Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Sep 29;22(1):101.
doi: 10.1186/s13058-020-01340-4.

Mammographic density change in a cohort of premenopausal women receiving tamoxifen for breast cancer prevention over 5 years

Adam R Brentnall  1 , Ruth Warren  2 , Elaine F Harkness  3   4 , Susan M Astley  3   4   5 , Julia Wiseman  4 , Jill Fox  4 , Lynne Fox  4 , Mikael Eriksson  6 , Per Hall  6 , Jack Cuzick  1 , D Gareth Evans  4   5   7   8 , Anthony Howell  9   10   11
Affiliations

Mammographic density change in a cohort of premenopausal women receiving tamoxifen for breast cancer prevention over 5 years

Adam R Brentnall et al. Breast Cancer Res. .

Abstract

Background: A decrease in breast density due to tamoxifen preventive therapy might indicate greater benefit from the drug. It is not known whether mammographic density continues to decline after 1 year of therapy, or whether measures of breast density change are sufficiently stable for personalised recommendations.

Methods: Mammographic density was measured annually over up to 5 years in premenopausal women with no previous diagnosis of breast cancer but at increased risk of breast cancer attending a family-history clinic in Manchester, UK (baseline 2010-2013). Tamoxifen (20 mg/day) for prevention was prescribed for up to 5 years in one group; the other group did not receive tamoxifen and were matched by age. Fully automatic methods were used on mammograms over the 5-year follow-up: three area-based measures (NN-VAS, Stratus, Densitas) and one volumetric (Volpara). Additionally, percentage breast density at baseline and first follow-up mammograms was measured visually. The size of density declines at the first follow-up mammogram and thereafter was estimated using a linear mixed model adjusted for age and body mass index. The stability of density change at 1 year was assessed by evaluating mean squared error loss from predictions based on individual or mean density change at 1 year.

Results: Analysis used mammograms from 126 healthy premenopausal women before and as they received tamoxifen for prevention (median age 42 years) and 172 matched controls (median age 41 years), with median 3 years follow-up. There was a strong correlation between percentage density measures used on the same mammogram in both the tamoxifen and no tamoxifen groups (all correlation coeficients > 0.8). Tamoxifen reduced mean breast density in year 1 by approximately 17-25% of the inter-quartile range of four automated percentage density measures at baseline, and from year 2, it decreased further by approximately 2-7% per year. Predicting change at 2 years using individual change at 1 year was approximately 60-300% worse than using mean change at 1year.

Conclusions: All measures showed a consistent and large average tamoxifen-induced change in density over the first year, and a continued decline thereafter. However, these measures of density change at 1 year were not stable on an individual basis.

Keywords: Breast density change; Mammographic density; Prevention; Tamoxifen.

PubMed Disclaimer

Conflict of interest statement

Prof Evans and Howell report receiving consultancy fees from AstraZeneca. Prof Cuzick has received funding from Sanofi-Aventis and AstraZeneca, and is a paid member of a speaker’s bureau for AstraZeneca. Prof Cuzick and Dr Brentnall report receiving royalty payments through Cancer Research UK for commercial use of the Tyrer–Cuzick algorithm to assess breast cancer risk. None of the other authors report any conflict of interest.

Figures

Fig. 1
Fig. 1
Flow diagram with number of women showing the number of women included in analysis samples A (all women included in the study), B (those with 1 year density change) and C (those with 1 year and 2 years density change measured)
Fig. 2
Fig. 2
Mean (standard error) standardised breast density at each time point from women a receiving tamoxifen and b not receiving tamoxifen, using all women included in the study (analysis sample A). Standardised breast density uses transformed percentage density (natural logarithm for Volpara, square root for others) that has been normalised to have mean zero and unit inter-quartile range at baseline
See this image and copyright information in PMC

References

    1. Rugo HS, Rumble RB, Macrae E, Barton DL, Connolly HK, Dickler MN, Fallowfield L, Fowble B, Ingle JN, Jahanzeb M, Johnston SRD, Korde LA, Khatcheressian JL, Mehta RS, Muss HB, Burstein HJ. Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology Guideline. J Clin Oncol. 2016;34(25):3069–103. - PubMed
    1. Early Breast Cancer Trialists’ Collaborative Group. Davies C, Godwin J, Gray R, Clarke M, Cutter D, Darby S, McGale P, Pan HC, Taylor C, Wang YC, Dowsett M, Ingle J, Peto R. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378(9793):771–84. - PMC - PubMed
    1. Cuzick J, Sestak I, Bonanni B, Costantino JP, Cummings S, DeCensi A, Dowsett M, Forbes JF, Ford L, LaCroix AZ, Mershon J, Mitlak BH, Powles T, Veronesi U, Vogel V, Wickerham DL, SERM Chemoprevention of Breast Cancer Overview Group Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data. Lancet. 2013;381(9880):1827–34. - PMC - PubMed
    1. Buus R, Yeo B, Brentnall AR, Klintman M, Cheang MCU, Khabra K, Sestak I, Gao Q, Cuzick J, Dowsett M. Novel 18-gene signature for predicting relapse in ER-positive, HER2-negative breast cancer. Breast Cancer Res. 2018;20(1):103. - PMC - PubMed
    1. van Veen EM, Brentnall AR, Byers H, Harkness EF, Astley SM, Sampson S, Howell A, Newman WG, Cuzick J, Evans DGR. Use of single-nucleotide polymorphisms and mammographic density plus classic risk factors for breast cancer risk prediction. JAMA Oncology. 2018;4(4):476–82. - PMC - PubMed

Publication types