Mammographic density and risk of breast cancer by age and tumor characteristics

Abstract

IntroductionUnderstanding whether mammographic density (MD) is associated with all breast tumor subtypes and whether the strength of association varies by age is important for utilizing MD in risk models.MethodsData were pooled from six studies including 3414 women with breast cancer and 7199 without who underwent screening mammography. Percent MD was assessed from digitized film-screen mammograms using a computer-assisted threshold technique. We used polytomous logistic regression to calculate breast cancer odds according to tumor type, histopathological characteristics, and receptor (estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2)) status by age (<55, 55–64, and ≥65 years).ResultsMD was positively associated with risk of invasive tumors across all ages, with a two-fold increased risk for high (>51%) versus average density (11-25%). Women ages <55 years with high MD had stronger increased risk of ductal carcinoma in situ (DCIS) compared to women ages 55–64 and ≥65 years (Page-interaction = 0.02). Among all ages, MD had a stronger association with large (>2.1 cm) versus small tumors and positive versus negative lymph node status (P’s < 0.01). For women ages <55 years, there was a stronger association of MD with ER-negative breast cancer than ER-positive tumors compared to women ages 55–64 and ≥65 years (Page-interaction = 0.04). MD was positively associated with both HER2-negative and HER2-positive tumors within each age group.ConclusionMD is strongly associated with all breast cancer subtypes, but particularly tumors of large size and positive lymph nodes across all ages, and ER-negative status among women ages <55 years, suggesting high MD may play an important role in tumor aggressiveness, especially in younger women.

Modifiers of breast and ovarian cancer risks for BRCA1 and BRCA2 mutation carriers

“…A meta-analysis of published studies estimated that the risk for women with mammographic density ≥75% is 4.64 times greater than that for women with <5% mammographic density (McCormack & dos Santos Silva 2006). Data from population-based studies also suggest that mammographic density is a risk factor for both ER-positive and ER-negative breast cancer (Bertrand et al 2013), although some studies found associations only with ER-positive disease. Only three studies have investigated the association between mammographic density and breast cancer risk for BRCA1 and BRCA2 mutation carriers (Mitchell et al 2006, Passaperuma et al 2010, Ramon et al 2015.…”

Comparison of Clinical and Automated Breast Density Measurements: Implications for Risk Prediction and Supplemental Screening

“…Mammographic sensitivity for women with almost entirely fatty breasts ranges from 81% to 93%, compared with 57% to 71% for those with extremely dense breasts (8,9). Breast density has also been shown to be a major risk factor for breast cancer (1)(2)(3)(10)(11)(12) when assessed on mammograms in the years prior to breast cancer diagnosis (2,3,13). Women with extremely dense breasts have a threeto fivefold increased risk of breast cancer relative to those with almost entirely fatty breasts (3,10,14).…”

Development of Multiple Primary Cancers in Lung Cancer Patients: Appalachian Versus Non-Appalachian Populations of Kentucky

“…A pooled analysis of six studies including more than 10,000 women found that the association between breast density and DCIS risk was largest for women younger than age 55. 23 In this age group, higher mammographic density was associated with about a 2-fold increased risk for DCIS as compared to women with lower breast density. For women ages 55-64, high density was associated with about a 1½-fold increased risk.…”