| dc.description.abstract | Breast cancer is the most common cancer in the UK, and mammographic density (‘density’) is one of its strongest known risk factors. At present, most research focuses on static measures of density to determine population effects. The central hypothesis of this thesis is that repeated measures of density are more valuable for personalised breast cancer prevention. This hypothesis was tested through the following research.
Study-I investigated within-women associations between body mass index (BMI) and density, to assess whether density (visual/Cumulus/volumetric ‘Stepwedge’) acts as a mediator for breast cancer risk reduction during a premenopausal weight-loss intervention (n=65). Study-II evaluated the benefit of using a woman’s longitudinal history of (BI-RADS) density to improve breast cancer risk estimation (n=132,439). Study-III was a Cochrane systematic review investigating the association between endocrine therapy-induced density reduction and breast cancer risk and mortality. Studies-IV and V (n=575) evaluated visually-assessed density reduction with prophylactic anastrozole during the International Breast Cancer Intervention Study-II, and its use as a biomarker for concurrent breast cancer risk reduction, respectively.
In Study-I, change in BMI was associated with change in breast fat but not dense tissue, negating density reduction as a biomarker for risk reduction with weight-loss. In Study-II, longitudinal density provided approximately a quarter more statistical information than most recent density and improved discriminatory accuracy. Study-III found evidence that density reduction may be a biomarker for reduction in risk and mortality with tamoxifen, but the level of evidence was limited by some study quality issues. Study-IV indicated that preventive anastrozole might marginally reduce density, but statistical significance was not obtained. In Study-V, sample size was too small to draw definitive conclusions.
Overall, changes in density were useful for the study of breast cancer risk and should be considered for personalised breast cancer prevention strategies. | en_US |
