Explaining the difference in prognosis between screen-detected and symptomatic breast cancers

Abstract

Background:We analysed 10-year survival data in 19 411 women aged 50–64 years diagnosed with invasive breast cancer in the West Midlands region of the United Kingdom. The aim was to estimate the survival advantage seen in cases that were screen detected compared with those diagnosed symptomatically and attribute this to shifts in prognostic variables or survival differences specific to prognostic categories.Methods:We studied tumour size, histological grade and the Nottingham Prognostic Index in very narrow categories and investigated the distribution of these prognostic factors within screen-detected and symptomatic tumours. We also adjusted for lead time bias.Results:The unadjusted 10-year breast cancer survival in screen-detected cases was 85.5% and in symptomatic cases 62.8% after adjustment for lead time bias, survival in the screen-detected cases was 79.3%. Within narrow categories of prognostic variables, survival differences were small, indicating that the majority of the survival advantage of screen detection is due to differences in the distributions of size and node status.Conclusion:Our results suggested that a combination of lead time with size and node status in 10 categories explained almost all (97%) of the survival advantage. Only a small proportion remained to be explained by biological differences, manifested as length bias or overdiagnosis.

Impact of screening on clinicopathological features and treatment for invasive breast cancer: Results of two national surveys

“…Indeed, a global downstaging trend was observed, with a significant decrease in median tumour size and axillary lymph-node involvement, and a parallel increase in well-differentiated and hormone-positive receptor tumours. Our results are similar to several recent reports comparing clinicopathological and molecular features of breast cancers detected in mammography screening and out of screening [26][27][28], and explain the better prognosis of screen-detected cancers. Indeed, the Swedish Two-County study compared the 16-year cumulative survival rates by tumour size and clinical versus screening detection.…”

Comparison between screen-detected and symptomatic breast cancers according to molecular subtypes

“…With these favorable clinicopathologic features, women with screen-detected cancers also enjoyed survival benefits in both overall and disease-free survival, compared to women with symptomatic cancers. In previous studies [10,11,34,37,38], most of this survival advantage could be explained by stage shift. However, as mentioned above, this stage shift only cannot fully explain the improved prognosis of patients whose tumor is detected by screening.…”

“…Compared with cancers found by the patients themselves after symptomatic presentation, screen-detected cancers are generally smaller in size and have a higher portion of in situ tumors, are better differentiated, are less frequently associated with lymph node metastasis, and are often of earlier stage [1][2][3]9]. These differences suggest that cancers found during screening are detected at an earlier stage of their natural course, and this stage shift at diagnosis extends observed survival time (lead time bias) [10][11][12][13]. The length bias also may be attributable to improved outcomes.…”

St Gallen molecular subtypes in screening-detected and symptomatic breast cancer in a prospective cohort with long-term follow-up

“…These findings are in agreement with published findings3, 19, although the previous results were not adjusted according to St Gallen molecular subtypes in either primary tumours or lymph node metastases, which is one of the strengths of the present study. A number of authors have related molecular profiles to mode of detection, but did not report any data regarding Ki‐67 or HER2 status by ISH21, 22, which is a prerequisite for the identification of St Gallen molecular subtypes3. Dawson and colleagues23 reported follow‐up after 15 years, but the pathological protocol for St Gallen classification did not include Ki‐67 scoring, and HER2 status was determined by IHC without fluorescence ISH.…”

“…Kim and colleagues4 performed survival analysis by individual St Gallen molecular subtypes with similar findings after a shorter follow‐up, but did not report any interaction analyses. Several groups3, 22, 25 have previously investigated the independent prognostic significance of mode of detection. Wishart et al 26.…”