Worldwide, ~7 million women live with or beyond Breast Cancer (BC), as 10-year survival rates exceeding 80% for early-stage (I-III) BC. Premenopausal BC accounts for 25% in the EU and 55% in low/middle income countries. Most premenopausal women with BC have high risk of recurrence, therefore standard treatment includes adjuvant chemo- (CT) and endocrine therapy (ET). However, treatment has substantial physical, emotional and social burden, which is often more pressing for younger compared to older patients. Gene-expression assays are used for post-menopausal patients to identify women who can safely forego CT without detriment on clinical outcomes, preserving Quality of Life (QOL). However, a definitive study has yet to be conducted among premenopausal women with high-risk HR+HER2-BC. The primary objective of PATH-FOR-YOUNG is to conduct a pragmatic randomized controlled trial (RCT) with 5000 patients validating the use of a gene-expression assay to drive adjuvant treatment decisions in this target population. PATH-FOR-YOUNG aims to achieve its objective in 7 years. The project (i) builds on and complements an ongoing twin RCT to ensure timely recruitment, (ii) leverages on a large international consortium of oncologists, pathologists, patient representatives, psychologists, sociologists, ethics and communication experts, biostatisticians, health economists, and technology providers, to assure complementary and multidisciplinary expertise, and (iii) highlights patient-engagement, participatory care, and early involvement of end users. PATH-FOR-YOUNG will also study implementation of digital self-management to support patients throughout the cancer journey and particularly while on ET to improve QOL and medication adherence. A full HTA will ensure a path towards cross-country implementation. PATH-FOR-YOUNG has the ambition to improve BC care, fully integrating the predictive, personalized, preventive, and participatory principles of health management.