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.

Background: The safety of immune‐checkpoint inhibitors (ICIs) has not been thoroughly investigated in non–small cell lung cancer (NSCLC) patients with chronic hepatitis B (CHB) or occult hepatitis B infection (OBI). The authors analyzed the incidence of hepatitis B virus (HBV) reactivation, immune‐related hepatitis and jaundice in NSCLC patients in a real‐world setting.Methods: A total of 1277 NSCLC patients treated with ICIs were analyzed. Among them, 52 patients were hepatitis B surface antigen (HBsAg) (+) (group A, CHB), 759 patients were HBsAg (–)/hepatitis B core antibody immunoglobulin G (anti‐HBc IgG) (+) (group B, OBI), and 466 patients were HBsAg (–)/anti‐HBc IgG (–) (group C). Among the 52 patients with CHB, 38 (73.1%) were receiving antiviral therapy. The primary end point was HBV reactivation, immune‐related hepatitis, and jaundice. The secondary end points included other immune‐related adverse events and efficacy.Results: HBV reactivation was observed in two patients (0.2%) who were both in group A (CHB). Among CHB patients who were not receiving antiviral therapy, HBV reactivation was observed in 14.3% (2 of 14 patients). The incidences of immune‐related hepatitis and jaundice were comparable among the three groups. The incidence of ≥grade 3 other immune‐related adverse events and efficacy were all comparable among the three groups (p > .05 for all comparisons).Conclusions: In this large, real‐world cohort study, the safety and efficacy of ICIs were comparable in patients with CHB and OBI. HBV reactivation was observed in patients with CHB without antiviral therapy indicating antiviral prophylaxis should be required for them. For patients with OBI, the risk of HBV reactivation was minimal.

Background: Given that peak age of breast cancer (BC) is younger in Asians than in Western populations, relatively higher prevalence of pregnancy-associated breast cancer (PABC) has been reported. This study aimed to analyze the characteristics and clinical outcomes of PABC in Korea. Methods: We defined PABC as BC diagnosed during pregnancy or in the first postpartum year. We compared the clinicopathological characteristics and BC outcomes between patients with PABC and non-PABC patients in the prospective YBC cohort from Samsung Medical Center. Results: In total, 1492 patients were initially enrolled, and 1364 patients were included, of which 93 had PABC (6.8%). The median age of patients with PABC was 34 years. Hormone receptor expression was lower (64.6% vs 74.6%) and frequency of HER2 overexpression was higher (26.9% vs 17.6%) in patients with PABC than in non-PABC patients. The 5-year overall survival (OS) rates were 83.2% and 93.4% in patients with PABC and non-PABC patients, respectively (p < 0.001). The 5-year disease-free survival (DFS) rates were 72.2% and 83.8% in PABC and non-PABC patients. Conclusion: Compared to non-PABC patients, patients with PABC had poorer OS and DFS in this prospective cohort. Exploratory biomarker analysis for PABC is warranted.

Genetic diagnosis for human epidermal growth factor receptor 2-negative metastatic breast cancer patients with the germline BRCA (gBRCA) mutation has been emphasized since the development of polyadenosine diphosphate-ribose polymerase inhibitors. Myriad Genetics, Inc.’s (Salt Lake City, UT, USA) companion diagnostics service is almost exclusively used for genetic testing. The aim of this study was to compare the results of germline BRCA mutation tests returned by a local laboratory and those performed by Myriad. Between April 2014 and February 2018, 31 patients with gBRCA 1/2 mutation test results from both Samsung Medical Center (Seoul, Korea) and Myriad were enrolled. “Discordant: Opposite classification” was observed for only one among 27 (3.7%). This discrepancy was due to the detection of a deleterious large genomic rearrangement of BRCA 1 by Myriad. Samsung Medical Center performed multiple ligation-dependent probe amplifications (MLPA) to detect large genomic rearrangements only in high-risk patients. This one case was not suspected as high risk and MLPA was not performed. The concordant rate was 74.1% for all 27 patients. “Discordant: Laboratory’s uncertain classification” was found in 22.2% of the sample (six patients). All discrepancies were generated during interpretation of BRCA 2 gene sequencing. Further studies and standardization of genetic testing for BRCA 1/2 genes are required.

Although human epidermal growth factor receptor 2 (HER2)-positive breast cancer was associated with poor prognosis, it has been changed after the development of trastuzumab. There has been great progress in perioperative HER2-targeting treatment, and investigations of several novel drugs and their combinations are ongoing. Adjuvant trastuzumab with or without pertuzumab for 1 year in combination with concomitant chemotherapy has become a standard treatment in high-risk node-negative tumors or node-positive HER2-positive early breast cancer patients without residual disease or who have not received neoadjuvant treatment. For low-risk HER2-positive early breast cancer patients, adjuvant paclitaxel and 1-year trastuzumab are possible alternatives. For residual disease after neoadjuvant treatment, adjuvant trastuzumab emtansine (T-DM1) for 14 cycles is a standard treatment. Non-anthracycline chemotherapy with dual anti-HER2 targeting of trastuzumab and pertuzumab represents one of the preferred neoadjuvant regimens to achieve higher pathologic complete response (pCR) rates and better clinical outcomes. Further research is needed to develop and validate potential biomarkers to predict pCR, which could help escalate or de-escalate anti-HER2 therapy. Trials incorporating novel agents such as T-DM1, trastuzumab deruxtecan (T-DXd), and immune checkpoint inhibitors and trying to de-escalate treatments in neoadjuvant setting are ongoing. In the future, tailored treatments such as no adjuvant therapy, various HER2-directed therapies alone with chemotherapy, combinations of various HER2-directed therapies and chemotherapy, addition of immune checkpoint inhibitors, and omission of surgery will be individualized in HER2-positive early breast cancer patients.