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. 2025 Oct 24;27(1):187.
doi: 10.1186/s13058-025-02142-2.

Mammographic density and breast cancer pathological subtypes by menopausal status and body mass index

Julia Fernández-Morata  1 , Marina Pollán  2   3 , Nerea Fernández de Larrea-Baz  2   3 , Vanessa Pachón-Olmos  4 , Javier García-Pérez  2   3 , Adela Castelló  2   3 , María Ángeles Sierra  2   3 , Pilar Lucas  2 , Rafael Llobet  5 , Agostina Stradella  6 , Blanca Cantos  7 , Teresa Ramón Y Cajal  8 , Marta Santisteban  9   10 , Miguel Ángel Seguí  11 , Ana Santaballa Bertrán  12 , Mónica Granja  13 , Julia Camps-Herrero  14 , Sabela Recalde  15 , Beatriz Nuñez-García  7 , Nuria Calvo Verges  8 , Beatriz Pérez-Gómez  2   3 , Roberto Pastor-Barriuso  2   3 , Virginia Lope  16   17
Affiliations

Mammographic density and breast cancer pathological subtypes by menopausal status and body mass index

Julia Fernández-Morata et al. Breast Cancer Res. .

Erratum in

  • Correction: Mammographic density and breast cancer pathological subtypes by menopausal status and body mass index.
    Fernández-Morata J, Pollán M, Fernández de Larrea-Baz N, Pachón-Olmos V, García-Pérez J, Castelló A, Sierra MÁ, Lucas P, Llobet R, Stradella A, Cantos B, Ramón Y Cajal T, Santisteban M, Seguí MÁ, Santaballa Bertrán A, Granja M, Camps-Herrero J, Recalde S, Nuñez-García B, Calvo Verges N, Pérez-Gómez B, Pastor-Barriuso R, Lope V. Fernández-Morata J, et al. Breast Cancer Res. 2025 Nov 12;27(1):201. doi: 10.1186/s13058-025-02169-5. Breast Cancer Res. 2025. PMID: 41225573 Free PMC article. No abstract available.

Abstract

Background: Mammographic density (MD) is an established biomarker of breast cancer (BC) risk. However, its relationship to BC pathological subtypes remains unclear. This study aimed to investigate this association and assess whether it differs by body mass index (BMI) and menopausal status.

Methods: MD percentage was assessed in the diagnostic mammograms of the contralateral breast of 714 BC patients recruited from eight Spanish hospitals. Participants completed an epidemiological questionnaire, and hospital researchers collected clinical and pathological data. Standardized prevalences (SPs) and standardized prevalence ratios (SPRs) for each BC pathological subtype across MD categories were estimated based on multinomial logistic regression models, both overall and stratified by BMI and menopausal status.

Results: Mean MD was 26.1% (SD = 17.3). Although no statistically significant differences were detected, women with MD ≥ 50% had a 13% lower SP of hormone receptor positive tumors (SPR = 0.87; 95% CI 0.67-1.13), a 36% higher SP of human epidermal growth factor receptor 2 positive (HER2+) tumors (SPR = 1.36; 95% CI 0.72-2.58), and a 23% higher SP of triple negative (TN) tumors (SPR = 1.23; 95% CI 0.47-3.22), compared to those with MD < 10%. These patterns were mainly observed in pre/perimenopausal women and in those with BMI ≥ 25 kg/m2.

Conclusions: High MD might be mainly associated with the development of more aggressive and non-hormone-dependent cancers, such as HER2+ and TN BC, especially among pre/perimenopausal an overweight women.

Keywords: Body mass index; Breast density; Breast neoplasm; Menopausal status; Molecular subtypes.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no potential conflicts of interest. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Research Ethics and Animal Welfare Committee of the ISCIII. Informed consent: Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
Standardized prevalence ratios for hormone receptor-positive and HER2-negative (A), HER2-positive (B), and triple-negative tumors (C) as a smooth function of mammographic density at diagnosis among women with breast cancer. Curves represent standardized prevalence ratios (solid lines) and their 95% confidence intervals (dashed lines) obtained from a multinomial logistic regression model based on restricted cubic splines for mammographic density with two internal knots at the 35th and 65th percentiles and boundary knots at the 5th and 95th percentiles. The reference value (prevalence ratio = 1) was set at 10% mammographic density. Prevalence ratios were standardized to the overall distribution of age, recruiting region, body mass index, educational level, age at menarche, age at first birth, menopausal status, alcohol consumption and previous breast biopsies in the entire sample of women with breast cancer. Results based on 696 women with complete information. Histogram represents the distribution of mammographic density
See this image and copyright information in PMC

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