Radiopharmaceutical therapy has been adopted with success in malignancies such as prostate cancer and neuroendocrine tumors. This approach often combines a diagnostic agent to measure and assess target availability prior to administering a parenteral radiotherapeutic agent against the same target. Emerging evidence and ongoing research suggest that this approach could have a beneficial impact in breast cancer treatment, with a number of different breast cancer-specific or tumor microenvironment targets. There are several agents under investigation, with the majority in early-phase trials. This narrative review will provide a brief introduction to radiopharmaceutical imaging and therapy for breast cancer, discuss emerging therapeutic targets under investigation in breast cancer, and discuss challenges with the implementation of radiopharmaceuticals in breast cancer.
Some patients with HER2-positive metastatic breast cancer (MBC) achieve prolonged disease control with first-line anti-HER2-based therapy, but associated clinical features remain poorly characterized in real-world populations.We conducted a retrospective study using the Epidemiological Strategy and Medical Economics (ESME) MBC cohort, including 18 French comprehensive cancer centers. Women with HER2-positive MBC who initiated first-line anti-HER2–based therapy between January 2008 and December 2021 and had at least 3 years of follow-up were eligible. Exceptional responders had no documented progression within 3 years. A secondary analysis evaluated factors associated with remaining progression-free at 5 years. Multivariable logistic regression with bootstrap cross-validation was used.Among 4307 eligible patients, 1016 (23.6%) were exceptional responders. Of 765 evaluable at 5 years, 523 (68.4%) remained progression-free. Factors associated with a lower likelihood of exceptional response included hormone receptor–negative (HR-) disease, a disease-free interval of 6–24 months, ≥3 metastatic sites, visceral metastases, and central nervous system involvement. First-line treatment with chemotherapy, trastuzumab, and pertuzumab was associated with exceptional response. Among exceptional responders, HR-disease, grade III tumors and first-line chemotherapy plus trastuzumab and pertuzumab were associated with progression-free at 5-year, whereas visceral metastases were associated with lower odds. Model discrimination was moderate (AUC 0.72 and 0.64, respectively).Nearly one quarter of patients remained progression-free for at least 3 years, and more than two thirds of those evaluable remained progression-free at 5 years. Clinical variables alone had limited predictive value, supporting the need for molecular and immune biomarkers to better identify this subgroup.
Background Breast cancer (BC) surveillance primarily aims to detect locoregional recurrence (LRR) and contralateral breast cancer (CBC), but current strategies are largely one-size-fits-all and not tailored to individual risks. The Dutch INFLUENCE 3.0 prediction model provides personalised 5-year LRR and CBC risks to support shared decision-making on surveillance. In this study, INFLUENCE 3.0 is externally validated in a Belgian population. Methods All female BC patients curatively treated between 2000 and 2018 at the University Hospitals of Leuven were included. Calibration was assessed using the Integrated Calibration Index (ICI), E50, E90 metrics, and calibration plots. Discrimination was evaluated by calculating the Area Under the Curve (AUC) for each year, based on cumulative events up to that year. Results The final Leuven cohort included 8548 patients, of whom 7549 were not treated with neoadjuvant systemic therapy (non-NST) and 999 were (NST). Calibration metrics were generally acceptable, with ICI and E50 values below 0.01 in most subgroups. Calibration plots showed overestimation of predicted risks, particularly at lower predicted risk levels. Discrimination for LRR risk was good to very good (AUC 0.72–0.86 in the non-NST group; >0.82 in the NST group). For CBC risk, discrimination was poor in the non-NST group (AUC ≈ 0.5) and moderate-to-very good in the NST group (AUC 0.68–0.88). Conclusion INFLUENCE 3.0 showed acceptable calibration and discrimination for LRR risk, and although CBC risk discrimination in the non-NST group was poor. The overall risk estimates – primarily the LRR risks – may still help in guiding tailored surveillance schemes.
