Precision oncology with next generation sequencing (NGS) using tumor tissue with or without blood has begun in Japan. Tumor molecular profiling tests are available, including the OncoGuide™ NCC Oncopanel System and FoundationOne ® CDx (F1CDx). Our purpose was to identify potentially actionable genetic alterations in breast cancer with this comprehensive tumor profiling test. We enrolled 115 patients with pathologically diagnosed advanced or metastatic breast cancer. Comprehensive tumor genomic profiling, microsatellite instability, and tumor mutational burden (TMB) were determined using F1CDx. Testing was successful in 109/115 cases (94.8%). Clinically actionable alterations were identified in 76% of advanced breast cancer patients. The most frequent short variants were in TP53 (48.6%), PIK3CA (38.5%), GATA3 (11.0%), PTEN (11.0%), and BRCA1 (10.1%), and structural variants were in ERBB2 (24.8%), MYC (21.1%), RAD21 (21.1%), CCND1 (11.9%), FGF19 (10.1%), and PTEN (10.1%). Regarding human epidermal growth factor receptor (HER)2 status, 106/109 samples (97.2%) were concordant between F1CDx and HER2 testing with immunohistochemistry/fluorescence in situ hybridization. However, ERBB2 amplification was newly detected in four samples and ERBB2 mutations were detected in five HER2‐negative breast cancer samples. Oncogenic BRCA mutations were found in three samples with F1CDx among 27 germline testing‐negative samples. The mean TMB in all samples was 6.28 mut/Mb and tended to be higher in luminal B and triple‐negative breast cancer (mean = 8.1 and 5.9 mut/Mb, respectively) compared with other subtypes. In conclusion, we established a system for precision oncology and obtained preliminary data with NGS as the first step. The information in this clinical sequencing panel will help guide the development of new treatments for breast cancer patients.
Background: A reduction in complications and mortality can be observed over the last few decades among elderly patients in the early postoperative period for colorectal cancer (CRC) surgery, but long-term outcomes are largely unknown. This study aimed to investigate the long-term outcomes of elderly patients 80 years and older after CRC surgery in comparison with younger age groups. The influence of clinical, oncological, and physical parameters on outcome were retrospectively analyzed.Methods: A total of 346 patients underwent CRC surgery with curative intent between January 2013 and December 2017. Patients were divided into three age groups: younger than 60 (n=47), between 60 and 79 (n=218), and 80 and older (n=81). Clinicopathological variables including comorbidity, modified frailty index, prognostic nutrition index (PNI), operative/postoperative data, and outcome including cause of death were compared among age groups. To identify factors associated with death from CRC and other causes, univariate and multivariate analyses using the Cox proportional hazards model were performed.Results: Immediate postoperative morbidity of patients with Clavien-Dindo grades of III or greater (16.0%) and the 30-day mortality rate (2.5%) of patients 80 years and older were not statistically different from those of younger age groups. Long-term disease-free survival was also similar among age groups, suggesting CRC surgery provides oncological benefit to patients irrespective of age. Multivariate analysis revealed that R1 resection, advanced tumor stage, carcinoembryonic antigen (CEA) level of >5 ng/mL, undifferentiated tumor, and longer postoperative hospital stay were risk factors for CRC death. Long-term overall survival was significantly reduced in comparison to younger age groups. Seventy percent of deaths in elderly patients during follow-up were primarily from respiratory failure and cardiovascular disease. Multivariate analysis demonstrated that advanced age, frailty, low PNI, and open procedure were risk factors for other causes of mortality.Conclusions: Elderly patients undergoing CRC surgery appeared to enjoy similar oncological benefits as younger age groups. Since both modified frailty index and PNI were correlated with mortality unrelated to CRC, preoperative assessment of these factors can be important for predicting outcome and selecting patients for prehabilitation.
Purpose T-box transcription factor 21 (T-bet), which is the master regulator of effector T-cell activation, is derived by stimulation of T-cell receptors. In this study, we focused on T-bet and examined the function of activated T cells. Methods This study included 242 patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. The immunohistochemistry scoring for CD8 and T-bet expression on tumor-infiltrating lymphocytes (TILs) was defined as ≥ 30 per 6.25 × 10 −3 mm 2 . Results Of the 242 TNBC cases, CD8 was positively expressed in 127 (52.5%) tumors, and T-bet was positively expressed in 67 (27.7%) tumors. T-bet expression was significantly correlated with CD8 expression ( p < 0.0001). Patients with T-bet + tumors had longer overall survival (OS) compared with patients with T-bet − tumors ( p = 0.047). The combination of CD8 + and T-bet + was associated with a better recurrence-free survival (RFS) and OS compared to CD8 + /T-bet − tumors ( p = 0.037 and p = 0.024, respectively). Adjuvant chemotherapy provided significantly greater benefit to patients with T-bet + tumors ( p = 0.031 for RFS, p = 0.0003 for OS). Multivariate analysis revealed that T-bet expression on TILs was an independent and positive prognostic indicator (HR = 0.36, 95% confidence interval (CI) 0.12–0.94, p = 0.037 for RFS, HR = 0.30, 95% CI 0.07–0.95, p = 0.039 for OS). Conclusions OS was significantly improved for patients with high T-bet-expressing TILs in TNBC. Thus, T-bet may be a predictive indicator for survival and various immunotherapy strategies in TNBC. Electronic supplementary material The online version of this article (10.1007/s10549-019-05256-2) contains supplementary material, which is available to authorized users.
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