Breast density assessment is an important part of breast cancer risk assessment, as it has been known to correlate with risk. Mammograms would typically be assessed for density by multiple expert readers, however, interobserver variability can be high. Meanwhile, automatic breast density assessment tools are becoming more prevalent, particularly those based on artificial intelligence. We evaluate one such method against expert readers. A cohort of 1329 women going through screening was used to compare between two expert readers selected from a pool of 19, and a single such reader versus a deep learning based model. Whilst the mean differences for the two experiments were statistically similar, the limits of agreement between the AI method and a single reader are substantially lower at +SD 21 (95% CI : 20.07, 22.13) -SD 22 (95% CI : -22.95, -20.90) against +SD 31 (95% CI : 33.09, 28.91) -SD 28 (95% CI : -30.09, -25.91) between two expert readers. Additionally, the absolute intraclass correlation coefficients (two-way random multiple measures) were 0.86 (95% CI : 0.85, 0.88) between the AI and reader and 0.77 (95% CI : 0.75, 0.80) between the two readers achieving statistical significance. Our AI-driven breast density assessment tool has better inter-observer agreement with a randomly selected expert reader than two expert readers (drawn from a pool) do with one another. Additionally, the automatic method has similar inter-view agreement to experts and maintains consistency across density quartiles. Deep learning enabled density methods can offer a solution to the reader bias issue and provide consistent density scores.
KEYWORDS: Breast density, Breast cancer, Mammography, Breast, Cancer, Brain-machine interfaces, Statistical analysis, Education and training, Visualization, Ovarian cancer
Introduction: Breast cancer is the most common female cancer worldwide; however ethnic differences have been observed in both prevalence and prognosis, with Black women often having less favorable outcomes. Increased breast density is an independent risk factor for breast cancer and reduces the efficacy of mammographic screening. We investigate how it relates to ethnicity, to facilitate the provision of appropriate screening and advice to all women. Method: We use data from the UK Predicting Risk of Cancer at Screening (PROCAS) study. This involved completion of a questionnaire to obtain personal risk factor information during routine breast screening. Mammographic density was assessed using Visual Analogue Scales (VAS), and these scores were used to train an AI-based density measure, pVAS, which we applied to raw mammographic data from 41,241 women in PROCAS. Analysis of covariance was used to assess the relationship between ethnicity and breast density after adjusting for age, body mass index (BMI), menopausal status, hormone replacement therapy (HRT) use, parity, alcohol consumption, and family history of breast cancer. Pairwise comparisons for each ethnic group were performed using a Bonferroni correction. Results: 91.0% of the study population were white, 1.6% Asian, 1.1% Black and 1.0% Jewish. Jewish women had higher breast density than all other ethnic groups studied (p<0.001), with a mean pVAS of 34.8% (95% CI 33.6-36.1). Asian women had a mean density of 31.4% (95% CI 30.4-32.4) and significantly denser breasts than White women who had a mean pVAS density of 28.6% (95% CI 28.4-28.7). Conclusion: Previous research has reported mixed results. The relationship between risk factors for breast cancer are complex, and data not always complete, making this a challenging area of research. Our results support published evidence that some groups have increased density, and this relationship should be considered to ensure equity in screening and diagnosis.
Breast density is an important factor in assessing individual breast cancer risk. We aim to identify women at increased risk of developing breast cancer before they enter routine screening, using mammography in combination with known risk factors. This will enable targeting of preventive therapies and personalised screening. To reduce radiation risk, this paper examines whether density measurements in one breast or mammographic view could be used to accurately reflect individual risk. We analysed breast cancer risk using breast density in a 1:3 case-control dataset of mammograms from the Predicting Risk of Cancer at Screening Study (PROCAS). Breast density was measured using pVAS, an AI-based approach. Cancer risk in low and high breast density groups was compared using conditional logistic regression. High breast density was independently associated with increased breast cancer risk. Women in the highest breast density quintile averaged across all views had an Odds Ratio (OR) of 4.16 (95% CI 2.90-5.97) compared to those in the lowest. A similar OR was found in both the left 3.77 (95% CI 2.68-5.31) and right 4.52 (95% CI 3.12-6.55) breasts individually. ORs were also significant for each individual view: right mediolateral oblique (MLO) 4.19 (2.92–6.00), right craniocaudal (CC) 4.40 (3.09–6.27), left MLO 3.27 (2.34–4.56) and left CC 3.65 (2.60–5.11). The ability to predict breast cancer risk due to increased breast density was achieved using one breast and even one mammographic view. This provides the possibility of a pre-screening risk assessment using fewer images and therefore less radiation.
The prevention and early detection of breast cancer hinges on precise prediction of individual breast cancer risk. Whilst well-established clinical risk factors can be used to stratify the population into risk groups, the addition of genetic information and breast density has been shown to improve prediction. Deep learning based approach have been shown to automatically extract complex information from images. However, this is a challenging area of research, partly due to the lack of data within the field, therefore there is scope for novel approaches. Our method uses Multiple Instance Learning in tandem with attention in order to make accurate, short-term risk predictions from full-sized mammograms taken prior to the detection of cancer. This approach ensures small features like calcifications are not lost in a downsizing process and the whole mammogram is analysed effectively. An attention pooling mechanism is designed to highlight patches of increased importance and improve performance. We also use transfer learning in order to utilise a rich source of screen-detected cancers and evaluate whether a model trained to detect cancers in mammograms allows us also to predict risk in priors. Our model achieves an AUC of 0.620 (0.585,0.657) in cancer-free screening mammograms of women who went on to a screen-detected or interval cancer between 5 and 55 months later, including for common breast cancer risk factors. Additionally, our model is able to discriminate interval cancers at an AUC of 0.638 (0.572, 0.703) and highlights the potential for such a model to be used alongside national screening programmes.
Accurate prediction of individual breast cancer risk paves the way for personalised prevention and early detection. Whilst well-established clinical risk factors can be used to stratify the population into risk groups, the addition of genetic information and breast density has been shown to improve prediction. Machine learning enabled automatic risk prediction provides key advantages over existing methods such as the ability to extract more complex information from mammograms. However, this is a challenging area of research, partly due to the lack of data within the field, therefore there is scope for novel approaches. Our method uses Multiple Instance Learning in tandem with attention in order to make accurate, short-term risk predictions from full-sized mammograms taken prior to the detection of cancer. This approach ensures small features like calcifications are not lost in a downsizing process and the whole mammogram is analysed effectively. An attention pooling mechanism is designed to highlight patches of increased importance and improve performance. Additionally, this increases the interpretability of our model as important patches can be shown in a saliency map. We also use transfer learning in order to utilise a rich source of screen-detected cancers and evaluate whether a model trained to detect cancers in mammograms allows us also to predict risk in priors. Our model achieves an AUC of 0.635 (0.600,0.669) in cancer-free screening mammograms of women who went on to a screen-detected or interval cancer between 5 and 55 months and an AUC of 0.804 (0.777,0.830) in screen-detected cancers.
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