Background: Detection of breast cancers by mammographic screening confers a survival advantage of 20-50% compared to symptomatic presentations. The improved prognosis is only partly explained by stage migration. The distribution of the molecular subtypes of screen-detected breast cancer (SDBC) or their HER2 status has not been studied extensively. We wished to address these issues through the study of a large series of SDBC, with other presentations serving as controls.
Design: Deidentified cases of female invasive cancer, diagnosed in Australia and New Zealand during 2005-2015, were retrieved from the BreastSurgANZ Quality Audit (BQA). Method of detection and selected patient, tumour and treatment data were assessed. Immunohistochemical surrogates for molecular subtypes were defined as Luminal A (ER+ and/or PR+, HER2-), Luminal B (ER+ and/or PR+, HER2+), HER2-enriched (ER-, PR- and HER2+) and basal-like (triple negative). Results were compared with the findings of controls and previous studies.
Result: 100983 invasive cancers were diagnosed, including 32493 (32.7%) SDBC and 66907 (67.3%) with other presentations. The biomarker profile for SDBC versus other presentations in the same population was ER 89.3 versus 80.3%, PR 78.8 versus 69.8% and for HER2 11 versus 15.6%. The distribution of molecular subtypes was Luminal A 81.9 versus 70.74%, Luminal B 7.39 versus 9.52%, HER2-enriched 3.63 versus 6.06% and Basal-like 7.08 versus 13.68%. These differences were significant (p < 0.0001).
Conclusion: Molecular profiles of SDBC are significantly different from those of symptomatic cancers, with over-representation of the Luminal A and proportionately lower rates of all other subtypes. We have shown, for the first time, significantly lower rates of HER2 positivity in SDBC. These differences may contribute to the better survival of SDBC and have implications for prognostication, targeted therapy decisions and for laboratory quality assurance programs in setting target ranges for proportions of ER-positive and HER2 results in heavily screened populations.
Keywords: Breast cancer; HER2; Mammography; Molecular classification; Screening.