TY - JOUR
T1 - Personalized ctDNA micro-panels can monitor and predict clinical outcomes for patients with triple-negative breast cancer
AU - Barnell, Erica K.
AU - Fisk, Bryan
AU - Skidmore, Zachary L.
AU - Cotto, Kelsy C.
AU - Basu, Anamika
AU - Anand, Aparna
AU - Richters, Megan M.
AU - Luo, Jingqin
AU - Fronick, Catrina
AU - Anurag, Meenakshi
AU - Fulton, Robert
AU - Ellis, Matthew J.
AU - Griffith, Obi L.
AU - Griffith, Malachi
AU - Ademuyiwa, Foluso O.
N1 - Funding Information:
These authors disclose the following: Erica Barnell is an owner, employee, and member of Geneoscopy Inc. Erica Barnell is an inventor of the intellectual property owned by Geneoscopy Inc. FOA receives research funding from Pfizer, Immunomedics, NeoImmuneTech, RNA Diagnostics, and Astellas, and fees from Teladoc Health, Pfizer, AstraZeneca, QED Therapeutics, Immunomedics, Cardinal Health, Athenex, and Biotheranostics. The remaining authors disclose no conflicts.
Funding Information:
Malachi Griffith was supported by the National Institutes of Health (NIH), National Human Genome Research Institute under award number R00HG007940. Malachi Griffith and Obi Griffith were supported by the NIH National Cancer Institute (NCI) under Award Numbers U01CA248235, U01CA209936, U01CA231844 and U24CA237719. Malachi Griffith was supported by the V Foundation for Cancer Research under Award Number V2018-007. Foluso Ademuyiwa was supported by the National Cancer Institute of the National Institutes of Health under Award Number K12 CA167540. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Circulating tumor DNA (ctDNA) in peripheral blood has been used to predict prognosis and therapeutic response for triple-negative breast cancer (TNBC) patients. However, previous approaches typically use large comprehensive panels of genes commonly mutated across all breast cancers. Given the reduction in sequencing costs and decreased turnaround times associated with panel generation, the objective of this study was to assess the use of custom micro-panels for tracking disease and predicting clinical outcomes for patients with TNBC. Paired tumor-normal samples from patients with TNBC were obtained at diagnosis (T0) and whole exome sequencing (WES) was performed to identify somatic variants associated with individual tumors. Custom micro-panels of 4–6 variants were created for each individual enrolled in the study. Peripheral blood was obtained at baseline, during Cycle 1 Day 3, at time of surgery, and in 3–6 month intervals after surgery to assess variant allele fraction (VAF) at different timepoints during disease course. The VAF was compared to clinical outcomes to evaluate the ability of custom micro-panels to predict pathological response, disease-free intervals, and patient relapse. A cohort of 50 individuals were evaluated for up to 48 months post-diagnosis of TNBC. In total, there were 33 patients who did not achieve pathological complete response (pCR) and seven patients developed clinical relapse. For all patients who developed clinical relapse and had peripheral blood obtained ≤ 6 months prior to relapse (n = 4), the custom ctDNA micro-panels identified molecular relapse at an average of 4.3 months prior to clinical relapse. The custom ctDNA panel results were moderately associated with pCR such that during disease monitoring, only 11% of patients with pCR had a molecular relapse, whereas 47% of patients without pCR had a molecular relapse (Chi-Square; p-value = 0.10). In this study, we show that a custom micro-panel of 4–6 markers can be effectively used to predict outcomes and monitor remission for patients with TNBC. These custom micro-panels show high sensitivity for detecting molecular relapse in advance of clinical relapse. The use of these panels could improve patient outcomes through early detection of relapse with preemptive intervention prior to symptom onset.
AB - Circulating tumor DNA (ctDNA) in peripheral blood has been used to predict prognosis and therapeutic response for triple-negative breast cancer (TNBC) patients. However, previous approaches typically use large comprehensive panels of genes commonly mutated across all breast cancers. Given the reduction in sequencing costs and decreased turnaround times associated with panel generation, the objective of this study was to assess the use of custom micro-panels for tracking disease and predicting clinical outcomes for patients with TNBC. Paired tumor-normal samples from patients with TNBC were obtained at diagnosis (T0) and whole exome sequencing (WES) was performed to identify somatic variants associated with individual tumors. Custom micro-panels of 4–6 variants were created for each individual enrolled in the study. Peripheral blood was obtained at baseline, during Cycle 1 Day 3, at time of surgery, and in 3–6 month intervals after surgery to assess variant allele fraction (VAF) at different timepoints during disease course. The VAF was compared to clinical outcomes to evaluate the ability of custom micro-panels to predict pathological response, disease-free intervals, and patient relapse. A cohort of 50 individuals were evaluated for up to 48 months post-diagnosis of TNBC. In total, there were 33 patients who did not achieve pathological complete response (pCR) and seven patients developed clinical relapse. For all patients who developed clinical relapse and had peripheral blood obtained ≤ 6 months prior to relapse (n = 4), the custom ctDNA micro-panels identified molecular relapse at an average of 4.3 months prior to clinical relapse. The custom ctDNA panel results were moderately associated with pCR such that during disease monitoring, only 11% of patients with pCR had a molecular relapse, whereas 47% of patients without pCR had a molecular relapse (Chi-Square; p-value = 0.10). In this study, we show that a custom micro-panel of 4–6 markers can be effectively used to predict outcomes and monitor remission for patients with TNBC. These custom micro-panels show high sensitivity for detecting molecular relapse in advance of clinical relapse. The use of these panels could improve patient outcomes through early detection of relapse with preemptive intervention prior to symptom onset.
UR - http://www.scopus.com/inward/record.url?scp=85140345613&partnerID=8YFLogxK
U2 - 10.1038/s41598-022-20928-8
DO - 10.1038/s41598-022-20928-8
M3 - Article
C2 - 36273232
AN - SCOPUS:85140345613
SN - 2045-2322
VL - 12
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 17732
ER -