Purpose: Mammographic density is an important breast cancer risk factor, although it is not clear whether the association differs across breast cancer tumor subtypes. We examined the association between indicators of mammographic density and breast cancer risk by tumor subtype among postmenopausal women by investigating heterogeneity across tumor characteristics.
Methods: Mammographic density measures were determined for 477 breast cancer cases and 588 controls, all postmenopausal, in Vancouver, British Columbia, using digitized screening mammograms and Cumulus software. Mammographic dense (DA), non-dense (NDA), and percent dense (PDA) areas were treated as continuous covariates and categorized into quartiles according to the distribution in controls. For cases only, tests for heterogeneity between tumor subtypes were assessed by multinomial logistic regression. Associations between mammographic density and breast cancer risk were modeled for each subtype separately through unconditional logistic regression.
Results: Heterogeneity was apparent for the association of PDA with tumor size (p-heterogeneity=0.04). Risk did not differ across the other assessed tumor characteristics (p-heterogeneity values >0.05).
Conclusion: These findings do not provide strong evidence that mammographic density parameters differentially affect specific breast cancer tumor characteristics.

Keywords: mammographic density, breast cancer, tumor characteristics, heterogeneity, multinomial logistic regression


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Mammographic density is an important breast cancer risk factor.1–3 The association between breast cancer and many well-established risk factors has been shown to be different according to the characteristics of the tumor.4–11 However, for mammographic density, this has not been established. Some studies report no heterogeneity in the association between mammographic density and breast cancer tumor characteristics;12–22 while others indicate differences by hormone receptor status,3,23–28 invasiveness,22,29 phenotype,30,31 tumor size,22,26,28,32,33 and stage.34 Most studies have limited the assessment of mammographic density qualitatively as defined by the BI-RADS classification, or quantitatively as percent dense area (PDA); the other mammographic density parameters, dense area (DA) and non-dense area (NDA) have seldom been taken into account.

It is important to elucidate whether mammographic density parameters are associated differentially across different breast cancer tumor characteristics. Such knowledge could help us understand pathological pathways, as well as identify susceptible groups of women in the general population, providing evidence that would improve the formulation of screening protocols and risk-reducing interventions.35

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