Objectives of the
Path-for-young project

To demonstrate that premenopausal patients with high-risk HR+HER2- BC and receiving optimal ET can be stratified to forego adjuvant CT without detriment to clinical outcome and resulting in improved long-term QOL.

• This will be achieved by conducting the international Optima-young trial across 20 European, 3 Latin American, and 2 Oceanian countries

To demonstrate the effectiveness of existing personalized digital health tools to address issues of particular relevance to premenopausal patients in a personalized supportive care pathway.

• This will be achieved as a substudy of Optima-young clinical trial, which will formally test, among patients from 3 European countries, a digital companion to empower patients towards rehabilitation actions of self-management, maximizing Quality Of Life, self-efficacy, and endocrine therapy adherence.

To evaluate issues of particular relevance to premenopausal patients, and societal impact of a personalized approach to tailor adjuvant treatment for premenopausal patients.

• This will be achieved by capturing, among patients enrolled in the Optima-young, the full patient experience over their care journey, including physical and psychosocial treatment-related burden and QOL as well as specific needs that are relevant to this patient population, using Patient Generated Data (PGD) including Patient Reported Outcome Measures (PROMs), Patient Reported Experience Measures (PREMs), and Patient Preference Information. Domains of interest include physical, emotional and functioning, social, cognitive functioning, sexual functioning and adherence to ET, bone health, fertility, cardiovascular health, return to work aspects and supportive care and communication needs. Patients’ motivation to enter the trial as well as decisional regret after entering the trial will also be explored. A multidisciplinary team including social-science-and-humanities expert will be involved.

To inform health policy makers and authorities of the role of a multiparameter gene expression assay in tailoring treatment for premenopausal patients, but also the role of digital companions in patient journey, ensuring its implementation strategy across distinct healthcare systems.

• This will be achieved by performing a comprehensive Health Technology Assessment (HTA), with an upfront mapping of HTA requirements in all participating countries. This will pave the way for the development and dissemination of pragmatic guidelines for international health authorities and the medical community in terms of tools for treatment de-escalation and supportive care.

To foster patient co-creation as an essential element of cancer research and promote engagement in patient-centred, survivorship research.

• We will create a culture of patient engagement and co-creation using Living Lab methodology and the expertise from social sciences and humanities and large patient advocacy groups, Europa Donna advocates, Independent Cancer Patients Voices (OPTIMA Patient and Public Involvement [PPI]) and the BIG Patient Partnership Initiative, but also patient empowerment organizations as EUPATI. Co-creation will be present across the whole project.

To consolidate and showcase a digital infrastructure (WeShare) focused on premenopausal patients, with an open science, open data mindset that ensures the protection of intellectual property generated during the project.

• This work will leverage an existing digital platform (WeShare) for inclusive and diverse, decentralized research, data sharing, and intercontinental networking (already developed and deployed by UNICANCER, to be consolidated and expanded during the project at the EU and extra-EU level. This type of infrastructure can facilitate implementation of pragmatic clinical trials using digitally enabled research tools. In addition, we will implement specific actions in the infrastructure to ensure diversity in inclusion (e.g., screening and navigation tools to check for eligibility, toolkit for inclusion and diversity).

To communicate, disseminate and exploit knowledge on improved treatment strategies for premenopausal patients with high-risk HR+HER2- BC and to promote intercontinental networking and coordinated efforts for improving BC care.

• This objective will represent a key bridge between the Path-for-young results and the adoption of a new Standard of Care for these patients, ensure maximum impact, and the widest possible coverage within all relevant stakeholders. Importantly, in United States and Canada, the OFSET study (PI: Terry Mamounas) is also addressing the role of CT in a genomically defined population (utilizing a different assay, the 21-gene Oncotype Recurrence Score), where all premenopausal patients will receive optimal ET. In OFSET, approximately 4000 patients with a recurrence score <25 are randomized to OFS plus ET, or to the addition of CT to OFS plus ET, with a primary objective of evaluating IBCFS. In addition, in OFSET, a joint registry focused on QOL is ongoing (Ann Partridge co-PI [DFCI] and partner in Path-for-young). We will ensure collaboration between the Path-for-young consortium and the North American OFSET study through the existing network. The Path-for-young – OFSET collaboration will allow exchange of research tools and results, including opening the possibility to subsequent pooled analyses and several exploratory studies that will be able to greatly accelerate research focused on young patients with BC. OFSET anticipates definitive results after 2034. In addition, the Path-for-young partners run several existing data bases focused on premenopausal patients (UNICANCER: CANTO-YOUNG; DFCI: YWC; GIM: BRCA BCY Collaboration) which will allow structuring a strong network to investigate issues of interest to this patient population.