Mammographic Density Change and Risk of Breast Cancer

Shadi Azam; Mikael Eriksson; Arvid Sjölander; Roxanna Hellgren; Marike Gabrielson; Kamila Czene; Per Hall


J Natl Cancer Inst. 2020;112(4):391-399. 

In This Article


Baseline Characteristics

Baseline characteristics are given in Table 1 for all 43 810 women separated by BC status. The mean (SD) number of years between first and last mammogram was 5.4 (0.6) years. The time interval between mammography rounds in this cohort was 18–24 months. The majority of women (77.6%) had completed three or more rounds of mammography, and the maximum number of the mammography rounds was five in this cohort.

A total of 563 women were diagnosed with BC during follow-up. Women with BC were older, more likely to be smokers and alcohol drinkers, and less likely to have a child before the age of 25 years compared with women without BC (Table 1). However, the proportions of nulliparous women were more or less the same in women with and without BC (13.3% and 14.1%, respectively). Both groups of women tended to breastfeed longer than a year. Finally, women with BC were more likely to have a first-degree relative diagnosed with BC (22.2%) compared with women without BC (13.3%) (Table 1).

Covariates and Risk of Breast Cancer

Premenopausal women with high BMI (≥30 kg/m2) had statistically significantly lower risk of BC (HR = 0.47, 95% CI = 0.24 to 0.92) compared with premenopausal women with low BMI (<20 kg/m2) (Table 2). No association between BMI and BC was seen for postmenopausal women, but the P value was statistically significant when considering BMI as a continuous variable (P= .002). A statistically significant greater risk of BC was seen in older women, women having their first child later in life, postmenopausal women using MHT, and women with a first-degree relative with BC (Table 2).

Relative MD Change and Risk of BC

The risk of BC was more or less the same among women with stable MD (HR =1.01, 95% CI = 0.82 to 1.23, P = .90) and women with more than a 10% annual increase in MD (HR = 0.98, 95% CI = 0.80 to 1.22, P = .90) compared with women with an annual decrease greater than 10% in MD (Table 3). The same results were seen among postmenopausal women. Among premenopausal women, there was a weak but statistically nonsignificant association between annual increase in MD greater than 10% and risk of BC (HR = 1.12, 95% CI = 0.77 to 1.64, P = .53) compared with premenopausal women with an annual decrease in MD greater than 10% (Table 3). Similar results were found using percent MD (Supplementary Table 1, available online).

Only for women aged 40–49 years did we see a tendency of a difference in risk related to MDC. Women with an increase in annual MD greater than 10% had a statistically nonsignificant 30% higher risk compared to perimenopausal women with greater than 10% annual MD reduction (Supplementary Table 2, available online).

Table 4 shows the joint effect of baseline MD and relative area MDC on BC risk separated by menopausal status. Women in the lowest category of baseline MD with a decrease in density over time were used as the reference. There was a two to three times higher risk of BC when contrasting the lowest and highest baseline MD among all women, regardless of MDC (Table 4). Among premenopausal women, there was a fourfold higher risk when comparing women at high and low baseline MD, and no difference in risk was seen when comparing the lowest and highest baseline MD in women who did and did not experience a density decrease. Among postmenopausal regardless of MDC, women with high baseline MD (>20 cm2) had two times higher risk of BC than postmenopausal women with low baseline MD (<9 cm2). Similar results were seen when using percent density (Supplementary Table 3, available online).

The correlation between baseline MD area and BMI was ρ = −0.30 and the correlation between baseline percent MD and BMI was ρ = −0.50. Both MD area and percent MD were negatively correlated with BMI, but the correlation was stronger for percent MD than MD area. Therefore, we chose to use MD area in the main analyses because it is less influenced by BMI.