Abstract

IntroductionThe mechanisms underlying the strong association between percentage dense area on a mammogram and the risk of breast cancer are unknown. We investigated separately the absolute dense area and the absolute nondense area on mammograms in relation to breast cancer risk.MethodsWe conducted a nested case-control study on prediagnostic mammographic density measurements and risk of breast cancer in the Nurses' Health Study and the Nurses' Health Study II. Premenopausal mammograms were available from 464 cases and 998 controls, and postmenopausal mammograms were available from 960 cases and 1,662 controls. We used a computer-assisted thresholding technique to measure mammographic density, and we used unconditional logistic regression to calculate OR and 95% CI data.ResultsHigher absolute dense area was associated with a greater risk of breast cancer among premenopausal women (ORtertile 3 vs 1 = 2.01, 95% CI = 1.45 to 2.77) and among postmenopausal women (ORquintile 5 vs 1 = 2.19, 95% CI = 1.65 to 2.89). However, increasing absolute nondense area was associated with a decreased risk of breast cancer among premenopausal women (ORtertile 3 vs 1 = 0.51, 95% CI = 0.36 to 0.72) and among postmenopausal women (ORquintile 5 vs 1 = 0.46, 95% CI = 0.34 to 0.62). These associations changed minimally when we included both absolute dense area and absolute nondense area in the same statistical model. As expected, the percentage dense area was the strongest risk factor for breast cancer in both groups.ConclusionsOur results indicate that absolute dense area is independently and positively associated with breast cancer risk, whereas absolute nondense area is independently and inversely associated with breast cancer risk. Since adipose tissue is radiographically nondense, these results suggest that adipose breast tissue may have a protective role in breast carcinogenesis.

Highlights

  • The mechanisms underlying the strong association between percentage dense area on a mammogram and the risk of breast cancer are unknown

  • Increasing absolute nondense area was associated with a decreased risk of breast cancer among premenopausal women (ORtertile 3 vs 1 = 0.51, 95% confidence interval (CI) = 0.36 to 0.72) and postmenopausal women (ORquintile 5 vs 1 = 0.46; 95% CI = 0.34 to 0.62)

  • We found that higher absolute dense area on a mammogram was associated with an increased risk of breast cancer, whereas higher absolute nondense area was associated with a decreased risk

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Summary

Introduction

The mechanisms underlying the strong association between percentage dense area on a mammogram and the risk of breast cancer are unknown. We investigated separately the absolute dense area and the absolute nondense area on mammograms in relation to breast cancer risk. Mammographic density is one of the strongest predictors of breast cancer risk. The biological mechanisms underlying the association between mammographic density and breast cancer risk are unclear. The association between absolute dense area and breast cancer risk supports this view, since the dense area on a mammogram is a measure of mammary tissue. Percentage dense area, appears to be a better predictor of breast cancer risk. A possible explanation of this paradox is that the nondense area on a mammogram, which is part of the denominator in percentage dense area, is inversely related to breast cancer risk

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