Abstract P3-11-17: A novel biodynamic imaging assay predicts success or failure of neoadjuvant chemotherapy in breast cancer patients
Authors: Whitacre E , Manahan E , Burak W , Morgan T , An R , Loesch D 
Published: May 2019

Background: Use of neoadjuvant chemotherapy (NAC) in breast cancer patients has increased significantly over the past decade. The clinical benefits of NAC, including potential to downstage disease, facilitation of breast conserving surgery and use of pathologic response as a prognostic marker, are well established. However, with multiple regimens approved and recommended for NAC, choosing the optimal therapy for individual patients remains a challenge. Biodynamic imaging (BI), a novel technology that captures cellular motility in living tissue via Doppler spectroscopy, could be used ex-vivo to prospectively evaluate the efficacy of systemic therapies in patient tumor samples prior to treatment. This study aimed to determine whether BI could accurately predict likelihood of response to NAC in breast cancer patients.

Methods: Fresh core biopsies were obtained from 84 patients prospectively enrolled in an IRB-approved clinical trial at 5 institutions between 1/5/17 and 8/3/2018. Patient tumor tissue was collected at time of routine diagnostic biopsy and sent to a central laboratory where it was divided into intact tumor fragments measuring approximately 1mm in diameter. Fragments were placed into 96 well plates and imaged using the BI assay (Onco4D™), while being challenged by various cytotoxic agents for up to 20 hours. Cellular characteristics and motility signatures were evaluated and compared to pathologic NAC response established upon surgical resection (mastectomy or lumpectomy).

Results: At the time of this analysis, centrally-confirmed pathologic response data were available for 17 patients treated with doxorubicin/cyclophosphamide + taxane (AC). Pathologic outcomes are pending for an additional 8 AC patients. The remainder of the 84 patients initially enrolled in the study either did not receive NAC (n=10), have not yet selected a course of therapy (n=12), or received NAC regimens other than AC (n=37). Of the 17 currently evaluable AC-treated patients, 4 had triple negative (TN) disease, 12 were hormone receptor positive, and 1 hormone receptor negative patient showed equivocal HER2 results. Two of the TN patients were known to harbor pathogenic BRCA1 mutations and received carboplatin in addition to AC. Seven of 17 patients (40%) displayed resistance to AC (2 with progressive and 5 with stable disease) while 10 experienced objective response (8 partial and 2 complete response). A multilinear regression model using 10 BI markers accurately classified 16 of 17 patients (94%) while producing 1 false prediction of partial response for a patient with stable disease clinically (R-squared=0.9994, p&lt;.0001). The positive predictive and negative predictive values of BI to AC response were 100% and 91%, respectively.

Table 1.Performance Characteristics  Clinical   OutcomeResponseNon-ResponseTotalClassifierResponse10111 Non-Response066 Total10717

Conclusion: BI was able to accurately predict patient response to neoadjuvant AC, demonstrating the potential for the platform to support personalized patient therapy. This clinical trial is ongoing and will report out results for TC (docetaxel/cyclophosphamide), TCHP (docetaxel/carboplatin/trastuzumab + pertuzumab), and additional AC patients as outcome data are accrued.

Citation Format: Whitacre E, Manahan E, Burak W, Morgan T, An R, Loesch D. A novel biodynamic imaging assay predicts success or failure of neoadjuvant chemotherapy in breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-11-17.