For women aged seventy and older with estrogen receptor–positive breast cancer, determining the appropriate intensity of treatment remains a persistent clinical challenge. Standard approaches often involve surgery and radiation, but these interventions may not always provide meaningful benefit—and can carry significant risks in older populations.
A new study from UPMC Hillman Cancer Center and the University of Pittsburgh School of Medicine published in Clinical Cancer Research, suggests that a blood-based biomarker could help clinicians better tailor treatment decisions. By measuring circulating tumor DNA (ctDNA), researchers identified patients who may safely rely on endocrine therapy alone, as well as those who may require additional interventions.
Right-sizing treatment decisions
Endocrine therapy is frequently used as a less invasive option for hormone receptor–positive breast cancer, particularly in older patients who may not tolerate surgery well. However, clinicians currently lack reliable tools to predict which patients will respond to this approach.
The study aimed to address this gap by identifying an early decision-making window using ctDNA analysis. As senior author Priscilla F. McAuliffe, MD, PhD, explained, “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.”
This concept of “right-sizing” treatment reflects a broader shift in precision oncology, from standardized protocols toward individualized care based on tumor biology and patient-specific factors.
ctDNA as an early response marker
Circulating tumor DNA consists of small fragments of genetic material shed by tumor cells into the bloodstream. Because it can be measured through a simple blood draw, ctDNA offers a minimally invasive way to monitor disease dynamics in real time.
In this study, researchers analyzed ctDNA levels at baseline and during endocrine therapy. They found that patients whose ctDNA was undetectable, either at the start of treatment or after initiation, were more likely to experience stable disease or tumor shrinkage.
These findings suggest that such patients may not benefit from additional interventions like surgery or radiation, which can lead to complications including scarring, infection, chronic swelling, and nerve damage.
Conversely, patients with persistent ctDNA positivity after starting endocrine therapy were more likely to experience tumor progression. This indicates that endocrine therapy alone may be insufficient for this group, and that additional treatment strategies should be considered.
Defining a clinical decision window
Rather than evaluating treatment efficacy directly, the study focused on identifying an early signal to guide clinical decision-making.
The researchers propose that ctDNA status during the first six to twelve months of therapy could serve as a critical window for assessing treatment response. This approach could enable clinicians to escalate or de-escalate therapy more confidently, reducing both overtreatment and undertreatment.
Although the study was small, enrolling fewer than 50 patients, it provides a proof-of-concept for integrating liquid biopsy into treatment planning for older patients.
Expanding access through remote testing
A key feature of the study was its decentralized design. Because ctDNA testing relies on blood samples, many participants were able to provide samples from home, reducing the need for frequent hospital visits.
This approach also allowed the researchers to enroll patients from multiple regional sites beyond the main academic center. “We worked really hard to include patients outside the main academic center, including UPMC Passavant Cranberry, UPMC Jameson and UPMC St. Margaret,” said lead author Neil Carleton, MD, PhD. “Making care more convenient for patients, including access to clinical trials, is a priority at UPMC Hillman Cancer Center.”
The ability to conduct monitoring remotely may be particularly valuable for older patients, who often face mobility limitations or logistical barriers to care.
Patient and caregiver perspectives
The study also incorporated feedback from patients and caregivers, a group often underrepresented in clinical research.
More than 80% of patients reported that ctDNA test results helped them feel more informed about their treatment decisions, especially during the early stages of care. Caregivers noted that supporting patients frequently required significant personal trade-offs, including reduced work and other responsibilities.
These findings highlight the broader impact of treatment decisions, not only on patients, but also on their support networks, and highlight the importance of shared decision-making.
Path to clinical implementation
Despite its promise, the approach is not yet ready for routine clinical use. The authors emphasize that larger studies are needed to validate the findings and determine how best to integrate ctDNA testing into treatment guidelines.
If confirmed, however, the strategy could represent a meaningful advance in precision oncology—particularly for older patients, where balancing treatment efficacy with quality of life is paramount.
By providing an early, minimally invasive signal of treatment response, ctDNA testing may help clinicians move closer to truly individualized care—ensuring that each patient receives neither too much nor too little treatment, but the right amount.
