Circulating tumor DNA detection of local recurrence in a patient with early stage triple-negative breast cancer.

Abstract

Triple-negative breast cancer (TNBC) comprises 10-15% of all breast cancers and is associated with high recurrence rates and limited treatment options. No guideline-recommended blood-based surveillance tests currently exist for early recurrence detection. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for molecular residual disease (MRD) assessment and recurrence prediction, though its role in detecting local recurrence remains unclear. We present the case of a 53-year-old postmenopausal woman with early stage TNBC who underwent neoadjuvant chemotherapy, bilateral mastectomy with axillary lymph node dissection, and adjuvant treatment. One month after completion of therapy, ctDNA monitoring using the Signatera MRD assay detected was positive at 0.07 mean tumor molecules per milliliter (MTM/mL) despite no radiographic evidence of disease. Serial ctDNA testing at 2, 3, and 6 months remained positive, with increasing MTM/mL values. Seven months after initial ctDNA detection, a breast MRI was done due to palpation of a lesion at the surgical site near the nipple, identifying multifocal masses within the reconstructed right breast, and surgical resection confirmed TNBC recurrence. Following post-mastectomy radiation, serial ctDNA testing was negative, and the patient remained radiographically and molecularly disease-free at 20 months following the resection of the recurrent disease. This case highlights the potential of ctDNA testing for MRD detection in the adjuvant setting and identifying local recurrence. If systemic imaging fails to detect metastases, dedicated breast imaging remains crucial, even after bilateral mastectomy. Early ctDNA testing may refine surveillance and treatment decisions. Prospective trials are needed to validate its role in improving breast cancer outcomes.