Precision De-escalation and Sequencing in Modern Breast Radiation Oncology

As breast cancer management shifts toward de-escalation and highly targeted systemic therapies, radiation oncologists must balance oncologic safety with patient quality of life. At the 2026 American College of Radiation Oncology (ACRO) Summit, Sunil W. Dutta, MD, shared insights into how recent landmark trials and the rise of antibody-drug conjugates (ADCs) are reshaping clinical workflows for both low-risk and metastatic populations.

In this interview with CancerNetwork®, Dutta, assistant professor in the Department of Radiation Oncology at Emory University School of Medicine, explored the nuances of shared decision-making and the practicalities of modern sequencing. He spoke about utilizing phase 3 PRIME II trial (ISRCTN95889329) data to discuss the omission of radiation in patients where the treatment improves local recurrence risk but offers no difference in overall survival. Additionally, he noted the role of ultra-hypofractionated regimens, such as the FAST-Forward (ISRCTN19906132) 5-day whole breast or partial breast schedules, for patients who elect for treatment.

Dutta also mentionedintegrating agents like fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu), with a strong preference for sequencing rather than concurrent administration to avoid potential toxicity or radiation recall.

Transcript:

How are you currently integrating recent trial data like FAST-Forward or PRIME II to de-escalate treatment in older patients or those with low-risk profiles without compromising oncologic safety?

The PRIME II data lowered the age limit where we can offer omission of radiation. I tell all patients in that age group that radiation is just improving recurrence risk in the breast, although that is already low and has no difference on survival. Once you tell the patient that, they often come at ease, and they can make a decision from there. I can give the same spiel to a patient about the radiation for that age group; some will say they don’t want the radiation, and then some will. It’s a very personal decision, and so I try to personalize the radiation to that patient. Oftentimes, we can offer 5 days of radiation for that patient group, if they do elect for radiation. Whether that's the UK FAST-Forward whole breast regimen or a partial breast regimen, they do quite well with those regimens.

With the rapid rise of antibody-drug conjugates like T-DXd, what is your current approach to sequencing radiation? Are you seeing any increased signal for radiation recall or toxicity that clinicians should be wary of?

There are some data to show that there should be some hesitation or concern with combining those newer agents. Thankfully, with breast cancer, it’s a relatively radiosensitive tumor because we are covering microscopic disease, and the regimens are getting more convenient, whether it be 5 or 15 days of radiation. I always prefer to sequence them and not combine them. There may be specific cases where there’s gross disease, and we don’t want to pause systemic therapy, but that’s a very rare situation.