Early Assessment Window for Predicting Breast Cancer Neoadjuvant Therapy using Biomarkers, Ultrasound, and Diffuse Optical Tomography

Quing Zhu, Foluso O. Ademuyiwa, Catherine Young, Catherine Appleton, Matthew F. Covington, Cynthia Ma, Souzan Sanati, Ian S. Hagemann, Atahar Mostafa, K. M.Shihab Uddin, Isabella Grigsby, Ashley E. Frith, Leonel F. Hernandez-Aya, Steven S. Poplack

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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 time: September 7, 2016

Original languageEnglish
Pages (from-to)615-630
Number of pages16
JournalBreast Cancer Research and Treatment
Volume188
Issue number3
DOIs
StatePublished - Aug 2021

Keywords

  • Near Infrared imaging
  • Personalized medicine
  • Predicting neoadjuvant therapy
  • Ultrasound

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