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

Marta Hernández-García,Ana Molina-Barceló,Óscar Zurriaga,Carmen Vidal,Rafael Marcos-Gragera,Jone M Altzibar,Inés Gómez-Acebo,Adonina Tardón,Gemma Castaño-Vinyals,Nuria Aragonés,Dolores Salas,Mercedes Vanaclocha-Espi,Manolis Kogevinas,Pilar Amiano,Vicente Martín,Marina Pollán,Beatriz Pérez-Gómez,María Ederra,María Sala

doi:10.1007/s10552-021-01511-4

Abstract

PurposeThe 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.MethodsWe 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.ResultsTN 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.ConclusionReproductive 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.

Highlights

Breast cancer (BC) is the most common tumor among women worldwide
This study examines whether the screening method affects risk factor associations, regardless of tumor phenotype
Significant differences are observed in the association with epidemiological factors and tumor characteristics, with heterogeneous results depending on the method of detection and phenotype

Summary

Introduction

Breast cancer (BC) is the most common tumor among women worldwide. The main associated risk factors include nulliparity, early menarche, and late menopause (all three factors related to endogenous hormone exposure), as well as alcohol consumption, being overweight, obesity, and lack of physical activity [2,3,4,5,6]. Breast cancer is a heterogeneous disease; it includes several entities with a different natural history and response to treatment. Reproductive behavior influences the development of HR+ (hormone receptor positive) tumors as it modifies estrogen levels, whereas lifestyle-related factors (body mass index [BMI], tobacco, alcohol, and physical activity) affect different tumor subtypes [8,9,10]. HR+ breast carcinomas often have smaller tumors and are in an

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