A quantitative centrosomal amplification score predicts local recurrence of ductal carcinoma in situ

Mittal, Karuna; Toss, Michael S; Wei, Guanhao; Choi, Da Hoon; Melton, Brian D.; Osan, Remus M.; Milligy, Islam M.; Green, Andrew R; Janssen, Emilius A.M.; S�iland, H�vard; Gogineni, Keerthi; Manne, Upender; Rida, Padmashree; Rakha, Emad A; Aneja, Ritu

Abstract

Purpose: The purpose of this study is to predict risk of local recurrence (LR) in ductal carcinoma in situ (DCIS) with a new visualization and quantification approach using centrosome amplification (CA), a cancer cell-specific trait widely associated with aggressiveness. Experimental Design: This first-of-its-kind methodology evaluates the severity and frequency of numerical and structural CA present within DCIS and assigns a quantitative centrosomal amplification score (CAS) to each sample. Analyses were performed in a discovery cohort (DC, n ¼ 133) and a validation cohort (VC, n ¼ 119). Results: DCIS cases with LR exhibited significantly higher CAS than recurrence-free cases. Higher CAS was associated with a greater risk of developing LR (HR, 6.3 and 4.8 for DC and VC, respectively; P < 0.001). CAS remained an independent predictor of relapse-free survival (HR, 7.4 and 4.5 for DC and VC, respectively; P < 0.001) even after accounting for potentially confounding factors [grade, age, comedo necrosis, and radiotherapy (RT)]. Patient stratification using CAS (P < 0.0001) was superior to that by Van Nuys Prognostic Index (VNPI; HR for CAS ¼ 6.2 vs. HR for VNPI ¼ 1.1). Among patients treated with breast-conserving surgery alone, CAS identified patients likely to benefit from adjuvant RT. Conclusions: CAS predicted 10-year LR risk for patients who underwent surgical management alone and identified patients who may be at low risk of recurrence, and for whom adjuvant RT may not be required. CAS demonstrated the highest concordance among the known prognostic models such as VNPI and clinicopathologic variables such as grade, age, and comedo necrosis.

Citation

Mittal, K., Toss, M. S., Wei, G., Choi, D. H., Melton, B. D., Osan, R. M., Milligy, I. M., Green, A. R., Janssen, E. A., Søiland, H., Gogineni, K., Manne, U., Rida, P., Rakha, E. A., & Aneja, R. (2020). A quantitative centrosomal amplification score predicts local recurrence of ductal carcinoma in situ. Clinical Cancer Research, 26(12), 2898-2907. https://doi.org/10.1158/1078-0432.ccr-19-1272

• Journal Article Type: Article
• Acceptance Date: Dec 18, 2019
• Online Publication Date: Jan 14, 2020
• Publication Date: Jun 15, 2020
• Deposit Date: Jan 20, 2020
• Publicly Available Date: Jan 15, 2021
• Journal: Clinical Cancer Research
• Print ISSN: 1078-0432
• Electronic ISSN: 1557-3265
• Publisher: American Association for Cancer Research
• Peer Reviewed: Peer Reviewed
• Volume: 26
• Issue: 12
• Pages: 2898-2907
• DOI: https://doi.org/10.1158/1078-0432.ccr-19-1272
• Keywords: Cancer Research; Oncology
• Public URL: https://nottingham-repository.worktribe.com/output/3753099
• Publisher URL: https://clincancerres.aacrjournals.org/content/early/2020/01/14/1078-0432.CCR-19-1272