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ESMO 2025 | Assessing risk and treatment options in HR+/HER2- breast cancer

Nicholas McAndrew, MD, MSCE, UCLA Health, Santa Monica, CA, discusses the potential use of neoadjuvant chemotherapy and ribociclib as a de-escalation strategy in HR+/HER2- breast cancer. Clinicians will need to identify the most suitable patient population for de-escalation, such as those with low-grade disease or low-risk molecular testing. Attempting de-escalation in patients with high-grade disease or high-risk markers may be risky, and therefore, a more targeted approach is necessary in this setting. This interview took place at the European Society for Medical Oncology (ESMO) 2025 Congress in Berlin, Germany.

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Transcript

I think the biggest unanswered question, obviously the biggest unanswered question is like, can this be used as a de-escalation maneuver? We don’t know that for sure yet. I mean, this is a finding where we saw a surrogate endpoint that we sort of defined in this analysis. So this is for sure not a standard endpoint, but it’s based on clinically meaningful data...

I think the biggest unanswered question, obviously the biggest unanswered question is like, can this be used as a de-escalation maneuver? We don’t know that for sure yet. I mean, this is a finding where we saw a surrogate endpoint that we sort of defined in this analysis. So this is for sure not a standard endpoint, but it’s based on clinically meaningful data. So I think that, you know, the next step of something like this would be important to define which population we feel is maybe the safest to attempt de-escalation. You know, I would suspect the lowest hanging fruit with that would probably be a patient who was, you know, node positive, premenopausal. So they would likely be recommended for chemotherapy, but maybe they were low grade or, you know, had low risk molecular testing or something like that. That would be, I think, a very low hanging fruit. Of course, you could attempt that, you know, across the board, but I think it would be potentially concerning to try and do that in patients with high-grade disease or high Oncotype or high MammaPrint or some other high proliferative marker where we would tend to think of there being benefit of chemotherapy, probably risking your patient population to study that in.

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