Circulating tumor DNA and its correlation with survival in hormone receptor positive HER2-negative stages I-III breast cancer: A systematic review.

e15035 Background: Hormone receptor-positive (HR+) HER2-negative (-) breast cancer comprises the majority of breast cancer cases. Neoadjuvant and adjuvant therapies have improved patient outcomes, but reliable biomarkers for predicting treatment response and long-term prognosis are still needed. Circulating tumor DNA (ctDNA) has emerged as a promising tool to monitor tumor dynamics and predict survival outcomes. This systematic review investigates the association between ctDNA detection during neoadjuvant or adjuvant treatment and survival outcomes in HR+/HER2- stages I-III breast cancer. Methods: We systematically reviewed studies published up to May 3, 2024, that evaluated ctDNA as a biomarker in HR+/HER2- breast cancer patients undergoing neoadjuvant or adjuvant therapies. Eligible studies reported survival outcomes, including recurrence/disease/ invasive disease-free survival and overall survival, and measured ctDNA. Data were extracted from Ovid MEDLINE and Embase, and studies were assessed for bias. We performed a qualitative synthesis of the results. Results: Eleven studies including 1,644 HR+/HER2- breast cancer patients were included. In the neoadjuvant setting, ctDNA positivity prior to treatment was associated with worse survival outcomes. In the adjuvant setting, ctDNA detection following or during treatment was linked to poorer recurrence-free survival and invasive disease-free survival outcomes. These findings further build on a growing body of evidence demonstrating that ctDNA positivity is a significant negative prognostic marker for predicting clinical outcomes in HR+ HER2– breast cancer. Conclusions: This systematic review highlights the prognostic value of ctDNA in HR+/HER2- breast cancer, with ctDNA positivity correlating with worse survival outcomes in the adjuvant and neoadjuvant settings. While ctDNA offers real-time insights into tumor dynamics, variability in study methodologies calls for standardization in future research. Studies are underway to evaluate therapeutic interventions for patients with ctDNA-positivity, underscoring the need for new therapeutic strategies. Studies in the neoadjuvant setting. Study Number of Patients (n) Outcome Metrics Findings HR (95% CI), if reported Li et al. (2020) 21 DFS and OS No correlation between ctDNA detection after neoadjuvant chemotherapy and survival outcomes 1.75 (95% CI 0.23–13.39) for DFS and 1.66 (95% CI 0.095–28.94) for OS Lin et al. (2021) 41 RFS ctDNA detection after neoadjuvant chemotherapy associated with worse outcomes No HRs reported Chen et al. (2021) 80 OS ctDNA detection after neoadjuvant therapy (endocrine therapy with exemestane) associated with worse outcomes 4.4 (95% CI 1.1–4.3) Magbanua et al. (2024) 145 DRFS ctDNA detection after neoadjuvant chemotherapy associated with worse outcomes 5.89 (95% CI 2.68–12.98)