Purpose: We evaluated the association of percent mammographic density (PMD), absolute dense area (DA), and non-dense area (NDA) with risk of “intrinsic” molecular breast cancer (BC) subtypes. Methods: We pooled 3492 invasive BC and 10,148 controls across six studies with density measures from prediagnostic, digitized film-screen mammograms. We classified BC tumors into subtypes [63% Luminal A, 21% Luminal B, 5% HER2 expressing, and 11% as triple negative (TN)] using information on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. We used polytomous logistic regression to calculate odds ratio (OR) and 95% confidence intervals (CI) for density measures (per SD) across the subtypes compared to controls, adjusting for age, body mass index and study, and examined differences by age group. Results: All density measures were similarly associated with BC risk across subtypes. Significant interaction of PMD by age (P = 0.001) was observed for Luminal A tumors, with stronger effect sizes seen for younger women < 45 years (OR = 1.69 per SD PMD) relative to women of older ages (OR = 1.53, ages 65–74, OR = 1.44 ages 75 +). Similar but opposite trends were seen for NDA by age for risk of Luminal A: risk for women: < 45 years (OR = 0.71 per SD NDA) was lower than older women (OR = 0.83 and OR = 0.84 for ages 65–74 and 75 + , respectively) (P < 0.001). Although not significant, similar patterns of associations were seen by age for TN cancers. Conclusions: Mammographic density measures were associated with risk of all “intrinsic” molecular subtypes. However, findings of significant interactions between age and density measures may have implications for subtype-specific risk models.
Bibliographical noteFunding Information:
This work was supported in part by the National Institutes of Health, National Cancer Institute (R01 CA140286, R01 CA128931, P50 CA58207, P50 CA116201, R01 CA97396, R01 CA 122340, P01 CA087969, R01 CA050385, R01 CA124865, and R01 CA131332), the Breast Cancer Research Foundation and the Department of Defense (DAMD 17-00-1-033).
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.
- Breast cancer
- Mammographic density
- “Intrinsic” molecular subtypes
ASJC Scopus subject areas
- Cancer Research