Skip to main content

Advertisement

SpringerLink
Log in

Breast density, benign breast disease, and risk of breast cancer over time

  • Breast
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

Assessing the combined effect of mammographic density and benign breast disease is of utmost importance to design personalized screening strategies.

Methods

We analyzed individual-level data from 294,943 women aged 50–69 years with at least one mammographic screening participation in any of four areas of the Spanish Breast Cancer Screening Program from 1995 to 2015, and followed up until 2017. We used partly conditional Cox models to assess the association between benign breast disease, breast density, and the risk of breast cancer.

Results

During a median follow-up of 8.0 years, 3697 (1.25%) women had a breast cancer diagnosis and 5941 (2.01%) had a benign breast disease. More than half of screened women had scattered fibroglandular density (55.0%). The risk of breast cancer independently increased with the presence of benign breast disease and with the increase in breast density (p for interaction = 0.84). Women with benign breast disease and extremely dense breasts had a threefold elevated risk of breast cancer compared with those with scattered fibroglandular density and without benign breast disease (hazard ratio [HR] = 3.07; 95%CI = 2.01–4.68). Heterogeneous density and benign breast disease was associated with nearly a 2.5 elevated risk (HR = 2.48; 95%CI = 1.66–3.70). Those with extremely dense breast without a benign breast disease had a 2.27 increased risk (95%CI = 2.07–2.49).

Conclusions

Women with benign breast disease had an elevated risk for over 15 years independently of their breast density category. Women with benign breast disease and dense breasts are at high risk for future breast cancer.

Key Points

• Benign breast disease and breast density were independently associated with breast cancer.

• Women with benign breast disease had an elevated risk for up to 15 years independently of their mammographic density category.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

BI-RADS:

Breast Imaging Reporting and Data System

CI:

Confidence interval

HR:

Hazard ratio

References

  1. Boyd NF, Lockwood GA, Byng JW, Tritchler DL, Yaffe MJ (1998) Mammographic densities and breast cancer risk. Cancer Epidemiol Biomark Prev 7(12):1133–1144

    CAS  Google Scholar 

  2. Wolfe JN, Saftlas AF, Salane M (1987) Mammographic parenchymal patterns and quantitative evaluation of mammographic densities: a case-control study. AJR Am J Roentgenol 148(6):1087–1092

    Article  CAS  Google Scholar 

  3. Byrne C, Schairer C, Wolfe J et al (1995) Mammographic features and breast cancer risk: effects with time, age, and menopause status. J Natl Cancer Inst 87(21):1622–1629

    Article  CAS  Google Scholar 

  4. McCormack VA, dos Santos Silva I (2006) Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev 15(6):1159–1169

    Article  Google Scholar 

  5. Castells X, Domingo L, Corominas JM et al (2015) Breast cancer risk after diagnosis by screening mammography of nonproliferative or proliferative benign breast disease: a study from a population-based screening program. Breast Cancer Res Treat 149(1):237–244

    Article  Google Scholar 

  6. Schousboe JT, Kerlikowske K, Loh A, Cummings SR (2011) Personalizing mammography by breast density and other risk factors for breast cancer: analysis of health benefits and cost-effectiveness. Ann Intern Med 155(1):10–20

    Article  Google Scholar 

  7. Vilaprinyo E, Forne C, Carles M et al (2014) Cost-effectiveness and harm-benefit analyses of risk-based screening strategies for breast cancer. PLoS One 9(2):e86858

    Article  Google Scholar 

  8. Byrne C, Schairer C, Brinton LA et al (2001) Effects of mammographic density and benign breast disease on breast cancer risk (United States). Cancer Causes Control 12(2):103–110

    Article  CAS  Google Scholar 

  9. Tice JA, O’Meara ES, Weaver DL, Vachon C, Ballard-Barbash R, Kerlikowske K (2013) Benign breast disease, mammographic breast density, and the risk of breast cancer. J Natl Cancer Inst 105(14):1043–1049

    Article  CAS  Google Scholar 

  10. Perry N, Broeders M, de Wolf C, Trnberg S, Holland R, von Karsa L (2006) European guidelines for quality assurance in breast cancer screening and diagnosis. Available from: http://screening.iarc.fr/doc/ND7306954ENC_002.pdf

  11. Castells X, Sala M, Ascunce N, Salas D, Zubizarreta R, Casamitjana M (2007) Descripción del cribado del cáncer en España. Proyecto DESCRIC. Madrid: Plan de Calidad para el Sistema Nacional de Salud. Ministerio de Sanidad y Consumo. Agència d’Avaluació de Tecnologia i Recerca Mèiques de Cataluña; 2006. Available from: http://aunets.isciii.es/ficherosproductos/70/AATRM%202006-01.pdf

  12. Ascunce N, Salas D, Zubizarreta R, Almazan R, Ibanez J, Ederra M (2010) Cancer screening in Spain. Annonc Suppl 21(Suppl 3):iii43–iii51

    Article  Google Scholar 

  13. Baré M, Bonfill X, Andreu X (2006) Relationship between the method of detection and prognostic factors for breast cancer in a community with a screening programme. J Med Screen 13(4):183–191

    Article  Google Scholar 

  14. Sickles EA, D’Orsi CJ, Bassett LW (2013) ACR BI-RADS® Mammography. In: ACR BI-RADS® Atlas, Breast Imaging Reporting and Data System. American College of Radiology, Reston, VA

    Google Scholar 

  15. Zheng Y, Heagerty PJ (2005) Partly conditional survival models for longitudinal data. Biometrics. 61(2):379–391

    Article  Google Scholar 

  16. Tice JA, Cummings SR, Ziv E, Kerlikowske K (2005) Mammographic breast density and the Gail model for breast cancer risk prediction in a screening population. Breast Cancer Res Treat 94(2):115–122

    Article  Google Scholar 

  17. Vacek PM, Geller BM (2004) A prospective study of breast cancer risk using routine mammographic breast density measurements. Cancer Epidemiol Biomark Prev 13(5):715–722

    Google Scholar 

  18. Ziv E, Shepherd J, Smith-Bindman R, Kerlikowske K (2003) Mammographic breast density and family history of breast cancer. J Natl Cancer Inst 95(7):556–558

    Article  Google Scholar 

  19. Hartmann LC, Sellers TA, Frost MH et al (2005) Benign breast disease and the risk of breast cancer. N Engl J Med 353(3):229–237

    Article  CAS  Google Scholar 

  20. Tice JA, Miglioretti DL, Li C-S, Vachon CM, Gard CC, Kerlikowske K (2015) Breast density and benign breast disease: risk assessment to identify women at high risk of breast cancer. J Clin Oncol 33(28):3137–3143

    Article  Google Scholar 

  21. Brentnall AR, Harkness EF, Astley SM et al (2015) Mammographic density adds accuracy to both the Tyrer-Cuzick and Gail breast cancer risk models in a prospective UK screening cohort. Breast Cancer Res 17(1):147

    Article  Google Scholar 

  22. Brinton JT, Hendrick RE, Ringham BM, Kriege M, Glueck DH (2019) Improving the diagnostic accuracy of a stratified screening strategy by identifying the optimal risk cutoff. Cancer Causes Control 30(10):1145–1155

    Article  Google Scholar 

  23. MyPeBs. Randomized comparison of risk-stratified versus standard breast cancer screening in European women aged 40–70 (MyPeBS). 2017.

  24. Esserman LJ, WISDOM Study and Athena Investigators (2017) The WISDOM Study: breaking the deadlock in the breast cancer screening debate. NPJ Breast Cancer 3:34

  25. Ciatto S, Houssami N, Apruzzese A et al (2005) Categorizing breast mammographic density: intra- and interobserver reproducibility of BI-RADS density categories. Breast Edinb Scotl 14(4):269–275

  26. Kerlikowske K, Grady D, Barclay J et al (1998) Variability and accuracy in mammographic interpretation using the American College of Radiology Breast Imaging Reporting and Data System. J Natl Cancer Inst 90(23):1801–1809

    Article  CAS  Google Scholar 

  27. Redondo A, Comas M, Macia F et al (2012) Inter- and intraradiologist variability in the BI-RADS assessment and breast density categories for screening mammograms. Br J Radiol 85(1019):1465–1470

    Article  CAS  Google Scholar 

  28. Kerlikowske K, Ichikawa L, Miglioretti DL et al (2007) Longitudinal measurement of clinical mammographic breast density to improve estimation of breast cancer risk. J Natl Cancer Inst 99(5):386–395

    Article  Google Scholar 

  29. Sartor H, Lang K, Rosso A, Borgquist S, Zackrisson S, Timberg P (2016) Measuring mammographic density: comparing a fully automated volumetric assessment versus European radiologists’ qualitative classification. Eur Radiol 26(12):4354–4360

    Article  Google Scholar 

  30. Irshad A, Leddy R, Lewis M et al (2017) Changes in breast density reporting patterns of radiologists after publication of the 5th Edition BI-RADS guidelines: a single institution experience. AJR Am J Roentgenol 209(4):943–948

    Article  Google Scholar 

  31. Cummings SR, Tice JA, Bauer S et al (2009) Prevention of breast cancer in postmenopausal women: approaches to estimating and reducing risk. J Natl Cancer Inst 101(6):384–398

    Article  Google Scholar 

  32. Sala M, Salas D, Belvis F et al (2011) Reduction in false-positive results after introduction of digital mammography: analysis from four population-based breast cancer screening programs in Spain. Radiology. 258(2):388–395

    Article  Google Scholar 

  33. Harvey JA, Gard CC, Miglioretti DL et al (2013) Reported mammographic density: film-screen versus digital acquisition. Radiology. 266(3):752–758

    Article  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the dedication and support of the entire BELE (Benign Lesion) and IRIS (Individualized Risk) Study Groups, listed here in alphabetical order and grouped by institution: (a) IMIM (Hospital Del Mar Medical Research Institute), Barcelona, Spain: Rodrigo Alcantara, Andrea Burón, Xavier Castells, Laura Comerma, Laia Domingo, Javier Louro, Margarita Posso, Marta Román, Maria Sala, Ignasi Tusquets, Ivonne Vazquez, Mar Vernet-Tomas; (b) Corporació Sanitària Parc Taulí, Sabadell, Spain: Marisa Baré, Javier del Riego; (c) Catalan Institute of Oncology, Barcelona, Spain: Llucia Benito, Carmen Vidal; (d) Hospital Santa Caterina, Girona, Spain: Joana Ferrer; (e) Catalan Institute of Oncology, Girona, Spain: Rafael Marcos-Gragera; (f) Hospital de la Santa Creu i Sant Pau, Barcelona, Spain: María Jesús Quintana, Judit Solà-Roca; (g) General Directorate of Public Health, Government of Cantabria, Spain: Mar Sánchez; (h) Principality of Astúrias Health Service, Spain: Miguel Prieto; (i) Fundació Lliga per a La Investigació i Prevenció Del Cáncer, Tarragona, Spain: Francina Saladié, Jaume Galceran; (j) Hospital Clinic, Barcelona, Spain; Xavier Bargalló, Isabel Torá-Rocamora; (k) Vallés Oriental Breast Cancer Early Detection Program, Spain; Lupe Peñalva; (l) Catalonian Cancer Strategy, Barcelona, Spain: Josep Alfons Espinàs.

Funding

This work was supported by grants from Instituto de Salud Carlos III FEDER, (PI15/00098) and (PI17/00047), and from the Network for Research into Healthcare in Chronic Diseases, REDISECC (RD12/0001/0015).

Author information

Authors and Affiliations

  1. Department of Epidemiology and Evaluation, IMIM (Hospital del Mar Medical Research Institute), Passeig Marítim 25-29, 08003, Barcelona, Spain

    Marta Román, Javier Louro, Margarita Posso, Maria Sala & Xavier Castells

  2. Research Network on Health Services in Chronic Diseases (REDISSEC), Barcelona, Spain

    Marta Román, Javier Louro, Margarita Posso, Maria Sala & Xavier Castells

  3. European Higher Education Area, Department of Pediatrics, Obstetrics and Gynecology, Preventive Medicine and Public Health, Universitat Autónoma de Barcelona, Barcelona, Spain

    Javier Louro

  4. Department of Radiology, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain

    Rodrigo Alcántara

  5. Breast Cancer Screening Technical Office, Private Foundation Asil Hospital, Granollers, Spain

    Lupe Peñalva

  6. Department of Radiology, Parc Taulí University Hospital-UAB, Sabadell, Catalonia, Spain

    Javier del Riego

  7. General Directorate of Public Health, Principality of Asturias Health Service, Asturias, Spain

    Miguel Prieto

  8. Cancer Prevention and Monitoring Program, Catalan Institute of Oncology, Barcelona, Spain

    Carmen Vidal

  9. General Directorate of Public Health, Government of Cantabria, Santander, Spain

    Mar Sánchez

  10. Department of Radiology, Hospital Clinic, Barcelona, Spain

    Xavier Bargalló

  11. Department of Medical Oncology, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain

    Ignasi Tusquets

Authors
  1. Marta Román
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Javier Louro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Margarita Posso
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rodrigo Alcántara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lupe Peñalva
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maria Sala
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Javier del Riego
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Miguel Prieto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Carmen Vidal
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mar Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Xavier Bargalló
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ignasi Tusquets
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Xavier Castells
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xavier Castells.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Marta Román (mroman@parcdesalutmar.cat).

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors has significant statistical expertise (Marta Román).

Informed consent

Written informed consent was waived by the Institutional Review Board. Informed consent was not required since we used anonymized retrospective data

Ethical approval

Data was obtained from the databases of the participating screening centres. The review boards of the institutions providing data (Costa de Ponent, Vallés Oriental, Sabadell-Cerdanyola, and Cantabria) granted approval for data analyses.

Study subjects or cohorts overlap

Some study subjects or cohorts have been previously reported in:

Román M, Sala M, Baré M, Posso M, Vidal C, Louro J, Sánchez M, Peñalva L, Castells X, on behalf of the BELE study group. Changes in mammographic density over time and the risk of breast cancer: an observational cohort study. Breast. 2019; 46:108–115. https://doi.org/10.1016/j.breast.2019.04.007.

Posso M, Louro J, Sánchez M, Román M, Vidal C, Sala M, Baré M, Castells X; BELE study group. Mammographic breast density: How it affects performance indicators in screening programmes?. Eur J Radiol. 2019; 110:81–87. doi: 10.1016/j.ejrad.2018.11.012.

Román M, Hofvind S, von Euler-Chelpin M, Castells X. Long-term risk of screen-detected and interval breast cancer after false-positive results at mammography screening: Joint analysis of three national cohorts. Br J Cancer. 2019; 120(2):269–275. doi: 10.1038/s41416-018-0358-5.

Román M, Quintana MJ, Ferrer J, Sala M, Castells X, on behalf of the BELE study group. Cumulative risk of breast cancer screening outcomes according to the presence of previous benign breast disease and family history of breast cancer: supporting personalised screening. Br J Cancer 2017; 116(11):1480–1485. doi: 10.1038/bjc.2017.107.

Castells X, Torá-Rocamora I, Posso M, Román M, Vernet-Tomas M, Rodríguez-Arana A, Domingo L, Vidal C, Baré M, Ferrer J, Quintana MJ, Sánchez M, Natal C, Espinàs JA, Saladié F, Sala M. Risk of Breast cancer in Women with False-Positive Results according to the Mammographic Features. Radiology 2016; 280(2): 379–386. doi: 10.1148/radiol.2016151174.

Methodology

• retrospective

• observational

• multicenter study

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 84 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Román, M., Louro, J., Posso, M. et al. Breast density, benign breast disease, and risk of breast cancer over time. Eur Radiol 31, 4839–4847 (2021). https://doi.org/10.1007/s00330-020-07490-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-020-07490-5

Keywords

Search

Navigation