Background: Metastatic breast cancer (mBC) causes nearly all BC-related deaths. Next-generation sequencing (NGS) technologies allow for the application of personalized medicine using targeted therapies that could improve patients' outcomes. However, NGS is not routinely used in the clinical practice and its cost induces access-inequity among patients. We hypothesized that promoting active patient participation in the management of their disease offering access to NGS testing and to the subsequent medical interpretation and recommendations provided by a multidisciplinary molecular advisory board (MAB) could contribute to progressively overcome this challenge. We designed HOPE (SOLTI-1903) breast cancer trial, a study where patients voluntarily lead their inclusion through a digital tool (DT). The main objectives of HOPE study are to empower mBC patients, gather real-world data on the use of molecular information in the management of mBC and to generate evidence to assess the clinical utility for healthcare systems., Trial Design: After self-registration through the DT, the study team validates eligibility criteria and assists patients with mBC in the subsequent steps. Patients get access to the information sheet and sign the informed consent form through an advanced digital signature. Afterwards, they provide the most recent (preferably) metastatic archival tumor sample for DNA-sequencing and a blood sample obtained at the time of disease progression for ctDNA analysis. Paired results are reviewed by the MAB, considering patient's medical history. The MAB provides a further interpretation of molecular results and potential treatment recommendations, including ongoing clinical trials and further (germline) genetic testing. Participants self-document their treatment and disease evolution for the next 2 years. Patients are encouraged to involve their physicians in the study. HOPE also includes a patient empowerment program with educational workshops and videos about mBC and precision medicine in oncology. The primary endpoint of the study was to describe the feasibility of a patient-centric precision oncology program in mBC patients when a comprehensive genomic profile is available to decide on a subsequent line of treatment., Clinical Trial Registration: www.soltihope.com, identifier NCT04497285., Competing Interests: ElS reports having obtained travel/accommodation paid by Gilead and Daiichi Sankyo and honoraria from Novartis. JC reports personal fees from NOVARTIS and Pfizer. Mafalda Oliveira reports financial relationships with AstraZeneca, Guardant Health, Roche, MSD, Pfizer, SeaGen, iTEOS, Eisai, Novartis, Relay Therapeutics and Gilead. PT reports honoraria and consulting fees from AstraZeneca, Daiichi-Sankyo, Novartis, Seagen, Pfizer and Lilly and travel and accommodation paid by AstraZeneca and Pfizer. MV reports honoraria and consulting fees from Roche, Novartis and Daiichi Sankyo- AstraZeneca. MaM reports honoraries received from Lilly and Prosenestar; and research agreements with Pfizer, Lilly, Prosenestar, PharmaMar and Circle Pharma. JG reports grants and personal fees from Novartis, grants and personal fees from Pfizer, grants, and personal fees from Roche, outside the submitted work. CS has served as consultant, participated in advisory boards or received travel grants from AstraZeneca, AX’s Consulting, Byondis BV, Celgene, Daiichi Sankyo, Eisai, F. Hoffmann - La Roche Ltd, Exact Sciences, Exeter Pharma, Genomic Health, Merck, Sharp and Dhome España S.A., Novartis, Odonate Therapeutics, Pfizer, Philips Healthwork, Pierre Fabre, Pint Pharma, prIME Oncology, Puma Biotechnology, Seagen, Synthon, Sanofi Aventis and Zymeworks. SP reports advisor/consultant role for AstraZeneca, Daiichi-Sankyo, Eisai, Pfizer, SeaGen, Polyphor, Roche, Gebro Pharma, Pierre Fabre, and conference travel and accommodation paid by Gilead and Pfizer. RL reports grants and personal fees from Roche, grants and personal fees from Merck, personal fees from AstraZeneca, personal fees from Bayer, personal fees, and non-financial support from BMS, personal fees from Pharmamar, personal fees from Leo, personal fees and non-financial support from Novartis, outside the submitted work. MiM has declared advisor role or consulting from Novartis, Pfizer, Lilly, Gilead, PiereFabre and MSD; research funding from Pfizer and travel expences from Pfizer and Gilead. JB reports personal fees from Astra Zeneca and Pfizer. MoM declares the following competing interests: expert testimony honoraria from Novartis, Roche, and Eisai; advisory board honoraria from Pierre Fabre, and Seagen; and conference travel grants from Roche, Pfizer, Gilead and Lilly. IB reports honoraria and consulting fees from AstraZeneca, Roche, Novartis, Eisai, Celgene, Pfizer, Lilly, Pierre-Fabre, Bristol-Myers Squibb, Daiichi Sankyo, Grünenthal, Seagen and Veracyte; and grant/Research Support to the Institution from AstraZeneca, Lilly and Roche and travel and accommodation paid by Roche, Lilly and Pierre-Fabre, outside the submitted work. VB reports consultant or Advisory Role fees from Puma Biotechnology; Ideaya Biosciences; Loxo Therapeutics, CytomX Therapeutics; Guidepoint; Oncoart, Lilly; Janssen; personal fees Nanobiotix NANORAY-312/and Honoraria from Eli Lilly; MSD; SOLTI; TACTICS; Getthi; Gedefo. Travel/inscription/accommodation: Bayer ESMO GI and Institutional financial support for clinical trials from: Abbvie; ACEO; Adaptaimmune; Amcure; AMGEN; Amunix, AstraZeneca; Bycicle; BMS Cytomx; GSK; Genentech/Roche; Genmab; Incyte; Ipsen; Janssen; Kura; Lilly; Loxo; Nektar; Macrogenics; Menarini; Merck; Merus; Nanobiotix; Novartis; Pfizer; PharmaMar; Principia; PUMA; Ryvu; Ribbon; Sanofi; Taiho; Tesaro; BeiGene; Transgene; Takeda; Incyte; Innovio; MSD; PsiOxus; Seattle Genetics; Mersana; Daiichi; Nektar; Astellas; ORCA; Boston Therapeutics; Dynavax; DebioPharm; Boehringer Ingelheim; Regeneron; Rigontec; Millennium; Seagen; Synthon; Spectrum; Urogen; Zenith. EC reports personal fees from Roche, Lilly, Novartis, Pfizer, during the conduct of the study. EG reports advisory or consultant role from Roche, AstraZeneca, Seattle Genetics, Gilead, Pfizer and Eisai and travel grants from Pfizer, AstraZeneca and Roche. RS-B reports personal honoraria from Novartis, AstraZeneca, MSD Oncology, Lilly Oncology, Glaxo Smith Kline, Clovis, and Seagen. SC reports advisory or consultant role from Pfizer, Daiichi Sankyo, and Seagen and travel grants from Pfizer and AstraZeneca. MH reports consulting fees from AstraZeneca. AlP has declared personal honoraria from Pfizer, Novartis, Roche, MSD Oncology, Lilly and Daiichi Sankyo, travel, accommodations, and expenses paid by Daiichi Sankyo, research funding from Nanostring Technologies, Roche and Novartis, consulting/advisory role for Nanostring Technologies, Roche, Novartis, Pfizer, Oncolytics Biotech, Amgen, Lilly, MSD, PUMA and Daiichi Sankyo, Inc. outside the submitted work. AC reports honoraria and consulting fees from Pfizer, Novartis, and AstraZeneca. TP reports having received Fees for Non-CME Services Received Directly from Commercial Interest or their Agents e.g., speakers’ bureaus from AstraZeneca, Consulting Fees e.g., advisory boards from Novartis, and Fees for Non-CME Services Received Directly from Commercial Interest or their Agents e.g., speakers’ bureaus from Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Olivera-Salguero, Seguí, Cejalvo, Oliveira, Tolosa, Vidal, Malumbres, Gavilá, Saura, Pernas, López, Margelí, Balmaña, Muñoz, Blancas, Boni, Ciruelos, Galve, Perelló, Sánchez-Bayona, de la Cruz, de la Hoya, Galván, Sanfeliu, Gonzalez-Farre, Sirenko, Blanch-Torras, Canes, Masanas, Olmos, Forns, Prat, Casas and Pascual.)