Association of mammographic density measures and breast cancer “intrinsic” molecular subtypes

Geffen Kleinstern, Christopher G. Scott, Rulla M. Tamimi, Matthew R. Jensen, V. Shane Pankratz, Kimberly A. Bertrand, Aaron D. Norman, Daniel W. Visscher, Fergus J. Couch, Kathleen Brandt, John Shepherd, Fang Fang Wu, Yunn Yi Chen, Steven R. Cummings, Stacey Winham, Karla Kerlikowske, Celine M. Vachon

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)215-224
Number of pages10
JournalBreast Cancer Research and Treatment
Issue number1
StatePublished - May 2021

Bibliographical note

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.


  • Breast cancer
  • Mammographic density
  • “Intrinsic” molecular subtypes
  • Breast Neoplasms/diagnostic imaging
  • Receptors, Progesterone/genetics
  • Receptors, Estrogen
  • Humans
  • Middle Aged
  • Risk Factors
  • Receptor, ErbB-2/genetics
  • Biomarkers, Tumor
  • Case-Control Studies
  • Female
  • Aged
  • Breast Density

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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