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Is mammographic density differentially associated with breast cancer according to receptor status? A meta-analysis

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Abstract

Mammographic density (MD) is a strong marker of breast cancer risk, but it is debated whether the association holds, and is of a similar magnitude, for different subtypes of breast cancer defined by receptor status or gene expression profiles. A literature search conducted in June 2012 was used to identify all studies that had investigated the association of MD with subtype-specific breast cancer, independent of age. 7 cohort/case–control and 12 case-only studies were included, comprising a total of >24,000 breast cancer cases. Random effects meta-analysis models were used to combine relative risks (RR) of MD with subtype-specific breast cancer for case–control studies, and in case-only studies to combine relative risk ratios (RRR) of receptor positive versus negative breast tumors. In case–control/cohort studies, relative to women in the lowest density category, women in the highest density category had 3.1-fold (95 % confidence interval [CI] 2.2, 4.2) and 3.2-fold (1.7, 5.9) increased risk of estrogen receptor positive (ER+) and ER− breast cancer, respectively. In case-only analyses, RRRs of breast tumors being ER+ versus ER− were 1.13 (95 % CI 0.89, 1.42) for medium versus minimal MD. MD remained associated with screen-detected ER+ tumors, despite the expectation of this association to be attenuated due to masking bias and overdiagnoses of ER+ tumors. In eight contributing studies, the association of MD did not differ by HER2 status. This combined evidence strengthens the importance of MD as a strong marker of overall and of subtype-specific risk, and confirms its value in overall breast cancer risk assessment and monitoring for both research and clinical purposes.

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Abbreviations

ER:

Estrogen receptor status

PR:

Progesterone receptor status

HER2:

Human epidermal growth factor 2

TRN:

Triple negative (ER−PR−HER2−)

BMI:

Body mass index (kg/m2)

MD:

Mammographic density

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Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. International Agency for Research on Cancer, 150 cours Albert Thomas, 69008, Lyon, France

    Sebastien Antoni & Valerie McCormack

  2. Centre INSERM U897-Epidemiologie-Biostatistique, INSERM, ISPED, 33000, Bordeaux, France

    Annie J. Sasco

  3. Centre INSERM U897-Epidemiologie-Biostatistique, ISPED, Université de Bordeaux, 33000, Bordeaux, France

    Annie J. Sasco

  4. Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK

    Isabel dos Santos Silva

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  1. Sebastien Antoni
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  2. Annie J. Sasco
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  3. Isabel dos Santos Silva
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  4. Valerie McCormack
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Corresponding author

Correspondence to Valerie McCormack.

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Antoni, S., Sasco, A.J., dos Santos Silva, I. et al. Is mammographic density differentially associated with breast cancer according to receptor status? A meta-analysis. Breast Cancer Res Treat 137, 337–347 (2013). https://doi.org/10.1007/s10549-012-2362-4

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  • DOI: https://doi.org/10.1007/s10549-012-2362-4

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