2025 delivered a remarkable volume of breast cancer data, with striking results across multiple subtypes and treatment settings. As we move into 2026, these advances need to find their place, and physicians are being asked to rethink treatment strategies across multiple settings and patient populations – navigating numerous forks in the road where choices, sequencing, and trade-offs must be weighed. While KOLs actively debate these questions, the wider oncology community faces the challenge of interpreting these signals and deciding where to focus time, attention, and confidence.
Treatment crossroads in 2026:
- Oral SERDs in adjuvant HR+/HER2- disease: For many, an unexpected win, yet a very convincing clinical benefit has been demonstrated, alongside a potentially improved tolerability and adherence profile. While the move from aromatase inhibitors (AIs) to a new endocrine backbone may seem straightforward, how will physicians reconcile this with the growing evidence supporting CDK4/6 inhibitors in combination with AI?
- Post-CDK4/6 HR+/HER2- mBC: Treatment options are expanding with new oral SERDs, PROTACs, and broad PAM inhibitors such as gedatolisib. With these advances come new questions: how should clinicians balance pathway blockade against optimizing ER targeting, and which patient subgroups are most likely to benefit from each approach?
- HER2+ first-line mBC: Positive readouts from DESTINY-Breast09, PATINA, and HER2CLIMB-05 in 2025 signal the erosion of a one-size-fits-all first-line approach. Treatment selection is becoming increasingly complex, balancing efficacy and tolerability alongside CNS considerations and discussion around shorter exposure to T-DXd.
- T-DXd in early-stage HER2+ disease: Results from DESTINY-Breast05 and DESTINY-Breast11 in 2025 raise a critical question: where should T-DXd be deployed in early HER2+ breast cancer? Neoadjuvant use is gaining attention, offering efficacy benefits while managing ILD risk, ensuring exposure, and with the hope of residual TDM1 activity for adjuvant treatment.
The 2025 data laid the groundwork; in 2026, the challenge is how that science translates into real-world decisions. Each development brings opportunities and questions around patient selection, sequencing, and trade-offs. And just as clinicians begin to orient themselves around today’s evolving pathways, new forks will emerge.
The integration of oral SERDs into 1L is likely to represent the next major junction in HR+/HER2- metastatic disease. For brand teams, understanding how clinicians interpret these signals – and where they choose to invest confidence and effort – will be critical.