Mammographic (breast) density as a potential biomarker for endocrine trial treatment efficacy in breast cancer prevention

Mammographic (breast) density is comprised of the glandular and connective tissues of the breast which appear dense (white) on mammograms, x-rays of the breast. Reductions in both mammographic density and breast cancer risk are associated with estrogen lowering therapies (endocrine treatments) such as tamoxifen and the aromatase inhibitors. The Primary Aim of this thesis was to compare the longitudinal mammographic density response in women at high (2-fold) risk of breast cancer treated with the aromatase inhibitor anastrozole for breast cancer prevention in the International Breast (cancer) Intervention Study II (IBIS-II) trial with the mammographic density response in similar women randomised to placebo treatment, to ascertain if mammographic density may be a biomarker during endocrine therapy for breast cancer (prevention). The literature review undertaken for this thesis confirmed breast cancer is a heterogenous disease with many risk factors; many breast cancer risk factors are also factors associated with mammographic density. A measurement technique reliability analysis revealed mammographic density measurements made using visual assessment were less consistent than measurements made with a semi-automated thresholding technique. A longitudinal statistical model of mammographic density change for 120 Calvary Mater Newcastle hospital IBIS-II participants was developed using a mixed regression model. The results for the Primary Aim show longitudinal change in mammographic density for anastrozole and placebo treated IBIS-II participants does not differ; this result however is constrained by the small number of participants sampled and confounded by frequent changes of the film and digital mammography equipment used to take the trial mammograms. A sensitivity analysis undertaken with participants’ film mammograms only hints at a possible reduction in the rate of annual change in mammographic density for anastrozole treated participants relative to controls. This latter result supports the recent findings of a volumetric mammographic density study which found significantly greater annual decreases in volumetric mammographic density for breast cancer cases treated with aromatase inhibitors compared to the rates of decrease in healthy controls.