Abstract P5-12-01: Predicting the effect of tamoxifen on the breast: Change in measures of breast density, serum markers and SNPs
Authors: Howell Anthony , Astley Sue , Harkness Elaine , Wiseman Julia , Fox Jill , Stavrinos Paula , Wilson Mary , Lim Yit , Reece Valerie , Beetles Ursula , Jain Anil , Sergeant Jamie , Cuzick Jack , Warren Ruth , Evans Gareth 
Published: May 2015

Abstract
Body: Introduction In the IBIS I Prevention Trial we demonstrated that tamoxifen prevented breast cancer in women with greater than 9 % absolute reduction in visually assessed mammographic density over a 12-18 month period as assessed by an expert radiologist, RW (1). In this study we investigated: whether RW obtained similar results in a different group of women treated with tamoxifen; how other expert mammographic film readers with experience of density assessment (radiologists, advanced practitioner radiographers and a breast physician) estimated mammographic change; how visual change relates to change in automated measures of volumetric density; and whether we can predict change by serum markers or SNPs. Methods 105 women aged 33 to 46 at greater than 1 in 6 lifetime breast cancer risk completed one year’s treatment with tamoxifen. RW assessed mammographic percentage density in increments of 5% for baseline and one year mammograms. Two or three of a pool of eight readers estimated % density using a visual analogue scale (VAS). Percent change was also estimated using a computer-assisted thresholding technique (Cumulus). Change in volume of dense tissue (Quantra™ & Volpara™) was measured. Changes in lipids, IGF1, insulin and relevant SNPs were measured to determine whether they predicted density change. Results. Estimates of change obtained by RW were broadly consistent with those from our previous study, as were those from Cumulus, but could not be replicated using estimates from the pooled results of VAS readers. Tamoxifen was associated with marked reductions of dense volume of the breast (Table 1) However the different methods were at best only moderately correlated with RW (r less than 0.6). Change in serum triglycerides significantly predicted density change as measured by RW but none of the other serum measures or SNPs did.
Table 1 Numbers of women and percentage change in density measures after one year of tamoxifen% Density changeRW %changeOther radiologists %changeCumulus %change_____% Dense volume change^Quantra %changeVolpara %change40+001 40+15930+503 30+141020+12013 20+202010+35630 10+17260+498143 0+16190-4188 0-1615Number10510598 9899RW = Ruth Warren. CUMULUS was measured by JS, a trained operator of the software. * Percentage point change eg if density changed from 40% to 30% this was regarded as a 10% change.^ Reduction in dense volume expressed as a percentage of baseline dense volume. We used Quantra version 2.0 and Volpara version 1.4.5
Conclusions Whilst RW remained consistent with previous density estimation it was not possible to use a pool of other expert readers to predict change. Cumulus gave similar results to RW but is difficult to use in practice. There was good agreement between the two objective volumetric measures used (r=0.5) and since these are automated they may be suitable for clinical practice. However their relationship to the long term breast cancer preventative effect of tamoxifen needs to be established.
Reference 1 Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case-control study. Cuzick J, Warwick J, Pinney E, Duffy JW, Cawthorn S, Howell A, Forbes JF, Warren RM. J Natl Cancer Inst. 2011 May 4; 103 (9): 744-52.
Citation Format: Anthony Howell, Sue Astley, Elaine Harkness, Julia Wiseman, Jill Fox, Paula Stavrinos, Mary Wilson, Yit Lim, Valerie Reece, Ursula Beetles, Anil Jain, Jamie Sergeant, Jack Cuzick, Ruth Warren, Gareth Evans. Predicting the effect of tamoxifen on the breast: Change in measures of breast density, serum markers and SNPs [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-12-01.