A comparison of five methods of measuring mammographic density: a case-control study.

BACKGROUND: High mammographic density is associated with both risk of cancers being missed at mammography, and increased risk of developing breast cancer. Stratification of breast cancer prevention and screening requires mammographic density measures predictive of cancer. This study compares five mammographic density measures to determine the association with subsequent diagnosis of breast cancer and the presence of breast cancer at screening. METHODS: Women participating in the "Predicting Risk Of Cancer At Screening" (PROCAS) study, a study of cancer risk, completed questionnaires to provide personal information to enable computation of the Tyrer-Cuzick risk score. Mammographic density was assessed by visual analogue scale (VAS), thresholding (Cumulus) and fully-automated methods (Densitas, Quantra, Volpara) in contralateral breasts of 366 women with unilateral breast cancer (cases) detected at screening on entry to the study (Cumulus 311/366) and in 338 women with cancer detected subsequently. Three controls per case were matched using age, body mass index category, hormone replacement therapy use and menopausal status. Odds ratios (OR) between the highest and lowest quintile, based on the density distribution in controls, for each density measure were estimated by conditional logistic regression, adjusting for classic risk factors. RESULTS: The strongest predictor of screen-detected cancer at study entry was VAS, OR 4.37 (95% CI 2.72-7.03) in the highest vs lowest quintile of percent density after adjustment for classical risk factors. Volpara, Densitas and Cumulus gave ORs for the highest vs lowest quintile of 2.42 (95% CI 1.56-3.78), 2.17 (95% CI 1.41-3.33) and 2.12 (95% CI 1.30-3.45), respectively. Quantra was not significantly associated with breast cancer (OR 1.02, 95% CI 0.67-1.54). Similar results were found for subsequent cancers, with ORs of 4.48 (95% CI 2.79-7.18), 2.87 (95% CI 1.77-4.64) and 2.34 (95% CI 1.50-3.68) in highest vs lowest quintiles of VAS, Volpara and Densitas, respectively. Quantra gave an OR in the highest vs lowest quintile of 1.32 (95% CI 0.85-2.05). CONCLUSIONS: Visual density assessment demonstrated a strong relationship with cancer, despite known inter-observer variability; however, it is impractical for population-based screening. Percentage density measured by Volpara and Densitas also had a strong association with breast cancer risk, amongst the automated measures evaluated, providing practical automated methods for risk stratification.

Mammographic density adds accuracy to both the Tyrer-Cuzick and Gail breast cancer risk models in a prospective UK screening cohort.

INTRODUCTION: The Predicting Risk of Cancer at Screening study in Manchester, UK, is a prospective study of breast cancer risk estimation. It was designed to assess whether mammographic density may help in refinement of breast cancer risk estimation using either the Gail model (Breast Cancer Risk Assessment Tool) or the Tyrer-Cuzick model (International Breast Intervention Study model). METHODS: Mammographic density was measured at entry as a percentage visual assessment, adjusted for age and body mass index. Tyrer-Cuzick and Gail 10-year risks were based on a questionnaire completed contemporaneously. Breast cancers were identified at the entry screen or shortly thereafter. The contribution of density to risk models was assessed using odds ratios (ORs) with profile likelihood confidence intervals (CIs) and area under the receiver operating characteristic curve (AUC). The calibration of predicted ORs was estimated as a percentage [(observed vs expected (O/E)] from logistic regression. RESULTS: The analysis included 50,628 women aged 47-73 years who were recruited between October 2009 and September 2013. Of these, 697 had breast cancer diagnosed after enrolment. Median follow-up was 3.2 years. Breast density [interquartile range odds ratio (IQR-OR) 1.48, 95 % CI 1.34-1.63, AUC 0.59] was a slightly stronger univariate risk factor than the Tyrer-Cuzick model [IQR-OR 1.36 (95 % CI 1.25-1.48), O/E 60 % (95 % CI 44-74), AUC 0.57] or the Gail model [IQR-OR 1.22 (95 % CI 1.12-1.33), O/E 46 % (95 % CI 26-65 %), AUC 0.55]. It continued to add information after allowing for Tyrer-Cuzick [IQR-OR 1.47 (95 % CI 1.33-1.62), combined AUC 0.61] or Gail [IQR-OR 1.45 (95 % CI 1.32-1.60), combined AUC 0.59]. CONCLUSIONS: Breast density may be usefully combined with the Tyrer-Cuzick model or the Gail model.

Variable size computer-aided detection prompts and mammography film reader decisions.

INTRODUCTION: The purpose of the present study was to investigate the effect of computer-aided detection (CAD) prompts on reader behaviour in a large sample of breast screening mammograms by analysing the relationship of the presence and size of prompts to the recall decision. METHODS: Local research ethics committee approval was obtained; informed consent was not required. Mammograms were obtained from women attending routine mammography at two breast screening centres in 1996. Films, previously double read, were re-read by a different reader using CAD. The study material included 315 cancer cases comprising all screen-detected cancer cases, all subsequent interval cancers and 861 normal cases randomly selected from 10,267 cases. Ground truth data were used to assess the efficacy of CAD prompting. Associations between prompt attributes and tumour features or reader recall decisions were assessed by chi-squared tests. RESULTS: There was a highly significant relationship between prompting and a decision to recall for cancer cases and for a random sample of normal cases (P < 0.001). Sixty-four per cent of all cases contained at least one CAD prompt. In cancer cases, larger prompts were more likely to be recalled (P = 0.02) for masses but there was no such association for calcifications (P = 0.9). In a random sample of 861 normal cases, larger prompts were more likely to be recalled (P = 0.02) for both mass and calcification prompts. Significant associations were observed with prompting and breast density (p = 0.009) for cancer cases but not for normal cases (P = 0.05). CONCLUSIONS: For both normal cases and cancer cases, prompted mammograms were more likely to be recalled and the prompt size was also associated with a recall decision.