@article{e935b67d714b4aab9d80288e985865cc,
title = "Risk-based decision-making in the treatment of HER2-positive early breast cancer: Recommendations based on the current state of knowledge",
abstract = "Treatment of HER2-positive early breast cancer (EBC) continues to evolve with neoadjuvant (pre-operative) and adjuvant (post-operative) HER2-targeted therapies as standard of care. There are two important decision points. The first involves deciding between neoadjuvant therapy or proceeding directly to surgery. Neoadjuvant chemotherapy (NACT) plus pertuzumab–trastuzumab is appropriate for patients with high-risk HER2-positive EBC (tumour diameter ≥2 cm, and/or node-positive disease). Patients with node-negative disease and tumour diameter <2 cm are candidates for upfront surgery followed by paclitaxel for 12 weeks plus 18 cycles of trastuzumab, with the option to add pertuzumab (if pN+). The second decision point involves the pathohistological result at surgery after neoadjuvant therapy. Total pathological complete response (tpCR: ypT0/is, ypN0) is associated with improved survival endpoints. Patients with tumours ≥2 cm and/or node-positive disease at diagnosis who have a tpCR after dual blockade should continue pertuzumab–trastuzumab in the adjuvant setting to complete 1 year (18 cycles) of treatment. For patients with invasive residual disease, 14 cycles of post-neoadjuvant trastuzumab emtansine (T-DM1) therapy significantly increases invasive-DFS compared with trastuzumab. Extended adjuvant therapy with neratinib is an option in selected patients (HER2-positive and oestrogen receptor [ER]-positive) who have completed adjuvant trastuzumab-based therapy. Less aggressive chemotherapy regimens are recommended in populations with a lower risk of recurrence (patients with small tumours without axillary involvement; patients unlikely to tolerate anthracycline-taxane or taxane-carboplatin regimens). Ultimately, treatment recommendations should be consistent with local and international guidelines. Further studies will guide optimisation of treatment for patients with HER2-positive EBC according to the risk of disease recurrence.",
keywords = "HER2-postive early breast cancer, Neoadjuvant therapy, Neratinib, Pertuzumab, T-DM1, Trastuzumab",
author = "Christian Jackisch and Patricia Cortazar and Geyer, {Charles E.} and Luca Gianni and Joseph Gligorov and Zuzana Machackova and Perez, {Edith A.} and Andreas Schneeweiss and Tolaney, {Sara M.} and Michael Untch and Andrew Wardley and Martine Piccart",
note = "Funding Information: All authors received medical writing support from Roche for this article. CJ reports personal fees from Roche, Novartis, Celgene, Exact Sciences, AstraZeneca, and Pfizer; and grants from Exact Sciences, during the conduct of the study. PC is an employee of Genentech, Inc. CEG reports non-financial support (unpaid advisory boards), grants and travel support from Genentech/Roche, Daiichi Sankyo, and AstraZeneca, during the conduct of the study; personal fees from Exact Sciences (paid advisory board) and Athenex (paid consultant); and research funding and non-financial support (writing support) from AbbVie, outside the submitted work. LG reports personal fees (advisory board meetings) from Amgen, ADC Therapeutics, AstraZeneca, Celgene, Eli Lilly, G1 Therapeutics, Genentech, Inc., Genomic Health, MSD, Oncolytics Biotech, Odonate Therapeutics, Onkaido Therapeutics, Roche, Pfizer, Taiho Pharmaceutical, Sandoz, Seattle Genetics, Synthon and Zymeworks; grants from Pfizer, Zymeworks and Revolution Medicines; free consultancy for Forty Seven and Metis Precision Medicine; and paid consultancy for Menarini Ricerche, Synaffix, Novartis and Revolution Medicines, during the conduct of the study. In addition, LG has a patent, EPA 12195182.6 12196177.5-ROCHE, pending (co-inventor). JG reports grants, personal fees and non-financial support for clinical trials, travel support, advisory boards and speakers{\textquoteright} bureaus from Roche-Genentech, Eisai, Genomic Health and Pfizer; personal fees and non-financial support for clinical trials, travel support, advisory boards and speakers{\textquoteright} bureaus from Novartis and Lilly; personal fees and non-financial support for clinical trials and advisory boards from Daiichi Sankyo and MSD; grants and personal fees for travel support, advisory boards and speakers{\textquoteright} bureaus from Mylan; personal fees and non-financial support for travel support, advisory boards and speakers{\textquoteright} bureaus from Pierre Fabre; and personal fees for advisory boards and speakers{\textquoteright} bureaus from AstraZeneca, outside the submitted work. ZM is an employee of Roche and owns stock in Roche Holding, Ltd. EAP reports no other conflicts of interest pertinent to this work outside of the above-mentioned medical writing support. AS reports research grants from AbbVie, Celgene and Roche; expert testimony for Roche and AstraZeneca; travel expenses from Celgene, Pfizer and Roche; honoraria from AstraZeneca, Celgene, Lilly, MSD, Novartis, Pfizer, Roche and Tesaro; and grants for medical writing from Roche, outside the submitted work. SMT reports grants to her institute as principal investigator on studies from AstraZeneca, Eli Lilly, Merck, Nektar Therapeutics, Novartis, Pfizer, Genentech/Roche, Immunomedics, Exelixis, BMS, Eisai, NanoString, Cyclacel, Sanofi and Odonate Therapeutics; personal fees (honorarium for consultancy and/or advisory boards) from AstraZeneca, Eli Lilly, Merck, Nektar Therapeutics, Pfizer, Genentech/Roche, Immunomedics, BMS, Eisai, NanoString, Puma, Sanofi, Celldex, Odonate, Seattle Genetics, Silverback Therapeutics, G1 Therapeutics, AbbVie, Athenex, OncoPep, Kyowa Kirin Pharmaceuticals, Daiichi-Sankyo, CytomX and Samsung Bioepis, Inc.; personal fees from Exelixis; and travel expense reimbursement for advisory boards from Nektar Therapeutics, outside the submitted work. MU reports compensation for his role as an advisor/consultant and for travel expenses to his institute from AbbVie, Amgen GmbH, AstraZeneca, BMS, Celgene GmbH, Daiichi Sankyo, Eisai GmbH, Lilly Deutschland, Lilly Int., MSD Merck, Mundipharma, Myriad Genetics, Odonate Therapeutics, Pfizer Germany, PUMA Biotechnology, Roche Pharma AG, Sanofi Aventis Deutschland GmbH, Teva Pharmaceuticals Ind. Ltd., Novartis, Pierre Fabre and Clovis Oncology. AW has received personal fees from Pierre Fabre, Roche, Amgen, MSD, Boehringer-Ingelheim, Novartis, Pfizer, AstraZeneca, Athenex, Gerson Lehmann Group, Coleman Expert Network Group, Guidepoint global, Helios Medical, Simon-Kucher and Partners, Lilly and Daiichi Sankyo. After completion of this work AW is employed by AstraZeneca. MP reports grants to her institute from Radius, AstraZeneca, Lilly, MSD, Novartis, Pfizer, Roche-Genentech, Synthon and Servier; personal fees from AstraZeneca, Lilly, MSD, Novartis, Odonate Therapeutics, Pfizer, Roche-Genentech, Camel-IDS, Debiopharm, Menarini, Seattle Genetics, Immunomedics, Oncolytics (for being on the Scientific Board) and Immutep, outside the submitted work. Funding Information: This article was funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Employees of the sponsor were involved in the writing and reviewing of the review; and in the decision to submit the article for publication in conjunction with the academic authors. Publisher Copyright: {\textcopyright} 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = sep,
doi = "10.1016/j.ctrv.2021.102229",
language = "English (US)",
volume = "99",
journal = "Cancer Treatment Reviews",
issn = "0305-7372",
publisher = "W.B. Saunders Ltd",
}