Changes in mammographic density over time in breast cancer cases and women at high risk for breast cancer

Abstract

High mammographic breast density is one of the strongest intermediate markers of breast cancer risk, and decreases in density over time have been associated with decreases in breast cancer risk. Using repeated measures of mammographic density in a cohort of high-risk women, the Women at Risk (WAR) cohort at Columbia University Medical Center (N=2670), we examined whether changes in pre-diagnostic mammographic density differed among 85 prospectively-ascertained breast cancer cases and 85 age-matched controls, using a nested case-control design. Median age at first mammogram was 51 years (range, 29-77 years), with a median of 4 years between first and second pre-diagnostic mammogram (range, 1-14 years). Using linear regression with change in percent density as the outcome, we found that in women who did not go on to be diagnosed with breast cancer, change in percent density decreased as time between first and second mammogram increased (β= -1.62% per year, p=0.004). However, in women who did go on to be diagnosed with breast cancer, there was no overall change in percent density associated with time between first and second mammogram (β= 0.29% per year, p=0.61); the change over time was statistically significantly different between cases versus controls (p <0.009). If replicated in larger cohorts, these results suggest that within-individual changes in mammographic density as measured by percent density may be a useful biomarker of breast cancer risk.

Bayesian joint ordinal and survival modeling for breast cancer risk assessment

“…A linear subject-specific trajectory of the latent variable is included in a relative risks survival model together with two of the most known breast cancer risk factors, family history of breast cancer and previous breast procedures. Our joint model for breast cancer and breast density is a good starting point that provides results consistent with the literature [16,18,19,21]. They are the basis for a rationale for extending the model and assessing its adequacy and accuracy.…”

“…Several studies have shown that high breast density is associated with increased breast cancer risk [7,[11][12][13][14], with risk estimates in the range four-fold to six-fold for women with very high breast density compared with women with low breast density [11,12]. Other studies have examined whether changes in breast density over time are associated to changes in breast cancer risk [15][16][17][18][19][20][21] and have suggested that monitoring changes in breast density could help to identify women at greater risk of disease. In most of the cases, the statistical methods used did not account for relevant characteristics of prospective studies like non-ignorable dropout mechanisms or internal time-dependent covariates [22].…”

One versus Two Breast Density Measures to Predict 5- and 10-Year Breast Cancer Risk

“…There is mounting evidence that women with sustained levels of high breast density are at highest risk of breast cancer, those with low levels of breast density over time are at lowest risk and those that change density over time can increase or decrease their risk (9, 31). The IBIS-I has reported for women on tamoxifen that had a reduction in breast density of 10% or more, the risk of breast cancer was significantly reduced 52% relative to controls (10).…”

Relationship Between Breast Density and Selective Estrogen-Receptor Modulators, Aromatase Inhibitors, Physical Activity, and Diet

“…Thus, it may be important to assess the effect of antidiabetes agents and changes in glucose homeostasis on BD. Finally and encouragingly, change in BD over time is consistent with change in BC risk, 107,108 and reduced BD is associated with a reduced risk of BC 108,109 and death from the disease. 110 Therefore, BD may have potential utility as a biomarker for the efficacy of chemopreventive interventions.…”