowed. Moreover, the PADMA trial evaluated the use of palbociclib plus ET vs mono-chemotherapy in women with high-risk, previously untreated, HR-positive, HER2-negative MBC. Finally, an exploratory post hoc analysis of the DESTINY-Breast06 trial assessed the efficacy of trastuzumab deruxtecan (T-DXd) according to pace of progression on prior endocrine-based therapy.

Discussing sexuality-related issues with breast cancer patients: When and how?

SUMMARY

The improvements in breast cancer treatment have resulted in an increased survival rate and a growing number of breast cancer survivors. These survivors have to learn to cope with the side effects of breast cancer treatment. These side effects often have an important impact on patient’s general and sexual well-being. In clinical care, sexual side effects are often un(der)recognised because physicians and patients experience barriers to discussing sexuality-related issues. It is, nevertheless, important and relevant to discuss sexuality during the various stages of (breast) cancer treatment. For young women at the start of breast cancer treatment, fertility-related questions may arise. During the different phases of breast cancer treatment, sexual functioning and sexual experience may be altered by the physical, psychosocial, and relational impact of breast cancer diagnosis and treatment. This article aimed to highlight easy-to-use methods to discuss sexuality proactively for any healthcare provider involved in the care of the cancer patient. Mentioning sexuality in the early stages of (breast) cancer treatment and addressing sexual sequelae of breast cancer diagnosis and treatment can significantly improve patients’ quality of life.

(BELG J MED ONCOL 2023;17(7):252–8)

Rethinking the reimbursement of innovative medicines in oncology: Looking beyond overall survival

SUMMARY

The oncological treatment landscape is evolving at a very rapid pace with a continuous stream of novel treatment options. To fully leverage these therapeutic advances in clinical practice it is important to facilitate a rapid access to innovative anticancer drugs for patients. Specifically for Belgium, the delay from EMA approval to reimbursement for anticancer drugs is very long, with an average of almost 600 days, and a substantial proportion of innovative drugs never make it to the patient. The stringent focus of the Belgian Commission for Reimbursement of Medicines (CRM) on overall survival (OS) data in reimbursement decisions is believed to be an important contributor to this situation. However, the ever-increasing pace at which new anticancer therapies are being developed in combination with an earlier detection of cancer will make it increasingly difficult to present mature OS data at the time of regulatory approval in the years to come. As such, there is an urgent need for a debate with the regulators to consider more readily available endpoints in their reimbursement assessments. In fact, when a strong treatment effect is seen on an intermediate endpoint such as disease-free or progression-free survival, a benefit in OS is quite likely. As such, our reimbursement system needs to be adapted to better align with the scientific progress in oncology. In this, a temporary reimbursement decision based on intermediate endpoints could give Belgian patients earlier access to promising lifesaving medicines. In this, we as oncologists, including specialists in haematology, respiratory oncology, and gastrointestinal cancer, strongly encourage the CRM to use the grading provided by the ESMO magnitude of clinical benefit scale to evaluate the clinical added value of future cancer treatments. This will not only facilitate a faster patient access to innovative therapies, but will also help policy-makers in advancing ‘accountability for reasonableness’ in their resource allocation deliberations.

(BELG J MED ONCOL 2023;17(6):211–5)

Highlights in breast cancer

The 2023 ASCO meeting again featured several ground-breaking presentations in the field of breast cancer (BC). Early-stage highlights include the long-awaited data of the NATALEE trial assessing adjuvant ribociclib in combination with endocrine therapy (ET) and the PHERGain trial exploring chemotherapy de-escalation using 18F-FDF PET/CT metabolic response assessment. Other studies discussed new molecular biomarkers for recurrence and response, and the impact of ET timing intake on outcomes. Finally, flibanserin was shown to be effective in countering sexual dysfunction in BC patients receiving adjuvant ET. In the metastatic setting, the SONIA trial questioned the universal use of CDK4/6 inhibitors in the first line treatment of patients with hormone-receptor (HR) positive metastatic BC. Furthermore, a pooled analysis of the DESTINY-Breast01, -02, and -03 trials reaffirmed trastuzumab deruxtecan as an effective treatment option for patients across all age subgroups in HER2-positive BC. Finally, a less toxic capecitabine regimen emerged as an alternative to standard treatment in metastatic BC. These results, along with other important findings, are summarised in this report. We would like to acknowledge Prof. Hans Wildiers and Prof. Patrick Neven (University Hospitals Leuven) for their help in selecting the abstracts and adding a clinical interpretation to this overview.

(BELG J MED ONCOL 2021;15(5):193–201)