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.

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.

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.

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.