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Breast Cancer Res Treat. 2018 Jun;169(2):371-379. doi: 10.1007/s10549-018-4690-5. Epub 2018 Feb 1.

A comprehensive tool for measuring mammographic density changes over time.

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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 171 77, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 171 77, Stockholm, Sweden.
Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
Department of Surgery, National University of Singapore, Singapore, Singapore.
Department of Radiology, South General Hospital, Stockholm, Sweden.
Department of Oncology, South General Hospital, Stockholm, Sweden.



Mammographic density is a marker of breast cancer risk and diagnostics accuracy. Density change over time is a strong proxy for response to endocrine treatment and potentially a stronger predictor of breast cancer incidence. We developed STRATUS to analyse digital and analogue images and enable automated measurements of density changes over time.


Raw and processed images from the same mammogram were randomly sampled from 41,353 healthy women. Measurements from raw images (using FDA approved software iCAD) were used as templates for STRATUS to measure density on processed images through machine learning. A similar two-step design was used to train density measures in analogue images. Relative risks of breast cancer were estimated in three unique datasets. An alignment protocol was developed using images from 11,409 women to reduce non-biological variability in density change. The protocol was evaluated in 55,073 women having two regular mammography screens. Differences and variances in densities were compared before and after image alignment.


The average relative risk of breast cancer in the three datasets was 1.6 [95% confidence interval (CI) 1.3-1.8] per standard deviation of percent mammographic density. The discrimination was AUC 0.62 (CI 0.60-0.64). The type of image did not significantly influence the risk associations. Alignment decreased the non-biological variability in density change and re-estimated the yearly overall percent density decrease from 1.5 to 0.9%, p < 0.001.


The quality of STRATUS density measures was not influenced by mammogram type. The alignment protocol reduced the non-biological variability between images over time. STRATUS has the potential to become a useful tool for epidemiological studies and clinical follow-up.


Breast cancer; Endocrine treatment; Longitudinal; Mammographic density; Recurrence; Risk; Therapy response; Time series

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