Effectiveness of Organized Mammography Screening for Different Breast Cancer Molecular Subtypes

Background: Screening program effectiveness is generally evaluated for breast cancer (BC) as one disease and without considering the regularity of participation, while this might have an impact on detection rate. Objectives: To evaluate the short-term effectiveness of a mammography screening program for the major molecular subtypes of invasive BC. Methods: All women who participated in the screening program and were diagnosed with screen-detected or interval BC in Flanders were included in the study (2008–2018). Molecular subtypes considered were luminal and luminal-HER2-positive, human epidermal growth factor receptor 2-positive, and triple-negative BC (TNBC). The relationship between the BC stage at diagnosis (early (I–II) versus advanced (III–IV)) and the method of detection (screen-detected or interval) and the relationship between the method of detection and participation regularity (regular versus irregular) were evaluated by multi-variable logistic regression models. All models were performed for each molecular subtype and adjusted for age. Results: Among the 12,318 included women, BC of luminal and luminal-HER2-positive subtypes accounted for 70.9% and 11.3%, respectively. Screen-detected BC was more likely to be diagnosed at early stages than interval BC with varied effect sizes for luminal, luminal-HER2-positive, and TNBC with OR:2.82 (95% CI: 2.45–3.25), OR:2.39 (95% CI: 1.77–3.24), and OR:2.29 (95% CI: 1.34–4.05), respectively. Regular participation was related to a higher likelihood of screening detection than irregular participation for luminal, luminal-HER2-positive, and TNBC with OR:1.21 (95% CI: 1.09–1.34), OR: 1.79 (95% CI: 1.38–2.33), and OR: 1.62 (95% CI: 1.10–2.41), respectively. Conclusions: Regular screening as compared to irregular screening is effective for all breast cancers except for the HER2 subtype

Overdiagnosis of invasive breast cancer in population-based breast cancer screening:A short- and long-term perspective

BACKGROUND: Overdiagnosis of invasive breast cancer (BC) is a contentious issue. OBJECTIVE: The aim of this paper is to estimate the overdiagnosis rate of invasive BC in an organised BC screening program and to evaluate the impact of age and follow-up time. METHODS: The micro-simulation model SiMRiSc was calibrated and validated for BC screening in Flanders, where women are screened biennially from age 50 to 69. Overdiagnosis rate was defined as the number of invasive BC that would not have been diagnosed in the absence of screening per 100,000 screened women during the screening period plus follow-up time (which was set at 5 years and varied from 2 to 15 years). Overdiagnosis rate was calculated overall and stratified by age. RESULTS: The overall overdiagnosis rate for women screened biennially from 50 to 69 was 20.1 (95%CI: 16.9-23.2) per 100,000 women screened at 5-year follow-up from stopping screening. Overdiagnosis at 5-year follow-up time was 12.9 (95%CI: 4.6-21.1) and 74.2 (95%CI: 50.9-97.5) per 100,000 women screened for women who started screening at age 50 and 68, respectively. At 2- and 15-year follow-up time, overdiagnosis rate was 98.5 (95%CI: 75.8-121.3) and 13.4 (95%CI: 4.9-21.9), respectively, for women starting at age 50, and 297.0 (95%CI: 264.5-329.4) and 34.2 (95%CI: 17.5-50.8), respectively, for those starting at age 68. CONCLUSIONS: Sufficient follow-up time (≥10 years) after screening stops is key to obtaining unbiased estimates of overdiagnosis. Overdiagnosis of invasive BC is a larger problem in older compared to younger women