PURPOSE: Nuclear grade is an important indicator of the biological behaviour of ductal carcinoma in situ (DCIS). De-escalation of treatment has been suggested for low-grade DCIS. Our aim is to estimate the relative rate of progression of DCIS by nuclear grade by analysing the distribution of nuclear grade by detection at initial or subsequent screening. METHODS: We asked International Cancer Screening Network sites to complete, based on their screening and clinical databases, an aggregated data file on DCIS detection, diagnosis and treatment. RESULTS: Eleven screening programs reported 5068 screen-detected pure DCIS in nearly 7 million screening tests in women 50-69 years of age. For all programs combined, low-grade DCIS were 20.1% (range 11.4-31.8%) of graded DCIS, intermediate grade 31.0% and high grade 48.9%. Detection rates decreased more steeply from initial to subsequent screening in low compared to high-grade DCIS: the ratios of subsequent to initial detection rates were 0.39 for low grade, 0.51 for intermediate grade, and 0.75 for high grade (p < 0.001). CONCLUSIONS: These results suggest that the duration of the preclinical detectable phase is longer for low than for high-grade DCIS. The findings from this large multi-centre, international study emphasize that the management of low-grade DCIS should be carefully scrutinized in order to minimize overtreatment of screen-detected slow-growing or indolent lesions. The high variation by site in the proportion of low grade suggests that further pathology standardization and training would be beneficial.

Breast Cancer Screening Program Public Health and Labour Institute of Navarra Pamplona Spain

Breast Cancer Screening Reference Centre AOU Città della Salute e della Scienza Torino Italy

Centre for Global Health National Cancer Institute Rockville MD USA

Centre for Primary Care and Public Health University of Lausanne Lausanne Switzerland

CPO Piemonte AOU Città della Salute e della Scienza Via Cavour 31 10123 Torino Italy

Department of Public Health University of Copenhagen Copenhagen Denmark

Dutch Expert Centre for Screening and Radboud University Medical Centre Nijmegen The Netherlands

Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University Brno Czech Republic

Mass Screening Registry Finnish Cancer Registry Helsinki Finland

National Screening Service Dublin Ireland

The Cancer Registry of Norway Oslo Norway

Unit of Pathology Department of Medical Sciences University of Torino Torino Italy

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