Ethical approval

All procedures performed in this study involved human participants and were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments. Approvals from the following regulatory authorities and ethics committees were obtained: Comité de Ético de la Investigación con medicamentos del Hospital Arnau de Vilanova (Spain), Comité de Protection des Personnes EST-III Hôpital de Brabois (France), Ethikkommission der Medizinischen Fakultät Heidelberg (Germany), The Ethics Committee of the Institut Jules Bordet (Belgium), CEIC—Comissao de Etica para a Investigacao Clinica, Parque Saude Lisboa (Portugal), Fulham Research Ethics Committee Charing Cross Hospital (United Kingdom), and Comitato Etico ASL Brindisi, Comitato Etico della provincia Monza Brianza, Comitato Etico Istituto Europeo di Oncologia e Centro Cardiologico Monzino, Comitato Etico Val Padana, Comitato Etico di Area Vasta Emilia Centro, and Comitati Etico dell’Area Vasta Emilia Nord (Italy).

Consent to participate

Informed consent was obtained from all individual participants included in this study.

Conflict of interest

A.LC. declares research support (Roche, Agendia, Lilly, Pfizer, Novartis, Merck Sharp & Dohme, Gilead, Daichii-Sanyo), a consulting or advisory role (Lilly, Roche, Pfizer, Novartis), speakers’ bureaus (Lilly, AstraZeneca, Merck Sharp & Dohme), travel support (Roche, Pfizer, AstraZeneca), and stock or other ownership (MEDSIR, Initia-Research). A.P. declares lecture fees (Roche, Pfizer, Novartis, Amgen, BMS, Nanostring Technologies & Daiichi Sankyo), advisory role/consultancy (Roche, Pfizer, Novartis, Amgen, BMS, Puma, Oncolytics Biotech, MSD, Guardan Health, Peptomyc & Lilly), leadership role (Reveal Genomics, sl; International Oncology Bureau, sl & 1TrialSP sl), institutional financial interests (Contracted research [Boehringer, Novartis, Roche, Nanostring, Sysmex Europa GmbH, Medica Scientia inno. Research, SL, Celgene, Astellas & Pzifer], lecture fees [Nanostring technologies] and clinical trials [Boehringer, Lilly, Roche, Novartis, Amgen & Daiichi Sankyo] and leadership roles (Executive boards [SOLTI cooperative group Int. Oncology Bureau & SL, 1TrialSP], patronage committee [SOLTI Foundation & Actitud Frente al Cáncer Foundation], and co-founder and CSO at Reveal Genomics, SL). J.M.PG. is an employee in MEDSIR and declares advisory role (Lilly, Roche, Eisai, Daichii Sankyo, AstraZeneca, Seattle Genetics, Gilead) and travel expenses (Roche). J.M. declares that he has no conflict of interest. T.P. reports having received fees for non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus; Astra Zeneca, Veracyte, Novartis), consulting fees (e.g., advisory boards; Novartis, Roche), and fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus; Pfizer, Novartis, Astra Zeneca). S.ER. declares consulting or AB (Daiichi Sankyo/Astra Zeneca; Seagen; Pierre-Fabre), speakers’ bureau (Daiichi Sankyo/Astra Zeneca; Pfizer; Novartis; Seagen), and research funding (Roche; Synthon; Byondis, medsir; SOLTI; Zymeworks; Daiichi Sankyo/Astra Zeneca). A.S. declares advisory board (Astra Zeneca, Novartis, Seagen), invited speaker (Daiichi, Novartis, and Boehringer Ingelheim), and travel and accommodations (Eisai, Pfizer, Novartis). M.RB. declares that he has no conflict of interest. B.B.H. declares that she has no conflict of interest. M.K. is a founder, shareholder, and member of the board of directors in Abscint NV/SA, holds patents related to sdAb imaging and therapy, and has a FWO clinical mandate. P.G. declares that she has no conflict of interest. F.BM. has the HER2DX patent filed and the DNADX patent filed. J.J.GM. declares that he has no conflict of interest. T.G. declares that he has no conflict of interest. M.G. declares honoraria (Roche, Novartis, Gilead, Daiichi-Sankyo) and travel grants and accommodation (Roche, Pfizer, Daiichi-Sankyo). M.SC. declares grants from Medica Scientia Innovation Research (MEDSIR), Syntax for Science, Optimapharm, MD Anderson Cancer Center Madrid, and Ability Pharma that are outside the funding for the submitted work. S.DC. declares speaker’s bureau (AstraZeneca) and AB (Pierre-Fabre; IQVIA; MEDSIR). J.PE. is a full-time employee at MEDSIR. M.A.F. is an employee in Lilly, Spain. J.C. declares consulting/advisor (Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies), honoraria (Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo, Astrazeneca), research funding to the institution (Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, F.Hoffman-La Roche, Guardant health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London), stock (MedSIR, Nektar Pharmaceuticals, Leuko [relative]), travel, accommodation, expenses (Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo, Astrazeneca, Gilead.), and patents: (Pharmaceutical Combinations of A Pi3k Inhibitor And A Microtubule Destabilizing Agent.Javier Cortés Castán, Alejandro Piris Giménez, Violeta Serra Elizalde. WO 2014/199294 A. ISSUED; Her2 as a predictor of response to dual HER2 blockade in the absence of cytotoxic therapy. Aleix Prat, Antonio Llombart, Javier Cortés.US 2019/0338368 A1_LICENSED). G.G. declares that she has no conflict of interest.