240P Age at diagnosis and survival in metastatic breast cancer (MBC)

The influence of age at diagnosis (dx) on prognosis of MBC patients remains unclear. While recent studies report better overall survival (OS) for younger women, they use primary v. metastatic tumor subtype, lack differentiation of luminal A v. B subtypes, and/or include only de novo patients. We examined OS by age at dx of MBC in the Ending Metastatic Breast Cancer for Everyone (EMBRACE) cohort, an ongoing prospective study of MBC patients seen at Dana-Farber Cancer Institute which collects clinicopathological characteristics, treatments, and outcomes. Kaplan-Meier curves assessed OS by age (55 y) and within inferred metastatic tumor molecular subtype (luminal A, HER2- luminal B, HR+/HER2+, HR-/HER2+, triple negative (TN)). Univariate Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for OS by clinical factors. A multivariate Cox model tested the association between age group at MBC dx and OS adjusting for metastatic tumor inferred subtype, primary tumor grade, disease-free interval (DFI, defined as: de novo,>0-2 y, >=2 y), and number and type of metastatic sites at MBC dx. Out of 4, 397 women in EMBRACE, 2, 268 (52%) died in follow-up (median=5.2 y (inter-quartile range (IQR)=2.1-9.7 y). At MBC diagnosis, 578 women were 55 y. Compared to older women, younger women were more likely to have de novo disease, shorter DFI if recurrent, and brain or liver metastases (p<0.001). In multivariate analysis, age was not associated with OS; all other included factors were significantly associated with OS. Factors most strongly associated with worse OS included luminal B (HR (95% CI) v. luminal A= 1.44 (1.24-1.66)) or TN (HR=2.98 (2.55-3.47)) metastatic tumor subtype, recurrent disease and DFI <2 years (HR v. de novo=2.15 (1.87-2.47)), and brain (HR=1.61 (1.39-1.88)) or liver (HR=1.71 (1.55-1.89)) metastasis. Survival following MBC did not differ by age at diagnosis after accounting for clinical factors. Notably, women with luminal B-like tumors experienced significantly worse OS than luminal A-like tumors regardless of age, highlighting the need to develop more effective therapies for this tumor subtype.