Breast Cancer Research and Treatment

, Volume 165, Issue 2, pp 421–431 | Cite as

Interaction of mammographic breast density with menopausal status and postmenopausal hormone use in relation to the risk of aggressive breast cancer subtypes

  • Lusine Yaghjyan
  • Rulla M. Tamimi
  • Kimberly A. Bertrand
  • Christopher G. Scott
  • Matthew R. Jensen
  • V. Shane Pankratz
  • Kathy Brandt
  • Daniel Visscher
  • Aaron Norman
  • Fergus Couch
  • John Shepherd
  • Bo Fan
  • Yunn-Yi Chen
  • Lin Ma
  • Andrew H. Beck
  • Steven R. Cummings
  • Karla Kerlikowske
  • Celine M. Vachon
Epidemiology
  • 158 Downloads

Abstract

Purpose

We examined the associations of mammographic breast density with breast cancer risk by tumor aggressiveness and by menopausal status and current postmenopausal hormone therapy.

Methods

This study included 2596 invasive breast cancer cases and 4059 controls selected from participants of four nested case–control studies within four established cohorts: the Mayo Mammography Health Study, the Nurses’ Health Study, Nurses’ Health Study II, and San Francisco Mammography Registry. Percent breast density (PD), absolute dense (DA), and non-dense areas (NDA) were assessed from digitized film-screen mammograms using a computer-assisted threshold technique and standardized across studies. We used polytomous logistic regression to quantify the associations of breast density with breast cancer risk by tumor aggressiveness (defined as presence of at least two of the following tumor characteristics: size ≥2 cm, grade 2/3, ER-negative status, or positive nodes), stratified by menopausal status and current hormone therapy.

Results

Overall, the positive association of PD and borderline inverse association of NDA with breast cancer risk was stronger in aggressive vs. non-aggressive tumors (≥51 vs. 11–25% OR 2.50, 95% CI 1.94–3.22 vs. OR 2.03, 95% CI 1.70–2.43, p-heterogeneity = 0.03; NDA 4th vs. 2nd quartile OR 0.54, 95% CI 0.41–0.70 vs. OR 0.71, 95% CI 0.59–0.85, p-heterogeneity = 0.07). However, there were no differences in the association of DA with breast cancer by aggressive status. In the stratified analysis, there was also evidence of a stronger association of PD and NDA with aggressive tumors among postmenopausal women and, in particular, current estrogen+progesterone users (≥51 vs. 11–25% OR 3.24, 95% CI 1.75–6.00 vs. OR 1.93, 95% CI 1.25–2.98, p-heterogeneity = 0.01; NDA 4th vs. 2nd quartile OR 0.43, 95% CI 0.21–0.85 vs. OR 0.56, 95% CI 0.35–0.89, p-heterogeneity = 0.01), even though the interaction was not significant.

Conclusion

Our findings suggest that associations of mammographic density with breast cancer risk differ by tumor aggressiveness. While there was no strong evidence that these associations differed by menopausal status or hormone therapy, they did appear more prominent among current estrogen+progesterone users.

Keywords

Breast density Breast cancer subtypes Tumor aggressiveness Postmenopausal hormone therapy 

Supplementary material

10549_2017_4341_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 15 kb)
10549_2017_4341_MOESM2_ESM.docx (22 kb)
Supplementary material 2 (DOCX 22 kb)

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Lusine Yaghjyan
    • 1
  • Rulla M. Tamimi
    • 2
    • 3
  • Kimberly A. Bertrand
    • 4
  • Christopher G. Scott
    • 5
  • Matthew R. Jensen
    • 5
  • V. Shane Pankratz
    • 5
  • Kathy Brandt
    • 6
  • Daniel Visscher
    • 7
  • Aaron Norman
    • 8
  • Fergus Couch
    • 8
    • 9
  • John Shepherd
    • 10
  • Bo Fan
    • 11
  • Yunn-Yi Chen
    • 11
  • Lin Ma
    • 12
  • Andrew H. Beck
    • 13
  • Steven R. Cummings
    • 14
  • Karla Kerlikowske
    • 15
    • 16
  • Celine M. Vachon
    • 8
  1. 1.Department of Epidemiology, College of Public Health and Health Professions and College of MedicineUniversity of FloridaGainesvilleUSA
  2. 2.Channing Division of Network Medicine, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  3. 3.Department of EpidemiologyHarvard T.H Chan School of Public HealthBostonUSA
  4. 4.Slone Epidemiology Center at Boston UniversityBostonUSA
  5. 5.Division of Biomedical Statistics and InformaticsMayo Clinic College of MedicineRochesterUSA
  6. 6.Department of RadiologyMayo ClinicRochesterUSA
  7. 7.Department of Anatomic PathologyMayo Clinic College of MedicineRochesterUSA
  8. 8.Division of Epidemiology, Department of Health Sciences ResearchMayo Clinic College of MedicineRochesterUSA
  9. 9.Division of Experimental Pathology, Department of Laboratory Medicine and PathologyMayo Clinic College of MedicineRochesterUSA
  10. 10.Department of RadiologyUniversity of CaliforniaSan FranciscoUSA
  11. 11.Department of PathologyUniversity of CaliforniaSan FranciscoUSA
  12. 12.Department of MedicineUniversity of CaliforniaSan FranciscoUSA
  13. 13.Department of PathologyBeth Israel Deaconess Medical Center and Harvard Medical SchoolBostonUSA
  14. 14.San Francisco Coordinating CenterCalifornia Pacific Medical Center Research InstituteSan FranciscoUSA
  15. 15.Departments of Medicine and Epidemiology and BiostatisticsUniversity of CaliforniaSan FranciscoUSA
  16. 16.General Internal Medicine Section, Department of Veterans AffairsUniversity of CaliforniaSan FranciscoUSA

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