by Matti Aapro, Fatima Cardoso, Giuseppe Curigliano,
Alexandru Eniu, Joseph Gligorov, Nadia Harbeck, Andreas Mueller, Olivia Pagani,
Shani Paluch-Shimon, Elzbieta Senkus, Beat Thürlimann, Khalil Zaman
The Breast: Published: July 30, 2022
Human epidermal growth factor receptor 2 oncogene
(HER2-positive) overexpression/amplification occurs in less than 20% of breast
cancers and has traditionally been associated with poor prognosis. Development
of therapies that target HER2 has significantly improved outcomes for patients
with HER2-positive advanced breast cancer (ABC). Currently available
HER2-targeted agents include the monoclonal antibodies trastuzumab, pertuzumab,
and margetuximab, the small-molecule inhibitors lapatinib, tucatinib,
neratinib, and pyrotinib, as well as the antibody-drug conjugates trastuzumab
emtansine and trastuzumab deruxtecan. Optimal sequencing of these agents in the
continuum of the disease is critical to maximize treatment outcomes. The large
body of clinical evidence generated over the past 2 decades aids clinicians in
treatment decision-making. However, patients with HER2-positive ABC and
specific disease characteristics and/or comorbidities, such as leptomeningeal
disease, brain metastases, or cardiac dysfunction, are generally excluded from
large randomized clinical trials, and elderly or frail patients are often
underrepresented. In addition, there is great inequality in the accessibility
of approved drugs across countries. This article addresses various challenging
clinical situations when treating patients with HER2-positive ABC. The
objective is to provide guidance to clinicians on how and when HER2-targeted
therapies and additional treatments can be best implemented in routine clinical
practice, on the basis of existing clinical evidence and expert opinion where
needed.
