Abstract P6-06-26: St Gallen molecular subtypes adds prognostic information beyond detection by screening mammography

Abstract

Abstract Background: The public mammography screening program was implemented in Sweden 30 years ago and has contributed to detection of primary breast cancer at an earlier stage, but it´s impact on survival is still controversial. In a prospective observational cohort including patients with primary breast cancer between 1999-2002, 442 patients were aged 45-75 and regularly invited to mammography screening. The aim of the study was to relate mode of detection and St Gallen molecular subtypes to 10 years breast cancer specific survival (BCSS) in order study if St Gallen molecular subtypes added prognostic information also in screening detected breast cancer. Methods: Tissue microarrays (TMA) were constructed from tissue blocks of primary tumors and lymph node metastasis. The samples were evaluated according to oestrogen receptor (ER), progesterone receptor (PR), Ki67 and human epidermal growth factor receptor 2 (HER2) by immunohistochemistry and in situ hybridisation. Classification according to the St Gallen molecular subtypes (Luminal A (ER+ and/or PR+, low Ki67 and HER2-), luminal B HER2- (ER+ and/or PR+, high Ki67 and HER2-), luminal B HER2+ (ER+ and/or PR+, any Ki67 and HER2+), HER2 type (ER-, PR- and HER2+) and triple-negative (ER-, PR- and HER2-) was possible in 372 primary tumors and 106 lymph node metastasis. The cause of death was retrieved from the National Board of Health. Results: Screening detected breast cancer was diagnosed in 52% of the patients. Patients with screening detected breast cancer had smaller tumor size (17.1mm compared to 21.6 mm in clinically detected (p<0.001), were more often node negative (p = 0.002) and had tumors of lower histological grade (p = 0.03). In contrast, there was no statistical difference in distribution of the St Gallen molecular subtypes related to mode of detection (p = 0.2). Patients with tumors detected within the screening program, had a more favorable prognosis with 91% BCSS compared to clinically detected tumors (BCSS 84%), p = 0.02 log rank test. St Gallen molecular subtypes added significant prognostic information in all patients (p = 0.008), which was true in both screening detected and clinically detected breast cancer (p = 0.02 in both groups). In Cox multivariate analysis including mode of detection, tumor size, node status and St Gallen molecular subtype, node status and St Gallen molecular subtypes remained significant prognostic factors. St Gallen molecular subtypes in lymph node metastasis had no prognostic information nor in the whole cohort or in clinically detected breast cancer, but showed that patients with lum A subtype in the lymph node metastasis had an excellent prognosis irrespective of subtype inherence in the primary tumor (p = 0.001) with 100% BCSS. Conclusion: St Gallen molecular subtypes in primary breast cancer shows similar distribution irrespective of mode of detection, but adds prognostic information in both clinically and screening detected breast cancer and outperforms tumor size and screening detection in multivariate analysis in terms of 10 years BCSS. For patients with screening detected tumors and lymph node metastasis, lum A inherence in the lymph node metastasis identifies a subgroup of patients with excellent prognosis irrespective of node positive disease. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-26.