Mammographic density phenotypes and risk of breast cancer: a meta-analysis

Abstract

Background: Fibroglandular breast tissue appears dense on mammogram, whereas fat appears nondense. It is unclear whether absolute or percentage dense area more strongly predicts breast cancer risk and whether absolute nondense area is independently associated with risk.

Methods: We conducted a meta-analysis of 13 case-control studies providing results from logistic regressions for associations between one standard deviation (SD) increments in mammographic density phenotypes and breast cancer risk. We used random-effects models to calculate pooled odds ratios and 95% confidence intervals (CIs). All tests were two-sided with P less than .05 considered to be statistically significant.

Results: Among premenopausal women (n = 1776 case patients; n = 2834 control subjects), summary odds ratios were 1.37 (95% CI = 1.29 to 1.47) for absolute dense area, 0.78 (95% CI = 0.71 to 0.86) for absolute nondense area, and 1.52 (95% CI = 1.39 to 1.66) for percentage dense area when pooling estimates adjusted for age, body mass index, and parity. Corresponding odds ratios among postmenopausal women (n = 6643 case patients; n = 11187 control subjects) were 1.38 (95% CI = 1.31 to 1.44), 0.79 (95% CI = 0.73 to 0.85), and 1.53 (95% CI = 1.44 to 1.64). After additional adjustment for absolute dense area, associations between absolute nondense area and breast cancer became attenuated or null in several studies and summary odds ratios became 0.82 (95% CI = 0.71 to 0.94; P heterogeneity = .02) for premenopausal and 0.85 (95% CI = 0.75 to 0.96; P heterogeneity < .01) for postmenopausal women.

Conclusions: The results suggest that percentage dense area is a stronger breast cancer risk factor than absolute dense area. Absolute nondense area was inversely associated with breast cancer risk, but it is unclear whether the association is independent of absolute dense area.

© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Odds ratios (ORs) and 95% confidence intervals (CIs) for mammographic density phenotypes and risk of breast cancer among women who were premenopausal at the time of mammography. Random effects models. All statistical tests were two-sided. Additional analytical details are in Supplementary Table 2 (available online). AGE = UK AGE Trial nested case–control study; CAHRES = Cancer and Hormones Replacement in Sweden study; CBDS = Canadian Breast Density Study; CC = craniocaudal; EPIC–NL = Dutch contribution to the European Prospective Investigation into Cancer and Nutrition study; HRT = hormone replacement therapy; MCCS = Melbourne Collaborative Cohort Study; MCMAM = Mayo Clinic Mammography Study; MEC = Hawaii component of the Multiethnic Cohort Study; ML = mediolateral oblique; MMHS = Mayo Mammography Health Study; NHS1 = Nurses’ Health Study 1; NHS2 = Nurses’ Health Study 2; SBSP = Singapore Breast Cancer Screening Project; UK NHS = Norwich & Cambridge UK NHS Breast Cancer Screening Program; USC = University of Southern California mammographic density study.

Figure 2.

Odds ratios (ORs) and 95% confidence intervals (CIs) for mammographic density phenotypes and risk of breast cancer among women who were postmenopausal at the time of mammography. Random effects models. All statistical tests were two-sided. Additional analytical details are in Supplementary Table 4 (available online). AGE = UK AGE Trial nested case–control study; CAHRES = Cancer and Hormones Replacement in Sweden study; CBDS = Canadian Breast Density Study; CC = craniocaudal; EPIC–NL = Dutch contribution to the European Prospective Investigation into Cancer and Nutrition study; HRT = hormone replacement therapy; MCCS = Melbourne Collaborative Cohort Study; MCMAM = Mayo Clinic Mammography Study; MEC = Hawaii component of the Multiethnic Cohort Study; ML = mediolateral oblique; MMHS = Mayo Mammography Health Study; NHS1 = Nurses’ Health Study 1; NHS2 = Nurses’ Health Study 2; SBSP = Singapore Breast Cancer Screening Project; UK NHS = Norwich & Cambridge UK NHS Breast Cancer Screening Program; USC = University of Southern California mammographic density study.