Real-World Data from a Refractory Triple-Negative Breast Cancer Cohort Selected Using a Clinical Data Warehouse Approach

SIMPLE SUMMARY: Patients with metastatic triple-negative breast cancer (mTNBC) have a very poor prognosis. We assume that some mTNBC patients have worse treatment outcomes and defined them as cases of refractory TNBC. We tried to investigate the characteristics and treatment outcomes of our refractory mTNBC cohort selected using a clinical data warehouse (CDW) approach. Between January 1997 and December 2019, TNBC patients were searched for in the breast cancer registry and, among them, pathologically confirmed mTNBC patients were selected as the study cohort (n = 451). Refractory TNBC was defined as cases of TNBC with confirmed distant metastasis within one year after adjuvant treatment. The refractory mTNBC group was younger and had a higher proportion of Ki-67 ≥ 3+ than the nonrefractory group. In addition, a much poorer prognosis existed among mTNBC patients, with an overall survival (OS) of 14.3 months and progression-free survival (PFS) of 4.2 months after first-line palliative chemotherapy compared to an OS of 24.8 months and PFS of 6.2 months in the nonrefractory TNBC group (p < 0.001). ABSTRACT: Purpose: Triple-negative breast cancer (TNBC) is well known for its aggressive course and poor prognosis. In this study, we sought to investigate clinical, demographic, and pathologic characteristics and treatment outcomes of patients with refractory, metastatic TNBC selected by a clinical data warehouse (CDW) approach. Patients and methods: Data were extracted from the real-time breast cancer registry integrated into the Data Analytics and Research Window for Integrated Knowledge C (DARWIN-C), the CDW of Samsung Medical Center. Between January 1997 and December 2019, a TNBC cohort was searched for in the breast cancer registry, which includes records from more than 40,000 patients. Among them, cases of pathologically confirmed metastatic TNBC (mTNBC) were selected as the cohort group (n = 451). The extracted data from the registry via the CDW platform included clinical, pathological, laboratory, and chemotherapy information. Refractory TNBC was defined as confirmed distant metastasis within one year after adjuvant treatment. Results: This study comprised a total of 451 patients with mTNBC, including 69 patients with de novo mTNBC, 131 patients in the nonrefractory TNBC group with confirmed stage IV disease after one year of adjuvant treatment, and 251 patients with refractory mTNBC, whose disease recurred as stage IV within one year after completing adjuvant treatment. The refractory mTNBC cohort was composed of patients with disease that recurred at stage IV after surgery (refractory mTNBC after surgery) (n = 207) and patients in whom metastasis was confirmed during neoadjuvant chemotherapy (unresectable TNBC due to progression during neoadjuvant chemotherapy) (n = 44). Patients in the refractory mTNBC group were younger than those in the nonrefractory group (median age 46 vs. 51 years; p < 0.001). Considering the pathological findings, the refractory group had a greater proportion of cases with Ki-67 ≥ 3+ than did the nonrefractory group (71% vs. 47%; p = 0.004). During a median 8.4 years of follow-up, the overall survival was 24.8 months in the nonrefractory mTNBC group and 14.3 months in the refractory mTNBC group (p < 0.001), and the median progression-free survival periods were 6.2 months and 4.2 months, respectively (p < 0.001). The median disease-free survival period was 30.1 months in the nonrefractory mTNBC group and only 7.6 months in the refractory mTNBC group. Factors related to metastatic sites affecting overall survival were liver metastasis at diagnosis (p < 0.001) and leptomeningeal involvement (p = 0.001). Conclusions: We revealed that patients with refractory mTNBC had a much poorer prognosis among all mTNBC cases and described the characteristics of this patient group.