Detection of circulating plasma tumour mutations in early stage triple negative breast cancer as an adjunct to pathological complete response assessment.
Zaikova, E.; Cheng, B. Y.; Cerda, V.; Kong, E.; Lai, D.; Lum, A.; Bates, C.; den Brok, W.; Kono, T.; Bourque, S.; Chan, A.; Feng, X.; Fenton, D.; Gurjal, A.; Levasseur, N.; Lohrisch, C.; Roberts, S.; Shenkier, T.; Simmons, C.; Taylor, S.; Villa, D.; Miller, R.; Aguirre-Hernandez, R.; Aparicio, S.; Gelmon, K.
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Circulating tumour DNA (ctDNA) detection in liquid biopsy is an emerging alternative to tissue biopsy, but its utility in treatment response monitoring and prognosis in triple negative breast cancer (TNBC) is not yet well understood. In this study, we determined the presence of ctDNA detectable actionable mutations with a clinically validated hotspot treatment indication panel in early stage TNBC patients, without local recurrence or metastatic disease at the time of evaluation. Sequencing of plasma DNA and validation of variants from 130 TNBC patients collected within 7 months of primary treatment completion revealed that 7.7% had detectable residual disease with a hotspot panel. Among neoadjuvant treated patients, we observed a trend where patients with incomplete pathologic response and positive ctDNA within 7 months of treatment completion were at much higher risk of reduced progression free survival. We propose that a high risk subset of early TNBC patients treated in NAT protocols may be identifiable by combining tissue response and sensitive ctDNA detection.
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