Multidisciplinary management of HER2-positive breast cancer with brain metastases: An evidence-based pragmatic approach moving from pathophysiology to clinical data.

Introduction: About 30-50 % of stage IV HER2+ breast cancers (BC) will present brain metastases (BMs). Their management is based on both local treatment and systemic therapy. Despite therapeutic advances, BMs still impact on survival and quality of life and the development of more effective systemic therapies represents an unmet clinical need.
Materials and Methods: A thorough analysis of the published literature including ongoing clinical trials has been performed, investigating concepts spanning from the pathophysiology of tumor microenvironment to clinical considerations with the aim to summarize the current and future locoregional and systemic strategies.
Results: Different trials have investigated monotherapies and combination treatments, highlighting how the blood-brain barrier (BBB) represents a major problem hindering diffusion and consequently efficacy of such options. Trastuzumab has long been the mainstay of systemic therapy and over the last two decades other HER2-targeted agents including lapatinib, pertuzumab, and trastuzumab emtansine, as well as more recently neratinib, tucatinib, and trastuzumab deruxtecan, have been introduced in clinical practice after showing promising results in randomized controlled trials.
Conclusions: We ultimately propose an evidence-based treatment algorithm for clinicians treating HER2 + BCs patients with BMs.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests Guido Giordano reports a relationship with Novartis that includes: consulting or advisory. Gaia Griguolo reports a relationship with Eli Lilly and Company that includes: consulting or advisory. Gaia Griguolo reports a relationship with Novartis that includes: consulting or advisory. Gaia Griguolo reports a relationship with Gilead Sciences Inc that includes: consulting or advisory. Maria Vittoria Dieci reports a relationship with Eli Lilly and Company that includes: consulting or advisory. Maria Vittoria Dieci reports a relationship with Exact Sciences Corporation that includes: consulting or advisory. Maria Vittoria Dieci reports a relationship with Novartis that includes: consulting or advisory. Maria Vittoria Dieci reports a relationship with Pfizer that includes: consulting or advisory. Maria Vittoria Dieci reports a relationship with Seagen Inc that includes: consulting or advisory. Maria Vittoria Dieci reports a relationship with Gilead Sciences Inc that includes: consulting or advisory. Maria Vittoria Dieci reports a relationship with MSD Italy that includes: consulting or advisory. Maria Vittoria Dieci reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory. Maria Vittoria Dieci reports a relationship with Daiichi Sankyo Inc that includes: consulting or advisory. We would like to thank Susanna Damato who created the figures presented in this manuscript, allowing for a clear yet synthetic iconographic representation of the pathophysiological and pharmacokinetic/dynamic processes described in the review.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)