Abstract P5-02-04: Opto-acoustic imaging of breast masses: Correlation with breast biopsy prognostic indicators
Authors: Grobmyer SR , Butler R , Neuschler EI , Stavros AT , Aitchison RD , Lavin PT , Tucker FL 
Published: February 2018

Abstract
Purpose: The Imagio™ OA/US breast imaging system, a diagnostic opto-acoustic (OA) imaging device bearing the CE Mark, is in the U.S. FDA Premarket Approval process. OA/US provides both functional (relative oxygenation/de-oxygenation) and anatomic (angiogenesis) information that is co-registered and temporally interleaved in real time with gray-scale ultrasound that may improve discrimination between benign and malignant masses. We recently reported correlation studies demonstrating tumor-zone specific OA attributes in histopathologic grade I versus grade III malignancies. The relationship between OA attributes (individual feature scores or summed feature results) and pathologically-determined prognostic markers (PDPM) in malignant lesions is the subject of this report.
Materials and Methods: In this HIPAA-compliant, IRB-approved prospective multi-center trial across 16 U.S clinical sites; 1,808 masses in 1,739 subjects assessed as BI-RADS 3, 4 or 5 were imaged with OA/US. Of these, 655 were invasive malignancies and the subject of this analysis. Each mass was scored by 8 blinded readers on 3 internal zone features of the tumor nidus and 2 external features (0-5, 6) of the tumor boundary and peripheral zones (OA attributes). Pathologic diagnoses were confirmed by an experienced central breast pathologist blinded to the OA assessment. Tumor histologic classification and grading was performed in all subjects.Evaluation of tumor estrogen receptor (ER) and progesterone receptor (PR) were performed at each site by immunohistochemistry (IHC) and was reported as percent of tumor cells expressing the receptor or, as positive if greater than 1%. Tumor HER2-neu expression was reported by IHC as 0, 1+ (negative, not over-expressed), 2+ (indeterminate) and 3+ (over-expressed). All 2+ results reflexed to fluorescence in-situ hybridization (FISH) and reported as over-expressed or not over-expressed. Tumor Ki-67 expression was evaluated with IHC and reported as percent of tumor cells positive for the antigen.
Statistical analysis of categorical measures of PDPM is in process and will be performed using a two-way Analysis of Variance (ANOVA) and Tukey HSD (honest significant difference) test for pairwise comparisons. This ANOVA will be repeated for each PDPM to test which specific PDPM sub-categories are related to OA attributes. Correlation coefficients will be generated for PDPM that are continuous, not categorical. All statistical testing will be done at a 5% significance level.
Results: A total of 655 invasive and 22 DCIS were scored for internal (nidus) and external (boundary and periphery) OA attributes and compared with PSBC as defined by ER, PR, Her2 and Ki-67 expression. Of these, 108 were Luminal-A (LA), 153 Luminal-B (LB), 80 Triple-negative (TN), 23 Her2-enriched (HER2) and 314 unclassified (including 22 DCIS). OA attributes differentiated LA (99%CI 2.8,3.1) from TN (99%CI 3.1,3.4), p=0.027 and HER2 (99%CI 3.1,3.6), p=0.036. OA features strongly suggested LA vs. LB (99%CI 3.1,3.3) subtype, p=0.060. LB vs.TN(p=0.59) and HER2(p=0.41) were non-significant. TNBC vs. HER2 was p=0.62.
Citation Format: Grobmyer SR, Butler R, Neuschler EI, Stavros AT, Aitchison RD, Lavin PT, Tucker FL. Opto-acoustic imaging of breast masses: Correlation with breast biopsy prognostic indicators [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-02-04.