Systemic Therapy for HER2-Positive Metastatic Breast Cancer: Current and Future Trends.

Content Provider	Europe PMC
Author	Vega Cano, Kreina Sharela Marmolejo Castañeda, David Humberto Escrivá-de-Romaní, Santiago Saura, Cristina
Editor	Batra, Jyotsna
Copyright Year	2022
Abstract	Simple SummaryTherapeutic advances in the treatment of HER2-positive metastatic breast cancer have dramatically improved the natural history of these patients. Although double anti-HER2 blockade associated with a taxane currently remains the best option in the first line, recently, T-DXd has positioned itself as the new standard in the second line. Eventually, most patients progress and develop resistance. In response to this need, new treatments and combinations are being developed. The aim of this paper was to review the new strategies that are in development for the treatment of these patients, the mechanisms of action and toxicities. Treatments are expected in the near future to change the treatment paradigm.AbstractApproximately 20% of breast cancers (BC) overexpress human epidermal growth factor receptor 2 (HER2). This subtype of BC is a clinically and biologically heterogeneous disease that was associated with an increased risk for the development of systemic and brain metastases and poor overall survival before anti-HER2 therapies were developed. The standard of care was dual blockade with trastuzumab and pertuzumab as first-line followed by TDM-1 as second-line. However, with the advent of new HER2-targeted monoclonal antibodies, tyrosine kinase inhibitors and antibody- drug conjugates, the clinical outcomes of patients with HER2-positive BC have changed dramatically in recent years, leading to a paradigm shift in the treatment of the disease. Notably, the development of new-generation ADCs has led to unprecedented results compared with T-DM1, currently establishing trastuzumab deruxtecan as a new standard of care in second-line. Despite the widespread availability of HER2-targeted therapies, patients with HER2-positive BC continue to face the challenges of disease progression, treatment resistance, and brain metastases. Response rate and overall life expectancy decrease with each additional line of treatment, and tumor heterogeneity remains an issue. In this review, we update the new-targeted therapeutic options for HER2-positive BC and highlight the future perspectives of treatment in this setting.
Journal	Cancers
Volume Number	15
PubMed Central reference number	PMC9817525
Issue Number	1
PubMed reference number	36612047
e-ISSN	20726694
DOI	10.3390/cancers15010051
Language	English
Publisher	MDPI
Publisher Date	2022-12-22
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2022 by the authors.
Subject Keyword	HER2 positive metastatic breast cancer targeted therapies trastuzumab antibody-drug conjugates trastuzumab deruxtecan tyrosine kinase inhibitors
Content Type	Text
Resource Type	Article
Subject	Oncology Cancer Research