Abstract
Mammographic percent density (MPD) is an independent risk factor for developing breast cancer, but its inclusion in clinical risk models provides only modest improvements in individualized risk prediction, and MPD is not typically assessed in younger women because of ionizing radiation concerns. Previous studies have shown that tissue sound speed, derived from whole breast ultrasound tomography (UST), a non-ionizing modality, is a potential surrogate marker of breast density, but prior to this study, sound speed has not been directly linked to breast cancer risk. To that end, we explored the relation of sound speed and MPD with breast cancer risk in a case-control study, including 61 cases with recent breast cancer diagnoses and a comparison group of 165 women, frequency matched to cases on age, race, and menopausal status, and with a recent negative mammogram and no personal history of breast cancer. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the relation of quartiles of MPD and sound speed with breast cancer risk adjusted for matching factors. Elevated MPD was associated with increased breast cancer risk, although the trend did not reach statistical significance (OR per quartile = 1.27, 95% CI: 0.95, 1.70; ptrend = 0.10). In contrast, elevated sound speed was significantly associated with breast cancer risk in a dose–response fashion (OR per quartile = 1.83, 95% CI: 1.32, 2.54; ptrend = 0.0003). The OR trend for sound speed was statistically significantly different from that observed for MPD (p = 0.005). These findings suggest that whole breast sound speed may be more strongly associated with breast cancer risk than MPD and offer future opportunities for refining the magnitude and precision of risk associations in larger, population-based studies, including women younger than usual screening ages.
Highlights
Mammographic percent density (MPD) is a strong breast cancer risk factor that typically confers a three—to fivefold elevation in risk for the highest versus lowest levels of density [1]
It is biologically implausible that the projected area of the breast should contain more information about risk than its volume, and the difficulty of trying to recover volume information from the thickness of a compressed breast likely limits the impact of MPD in breast cancer risk models
Elevated mammographic density may produce its strongest effect among young women who are below the mammographic screening age, but who might benefit from preventive interventions [7]
Summary
Mammographic percent density (MPD) is a strong breast cancer risk factor that typically confers a three—to fivefold elevation in risk for the highest versus lowest levels of density [1]. Evaluating density without exposing young women to ionizing radiation is critical because of concerns that mammography induces a small but significant number of cancers [8,9] No such approaches have been implemented in clinical practice. The potential gains in risk prediction that might be realized by using alternative measures of BD obtained through emerging non-ionizing technologies have not been fully explored The impetus for such technologies is to advance risk stratification, and thereby improve breast cancer risk assessment and monitoring and facilitate research into the etiology and prevention of the disease. The motivation for our current study was to explore whether UST-derived sound speed is associated with breast cancer risk
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