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A Quantitative Centrosomal Amplification Score Predicts Local Recurrence of Ductal Carcinoma In Situ.


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 = 133) and a validation cohort (VC, n = 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 = 6.2 vs. HR for VNPI = 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.

SUBMITTER: Mittal K 

PROVIDER: S-EPMC7299818 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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A Quantitative Centrosomal Amplification Score Predicts Local Recurrence of Ductal Carcinoma <i>In Situ</i>.

Mittal Karuna K   Toss Michael S MS   Wei Guanhao G   Kaur Jaspreet J   Choi Da Hoon DH   Melton Brian D BD   Osan Remus M RM   Miligy Islam M IM   Green Andrew R AR   Janssen Emiel A M EAM   Søiland Håvard H   Gogineni Keerthi K   Manne Upender U   Rida Padmashree P   Rakha Emad A EA   Aneja Ritu R  

Clinical cancer research : an official journal of the American Association for Cancer Research 20200114 12


<h4>Purpose</h4>The purpose of this study is to predict risk of local recurrence (LR) in ductal carcinoma <i>in situ</i> (DCIS) with a new visualization and quantification approach using centrosome amplification (CA), a cancer cell-specific trait widely associated with aggressiveness.<h4>Experimental design</h4>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)  ...[more]

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