Case-control study of mammographic density and breast cancer risk using processed digital mammograms

Abstract

BackgroundFull-field digital mammography (FFDM) has largely replaced film-screen mammography in the US. Breast density assessed from film mammograms is strongly associated with breast cancer risk, but data are limited for processed FFDM images used for clinical care.MethodsWe conducted a case-control study nested among non-Hispanic white female participants of the Research Program in Genes, Environment and Health of Kaiser Permanente Northern California who were aged 40 to 74 years and had screening mammograms acquired on Hologic FFDM machines. Cases (n = 297) were women with a first invasive breast cancer diagnosed after a screening FFDM. For each case, up to five controls (n = 1149) were selected, matched on age and year of FFDM and image batch number, and who were still under follow-up and without a history of breast cancer at the age of diagnosis of the matched case. Percent density (PD) and dense area (DA) were assessed by a radiological technologist using Cumulus. Conditional logistic regression was used to estimate odds ratios (ORs) for breast cancer associated with PD and DA, modeled continuously in standard deviation (SD) increments and categorically in quintiles, after adjusting for body mass index, parity, first-degree family history of breast cancer, breast area, and menopausal hormone use.ResultsMedian intra-reader reproducibility was high with a Pearson’s r of 0.956 (range 0.902 to 0.983) for replicate PD measurements across 23 image batches. The overall mean was 20.02 (SD, 14.61) for PD and 27.63 cm2 (18.22 cm2) for DA. The adjusted ORs for breast cancer associated with each SD increment were 1.70 (95 % confidence interval, 1.41–2.04) for PD, and 1.54 (1.34–1.77) for DA. The adjusted ORs for each quintile were: 1.00 (ref.), 1.49 (0.91–2.45), 2.57 (1.54–4.30), 3.22 (1.91–5.43), 4.88 (2.78–8.55) for PD, and 1.00 (ref.), 1.43 (0.85–2.40), 2.53 (1.53–4.19), 2.85 (1.73–4.69), 3.48 (2.14–5.65) for DA.ConclusionsPD and DA measured using Cumulus on processed FFDM images are positively associated with breast cancer risk, with similar magnitudes of association as previously reported for film-screen mammograms. Processed digital mammograms acquired for routine clinical care in a general practice setting are suitable for breast density and cancer research.

Age at Menarche and Late Adolescent Adiposity Associated with Mammographic Density on Processed Digital Mammograms in 24,840 Women

“…The methods related to this resource have been described previously (5). Briefly, the RPGEH was developed and is administered by the Division of Research, Kaiser Permanente Northern California (KPNC) as a resource for research on the genetic and environmental determinants of common, age-related complex health conditions.…”

“…Density measurements were estimated with the Cumulus interactive threshold method [9]. We previously found that noise reduction of processed Hologic FFDM images to make them appear more film-like can significantly (p < 0.001) improve the reproducibility of readers with little prior experience applying Cumulus to processed FFDM images (5). As readers gained experience over time, high levels of reproducibility (Pearson’s r >0.90) were attained on processed FFDM images with or without noise reduction.…”

“…Most previous epidemiologic studies using Cumulus have assessed breast density using images from film-screen mammography, whereas full-field digital mammography (FFDM) has largely replaced conventional film mammography in health care settings over the last decade. Recently, we (5) and others (6,7) have shown that mammographic density measured with Cumulus on processed digital mammograms is also significantly associated with breast cancer risk.…”

Short-term early exposure to lapatinib confers lifelong protection from mammary tumor development in MMTV-erbB-2 transgenic mice

“…Advanced mammary morphology is associated with breast cancer susceptibility in humans and is typically present in premalignant mammary tissues of MMTV-erbB-2 transgenic mice [29, 30]. To this end, we collected mammary glands of 24-week-old mice to examine the effects of lapatinib on breast tissue morphogenesis.…”

Breast Cancer Risk and Mammographic Density Assessed with Semiautomated and Fully Automated Methods and BI-RADS

“…The reader was trained by the providers of the Cumulus software (9). We previously found that noise reduction of processed FFDM images makes them appear more like film mammograms, and this can significantly improve reproducibility for readers with relatively little prior experience (15). Here, we applied a median filter with a radius of 2 pixels to assist the study reader (16).…”