Evidence that breast tissue stiffness is associated with risk of breast cancer

Abstract

Background: Evidence from animal models shows that tissue stiffness increases the invasion and progression of cancers, including mammary cancer. We here use measurements of the volume and the projected area of the compressed breast during mammography to derive estimates of breast tissue stiffness and examine the relationship of stiffness to risk of breast cancer.

Methods: Mammograms were used to measure the volume and projected areas of total and radiologically dense breast tissue in the unaffected breasts of 362 women with newly diagnosed breast cancer (cases) and 656 women of the same age who did not have breast cancer (controls). Measures of breast tissue volume and the projected area of the compressed breast during mammography were used to calculate the deformation of the breast during compression and, with the recorded compression force, to estimate the stiffness of breast tissue. Stiffness was compared in cases and controls, and associations with breast cancer risk examined after adjustment for other risk factors.

Results: After adjustment for percent mammographic density by area measurements, and other risk factors, our estimate of breast tissue stiffness was significantly associated with breast cancer (odds ratio = 1.21, 95% confidence interval = 1.03, 1.43, p = 0.02) and improved breast cancer risk prediction in models with percent mammographic density, by both area and volume measurements.

Conclusion: An estimate of breast tissue stiffness was associated with breast cancer risk and improved risk prediction based on mammographic measures and other risk factors. Stiffness may provide an additional mechanism by which breast tissue composition is associated with risk of breast cancer and merits examination using more direct methods of measurement.

Figure 1. Estimation of breast stiffness.

A. Estimation of radius (R1) from measure of breast volume B. Estimation of radius (R2) from measure of compressed breast area C. Calculation of breast stiffness from R1, R2 and compression force.

Figure 2. Histograms of the distributions of the stiffness measures in cases and controls.

The stiffness measures were natural logarithm transformed. In each plot, the thin vertical line represents the mean of the distribution.

Figure 3. Least square means of stiffness in cases and controls, adjusted for risk factors.

Risk factors include: age at mammogram (linear and quadratic terms), age at birth of first child, weight (kg), height (cm), menopausal status (pre/post) and parity (parous/nonparous). Stiffness (N/cm) was natural logarithm transformed in the analysis. The least square means shown are back transformed to the original scale. Bars show 95% confidence interval. P is the p-value for the significance of case control difference. When adjusted for percent dense area, square root transformation was used and model includes linear and quadratic terms. When adjusted for percent dense volume, cubic root transformation was used and model includes linear and quadratic terms.