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Table 3 Summary of studies of the association of mammographic density and tumor characteristics

From: Mammographic density and breast cancer risk: current understanding and future prospects

     Association with  
Authors, region (year) Design Sample size Measurement of MD ER status/phenotypea Sizea, b Nodal statusa, b Adjustmentsc
Yaghjyan et al. [70], USA (2011) Nested case control 1,042 cases 1,794 controls Computer-assisted Case control: Increased risk of ER+ and ER- tumors (greater for ER-) Increased risk of PR+ and PR- and HER2- and HER2+ tumors Increased risk for tumors >2 cm but not for tumors <2 cm Increased risk with node+ and node- disease Age, BMI, age at menarche, age at first birth, parity, age at menopause, HRT use, family history, history of benign breast disease, alcohol intake, and smoking
Conroy et al. [71], USA (2011) Nested case control 607 cases 667 controls Computer- assisted Case control: Increased risk of ER+ tumors only Case only: ER+ > PMD than ER- cases n/a n/a Age, ethnicity, BMI, parity, age at first birth, age at menarche, menopausal status, HRT use, and family history
Ding et al. [72], Europe (2010) Nested case control 370 cases 1,904 controls Computer- assisted Case control: Increased risk of ER+ tumors only Increased risk for tumors of all sizes Increased risk with node+ and node- disease Age
     Case only: ER+ > PMD than ER- cases No association No association  
Olsen et al. [73], Europe (2009) Cohort 694 cases 48,052 total Mixed/dense versus fatty Increased risk of ER+ and ER- tumors (greater for ER+) n/a n/a Age
Ziv et al. [74], USA (2004) Cohort 701 cases 44,811 total BI-RADS Increased risk of ER+ and ER- tumors n/a n/a Age, HRT use, BMI, parity, family history, menopause, and race
Ma et al. [75], USA (2009) Case control 479 cases 376 controls Computer-assisted Case control: Increased risk of ER+/PR+, ER-/PR-, HER2-, luminal A, and triple-negative tumorsd Case analysis: Molecular subtyped: no association n/a n/a Age, family history, BMI, age at menarche, parity, age at first birth, menopause, and HRT use
Gierach et al. [76], Europe (2010 abstract) Case only 227 cases Computer- assisted No significant difference in PMD between luminal A, luminal B, HER2+, basal-like, or unclassified tumorsd n/a n/a Not available (abstract only)
Arora et al. [77], USA (2010) Case only 1,323 cases BI-RADS Molecular subtype: no association No association No association Age
Yang et al. [78], USA (2008) Case only 198 cases BI-RADS Molecular subtyped: no association n/a n/a None
Cil et al. [79], Canada (2009) Case only 335 cases Wolfe score No association No association No association None
Nickson and Kavanagh [86], Australia (2009) Case only 1,348 cases Semi- automated n/a No association n/a Age, HRT use, and family history
Ghosh et al. [80], USA (2008) Case only 286 cases Computer- assisted No association No association n/a Age, parity, BMI, family history, and HRT use
Porter et al. [87], Europe (2007) Case only 759 cases BI-RADS n/a Positive (screen- detected) No association None
Fasching et al. [81], Europe (2006) Case only 434 cases BI-RADS No association Negative No association None
Aiello et al. [82], USA (2005) Case only 546 cases BI-RADS No association Positive Positive Age, BMI, menopause, and age at first birth
Morishita et al. [83], Japan (2005) Case only 163 cases BI-RADS No association No association n/a None
Roubidoux et al. [84], USA (2004) Case only 121 cases BI-RADS No association Positive No association Age
Sala et al. [88], Europe (2000) Nested case control 875 cases Wolfe n/a Positive Positive None
Hinton et al. [85], Europe (1985) Case only 337 cases Wolfe DY pattern associated with greater frequency of ER+ versus ER- tumors n/a n/a None
Boyd et al. [89], Canada (1982) Case only 183 cases Wolfe n/a No association No association None
  1. aNo association: association is not statistically significant. bPositive: higher percent mammographic density (PMD) associated with higher tumor size or higher frequency of positive nodal status (node+); negative (inverse) association: higher PMD associated with smaller tumor size or lower frequency of positive nodal status (node+). cFactors included in the analysis of risk associated with mammographic density or of the association of mammographic density with tumor characteristics. dMolecular subtypes determined by immunohistochemistry. BI-RADS, Breast Imaging-Reporting and Data System; BMI, body mass index; DY, dysplastic; ER, estrogen receptor; HRT, hormone replacement therapy; MD, mammographic density; n/a: not assessed; PR, progesterone receptor.