TY - JOUR
T1 - Early Assessment Window for Predicting Breast Cancer Neoadjuvant Therapy using Biomarkers, Ultrasound, and Diffuse Optical Tomography
AU - Zhu, Quing
AU - Ademuyiwa, Foluso O.
AU - Young, Catherine
AU - Appleton, Catherine
AU - Covington, Matthew F.
AU - Ma, Cynthia
AU - Sanati, Souzan
AU - Hagemann, Ian S.
AU - Mostafa, Atahar
AU - Uddin, K. M.Shihab
AU - Grigsby, Isabella
AU - Frith, Ashley E.
AU - Hernandez-Aya, Leonel F.
AU - Poplack, Steven S.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/8
Y1 - 2021/8
N2 - Purpose: The purpose of the study was to assess the utility of tumor biomarkers, ultrasound (US) and US-guided diffuse optical tomography (DOT) in early prediction of breast cancer response to neoadjuvant therapy (NAT). Methods: This prospective HIPAA compliant study was approved by the institutional review board. Forty one patients were imaged with US and US-guided DOT prior to NAT, at completion of the first three treatment cycles, and prior to definitive surgery from February 2017 to January 2020. Miller-Payne grading was used to assess pathologic response. Receiver operating characteristic curves (ROCs) were derived from logistic regression using independent variables, including: tumor biomarkers, US maximum diameter, percentage reduction of the diameter (%US), pretreatment maximum total hemoglobin concentration (HbT) and percentage reduction in HbT (%HbT) at different treatment time points. Resulting ROCs were compared using area under the curve (AUC). Statistical significance was tested using two-sided two-sample student t-test with P < 0.05 considered statistically significant. Logistic regression was used for ROC analysis. Results: Thirty-eight patients (mean age = 47, range 24–71 years) successfully completed the study, including 15 HER2 + of which 11 were ER + ; 12 ER + or PR + /HER2−, and 11 triple negative. The combination of HER2 and ER biomarkers, %HbT at the end of cycle 1 (EOC1) and %US (EOC1) provided the best early prediction, AUC = 0.941 (95% CI 0.869–1.0). Similarly an AUC of 0.910 (95% CI 0.810–1.0) with %US (EOC1) and %HbT (EOC1) can be achieved independent of HER2 and ER status. The most accurate prediction, AUC = 0.974 (95% CI 0.933–1.0), was achieved with %US at EOC1 and %HbT (EOC3) independent of biomarker status. Conclusion: The combined use of tumor HER2 and ER status, US, and US-guided DOT may provide accurate prediction of NAT response as early as the completion of the first treatment cycle. Clinical Trial Registration number: NCT02891681. https://clinicaltrials.gov/ct2/show/NCT02891681,Registration
AB - Purpose: The purpose of the study was to assess the utility of tumor biomarkers, ultrasound (US) and US-guided diffuse optical tomography (DOT) in early prediction of breast cancer response to neoadjuvant therapy (NAT). Methods: This prospective HIPAA compliant study was approved by the institutional review board. Forty one patients were imaged with US and US-guided DOT prior to NAT, at completion of the first three treatment cycles, and prior to definitive surgery from February 2017 to January 2020. Miller-Payne grading was used to assess pathologic response. Receiver operating characteristic curves (ROCs) were derived from logistic regression using independent variables, including: tumor biomarkers, US maximum diameter, percentage reduction of the diameter (%US), pretreatment maximum total hemoglobin concentration (HbT) and percentage reduction in HbT (%HbT) at different treatment time points. Resulting ROCs were compared using area under the curve (AUC). Statistical significance was tested using two-sided two-sample student t-test with P < 0.05 considered statistically significant. Logistic regression was used for ROC analysis. Results: Thirty-eight patients (mean age = 47, range 24–71 years) successfully completed the study, including 15 HER2 + of which 11 were ER + ; 12 ER + or PR + /HER2−, and 11 triple negative. The combination of HER2 and ER biomarkers, %HbT at the end of cycle 1 (EOC1) and %US (EOC1) provided the best early prediction, AUC = 0.941 (95% CI 0.869–1.0). Similarly an AUC of 0.910 (95% CI 0.810–1.0) with %US (EOC1) and %HbT (EOC1) can be achieved independent of HER2 and ER status. The most accurate prediction, AUC = 0.974 (95% CI 0.933–1.0), was achieved with %US at EOC1 and %HbT (EOC3) independent of biomarker status. Conclusion: The combined use of tumor HER2 and ER status, US, and US-guided DOT may provide accurate prediction of NAT response as early as the completion of the first treatment cycle. Clinical Trial Registration number: NCT02891681. https://clinicaltrials.gov/ct2/show/NCT02891681,Registration
KW - Near Infrared imaging
KW - Personalized medicine
KW - Predicting neoadjuvant therapy
KW - Ultrasound
UR - http://www.scopus.com/inward/record.url?scp=85105508435&partnerID=8YFLogxK
U2 - 10.1007/s10549-021-06239-y
DO - 10.1007/s10549-021-06239-y
M3 - Article
C2 - 33970392
AN - SCOPUS:85105508435
SN - 0167-6806
VL - 188
SP - 615
EP - 630
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -