UCSF

Background

Mammographic density (MD) is a strong breast cancer risk factor. We previously reported associations of percent mammographic density (PMD) with larger and node-positive tumors across all ages, and estrogen receptor (ER)-negative status among women ages <55 years. To provide insight into these associations, we examined the components of PMD [dense area (DA) and nondense area (NDA)] with breast cancer subtypes.

Methods

Data were pooled from six studies including 4,095 breast cancers and 8,558 controls. DA and NDA were assessed from digitized film-screen mammograms and standardized across studies. Breast cancer odds by density phenotypes and age according to histopathologic characteristics and receptor status were calculated using polytomous logistic regression.

Results

DA was associated with increased breast cancer risk [OR for quartiles: 0.65, 1.00 (Ref), 1.22, 1.55; P(trend) <0.001] and NDA was associated with decreased risk [ORs for quartiles: 1.39, 1.00 (Ref), 0.88, 0.72; P(trend) <0.001] across all ages and invasive tumor characteristics. There were significant trends in the magnitude of associations of both DA and NDA with breast cancer by increasing tumor size (P(trend) < 0.001) but no differences by nodal status. Among women <55 years, DA was more strongly associated with increased risk of ER(+) versus ER(-) tumors (P(het) = 0.02), while NDA was more strongly associated with decreased risk of ER(-) versus ER(+) tumors (P(het) = 0.03).

Conclusions

DA and NDA have differential associations with ER(+) versus ER(-) tumors that vary by age.

Impact

DA and NDA are important to consider when developing age- and subtype-specific risk models.