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. 2021 May 20;7:56. doi: 10.1038/s41523-021-00265-1

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — This is a suggested treatment algorithm for early stage and advanced human epidermal growth factor 2 positive BC, based on the current United States Food and Drug Administration approvals. Radiation therapy and endocrine therapy should be incorporated when appropriate. There are multiple options for metastatic disease beyond second line, tucatinib can be considered in the third line setting based on the results of the phase 3 HER2CLIMB study. Other agents can be considered as fourth line or beyond, based on prior therapies, toxicity profile and comorbidities. *Subgroup analysis of APHINITY showed that patients with node positive disease have a greater benefit from adjuvant dual HER2 blockade. **Benefit seen in patients with hormone receptor positive and HER2 positive disease. There are no data about the use of neratinib after treatment with pertuzumab and/or ado-trastuzumab emtansine. ***Tucatinib is FDA approved in the second line setting after treatment with trastuzumab, pertuzumab and ado-trastuzumab emtansine. Can be considered for patients with CNS involvement.