HER2-positive breast cancer has undergone one of the most profound therapeutic transformations in oncology: once associated with poor outcomes, it is now a highly curable disease in the early-stage setting, and a substantial proportion of patients with metastatic disease survive beyond five years. A review published in Nature Reviews Clinical Oncology examines how to right-size treatment intensity across the whole disease continuum.
What was known
That change has been built on several families of HER2-targeted agents: monoclonal antibodies, antibody-drug conjugates and tyrosine-kinase inhibitors. The result is a landscape with many options at each line of therapy and new questions about the order in which to use them.
What this work adds
This is a review, not a clinical trial: the authors organise the available evidence and the open questions on HER2-directed treatment across the disease continuum. The starting point is the movement of the antibody-drug conjugate trastuzumab deruxtecan into earlier and earlier lines — first-line metastatic disease, adjuvant treatment of high-risk residual disease and neoadjuvant therapy. That expansion creates opportunities, but also crucial evidence gaps regarding optimal sequencing, retreatment and the selection of patients who should receive intensified treatment.
Main results
In early-stage disease, right-sizing means carefully de-intensifying treatment for low-risk tumours, optimising neoadjuvant chemotherapy backbones and escalating therapy when residual disease remains after neoadjuvant treatment. In advanced disease, it requires optimising maintenance treatment after the induction phase — with options such as palbociclib or tucatinib — and integrating those regimens with the new first-line possibility of trastuzumab deruxtecan plus pertuzumab, whose optimal duration and subsequent sequencing remain uncertain. Tissue, plasma and dynamic imaging-based biomarkers are beginning to inform this process, and several show promising potential for clinical implementation.
What it means
The review adds no new patient data: it maps the decisions now faced in HER2-positive disease. The central message is that having more drugs does not mean using all of them, but rather choosing the right intensity in each situation and for each person, for the expected benefit and for toxicity.
A view from the breast unit
For a breast unit, the paper describes a recognisable problem: in the same disease, two patients may receive different treatment intensity depending on how risk and biomarkers are read. Using those tools well and ordering expensive treatments is both quality of care and equity of access.
Reference: Tarantino P, Valenza C, Segui E, Lin NU, Prat A, Curigliano G, et al. Right-sizing treatment for HER2-positive breast cancer: evolving algorithms across the disease continuum. Nature Reviews Clinical Oncology, 2026. https://doi.org/10.1038/s41571-026-01211-5
