Prognosis in women with interval breast cancer: population based observational cohort study OPEN ACCESS

Objective To compare the prognosis in women with interval breast cancer (cancer detected after a normal screening mammogram and before the next scheduled mammogram) with breast cancer detected among women not yet invited to mammography screening (non-screened). Design Population based observational study. Setting Norwegian breast cancer screening programme, implemented in different counties from 1996 to 2005. Participants 7116 women with a diagnosis of breast cancer at age 50 to 72 years; 1816 had interval breast cancer and 5300 had a diagnosis of breast cancer but had not yet been invited to screening. Main outcome measures Characteristics of the breast tumours, and survival of the women using Kaplan Meier curves and multivariable Cox proportional hazard models. Results Although interval cancers on average were slightly larger than the cancers in women not invited to screening, the histological type or status of axilliary lymph nodes did not differ noticeably between the two groups. Among interval cancers, there were no appreciable trends in size, nodal status, grade, or hormone receptor positivity associated with time since the last normal mammogram as a marker of growth rate. After 10 years of follow-up, the survival rates were 79.1% (95% confidence interval 75.4% to 82.3%) among women with interval cancers and 76.8% (75.3% to 78.2%) among women in the non-screened cancer group (hazard ratio 0.98, 95% confidence interval 0.84 to 1.15; P=0.53). Analyses stratified by time since last normal mammogram, age at diagnosis, or screening round showed similar results. Conclusion The prognosis of women with interval breast cancers was the same as that of women with breast cancers diagnosed without mammography screening. Introduction When mammography screening programmes are fully implemented, interval cancers comprise a substantial proportion of incident breast cancers. Interval cancers may have been overlooked at the last mammography examination or become apparent because they grew so rapidly that the detectable preclinical phase (sojourn time) was shorter than the screening interval. Because interval breast cancers in some studies on average are larger, 2 of a more advanced stage, and express proliferative markers more than screen detected tumours, 3 it has been suggested that prognosis of interval breast cancers is poorer than that of screen detected breast cancers.However, prognostic studies may be misleading when comparing interval breast cancers with screen detected breast cancers because the screen detected breast cancers are affected by length bias sampling, lead time bias, and overdiagnosis bias. Therefore the valid comparison group for assessment of prognosis in women with interval breast cancers is non-screen detected cancers among women not invited to mammography screening, which are unaffected by the biases that screening entails. Comparisons with historical groups, as in many previous studies, may also lead to confounding because survival from breast cancer has improved over time. Only a few, small studies have compared the survival of women with interval breast cancer with those with non-screen detected breast cancer, with inconsistent findings. In this population based study we took advantage of the nationwide breast cancer screening programme in Norway, which has been gradually implemented over a nine year period. This staggered roll out allowed a comparison between women with interval breast cancer and those with breast cancer Correspondence to: M Kalager Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, Boston, USA [email protected] No commercial reuse: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe BMJ 2012;345:e7536 doi: 10.1136/bmj.e7536 (Published 16 November 2012) Page 1 of 10