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CC BY 4.0 · Indian J Med Paediatr Oncol
DOI: 10.1055/s-0045-1810005
Review Article

Optimizing Post-CDK4/6i Strategies In HR +/HER2− Advanced Breast Cancer: A Contemporary Evidence-Based Framework

Teena Rajan
1   Department of Medical Oncology, N. Sreedharan Memorial Institute of Medical Sciences, Kollam, Kerala, India
,
Amol Akhade
2   Department of Medical Oncology, Nair Hospital, Mumbai, Maharashtra, India
3   Department of Medical Oncology, Bethany Hospital, Thane, Maharashtra, India
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Abstract

The advent of CDK4/6 inhibitors has transformed the frontline management of HR +/HER2− metastatic breast cancer. However, resistance to these agents is inevitable, leading to a growing need for evidence-based post-progression strategies. This review synthesizes data from major trials—SONIA, PALMIRA, MAINTAIN, postMONARCH, and EMBER-3—exploring both rechallenge and class-switching strategies. We evaluate the clinical impact of switching versus continuing CDK4/6 inhibitors, mechanisms of resistance, and emerging agents such as oral SERDs (selective estrogen receptor degraders) and PROTACs. The evidence suggests limited benefit for same-agent rechallenge and supports the use of novel combinations in biomarker-selected populations. Personalized sequencing guided by molecular profiling may define the next frontier in HR +/HER2− metastatic breast cancer management.

Keywords

HR+ breast cancer - CDK4/6 inhibitors - SERDs - endocrine resistance - imlunestrant - biomarker-driven treatment

Patient Consent

Patient consent is not required.




Publication History

Article published online:
16 July 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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