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Predicting breast cancer response to neoadjuvant chemotherapy based on tumor vascular features in needle biopsies
Terisse A. Brocato, … , C. Jeffrey Brinker, Vittorio Cristini
Terisse A. Brocato, … , C. Jeffrey Brinker, Vittorio Cristini
Published March 5, 2019
Citation Information: JCI Insight. 2019;4(8):e126518. https://doi.org/10.1172/jci.insight.126518.
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Resource and Technical Advance Oncology

Predicting breast cancer response to neoadjuvant chemotherapy based on tumor vascular features in needle biopsies

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Abstract

In clinical breast cancer intervention, selection of the optimal treatment protocol based on predictive biomarkers remains an elusive goal. Here, we present a modeling tool to predict the likelihood of breast cancer response to neoadjuvant chemotherapy using patient-specific tumor vasculature biomarkers. A semiautomated analysis was implemented and performed on 3990 histological images from 48 patients, with 10–208 images analyzed for each patient. We applied a histology-based mathematical model to 30 resected primary breast cancer tumors and then evaluated a cohort of 18 patients undergoing neoadjuvant chemotherapy, collecting pre- and posttreatment pathology specimens and MRI data. We found that core biopsy samples can be used with acceptable accuracy to determine histological parameters representative of the whole tissue region. Analysis of model histology parameters obtained from tumor vasculature measurements, specifically diffusion distance divided by the radius of the drug-delivering blood vessel (L/rb) and blood volume fraction (BVF), provides a statistically significant separation of patients obtaining a pathologic complete response (pCR) from those who do not. With this model, it is feasible to evaluate primary breast tumor vasculature biomarkers in a patient-specific manner, thereby allowing a precision approach to breast cancer treatment.

Authors

Terisse A. Brocato, Ursa Brown-Glaberman, Zhihui Wang, Reed G. Selwyn, Colin M. Wilson, Edward F. Wyckoff, Lesley C. Lomo, Jennifer L. Saline, Anupama Hooda-Nehra, Renata Pasqualini, Wadih Arap, C. Jeffrey Brinker, Vittorio Cristini

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Figure 3

Histopathological parameters separate patient groups (pCR and no pCR).

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Histopathological parameters separate patient groups (pCR and no pCR).
L...
Left: Patient groups can be separated by a L/rb value within the range of 18.46 (the highest value in the “no pCR” group) and 22.73 (the second-lowest value in the pCR group); see the gray zone. The patient from the pCR group that had the lowest L/rb value may be an outlier; see main text for details. Right: Student’s t test determined a statistically significant difference between the 2 groups with respect to L/rb (P < 0.05). For each group, the box indicates the interquartile range and median, and the error bar denotes SD.

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