학술논문

Does mammographic density mediate risk factor associations with breast cancer? An analysis by tumor characteristics
Document Type
article
Source
Breast Cancer Research and Treatment. 170(1)
Subject
Biomedical and Clinical Sciences
Oncology and Carcinogenesis
Cancer
Clinical Research
Breast Cancer
Prevention
Estrogen
Aging
Adult
Aged
Biomarkers
Tumor
Breast
Breast Density
Breast Neoplasms
Female
Humans
Mammography
Middle Aged
Pregnancy
Receptor
ErbB-2
Receptors
Estrogen
Receptors
Progesterone
Risk Factors
Mammographic density
Breast cancer
Receptor
erbB-2
Clinical Sciences
Oncology & Carcinogenesis
Clinical sciences
Oncology and carcinogenesis
Language
Abstract
BackgroundThough mammographic density (MD) has been proposed as an intermediate marker of breast cancer risk, few studies have examined whether the associations between breast cancer risk factors and risk are mediated by MD, particularly by tumor characteristics.MethodsOur study population included 3392 cases (1105 premenopausal) and 8882 (3192 premenopausal) controls from four case-control studies. For established risk factors, we estimated the percent of the total risk factor association with breast cancer that was mediated by percent MD (secondarily, by dense area and non-dense area) for invasive breast cancer as well as for subtypes defined by the estrogen receptor (ER+/ER-), progesterone receptor (PR+/PR-), and HER2 (HER2+/HER2-). Analyses were conducted separately in pre- and postmenopausal women.ResultsPositive associations between prior breast biopsy and risk of invasive breast cancer as well as all subtypes were partially mediated by percent MD in pre- and postmenopausal women (percent mediated = 11-27%, p ≤ 0.02). In postmenopausal women, nulliparity and hormone therapy use were positively associated with invasive, ER+ , PR+ , and HER2- breast cancer; percent MD partially mediated these associations (percent mediated ≥ 31%, p ≤ 0.02). Further, among postmenopausal women, percent MD partially mediated the positive association between later age at first birth and invasive as well as ER+ breast cancer (percent mediated = 16%, p ≤ 0.05).ConclusionPercent MD partially mediated the associations between breast biopsy, nulliparity, age at first birth, and hormone therapy with risk of breast cancer, particularly among postmenopausal women, suggesting that these risk factors at least partially influence breast cancer risk through changes in breast tissue composition.