Are mammographic density phenotypes associated with breast cancer treatment response and clinical outcomes? A systematic review and meta-analysis.

Mammographic density (MD) increases breast cancer (BC) risk, however, its association with patient outcomes is unclear. We examined the association of baseline MD (BMD), and MD reduction (MDR) following BC treatment with patient outcomes. Six databases (CINAHL, Scopus, PubMed, Web of Science, MEDLINE, and Embase) were used to identify relevant articles. The PRISMA strategy was used to extract relevant details. Study quality and risk of bias were assessed using the "Quality In Prognosis Studies" (QUIPS) tool. A Meta-analysis and pooled risk estimates were performed. Results showed that BMD is associated with contralateral breast cancer (CBC) risk (HR = 1.9; 95%CI: 1.3-3.0, p = 0.0007), recurrence (HR = 2.0; 95%CI: 1.0-4.0, p = 0.04), and mortality (HR = 1.4; 95%CI: 1.1-1.9, p = 0.003). No association was found between BMD and prognosis (HR = 3.2; 95%CI: 0.9-11.2, p = 0.06). Data on risk estimates (95%CI) from BMD for survival [RR: 1.75; 0.99-3.1 to 2.4; 1.4-4.1], ipsilateral BC [HR: 1; 0.6-1.6 to 3; 1.2-7.5], and treatment response (OR, 1.8; 0.98-3.3) are limited. MDR showed no association with mortality (HR = 0.5; 95%CI: 0.2-1.2, p = 0.13). MDR is associated with a reduced risk of recurrence [HR/RR: 0.35; 0.17-0.68 to 1.33; 0.67-2.65)], however data on MDR and outcomes such as mortality [HR/RR: 0.5; 0.27-0.93 to 0.59; 0.22-0.88], and CBC risk [RR/HR: 0.53; 0.24-0.84 to 1.3; 0.6-2.7] are limited. Evidence, although sparse, demonstrates that high BMD is associated with an increased risk of recurrence, CBC, and mortality. Conversely, MDR is associated with a reduced risk of BC recurrence, CBC, and BC-related mortality.