Researchers found that circulating tumor DNA testing could identify which older patients with estrogen receptor–positive breast cancer are less likely to respond to hormone therapy alone.

A blood-based test measuring circulating tumor DNA (ctDNA) may help clinicians determine which older women with a common form of breast cancer can safely forgo surgery and radiation, according to a new study published in Clinical Cancer Research.

Scientists at UPMC Hillman Cancer Center and the University of Pittsburgh School of Medicine analyzed blood samples from women age 70 and over with estrogen receptor–positive breast cancer who were considering endocrine therapy—also known as hormone-blocking therapy—as their primary treatment.

“We are learning that not every patient needs the same treatment based simply on their diagnosis, and instead, care should be right-sized for each individual,” says Priscilla F. McAuliffe, MD, PhD, breast surgical oncologist at UPMC Hillman and associate professor of surgery at Pitt’s School of Medicine, in a release.

How ctDNA Testing Was Applied

Researchers examined whether the presence or absence of ctDNA—small fragments of genetic material shed by cancer cells into the bloodstream—could predict which patients were unlikely to respond to endocrine therapy alone.

Patients whose ctDNA test returned negative, either at the start of treatment or after beginning endocrine therapy, were more likely to experience stable disease or tumor shrinkage. According to researchers, this suggests that surgery and radiation—both of which can lead to side effects including scarring, chronic swelling, infection, and nerve damage—would likely not improve outcomes for these patients.

Conversely, patients whose ctDNA remained positive after receiving endocrine therapy were more likely to experience tumor growth, indicating that surgery or additional interventions may still be necessary to achieve tumor control.

A Decentralized, Patient-Centered Trial Design

Because ctDNA can be measured through a standard blood draw, the study was designed with patient convenience in mind. Blood samples were frequently collected from patients’ homes, reducing the burden of travel and enabling researchers to enroll participants from multiple UPMC Hillman network oncology sites across the region—not only from the main UPMC Hillman location in Shadyside.

“We worked really hard to include patients outside the main academic center, including UPMC Passavant Cranberry, UPMC Jameson, and UPMC St. Margaret,” says lead author Neil Carleton, MD, PhD, a post-doctoral fellow at Pitt, in a release. “Making care more convenient for patients, including access to clinical trials, is a priority at UPMC Hillman Cancer Center.”

The study also incorporated feedback from both patients and their caregivers—a population frequently excluded from clinical trials. More than 80% of patients surveyed reported that ctDNA test results could help them feel more informed about their treatment decisions, particularly during the first six to 12 months of care. Caregivers reported that supporting loved ones through breast cancer treatment often required prioritizing caregiving responsibilities over work and other activities.

Based on those findings, researchers suggest that home-based monitoring options could be an important consideration—especially for caregivers managing competing responsibilities. The authors also emphasized the importance of patient education and shared decision-making throughout the treatment process.

Study Limitations and Next Steps

Researchers caution that the study was small, involving fewer than 50 patients, and that the findings are not yet applicable to standard clinical practice. Larger studies are needed before ctDNA monitoring could be used routinely to guide surgical de-escalation decisions in this patient population.

The study was funded by the Hillman Cancer Center Developmental Pilot Program, the Shear Family Foundation, and the National Institutes of Health.

ID 303689121 © Konstantin Iuganov | Dreamstime.com

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