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

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.

Rapid Reductions in Breast Density following Tamoxifen Therapy as Evaluated by Whole-Breast Ultrasound Tomography

“…Lastly, this was a short-term longitudinal study with change in VASS as a biomarker endpoint. Prior studies have observed that mammographic breast density measurements approximately 1 year after tamoxifen initiation are generally representative of longer-term changes [31,32]. Future work is needed to evaluate the persistence of effects of UST sound speed declines on breast cancer outcomes to establish VASS as a clinically relevant biomarker.…”

Quantitative Breast Density in Contrast-Enhanced Mammography

“…Furthermore, younger high-risk women who may benefit from CESM screening are also a target population for prevention strategies. Mammographic VBD and measurements of fibroglandular volume have been demonstrated as useful markers of breast density change associated with interventions that include chemoprevention [ 46 , 47 , 48 ], oophorectomy [ 49 ], diet [ 50 ], and weight loss [ 51 ].…”

Australian Women’s Intentions and Psychological Outcomes Related to Breast Density Notification and Information

“… 1 Dense breast tissue can obscure a tumor when examining a mammogram image because both appear white and therefore can lead to reduced mammographic sensitivity and an increased chance of being diagnosed as breast cancer between routine screening mammograms. 2 , 3 Although there have been investigations into the interactions of some drugs with breast density, 4 the density remains relatively nonmodifiable, unlike other risk factors, such as body mass index and alcohol consumption. 5 It is estimated that a quarter to half of the population of women who are of breast screening age (40-75 years) have heterogeneously and extremely dense breasts.…”