Racial/ethnic differences in the outcomes of patients with metastatic breast cancer: contributions of demographic, socioeconomic, tumor and metastatic characteristics.

PURPOSE: Population-based estimates of racial disparities in metastatic breast cancer are lacking. We quantified the contributions of demographic, socioeconomic, tumor, and metastatic characteristics to racial differences in metastatic breast cancer and characterized the most disproportional subgroup. METHODS: Patients diagnosed with metastatic breast cancer between 2010 and 2014 were identified using the Surveillance, Epidemiology, and End Results database. A multivariable Cox proportional hazards model was used to adjust each set of variables. The excess relative risk of cancer-specific and all-cause death in non-Hispanic black (NHB) versus non-Hispanic white women diagnosed with metastatic breast cancer was expressed as a percentage and was stratified by the age at diagnosis. RESULTS: We identified 13,066 female patients. NHB women exhibited substantially higher morbidity and mortality than women of other races/ethnicities. The greatest excess mortality risk for NHB women was observed in the young-onset group (18-49 years; hazard ratio: 1.57), followed by the middle-age group (50-64 years; hazard ratio: 1.42); the trend was not significant among the elderly group. Socioeconomic factors stably explained one-half of the excess risk, whereas the contribution of tumor characteristics obviously decreased with age (18-49 years, 40.7%; 50-64 years, 33.9%), and the metastatic pattern accounted for approximately one-tenth of the excess risk. Additionally, the disproportional death burden of NHB women persisted in less aggressive subgroups. CONCLUSIONS: By providing a comprehensive assessment of racial differences in the incidence and outcomes of patients with metastatic breast cancer, we urge the implementation of targeted preventive efforts in both the public health and clinical arenas.

Molecular Features and Functional Implications of Germline Variants in Triple-Negative Breast Cancer.

BACKGROUND: The germline variant spectrum of triple-negative breast cancer (TNBC) is different from that of other subtypes and has demonstrated ethnic differences. However, the germline variants of TNBC among Chinese patients and its clinical significance remain unclear. METHODS: Using our multi-omics TNBC cohort (n = 325), we determined the spectrum of germline variants in TNBC and aimed to illustrate their biological and clinical implications. RESULTS: Overall, 16.0% (52 of 325) of TNBC patients harbored at least 1 pathogenic or likely pathogenic germline variant. These germline variants were associated with early onset of TNBC, the occurrence of contralateral breast cancer, the basal-like immune-suppressed mRNA subtype, and the homologous recombination deficiency (HRD) mutation subtype. Somatic allele-specific imbalance was observed in 54.1% of these germline variants, which was correlated with early onset of breast cancer and elevated HRD. The genes BRCA1 (7.4%), RAD51D (2.8%), and BRCA2 (2.2%) were those most frequently mutated. The RAD51D germline variants, especially K91fs, were enriched in Chinese patients with TNBC compared with Caucasian and African American patients. The Chinese-specific RAD51D germline variants were functionally associated with the instability of the RAD51D protein, HRD, and sensitivity to PARP inhibitors. CONCLUSIONS: Chinese TNBC patients have a distinct spectrum of germline variants, with a remarkable impact on the clinical and molecular characteristics of the tumor. Integrative germline-somatic analysis may help identify TNBC patients who are most likely to be affected by their germline variants and in performing clinical interventions more precisely. The RAD51D variants enriched in our cohort may serve as therapeutic targets and guide precision treatment of TNBC.