Skip to main content
SpringerLink
Log in

Mammographic density changes following discontinuation of tamoxifen in premenopausal women with oestrogen receptor-positive breast cancer

European Radiology Aims and scope Submit manuscript

Cite this article

Abstract

Objectives

To evaluate the changes in mammographic density after tamoxifen discontinuation in premenopausal women with oestrogen receptor-positive breast cancers and the underlying factors

Methods

A total of 213 consecutive premenopausal women with breast cancer who received tamoxifen treatment after curative surgery and underwent three mammograms (baseline, after tamoxifen treatment, after tamoxifen discontinuation) were included. Changes in mammographic density after tamoxifen discontinuation were assessed qualitatively (decrease, no change, or increase) by two readers and measured quantitatively by semi-automated software. The association between % density change and clinicopathological factors was evaluated using univariate and multivariate regression analyses.

Results

After tamoxifen discontinuation, a mammographic density increase was observed in 31.9% (68/213, reader 1) to 22.1% (47/213, reader 2) by qualitative assessment, with a mean density increase of 1.8% by quantitative assessment compared to density before tamoxifen discontinuation. In multivariate analysis, younger age (≤ 39 years) and greater % density decline after tamoxifen treatment (≥ 17.0%) were independent factors associated with density change after tamoxifen discontinuation (p < .001 and p = .003, respectively).

Conclusions

Tamoxifen discontinuation was associated with mammographic density change with a mean density increase of 1.8%, which was associated with younger age and greater density change after tamoxifen treatment.

Key Points

• Increased mammographic density after tamoxifen discontinuation can occur in premenopausal women.

• Mean density increase after tamoxifen discontinuation was 1.8%.

• Density increase is associated with age and density decrease after tamoxifen.

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
Fig. 2

Similar content being viewed by others

References

  1. Early Breast Cancer Trialists' Collaborative G, Davies C, Godwin J et al (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 378:771–784

    Article  CAS  Google Scholar 

  2. MacNab MW, Tallarida RJ, Joseph R (1984) An evaluation of tamoxifen as a partial agonist by classical receptor theory–an explanation of the dual action of tamoxifen. Eur J Pharmacol 103:321–326

    Article  PubMed  CAS  Google Scholar 

  3. Desta Z, Ward BA, Soukhova NV, Flockhart DA (2004) Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther 310:1062–1075

    Article  PubMed  CAS  Google Scholar 

  4. Deroo BJ, Korach KS (2006) Estrogen receptors and human disease. J Clin Invest 116:561–570

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Cuzick J, Warwick J, Pinney E et al (2011) Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case-control study. J Natl Cancer Inst 103:744–752

    Article  PubMed  CAS  Google Scholar 

  6. Li J, Humphreys K, Eriksson L, Edgren G, Czene K, Hall P (2013) Mammographic density reduction is a prognostic marker of response to adjuvant tamoxifen therapy in postmenopausal patients with breast cancer. J Clin Oncol 31:2249–2256

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Kim J, Han W, Moon HG et al (2012) Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in hormone receptor positive breast cancer. Breast Cancer Res 14:R102

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Ko KL, Shin IS, You JY, Jung SY, Ro J, Lee ES (2013) Adjuvant tamoxifen-induced mammographic breast density reduction as a predictor for recurrence in estrogen receptor-positive premenopausal breast cancer patients. Breast Cancer Res Treat 142:559–567

    Article  PubMed  CAS  Google Scholar 

  9. 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 15:R57

    Article  PubMed  PubMed Central  Google Scholar 

  10. Nyante SJ, Sherman ME, Pfeiffer RM et al (2015) Prognostic significance of mammographic density change after initiation of tamoxifen for ER-positive breast cancer. J Natl Cancer Inst 107

  11. Slanetz PJ, Grandpre LE, Yeh ED, Kopans DB, Mendel JB (2004) Effect of tamoxifen on breast tissue density in premenopausal breast cancer. Breast J 10:27–32

    Article  PubMed  Google Scholar 

  12. Byng JW, Yaffe MJ, Jong RA et al (1998) Analysis of mammographic density and breast cancer risk from digitized mammograms. Radiographics 18:1587–1598

    Article  PubMed  CAS  Google Scholar 

  13. Laya MB, Gallagher JC, Schreiman JS, Larson EB, Watson P, Weinstein L (1995) Effect of postmenopausal hormonal replacement therapy on mammographic density and parenchymal pattern. Radiology 196:433–437

    Article  PubMed  CAS  Google Scholar 

  14. McTiernan A, Chlebowski RT, Martin C et al (2009) Conjugated equine estrogen influence on mammographic density in postmenopausal women in a substudy of the women's health initiative randomized trial. J Clin Oncol 27:6135–6143

    Article  PubMed  PubMed Central  Google Scholar 

  15. Rutter CM, Mandelson MT, Laya MB, Seger DJ, Taplin S (2001) Changes in breast density associated with initiation, discontinuation, and continuing use of hormone replacement therapy. JAMA 285:171–176

    Article  PubMed  CAS  Google Scholar 

  16. Sterns EE, Zee B (2000) Mammographic density changes in perimenopausal and postmenopausal women: is effect of hormone replacement therapy predictable? Breast Cancer Res Treat 59:125–132

    Article  PubMed  CAS  Google Scholar 

  17. Stomper PC, Van Voorhis BJ, Ravnikar VA, Meyer JE (1990) Mammographic changes associated with postmenopausal hormone replacement therapy: a longitudinal study. Radiology 174:487–490

    Article  PubMed  CAS  Google Scholar 

  18. Cuzick J, Warwick J, Pinney E, Warren RM, Duffy SW (2004) Tamoxifen and breast density in women at increased risk of breast cancer. J Natl Cancer Inst 96:621–628

    Article  PubMed  CAS  Google Scholar 

  19. Peyrade F, Frenay M, Etienne MC et al (1996) Age-related difference in tamoxifen disposition. Clin Pharmacol Ther 59:401–410

    Article  PubMed  CAS  Google Scholar 

  20. Kim JY, Cho N, Jeyanth JX et al (2014) Smaller reduction in 3D breast density associated with subsequent cancer recurrence in patients with breast cancer receiving adjuvant tamoxifen therapy. AJR Am J Roentgenol 202:912–921

    Article  PubMed  Google Scholar 

  21. Davies C, Pan H, Godwin J et al (2013) Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 381:805–816

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Ko SY, Kim EK, Kim MJ, Moon HJ (2014) Mammographic density estimation with automated volumetric breast density measurement. Korean J Radiol 15:313–321

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study has received funding by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (NRF-2014R1A1A2053682).

Author information

Authors and Affiliations

  1. Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea

    Won Hwa Kim, Nariya Cho & Young-Seon Kim

  2. Department of Radiology, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea

    Won Hwa Kim

  3. Department of Radiology, Seoul National College of Medicine, Seoul, Republic of Korea

    Nariya Cho & Ann Yi

  4. Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea

    Nariya Cho

  5. Department of Radiology, College of Medicine, Yeungnam University, Daegu, Republic of Korea

    Young-Seon Kim

  6. Department of Radiology, Gangnam Healthcare Center, Seoul, Republic of Korea

    Ann Yi

Authors
  1. Won Hwa Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nariya Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Young-Seon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ann Yi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nariya Cho.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Nariya Cho.

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

No complex statistical methods were necessary for this paper.

Ethical approval

Institutional review board approval was obtained.

Informed consent

Written informed consent was waived by the institutional review board.

Methodology

• retrospective

• observational

• performed at one institution

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, W.H., Cho, N., Kim, YS. et al. Mammographic density changes following discontinuation of tamoxifen in premenopausal women with oestrogen receptor-positive breast cancer. Eur Radiol 28, 3176–3184 (2018). https://doi.org/10.1007/s00330-017-5293-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-017-5293-y

Keywords

search

Navigation