Navigating first- and second-line treatment options in hormone receptor-positive HER2-negative advanced breast cancer
Sandoval J, Neven P, Emde A, Bidard FC, Aftimos P, Llombart A, Ciruelos E, Fasching P, Li H, Campone M, Coersmeyer M, Srock S, Gnant M, Barrios C (2026)
Publication Type: Journal article, Review article
Publication year: 2026
Journal
Book Volume: 31
Journal Issue: 8
Abstract
Outcomes for patients with hormone receptor-positive HER2-negative (HR+ HER2-) advanced breast cancer (ABC) have improved considerably in recent years and CDK4/6 inhibitors are the preferred first-line therapy for most patients. Newer therapeutic classes include PI3K/AKT inhibitors, oral selective estrogen receptor degraders, proteolysis-targeting chimeras, PARP inhibitors, and antibody-drug conjugates. The development and regulatory approval of these new therapies to treat HR+ HER2- breast cancer raises the question of how to use and sequence this fast-growing armamentarium to maximize benefit for individual patients. Disease progression and resistance mechanisms emerging on treatment (therapeutic pressure) add further complexity by inducing molecular alterations; thus, a clear understanding of the mechanisms behind resistance to both endocrine and CDK4/6 inhibitor therapies and their implications for subsequent treatment is critical. In principle, the most effective and tolerable drugs should be used first with the goals of delaying chemotherapy and offering patients the best quality and duration of life. This review aims to explain the evolving treatment landscape for HR+ HER2- ABC and provides the scientific background for developing future treatment algorithms driven by preclinical and clinical results.
Authors with CRIS profile
Involved external institutions
Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG)
Switzerland (CH)
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Belgium (BE)
Université Paris-Saclay
France (FR)
Institut Jules Bordet
Belgium (BE)
Universidad Cardenal Herrera
Spain (ES)
Hospital Universitario 12 de Octubre
Spain (ES)
Institut de Cancérologie de l'Ouest
France (FR)
Eli Lilly (Switzerland)
Switzerland (CH)
Eli Lilly Deutschland
Germany (DE)
Medizinische Universität Wien
Austria (AT)
LACOG - Latin American Cooperative Oncology Group
Brazil (BR)
Switzerland (CH)
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Belgium (BE)
Université Paris-Saclay
France (FR)
Institut Jules Bordet
Belgium (BE)
Universidad Cardenal Herrera
Spain (ES)
Hospital Universitario 12 de Octubre
Spain (ES)
Institut de Cancérologie de l'Ouest
France (FR)
Eli Lilly (Switzerland)
Switzerland (CH)
Eli Lilly Deutschland
Germany (DE)
Medizinische Universität Wien
Austria (AT)
LACOG - Latin American Cooperative Oncology Group
Brazil (BR)
How to cite
APA:
Sandoval, J., Neven, P., Emde, A., Bidard, F.C., Aftimos, P., Llombart, A.,... Barrios, C. (2026). Navigating first- and second-line treatment options in hormone receptor-positive HER2-negative advanced breast cancer. Oncologist, 31(8). https://doi.org/10.1093/oncolo/oyag215
MLA:
Sandoval, Jose, et al. "Navigating first- and second-line treatment options in hormone receptor-positive HER2-negative advanced breast cancer." Oncologist 31.8 (2026).
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