Advertisement

Breast Cancer Research and Treatment

, Volume 170, Issue 1, pp 143–148 | Cite as

Dose-dependent effect of mammographic breast density on the risk of contralateral breast cancer

  • Marzana Chowdhury
  • David Euhus
  • Maureen O’Donnell
  • Tracy Onega
  • Pankaj K. ChoudharyEmail author
  • Swati BiswasEmail author
Epidemiology

Abstract

Purpose

Increased mammographic breast density is a significant risk factor for breast cancer. It is not clear if it is also a risk factor for the development of contralateral breast cancer.

Methods

The data were obtained from Breast Cancer Surveillance Consortium and included women diagnosed with invasive breast cancer or ductal carcinoma in situ between ages 18 and 88 and years 1995 and 2009. Each case of contralateral breast cancer was matched with three controls based on year of first breast cancer diagnosis, race, and length of follow-up. A total of 847 cases and 2541 controls were included. The risk factors included in the study were mammographic breast density, age of first breast cancer diagnosis, family history of breast cancer, anti-estrogen treatment, hormone replacement therapy, menopausal status, and estrogen receptor status, all from the time of first breast cancer diagnosis. Both univariate analysis and multivariate conditional logistic regression analysis were performed.

Results

In the final multivariate model, breast density, family history of breast cancer, and anti-estrogen treatment remained significant with p values less than 0.01. Increasing breast density had a dose-dependent effect on the risk of contralateral breast cancer. Relative to ‘almost entirely fat’ category of breast density, the adjusted odds ratios (and p values) in the multivariate analysis for ‘scattered density,’ ‘heterogeneously dense,’ and ‘extremely dense’ categories were 1.65 (0.036), 2.10 (0.002), and 2.32 (0.001), respectively.

Conclusion

Breast density is an independent and significant risk factor for development of contralateral breast cancer. This risk factor should contribute to clinical decision making.

Keywords

Contralateral breast cancer Breast density Breast Cancer Surveillance Consortium Contralateral prophylactic mastectomy 

Notes

Acknowledgements

This work was supported in part by the National Cancer Institute-funded Breast Cancer Surveillance Consortium (HHSN261201100031C). The collection of cancer and vital status data used in this study was supported in part by several state public health departments and cancer registries throughout the US. For a full description of these sources, please see: http://breastscreening.cancer.gov/work/acknowledgement.html. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. We thank the participating women, mammography facilities, and radiologists for the data they have provided for this study. You can learn more about the BCSC at: http://www.bcsc-research.org/. We thank Linn Abraham for providing BCSC data-related support. We are also thankful to an anonymous reviewer for providing constructive comments, which led to an improved version of the paper.

Funding

This work was funded by the National Cancer Institute at the National Institutes of Health (Grant Number R21 CA186086). This work was also supported in part by the National Cancer Institute-funded Breast Cancer Surveillance Consortium (HHSN261201100031C).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Tuttle TM, Habermann EB, Grund EH et al (2007) Increasing use of contralateral prophylactic mastectomy for breast cancer patients: a trend toward more aggressive surgical treatment. J Clin Oncol 25:5203–5209CrossRefPubMedGoogle Scholar
  2. 2.
    Tuttle TM, Jarosek S, Habermann EB et al (2009) Increasing rates of contralateral prophylactic mastectomy among patients with ductal carcinoma in situ. J Clin Oncol 27:1362–1367CrossRefPubMedGoogle Scholar
  3. 3.
    King TA, Sakr R, Patil S et al (2011) Clinical management factors contribute to the decision for contralateral prophylactic mastectomy. J Clin Oncol 29:2158–2164CrossRefPubMedGoogle Scholar
  4. 4.
    Yao K, Stewart AK, Winchester DJ, Winchester DP (2010) Trends in contralateral prophylactic mastectomy for unilateral cancer: a report from the national cancer data base, 1998–2007. Ann Surg Oncol 17:2554–2562CrossRefPubMedGoogle Scholar
  5. 5.
    Katipamula R, Degnim AC, Hoskin T et al (2009) Trends in mastectomy rates at the Mayo Clinic Rochester: effect of surgical year and preoperative magnetic resonance imaging. J Clin Oncol 27:4082–4088CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Wong SM, Freedman RA, Sagara Y et al (2016) Growing use of contralateral prophylactic mastectomy despite no improvement in long-term survival for invasive breast cancer. Ann Surg 265:581–589CrossRefGoogle Scholar
  7. 7.
    Nichols HB, Berrington de Gonzalez A, Lacey JV et al (2011) Declining incidence of contralateral breast cancer in the United States from 1975 to 2006. J Clin Oncol 29:1564–1569CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Uyeno L, Behrendt, Vito C (2012) Contralateral breast cancer: Impact on survival after unilateral breast cancer is stage-dependent. ASCO Breast Cancer Symposium Abstract vol 69Google Scholar
  9. 9.
    Bertelsen L, Bernstein L, Olsen JH et al (2008) Effect of systemic adjuvant treatment on risk for contralateral breast cancer in the women’s environment, cancer and radiation epidemiology study. J Natl Cancer Inst 100:32–40CrossRefPubMedGoogle Scholar
  10. 10.
    Kurian AW, McClure LA, John EM et al (2009) Second primary breast cancer occurrence according to hormone receptor status. J Natl Cancer Inst 101:1058–1065CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Brewster AM, Parker PA (2011) Current knowledge on contralateral prophylactic mastectomy among women with sporadic breast cancer. Oncologist 16:935–941CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Bouchardy C, Benhamou S, Fioretta G et al (2011) Risk of second breast cancer according to estrogen receptor status and family history. Breast Cancer Res Treat 127:233–241CrossRefPubMedGoogle Scholar
  13. 13.
    Khan SA (2011) Contralateral prophylactic mastectomy: what do we know and what do our patients know? J Clin Oncol 29:2132–2135CrossRefPubMedGoogle Scholar
  14. 14.
    Murphy JA, Milner TD, O’Donoghue JM (2013) Contralateral risk-reducing mastectomy in sporadic breast cancer. Lancet Oncol 14:e262–e269CrossRefPubMedGoogle Scholar
  15. 15.
    Abbott A, Rueth N, Pappas-Varco S et al (2011) Perceptions of contralateral breast cancer: an overestimation of risk. Ann Surg Oncol 18:3129–3136CrossRefPubMedGoogle Scholar
  16. 16.
    Portschy PR, Abbott AM, Burke EE et al (2015) Perceptions of contralateral breast cancer risk: a prospective, longitudinal study. Ann Surg Oncol 22:3846–3852.  https://doi.org/10.1245/s10434-015-4442-2 CrossRefPubMedGoogle Scholar
  17. 17.
    Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ Group (2008) Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 9:45–53CrossRefGoogle Scholar
  18. 18.
    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717CrossRefGoogle Scholar
  19. 19.
    Cuzick J, Sestak I, Baum M et al (2010) Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol 11:1135–1141CrossRefPubMedGoogle Scholar
  20. 20.
    Chen Y, Thompson W, Semenciw R, Mao Y (1999) Epidemiology of contralateral breast cancer. Cancer Epidemiol Biomarkers Prev 8:855–861PubMedGoogle Scholar
  21. 21.
    Schaapveld M, Visser O, Louwman WJ et al (2008) The impact of adjuvant therapy on contralateral breast cancer risk and the prognostic significance of contralateral breast cancer: a population based study in the Netherlands. Breast Cancer Res Treat 110:189–197CrossRefPubMedGoogle Scholar
  22. 22.
    Graeser MK, Engel C, Rhiem K et al (2009) Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 27:5887–5892CrossRefPubMedGoogle Scholar
  23. 23.
    Mccormack VA (2006) Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev 15:1159–1169.  https://doi.org/10.1158/1055-9965.epi-06-0034 CrossRefGoogle Scholar
  24. 24.
    Boyd NF, Martin LJ, Bronskill M et al (2010) Breast tissue composition and susceptibility to breast cancer. JNCI J. Nat. Cancer Inst 102:1224–1237.  https://doi.org/10.1093/jnci/djq239 CrossRefPubMedGoogle Scholar
  25. 25.
    Habel LA, Capra AM, Achacoso NS et al (2010) Mammographic density and risk of second breast cancer after ductal carcinoma in situ. Cancer Epidemiol Biomarkers Prev 19:2488–2495CrossRefPubMedGoogle Scholar
  26. 26.
    Hwang ES, Miglioretti DL, Ballard-Barbash R et al (2007) Association between breast density and subsequent breast cancer following treatment for ductal carcinoma in situ. Cancer Epidemiol Biomarkers Prev 16:2587–2593CrossRefPubMedGoogle Scholar
  27. 27.
    Raghavendra A, Sinha AK, Le-Petross HT et al (2017) Mammographic breast density is associated with the development of contralateral breast cancer. Cancer 123:1935–1940CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Sandberg ME, Li J, Hall P et al (2013) Change of mammographic density predicts the risk of contralateral breast cancer—a case-control study. Breast Cancer Res.  https://doi.org/10.1186/bcr3451 PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Breast Cancer Surveillance Consortium (http://breastscreening.cancer.gov/) (2016). National Cancer Institute, Applied Research Program
  30. 30.
    Breslow NE, Day NE (1980) Statistical Methods in Cancer Research. International Agency for Research on Cancer, LyonGoogle Scholar
  31. 31.
    Chowdhury M, Euhus D, Onega T et al (2017) A model for individualized risk prediction of contralateral breast cancer. Breast Cancer Res Treat 161:153–160.  https://doi.org/10.1007/s10549-016-4039-x CrossRefPubMedGoogle Scholar
  32. 32.
    Hosmer DW, Lemeshow S (2000) Applied Logistic Regression, 2nd ed. Wiley, hobokenGoogle Scholar
  33. 33.
    Development Core Team R (2016) R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, ViennaGoogle Scholar
  34. 34.
    Therneau TM (2015) A package for survival analysis in S. version 2.41-3. https://CRAN.R-project.org/package=survival Accessed Nov 22 2017
  35. 35.
    Therneau TM, Grambsch PM (2000) Modeling survival data: extending the cox model. Springer, BerlinCrossRefGoogle Scholar
  36. 36.
    Murphy JA, Milner TD, O’Donoghue JM (2013) Contralateral risk-reducing mastectomy in sporadic breast cancer. Lancet Oncol 14:e262–e269CrossRefPubMedGoogle Scholar
  37. 37.
    Innos K, Horn-Ross PL (2007) Risk of second primary breast cancers among women with ductal carcinoma in situ of the breast. Breast Cancer Res Treat 111(3):531–540.  https://doi.org/10.1007/s10549-007-9807-1 CrossRefPubMedGoogle Scholar
  38. 38.
    Basu NN, Ross GL, Evans DG, Barr L (2015) The Manchester guidelines for contralateral risk-reducing mastectomy. World J Surg Oncol 13:237.  https://doi.org/10.1186/s12957-015-0638-y CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Mathematical SciencesUniversity of Texas at DallasRichardsonUSA
  2. 2.Division of Surgical OncologyJohns Hopkins UniversityBaltimoreUSA
  3. 3.Johns Hopkins Sibley Memorial HospitalWashington D.C.USA
  4. 4.Department of Community and Family MedicineGeisel School of Medicine at DartmouthHanoverUSA

Personalised recommendations