Abstract
IntroductionIt is not clear whether high mammographic density (MD) is equally associated with all subtypes of breast cancer (BC). We investigated the association between MD and subsequent BC, considering invasiveness, means of detection, pathologic subtype, and the time elapsed since mammographic exploration and BC diagnosis.MethodsBC cases occurring in the population of women who attended screening from 1997 through 2004 in Navarre, a Spanish region with a fully consolidated screening program, were identified via record linkage with the Navarre Cancer Registry (n = 1,172). Information was extracted from the records of their first attendance at screening in that period. For each case, we randomly selected four controls, matched by screening round, year of birth, and place of residence. Cases were classified according to invasiveness (ductal carcinoma in situ (DCIS) versus invasive tumors), pathologic subtype (considering hormonal receptors and HER2), and type of diagnosis (screen-detected versus interval cases). MD was evaluated by a single, experienced radiologist by using a semiquantitative scale. Data on BC risk factors were obtained by the screening program in the corresponding round. The association between MD and tumor subtype was assessed by using conditional logistic regression.ResultsMD was clearly associated with subsequent BC. The odds ratio (OR) for the highest MD category (MD >75%) compared with the reference category (MD <10%) was similar for DCIS (OR = 3.47; 95% CI = 1.46 to 8.27) and invasive tumors (OR = 2.95; 95% CI = 2.01 to 4.35). The excess risk was particularly high for interval cases (OR = 7.72; 95% CI = 4.02 to 14.81) in comparison with screened detected tumors (OR = 2.17; 95% CI = 1.40 to 3.36). Sensitivity analyses excluding interval cases diagnosed in the first year after MD assessment or immediately after an early recall to screening yielded similar results. No differences were seen regarding pathologic subtypes. The excess risk associated with MD persisted for at least 7 to 8 years after mammographic exploration.ConclusionsOur results confirm that MD is an important risk factor for all types of breast cancer. High breast density strongly increases the risk of developing an interval tumor, and this excess risk is not completely explained by a possible masking effect.
Highlights
It is not clear whether high mammographic density (MD) is associated with all subtypes of breast cancer (BC)
MD was associated with screen-detected tumors, but the excess risk was substantially higher for interval cases
This study found a modest association between alcohol intake and MD only in postmenopausal women [31], far too small to explain the strong association between MD and BC reported here
Summary
It is not clear whether high mammographic density (MD) is associated with all subtypes of breast cancer (BC). In Spain, a European country with moderate incidence of breast cancer (BC), all the Autonomous Regions introduced population-based BC screening programs during the 1990s, with full coverage being attained by the beginning of this century [1]. Screening has had a clear influence on Spanish BC trends [2]. All Spanish women aged 50 to 69 or 45 to 69 years, depending on the region, are invited to have a mammogram every other year, amounting to a total catchment population of more than 5 million. Mammographic density (MD), or the percentage of the mammogram occupied by radiologically dense tissue, is a well-established BC risk factor [3]. Even though the biologic basis of the association between MD and BC is not fully understood, breast density is increasingly used as a phenotype risk marker [5]
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