The influence of mammogram acquisition on the mammographic density and breast cancer association in the mayo mammography health study cohort

INTRODUCTION: Mammographic density is a strong risk factor for breast cancer. Image acquisition technique varies across mammograms to limit radiation and produce a clinically useful image. We examined whether acquisition technique parameters at the time of mammography were associated with mammographic density and whether the acquisition parameters confounded the density and breast cancer association. METHODS: We examined this question within the Mayo Mammography Health Study (MMHS) cohort, comprised of 19,924 women (51.2% of eligible) seen in the Mayo Clinic mammography screening practice from 2003 to 2006. A case-cohort design, comprising 318 incident breast cancers diagnosed through December 2009 and a random subcohort of 2,259, was used to examine potential confounding of mammogram acquisition technique parameters (x-ray tube voltage peak (kVp), milliampere-seconds (mAs), thickness and compression force) on the density and breast cancer association. The Breast Imaging Reporting and Data System four-category tissue composition measure (BI-RADS) and percent density (PD) (Cumulus program) were estimated from screen-film mammograms at time of enrollment. Spearman correlation coefficients (r) and means (standard deviations) were used to examine the relationship of density measures with acquisition parameters. Hazard ratios (HR) and C-statistics were estimated using Cox proportional hazards regression, adjusting for age, menopausal status, body mass index and postmenopausal hormones. A change in the HR of at least 15% indicated confounding. RESULTS: Adjusted PD and BI-RADS density were associated with breast cancer (p-trends < 0.001), with a 3 to 4-fold increased risk in the extremely dense vs. fatty BI-RADS categories (HR: 3.0, 95% CI, 1.7 - 5.1) and the ≥ 25% vs. ≤ 5% PD categories (HR: 3.8, 95% CI, 2.5 - 5.9). Of the acquisition parameters, kVp was not correlated with PD (r = 0.04, p = 0.07). Although thickness (r = -0.27, p < 0.001), compression force (r = -0.16, p < 0.001), and mAs (r = -0.06, p = 0.008) were inversely correlated with PD, they did not confound the PD or BI-RADS associations with breast cancer and their inclusion did not improve discriminatory accuracy. Results were similar for associations of dense and non-dense area with breast cancer. CONCLUSIONS: We confirmed a strong association between mammographic density and breast cancer risk that was not confounded by mammogram acquisition technique.