Human epidermal growth factor receptor 2 (HER2) is a major prognostic and predictive marker overexpressed in 15–20% of breast cancers. The diagnostic reference standard for selecting patients for HER2-targeted therapy is based on the analysis of tumor biopsies. Previously patients were defined as HER2-positive or -negative; however, with the approval of novel treatment options, specifically the antibody–drug conjugate trastuzumab deruxtecan, many breast cancer patients with tumors expressing low levels of HER2 have become eligible for HER2-targeted therapy. Such patients will need to be reliably identified by suitable diagnostic methods. Biopsy-based diagnostics are invasive, and repeat biopsies are not always feasible. They cannot visualize the heterogeneity of HER2 expression, leading to a substantial number of misdiagnosed patients. An alternative and highly accurate diagnostic method is molecular imaging with radiotracers. In the case of HER2, various studies demonstrate the clinical utility and feasibility of such approaches. Radiotracers based on Affibody^® molecules, small, engineered affinity proteins with a size of ~6.5 kDa, are clinically validated molecules with favorable characteristics for imaging. In this article, we summarize the HER2-targeted therapeutic landscape, describe our experience with imaging diagnostics for HER2, and review the currently available clinical data on HER2-Affibody-based molecular imaging as a novel diagnostic tool in breast cancer and beyond.

Purpose: We evaluate longitudinal changes in symptom clusters and core burdensome symptoms in breast cancer patients who participated in the OptiTrain trial. Methods: 240 women were randomized to 16 weeks of supervised exercise (RT-HIIT or AT-HIIT) or usual care (UC) during adjuvant chemotherapy. Symptom clusters were composed using the Memorial Symptom Assessment Scale (MSAS), assessed at baseline, 16 weeks and 12 months later. Three symptom clusters were formed. Results: Three symptom clusters were identified: “emotional,” “treatment-related toxicity,” and “physical,” with core burdensome symptoms present over time. At 16 weeks, the reported burdens of “feeling sad” (RT-HIIT vs UC: effect size [ES] = −0.69; AT-HIIT vs UC: ES = −0.56) and “feeling irritable” (ES = −0.41 RT-HIIT; ES = −0.31 AT-HIIT) were significantly lower in both intervention groups compared with UC. At 12 months, the AT-HIIT group continued to have significantly lower scores for the core burdensome symptoms “feeling sad” (ES = −0.44), “feeling irritable” (ES = −0.44), and “changes in the way food tastes” (ES = −0.53) compared with UC. No between-group differences were found for physical symptoms. Conclusion: We identified 3 symptom clusters in breast cancer patients during and after adjuvant chemotherapy, composed of “emotional,” “treatment-related toxicity,” and “physical” symptoms. After treatment completion up to 12 months post-baseline, patients in the physical exercise groups reported lower symptom burden scores for emotional symptoms, compared with UC. Our findings indicate a preserved and long-term beneficial effect of physical exercise on self-reported emotional well-being in chemotherapy-treated breast cancer patients.

Background: Expanding therapeutic possibilities have improved disease-related prospects for breast cancer patients. Pathological analysis on a tumor biopsy is the current reference standard biomarker used to select for treatment with targeted anticancer drugs. This method has, however, several limitations, related to intra- and intertumoral as well as spatial heterogeneity in receptor expression as well as the need to perform invasive procedures that are not always technically feasible. Main body: In this narrative review, we focus on the current role of molecular imaging with contemporary radiotracers for positron emission tomography (PET) in breast cancer. We provide an overview of diagnostic radiotracers that represent treatment targets, such as programmed death ligand 1, human epidermal growth factor receptor 2, polyadenosine diphosphate-ribose polymerase and estrogen receptor, and discuss developments in therapeutic radionuclides for breast cancer management. Conclusion: Imaging of treatment targets with PET tracers may provide a more reliable precision medicine tool to find the right treatment for the right patient at the right time. In addition to visualization of the target of treatment, theranostic trials with alpha- or beta-emitting isotopes provide a future treatment option for patients with metastatic breast cancer.

Background: Cancer treatment-related morbidity relevantly compromises health status in cancer survivors, and efforts to optimise health-related outcomes in this population are vital to maximising healthy survivorship. A pre-treatment assessment – and possibly preventive management strategies – of cancer patients at increased risk for cardiovascular disease (CVD) seems a rational approach in this regard. Definitive evidence for such strategies is largely lacking, thereby impeding the formulation of firm recommendations.Results: The current scoping review aims to summarise and grade the evidence regarding strategies for prediction and prevention of CVD in adults in relation to oncological treatments. We conducted a scoping literature search for different strategies for primary prevention, such as medical and lifestyle interventions, as well as the use of predictive risk scores. We identified studies with moderate to good strength and up to now limited evidence to recommend primary preventive strategies in unselected patients treated with potentially cardiotoxic oncologic therapies.Conclusion: Efforts to minimize the CVD burden in cancer survivors are needed to accomplish healthy survivorship. This can be done by means of robust models predictive for CVD events or application of interventions during or after oncological treatments. Up to now there is insufficient evidence to implement preventive strategies in an unselected group of patients treated with potential cardiotoxic oncological treatments. We conclude that randomised controlled trials are needed that evaluate medical and lifestyle interventions in groups at increased risk for complications, in order to be able to influence chronic illness risks, such as cardiovascular complications, for cancer survivors.

PURPOSE: To evaluate the cost utility of a 9-month supervised exercise program for patients with metastatic breast cancer (mBC), compared with control (usual care, supplemented with general activity advice and an activity tracker). Evidence on the cost-effectiveness of exercise for patients with mBC is essential for implementation in clinical practice and is currently lacking. METHODS: A cost-utility analysis was performed alongside the multinational PREFERABLE-EFFECT randomized controlled trial, conducted in 8 centers across Europe and Australia. Patients with mBC (N = 357) were randomly assigned to either a 9-month, twice-weekly, supervised exercise group (EG) or control group (CG). Costs of the exercise program were calculated through a bottom-up approach. Other health care resource use, productivity losses, and quality of life were collected using country-adapted, self-reported questionnaires. Analyses were conducted from a societal perspective with a time horizon of 9 months. Costs were collected and reported in 2021 Euros (€1 = $1.18 US dollars). RESULTS: Compared with the CG, EG resulted in a quality-adjusted life-year (QALY) gain of 0.013 (95% CI, –0.02 to 0.05) over a 9-month period. The mean costs of the exercise program were €1,696 per patient with one-on-one supervision (scenario 1) and €609 with one-on-four supervision (scenario 2). These costs were offset by savings in health care and productivity costs, resulting in mean total cost differences of –€163 (scenario 1) and –€1,249 (scenario 2) in favor of EG. The probability of supervised exercise being cost-effective was 65% in scenario 1 and 91% in scenario 2 at a willingness-to-pay threshold of €20,000 per QALY. CONCLUSION: Exercise for patients with mBC increases quality of life, decreases costs, and is likely to be cost-effective. Group-based supervision is expected to have even higher cost-savings. Our positive findings can inform reimbursement of supervised exercise interventions for patients with mBC.

Background: In cardio-oncology, a range of clinical dilemmas can be identified where high-quality evidence for management is still lacking. The aim of this project was to study clinical practices and expert approaches to several clinical cardio-oncological dilemmas regarding prediction, prevention and treatment of cardiovascular disease in adult cancer patients. Methods: A cross-sectional online survey was sent out to internationally renowned experts in the field of cardio-oncology. Participants were selected based on being first or last authors of papers in the field of cardio-oncology, or principal investigators to trials in this field. Results: Topics discussed include, among others, the use of biomarkers for subclinical cardiovascular toxicity, approaches towards primary prevention and follow-up with medication and life-style recommendations, and management of fluoropyrimidine-vasospasm, QTc-prolongation and asymptomatic declines in left ventricular ejection fraction. Conclusion: The answers provided in this survey have shed light on expert-based practices in cardio-oncologic dilemmas. Attitudes towards, as well as discrepancies in those dilemmas are presented. Existing discrepancies clearly indicate the need for generation of high-quality data that allows for more evidence-based recommendations in the future.