ctDNA and Radiation Trial Data Guide De-escalation in Breast Cancer Treatment
Recent studies and expert discussions highlight using ctDNA testing to guide surgery decisions for older ER-positive breast cancer patients and integrating FAST-Forward and PRIME II trial data to personalize radiation therapy and sequence with ADCs like T-DXd.
A recent study suggests ctDNA testing may help identify older ER-positive breast cancer patients who can safely forgo surgery in favor of primary endocrine therapy. Concurrently, radiation oncologists are integrating data from the PRIME II and FAST-Forward trials to personalize treatment and sequence radiation with antibody-drug conjugates like T-DXd.
For older women with ER-positive breast cancer, the decision to undergo surgery is not always straightforward. The study explored whether ctDNA testing could guide treatment de-escalation, helping to identify which elderly patients could safely forego surgery during primary endocrine therapy. The lead author noted that identifying such patients remains a challenge, largely because real-time information is lacking.
In radiation oncology, phase 3 PRIME II trial data are used to discuss the omission of radiation in patients where the treatment improves local recurrence risk but offers no difference in overall survival. The FAST-Forward trial provides ultra-hypofractionated regimens, such as 5-day whole breast or partial breast schedules, for patients who elect for treatment.
Experts also emphasize integrating 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. Data show hesitation when combining these newer agents with radiation, with a preference to sequence them due to breast cancer's radiosensitivity and the convenience of modern regimens.
Shared decision-making is crucial, with radiation oncologists personalizing treatment based on patient preferences. The PRIME II data lowered the age limit where omission of radiation can be offered, and when patients elect for radiation, they can be offered 5- or 15-day regimens like the FAST-Forward whole breast or partial breast schedules.