Hermione Exchange Educational Program: How to Integrate Multidisciplinary Approaches to Manage HR+/HER2- Metastatic Breast Cancer

Background/objective: Given the increasing complexity of the luminal breast cancer landscape, a proper characterization is required in everyday clinical practice, and the recurrence after the standard first-line treatment with CDK4/6 inhibitors with/without endocrine therapy should be managed. Method: The Hermione Exchange Educational Program was held in Milan, Italy, between September 2024 and January 2025. Two questionnaires were proposed regarding the use of targeted treatment or chemotherapy after progression from CDK4/6 inhibitors. The lecture and use cases enhanced the discussion during the workshops. Results: From the surveys, it emerged that most participants (69%) considered liver metastases at CDK4/6-inhibitor progression as a key reason to initiate chemotherapy, while lung progression influenced this choice for 50% of participants. Liver involvement guided the use of targeted therapy for 56%, and attitudes were divided on whether the duration of first-line CDK4/6 therapy should affect decisions (44% in agreement vs. 38% in disagreement). The willingness of patients to receive chemotherapy (88%) and comorbidities (81%) were significant drivers. Almost all participants agreed that both the duration of response and the molecular status were key aspects to consider when choosing a second line of therapy, along with the general clinical condition of the patient. In the lecture, tissue and liquid biopsy are considered powerful tools to describe tumor molecular features over time; such complexity should be harnessed by a close dialogue between oncologists, molecular biologists, and pathologists to optimize the therapeutic choice according to the mutational status of patients. The use cases illustrate three patients with visceral progression, non-visceral progression within 12 months, and non-visceral progression after 12 months following CDK4/6 inhibitors. Conclusion: Genomic testing should be considered at diagnosis and repeated during treatment to monitor the disease. The clinical experience acquired over the years must be integrated with new molecular knowledge.