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. 2021 May;187(1):215-224.
doi: 10.1007/s10549-020-06049-8. Epub 2021 Jan 4.

Association of mammographic density measures and breast cancer "intrinsic" molecular subtypes

Geffen Kleinstern  1   2 , Christopher G Scott  2 , Rulla M Tamimi  3   4 , Matthew R Jensen  2 , V Shane Pankratz  5 , Kimberly A Bertrand  6 , Aaron D Norman  2 , Daniel W Visscher  7 , Fergus J Couch  8 , Kathleen Brandt  9 , John Shepherd  10 , Fang-Fang Wu  11 , Yunn-Yi Chen  12 , Steven R Cummings  13 , Stacey Winham  2 , Karla Kerlikowske  14 , Celine M Vachon  15
Affiliations

Association of mammographic density measures and breast cancer "intrinsic" molecular subtypes

Geffen Kleinstern et al. Breast Cancer Res Treat. 2021 May.

Abstract

Purpose: We evaluated the association of percent mammographic density (PMD), absolute dense area (DA), and non-dense area (NDA) with risk of "intrinsic" molecular breast cancer (BC) subtypes.

Methods: We pooled 3492 invasive BC and 10,148 controls across six studies with density measures from prediagnostic, digitized film-screen mammograms. We classified BC tumors into subtypes [63% Luminal A, 21% Luminal B, 5% HER2 expressing, and 11% as triple negative (TN)] using information on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. We used polytomous logistic regression to calculate odds ratio (OR) and 95% confidence intervals (CI) for density measures (per SD) across the subtypes compared to controls, adjusting for age, body mass index and study, and examined differences by age group.

Results: All density measures were similarly associated with BC risk across subtypes. Significant interaction of PMD by age (P = 0.001) was observed for Luminal A tumors, with stronger effect sizes seen for younger women < 45 years (OR = 1.69 per SD PMD) relative to women of older ages (OR = 1.53, ages 65-74, OR = 1.44 ages 75 +). Similar but opposite trends were seen for NDA by age for risk of Luminal A: risk for women: < 45 years (OR = 0.71 per SD NDA) was lower than older women (OR = 0.83 and OR = 0.84 for ages 65-74 and 75 + , respectively) (P < 0.001). Although not significant, similar patterns of associations were seen by age for TN cancers.

Conclusions: Mammographic density measures were associated with risk of all "intrinsic" molecular subtypes. However, findings of significant interactions between age and density measures may have implications for subtype-specific risk models.

Keywords: Breast cancer; Mammographic density; “Intrinsic” molecular subtypes.

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Conflict of interest statement

Conflict of Interest

All authors have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Associations of continuous PMD (a), DA (b), and NDA (c) for risk of ‘intrinsic’ molecular subtypes (HER2 expressing, Luminal A, Luminal B, and TN) by age group
Fig. 1
Fig. 1
Associations of continuous PMD (a), DA (b), and NDA (c) for risk of ‘intrinsic’ molecular subtypes (HER2 expressing, Luminal A, Luminal B, and TN) by age group
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References

    1. McCormack VA, dos Santos Silva I. Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2006. 15(6):1159–1169. - PubMed
    1. Eriksson L, Czene K, Rosenberg L, Humphreys K, Hall P. The influence of mammographic density on breast tumor characteristics. Breast Cancer Res Treat. 2012. 134(2):859–866. - PubMed
    1. Yaghjyan L, Colditz GA, Collins LC, Schnitt SJ, Rosner B, Vachon C, Tamimi RM. Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to tumor characteristics. J Natl Cancer Inst. 2011. 103(15):1179–1189. - PMC - PubMed
    1. Chen JH, Hsu FT, Shih HN, Hsu CC, Chang D, Nie K, Nalcioglu O, Su MY. Does breast density show difference in patients with estrogen receptor-positive and estrogen receptor-negative breast cancer measured on MRI? Ann Oncol. 2009. 20(8):1447–1449. - PMC - PubMed
    1. Eriksson L, Hall P, Czene K, dos Santos Silva I, McCormack V, Bergh J, Bjohle J, Ploner A. Mammographic density and molecular subtypes of breast cancer. Br J Cancer. 2012. 107(1):18–23. - PMC - PubMed