Evaluation of ductal carcinoma in situ grade via triple-modal molecular imaging of B7-H3 expression

Sunitha Bachawal,Katheryne E Wilson,Gregor Krings,Gregory R Bean

doi:10.1038/s41523-020-0158-y

Sunitha Bachawal, Katheryne E Wilson + Show 2 more

Open Access

https://doi.org/10.1038/s41523-020-0158-y

Copy DOI

Abstract

Ductal carcinoma in situ (DCIS) will account for 62,930 cases of breast cancer in 2019. DCIS is a pre-invasive lesion which may not progress to invasive carcinoma, yet surgery remains the mainstay treatment. Molecular imaging of a specific marker for DCIS grade for detection and active surveillance are critically needed to reduce potential overtreatment. First, breast cancer marker B7-H3 (CD276) expression was evaluated by immunohistochemical staining in 123 human specimens including benign epithelium (H-score 10.0 ± 8.2) and low (20.8 ± 17.7), intermediate (87.1 ± 69.5), and high (159.1 ± 87.6) grade DCIS, showing a positive association with DCIS nuclear grade (P < 0.001, AUC 0.96). Next, a murine DCIS model was combined with ultrasound molecular imaging of B7-H3 targeted microbubbles to differentiate normal glands from those harboring DCIS (n = 100, FVB/N-Tg(MMTVPyMT)634Mul, AUC 0.89). Finally, photoacoustic and fluorescence molecular imaging with an anti-B7-H3 antibody-indocyanine green conjugate were utilized for DCIS detection (n = 53). Molecular imaging of B7-H3 expression may allow for active surveillance of DCIS.

Highlights

Breast cancer remains the second leading cause of cancer-related death in women with ~268,600 new cases and 41,760 deaths predicted in 20191
receiver operating characteristic (ROC) analysis of the ability of ultrasound molecular imaging to differentiate between normal tissues and ductal carcinoma in situ (DCIS) provided an area under the curve (AUC) of 0.89
Ductal carcinoma in situ, a pre-invasive lesion, represents one-fifth of breast cancers detected in the United States

Summary

Introduction

Breast cancer remains the second leading cause of cancer-related death in women with ~268,600 new cases and 41,760 deaths predicted in 20191. With an estimated 62,930 new cases in 2019, DCIS accounts for approximately 20% of all breast cancers detected during screening exams[1]. It is estimated that only 16% of low grade DCIS and 60% of highgrade DCIS cases will progress to invasive carcinomas[2]. Given this wide range of biologic behavior, it is debated whether there is a role for “watchful waiting” for low-risk DCIS, and large clinical trials to determine the best treatment options are currently underway[5]

Objectives

Methods

Findings

Conclusion