The impact of mammographic breast density on locoregional recurrence in breast cancer: a systematic review and meta-analysis

Understanding locoregional recurrence (LRR) risk is important in breast cancer, as it relates directly to breast cancer-associated mortality. Individualised LRR risk estimation should inform treatment and surveillance strategies. Increased mammographic breast density has been identified as a risk factor for the development of breast cancer. However, the precise relationship between mammographic density and breast cancer LRR remains unclear. To perform a systematic review and relative risk meta-analysis to explore the assocation between breast mammographic density and breast cancer LRR. A systematic review was performed as per PRISMA guidelines. Mammographic breast density (MBD) was classified as BI-RADs A-B (breast density < 50%, predominately fatty or scattered areas of fibroglandular density) or BI-RADs C-D breast density > 50%, heterogeneously dense or extremely dense). A meta-anlysis was performed using Meta-Disc and Statsdirect 2.8.0. Seven studies published between 2004 and 2023 met the inclusion criteria, comprising 3008 patients with reported mammographic breast density (MBD) (age range: 20–94 years). Overall, 59.1% (1779/3008) were classified as low MBD (BI-RADS A-B) and 40.9% (1229/3008) were classified as high MBD (BI-RADS C-D). Of these patients, 68.9% (2073/3008) were treated for invasive breast carcinoma and 31.1% had ductal carcinoma in-situ (DCIS). Breast-conserving surgery (BCS) was performed in 71.1% (2139/3008) of patients, mastectomy was performed in 28.2% (850/3008),. The median follow-up was 94.1 months, and the overall LRR rate was 12.8% (386/3008). Five of the seven studies reported a correlation between BI-RADs C-D and the development of LRR. LRR rates were lower in patients with low mammographic breast density (9.9% for BI-RADS A-B (177/1779)) compared to those with higher mammogaphic breast density (17.0% for BI-RADs C-D. (209/1229)) [P < 0.001, Chi Square]. BI-RADS C-D density on mammography was associated with an increased risk of locoregional recurrence (pooled relative risk 1.41; 95% confidence interval 1.17 to 1.70). Increased mammographic breast density may be associated with an increased risk of LRR. Multidisciplinary team discussions should consider MBD as a potential prognostic factor in when considering surveillance and locoregional control after breast cancer treatment.