Differences in breast cancer-risk factors between screen-detected and non-screen-detected cases (MCC-Spain study)

Purpose: The variation in breast cancer (BC)-risk factor associations between screen-detected (SD) and non-screen-detected (NSD) tumors has been poorly studied, despite the interest of this aspect in risk assessment and prevention. This study analyzes the differences in breast cancer-risk factor associations according to detection method and tumor phenotype in Spanish women aged between 50 and 69. Methods: We examined 900 BC cases and 896 controls aged between 50 and 69, recruited in the multicase-control MCC-Spain study. With regard to the cases, 460 were detected by screening mammography, whereas 144 were diagnosed by other means. By tumor phenotype, 591 were HR+, 153 were HER2+, and 58 were TN. Lifestyle, reproductive factors, family history of BC, and tumor characteristics were analyzed. Logistic regression models were used to compare cases vs. controls and SD vs. NSD cases. Multinomial regression models (controls used as a reference) were adjusted for case analysis according to phenotype and detection method. Results: TN was associated with a lower risk of SD BC (OR 0.30 IC 0.10-0.89), as were intermediate (OR 0.18 IC 0.07-0.44) and advanced stages at diagnosis (OR 0.11 IC 0.03-0.34). Nulliparity in postmenopausal women and age at menopause were related to an increased risk of SD BC (OR 1.60 IC 1.08-2.36; OR 1.48 IC 1.09-2.00, respectively). Nulliparity in postmenopausal women was associated with a higher risk of HR+ (OR 1.66 IC 1.15-2.40). Age at menopause was related to a greater risk of HR+ (OR 1.60 IC 1.22-2.11) and HER2+ (OR 1.59 IC 1.03-2.45) tumors. Conclusion: Reproductive risk factors are associated with SD BC, as are HR+ tumors. Differences in BC-risk factor associations according to detection method may be related to prevailing phenotypes among categories.This research was supported by Acción Transversal del Cáncer, approved by the Spanish Council of Ministeres on the 11th October 2007, by the Carlos III Health Institute-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/ 01662, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI11/01810, PI14/01219, PI11/02213, PIE16/00049, PI17/01179, PI17-00092), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL (the ICGC CLL-Genome Project is funded by the Spanish Ministry of Economy and Competitiveness through the Carlos III Health Institute (ISCIII)), by the ISCIII Red Temática de Investigación del Cáncer (RTICC) (RD12/0036/0036), by the Regional Government of Castile and León (LE22A10-2), by the Regional Health Ministry of Andalusia (PI-0571–2009, PI-0306–2011, salud201200057018tra), by the Regional Health Ministry of Valencia (AP_061/10), by Recercaixa (2010ACUP00310), by the Regional Government of the Basque Country, by the Regional Health Ministry of Murcia, by the European Commission (grants FOOD-CT-2006–036224-HIWATE), by the Spanish Association Against Cancer (AECC) Scientific Foundation (GCTRA18022MORE), by the Catalan Regional Government Agency for Management of University and Research Grants (AGAUR) (2014SGR647, 2014SGR850, and 2017SGR723), by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo. ISGlobal is a member of the CERCA Programme, Regional Government of Catalonia. Sample collection was supported by the Carlos III Health Institute- FEDER: Parc de Salut MAR Biobank (MARBiobanc) (RD09/0076/00036), the La Fe Biobank (PT17/0015/0043RD 09 0076/00021), and the FISABIO Biobank (PT17/0015/0017) RD09 0076/00058);S