Methodological issues in international comparison of interval breast cancers.

International comparisons of interval cancers (IC) are important to better understand the relationship between programmes' performance and screening practices. In this respect, differences in (i) definition, (ii) identification and (iii) quantification of IC have received little attention. To examine these 3 comparability issues and activities involving IC, an assessment was conducted among member countries of the International Breast Cancer Screening Network, and the impact of accuracy of identification and quantification practices was estimated using 1996-98 data from the Dutch breast cancer screening programme. Information was obtained from 19 screening programmes in 18 countries, 16 of which acknowledged the coexistence of opportunistic screening. IC data were collected to evaluate performance of the screening programme (100% of programmes) and the radiologists (89%); 53% of programmes had a designated review process for IC. Most programmes (84%) agreed with the European Guidelines definition of IC, but a case situation exercise evidenced substantial discrepancy in classification of cancers that occurred after a positive screen. Completeness of identification of IC appears to contribute most to international variation, and cannot be easily controlled for in methodologically rigorous comparisons. Statistically significant differences of about 4% were measured between quantification methods for IC. An operational definition of IC is proposed to enhance international comparability. Valid comparisons of IC are possible with careful attention to the definition but true differences in IC frequency across screening programmes should exceed 10% to be possibly indicative of real differences between programmes. Copyright 2006 Wiley-Liss, Inc.