ctDNA Detection Tied to Tumor Burden, Recurrence in HR+ Early Breast Cancer

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In a phase 2 trial presented at the 2024 San Antonio Breast Cancer Symposium revealed that ultra-sensitive tissue-free circulating tumor DNA (ctDNA) was detected in patients with hormone receptor (HR)-positive early breast cancer. Baseline ctDNA presence was associated with larger pathological tumor size and higher residual cancer burden (RCB) scores following neoadjuvant endocrine therapy. Additionally, persistent ctDNA after therapy correlated with increased recurrence rates, according to Dr. Albert Grinshpun and colleagues.

The phase 2 PELOPS trial included 49 patients with stages 1 to 3 HR-positive, HER2-negative breast cancer and were randomly assigned to receive either neoadjuvant endocrine therapy plus Ibrance (palbociclib; 35 patients) or neoadjuvant endocrine therapy alone (13 patients).

“This study is the first investigation into the dynamics of ctDNA during neoadjuvant endocrine therapy using the Guardant Infinity platform,” Albert Grinshpun and colleagues wrote in their poster. “Our findings suggest that ctDNA has the potential to provide valuable insights into tumor burden, sensitivity to endocrine therapy and the emergence of endocrine resistance mutations.”

ctDNA Detection in HR-Positive Early Breast Cancer

The study’s main goal was to evaluate whether baseline ctDNA and dynamic changes during neoadjuvant endocrine therapy as a biomarker could help guide systemic treatment decisions, Grinshpun and colleagues noted on the poster.

At baseline, ctDNA positivity (present ctDNA) was shown in 19% of patients and ctDNA negativity (no presence of ctDNA) was shown in 30% of patients. Before patients underwent surgery and after treatment, ctDNA positivity was shown in 6% of patients and ctDNA negativity was shown in 38% of patients.

Twenty-six of 40 patients (65%) with undetectable ctDNA at baseline remained with undetectable ctDNA after receiving neoadjuvant endocrine therapy. Specifically, six patients (14.6%) with lobular breast cancer and a RCB score of 3 had present ctDNA at baseline and before surgery, according to the poster. Among these six patients, four (67%) developed metastatic breast cancer recurrence within three years of surgery. Tumor fraction levels were reported to be lower before surgery compared with baseline in these respective patients.

Among 40 patients in the study, ctDNA dynamics were categorized by persistent or emergent ctDNA, cleared ctDNA or no ctDNA at all. At baseline and before surgery, ctDNA was persistent or emergent in six patients (15%) and in four patients (66.7%) at three-year distant recurrence. Of note, no patients in the study became ctDNA positive before surgery and 20% of patients experienced ctDNA clearance (no present ctDNA) from baseline to before surgery. At baseline and before surgery, no ctDNA was reported in 26 patients (65%) and in one patient (3.8%) at three-year distant recurrence.

“These results are limited by the sample size but merit further investigation of the role of ctDNA as a tool to predict sensitivity to endocrine therapy and long-term outcomes,” Grinshpun and colleagues concluded. “Such a tool could be valuable in tailoring surgical and systemic treatment approaches, particularly given the ongoing development of novel endocrine therapies and the addition of CDK4/6 inhibitors in the adjuvant setting.”

Reference:

“PS9-08: Ultra-sensitive detection of circulating tumor DNA (ctDNA) in patients undergoing neoadjuvant endocrine therapy for hormone receptor-positive (HR+) early breast cancer” by Dr. Albert Grinshpun, et al. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-13, 2024; San Antonio, TX. Abstract PS9-08.