Breast density and outcome of mammography screening: a cohort study

Abstract

The purpose of this study was to investigate the effect of breast density on breast cancer (BC) mortality in a mammography screening programme. The cohort included 48 052 women participating in mammography screening in Copenhagen, Denmark, where biennial screening is offered to women aged 50 -69 years. We collected information for the years 1991 -2001 on screening outcome, incident BCs (screen-, interval-, and later detected), and BC deaths. Breast density was dichotomised into fatty (F) and mixed/dense (M/D) breasts. Screening sensitivity was measured as the odds ratio of interval versus screen-detected cancer for dense versus F breasts. Poisson regression was used to estimate the ratios for BC incidence, case fatality, and mortality between women with M/D and F breasts. For women with M/D breasts, the odds ratio of an interval cancer was 1.62 (95% confidence interval, CI, 1.14 -2.30), and the age-adjusted rate ratios were 2.45 (95% CI 2.14 -2.81) for BC incidence, 0.60 (95% CI 0.43 -0.84) for case fatality, and 1.78 (95% CI 1.17 -2.72) for BC mortality. The study shows that BC in women with M/D breasts is more frequent, but on average less severe, than in women with F breasts. British Journal of Cancer (2009) Breast density is a measure of the composition of the breast tissue. Breasts with low density have a high proportion of fatty (F) tissue, whereas breasts with high density have a high proportion of epithelial and connective tissue. Mammography has a lower sensitivity in women with mixed/dense (M/D) breasts than in women with F breasts (Mandelson et al, 2000, Ciatto et al, 2004Chiarelli et al, 2006), and women with M/D breasts have a higher incidence of breast cancer (BC) than women with F breasts (McCormack and dos Santos Silva, 2006;Boyd et al, 2007). We therefore examined whether breast density affects the outcome of mammography screening using data from the organised mammography screening programme in Copenhagen, Denmark, earlier shown to reduce BC mortality in targeted women by 25% and in participating women by 37% (Olsen et al, 2005).We tested the following hypotheses: compared with women with F breasts, (1) the sensitivity of mammography is lower in women with M/D breasts, and (2) women with M/D breasts have a higher BC incidence. Our results were well in accordance with those of earlier studies. We further tested whether: (3) because of the lower sensitivity the case fatality rate of BC patients with M/D breasts will be higher than that of patients with F breasts, and (4) screened women with M/D breasts will experience a higher BC mortality than screened women with F breasts. This study is the first to report on the effect of breast density on BC mortality in screened women.

Effect of Baseline Breast Density on Breast Cancer Incidence, Stage, Mortality, and Screening Parameters: 25-Year Follow-up of a Swedish Mammographic Screening

“…Multiplying the relative risk for incidence, 1.40, by the relative hazard from the Cox regression, also 1.41, gives 1.97, which was close to the observed mortality relative risk of 1.91. This result was slightly higher but consistent with the mortality result based on the data from a Demark mammographic screening with 10 years of follow-up (6). The association of dense breast tissue with aggressive tumors was similar to the study of Aiello et al (27).…”

“…Note that the relative risk for developing breast cancer in our study was lower than that in other antecedent studies (5,6,15,30). Two unique characteristics account for this inconsistency.…”

“…Our prospective cohort design was made to classify breast density (exposure) at the entry of study rather than the date closer to diagnosis (age of incident cases) adopted in most of the previous studies. The other characteristic is that our cohort had 25 years of long-term follow-up, which was longer than in other studies (6,30). The merit of such a study design with long-term follow-up can predict the risk of dense breast even if a woman's breast changes.…”

“…The positive association between breast density and breast cancer risk has been reported by a meta-analysis study (1) and several well-designed longitudinal studies in recent years (2)(3)(4)(5)(6). The underlying biological role is upheld by its associated factors including younger age (7), premenopausal status, exogenous hormone use (8,9), conventional risk factors (10), and genetic influence (11,12), possibly through mutagenesis and mitogenesis mechanisms (13,14).…”

Automated Measurement of Volumetric Mammographic Density: A Tool for Widespread Breast Cancer Risk Assessment

“…After age, mammographic density is the strongest breast cancer risk factor with the highest population attributable fraction (5,6). The impact of mammographic density is 2-fold, as women with dense breasts are not only at increased risk of developing breast cancer (7) but also have a greater chance of a tumor going undetected because of the masking effect of mammographic density (8,9). As such, mammographic density is a promising tool for optimizing screening programs where resources and extra imaging modalities can be targeted to those with the highest density (10).…”