Mammographic Density and Screening Sensitivity, Breast Cancer Incidence and Associated Risk Factors in Danish Breast Cancer Screening

Abstract

Background: Attention in the 2000s on the importance of mammographic density led us to study screening sensitivity, breast cancer incidence, and associations with risk factors by mammographic density in Danish breast cancer screening programs. Here, we summarise our approaches and findings.

Methods: Dichotomized density codes: fatty, equal to BI-RADS density code 1 and part of 2, and other mixed/dense data from the 1990s-were available from two counties, and BI-RADS density codes from one region were available from 2012/13. Density data were linked with data on vital status, incident breast cancer, and potential risk factors. We calculated screening sensitivity by combining data on screen-detected and interval cancers. We used cohorts to study high density as a predictor of breast cancer risk; cross-sectional data to study the association between life style factors and density, adjusting for age and body mass index (BMI); and time trends to study the prevalence of high density across birth cohorts.

Results: Sensitivity decreased with increasing density from 78% in women with BI-RADS 1 to 47% in those with BI-RADS 4. For women with mixed/dense compared with those with fatty breasts, the rate ratio of incident breast cancer was 2.45 (95% CI 2.14-2.81). The percentage of women with mixed/dense breasts decreased with age, but at a higher rate the later the women were born. Among users of postmenopausal hormone therapy, the percentage of women with mixed/dense breasts was higher than in non-users, but the patterns across birth cohorts were similar. The occurrence of mixed/dense breast at screening age decreased by a z-score unit of BMI at age 13-odds ratio (OR) 0.56 (95% CI 0.53-0.58)-and so did breast cancer risk and hazard ratio (HR) 0.92 (95% CI 0.84-1.00), but it changed to HR 1.01 (95% CI 0.93-1.11) when controlled for density. Age and BMI adjusted associations between life style factors and density were largely close to unity; physical activity OR 1.06 (95% CI 0.93-1.21); alcohol consumption OR 1.01 (95% CI 0.81-1.27); air pollution OR 0.96 (95% 0.93-1.01) per 20 μg/m³; and traffic noise OR 0.94 (95% CI 0.86-1.03) per 10 dB. Weak negative associations were seen for diabetes OR 0.61 (95% CI 0.40-0.92) and cigarette smoking OR 0.86 (95% CI 0.75-0.99), and a positive association was found with hormone therapy OR 1.24 (95% 1.14-1.35).

Conclusion: Our data indicate that breast tissue in middle-aged women is highly dependent on childhood body constitution while adult life-style plays a modest role, underlying the need for a long-term perspective in primary prevention of breast cancer.

Keywords: body constitution; breast cancer incidence; mammographic density; risk factor; sensitivity.

Figure 1

Danish studies on the association between childhood body constitution, mammographic density in mid-life age and risk of breast cancer. Boxes: studies; ovals: data sources.