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Abnormalities in the cyclin D1-CDK4/6 complex have been implicated in breast cancer proliferation and resistance to treatment. Recently, new drugs have been developed to target CDK4/6. Meanwhile, liquid biopsy has received great interest in oncology. In this study, we analyzed cyclin D1 gene (CCND1) copy number variation (CNV) in circulating tumor DNA (ctDNA) from luminal B breast cancer patients.This study included 31 patients with luminal B breast cancer who underwent resection. We analyzed CCND1 CNV in ctDNA by digital droplet PCR.Of the 31 luminal B breast cancers, CCND1 CNV was positive in 5 cases. Patients with CCND1 CNV positivity had significantly shorter recurrence-free survival than patients with negative CCND1 CNV.CCND1 CNV in ctDNA was associated with poor prognosis in patients with luminal B breast cancer. This biomarker could be a useful prognostic factor.

Introduction PREDICT is a prognostication tool that calculates the potential benefit of various postsurgical treatments on the overall survival (OS) of patients with nonmetastatic invasive breast cancer. Once patient, tumor, and treatment details have been entered, the tool will show the estimated 5‐, 10‐, and 15‐year OS outcomes, both with and without adjuvant therapies. This study aimed to conduct an external validation of the prognostication tool PREDICT version 2.2 by evaluating its predictive accuracy of the 5‐ and 10‐year OS outcomes among female patients with nonmetastatic invasive breast cancer in Japan. Methods All female patients diagnosed from 2001 to 2013 with unilateral, nonmetastatic, invasive breast cancer and had undergone surgical treatment at Kyushu University Hospital, Fukuoka, Japan, were selected. Observed and predicted 5‐ and 10‐year OS rates were analyzed for the validation population and the subgroups. Calibration and discriminatory accuracy were assessed using Chi‐squared goodness‐of‐fit test and area under the receiver operating characteristic curve (AUC). Results A total of 636 eligible cases were selected from 1, 213 records. Predicted and observed OS differed by 0.9% (p = 0.322) for 5‐year OS, and 2.4% (p = 0.086) for 10‐year OS. Discriminatory accuracy results for 5‐year (AUC = 0.707) and 10‐year (AUC = 0.707) OS were fairly well. Conclusion PREDICT tool accurately estimated the 5‐ and 10‐year OS in the overall Japanese study population. However, caution should be used for interpretation of the 5‐year OS outcomes in patients that are ≥65 years old, and also for the 10‐year OS outcomes in patients that are ≥65 years old, those with histologic grade 3 and Luminal A tumors, and in those considering ETx or no systemic treatment., This study conducted an external validation of the online PREDICT tool version 2.2 by studying its predictive accuracy of the 5‐ and 10‐year overall survival (OS) in a population of breast cancer patients in Japan. Based on analysis of 636 eligible patients, the differences of the predicted and observed 5‐ and 10‐year OS were not statistically significant and the discriminatory accuracy results were fairly well. Hence, we can say that PREDICT tool accurately estimated the 5‐ and 10‐year overall survival in the Japanese validation population.

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., Precision oncology with next generation sequencing (NGS) using tumor tissue with/without blood has begun in Japan. Our purpose was to identify potentially actionable genetic alterations in breast cancer with the comprehensive tumor profiling test, FoundationOne® CDx. Clinically actionable alterations were identified in 76% of advanced breast cancer patients. We have established a system for precision oncology and obtained preliminary data with NGS as the first step.

Background: Immune checkpoint inhibitors (ICIs) has become a new promising treatment in the field of cancer therapy. Therefore, it is important to identify predictors of effect for ICIs in breast cancers (BC). PD-L1 expression and the abundance of TILs were known to be related to tumor mutational burden (TMB). TMB is associated with clinical benefit to ICIs in patients with melanoma, lung and colon cancer. However, the significance of TMB is unclear in BC. In this study, we assessed TMB using the TruSightOncology 500 panel (TSO500) (Illumina, San Diego), which the US Food and Drug Administration had designated as a breakthrough device, and identify characteristics of higher TMB tumors in triple negative breast cancer (TNBC), one of the most clinically aggressive subtypes. Methods: This study included 30 patients with primary TNBC underwent resection without neoadjuvant chemotherapy. DNA was extracted from FFPE tissue. Next-generation sequencing assay was performed by using the TSO500. The DNA of 523 genes for assessment of small variants, as well as biomarkers related to response to immunotherapy, such as TMB and MSI. TMB was measured in synonymous and/or non-synonymous mutation (mut) per megabase (mb). Total TMB levels were divided into three groups: low (1-5 mut/mb), intermediate (int) (6-19 mut/mb), and high (≥20 mut/mb). PD-L1 were assessed in IHC staining and PD-L1 positivity was defined as PD-L1 expression in ≥1% of tumor cells. TILs were assessed in HE staining and TILs were defined as TILs-high for ≥50% stromal TILs and TILs-low for Results: The median age of patients was 63 years old (range: 32-81). The median TMB was 8.56 mut/mb (2.35-14.22). Among the 30 tumors, 8 (26.7%) were TMB-low, 22 (73.3%) were TMB-int, and none was TMB-high. TMB-int tumors had more aggressive features than TMB-low tumors. In TMB-int tumors, nuclear grade 3 were 72.7%, high labeling index of Ki-67 (≥20%) were 54.5%, and PD-L1 positivity on tumor cells were 68.2%. Whereas, PD-L1 positivity were 25.0% in TMB-low tumors (p=0.03). TILs-high were 72.7% in TMB-int and TILs-low were 75.0% in TMB-low (p=0.02). Twelve patients in TMB-int (54.5%) and 1 patient in TMB-low (12.5%) were treated by anthracycline based chemotherapy as an adjuvant chemotherapy. Six patients with TMB-int had recurred within 5 years and 3 of them died. Meanwhile, no one with TMB-low had recurred and died. Conclusions: Findings of our study demonstrated that higher TMB in TNBC might be a poor prognostic factor. We could expect this breakthrough device to be useful for the treatment strategy in patients with TNBC. Citation Format: Kanako Kurata, Makoto Kubo, Yuan Yuan, Yurina Harada, Takafumi Morisaki, Akiko Shimazaki, Saori Hayashi, Hitomi Kawaji, Kazuhisa Kaneshiro, Mai Yamada, Masaya Kai, Masafumi Nakamura. Tumor mutational burden in Japanese patients with triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-09-08.

Background: Oncogenic genetic alterations leading to identify patients who may benefit from the target therapy are essential biomarkers for them, and to review widely what kind of driver gene alteration that each cancer has is important for effective cancer treatments. Next-generation sequencing (NGS) is a powerful tool to comprehensively analyze driver gene mutations. In Japan, some multiplex cancer genetic testings were covered from national health insurance from June, 2019. Therefore, we reviewed our data using a targeted NGS platform (FoundationOne CDx (F1CDx)) in Japanese breast cancer patients. Methods: This study included 105 local advanced or metastatic breast cancer patients in Kyushu University Hospital between October 2018 and June 2019. We prospectively assessed NGS results, clinical characteristics and therapies received for the patients. Primary endpoint was a frequency at which actionable genetic alterations were detected, and coprimary secondary endpoints were the sequence success rate, the rate at which the corresponding therapeutic agent was administered, the percentage of agreement to results with approved in vitro diagnostic agents, and the overall survival. This study was approved by the Institutional Review Board of our hospital (No. 758-00). Results: Samples from 105 breast cancer patients were tested, all of who were women. Then, 99 samples (94.3 %) were success for sequencing and 6 (5.7 %) were failure. Among the succeeded samples, tested from primary tumor is 71 (71.7 %) and metastasis is 34 (34.3 %), while 62 (62.6 %) were biopsied tumor specimen and 43 (37.4 %) resected. The clinical subtypes of them were 45 HR +/ HER2 - (45.5 %), 22 HER2+ (22.2 %), and 32 TNBC (32.3 %). Based on the biomarker findings from F1CDx, microsatellite statuses in 97 samples were stable and 1 sample high, who was diagnosed with Lynch syndrome. Regarding tumor mutation burden (TMB), of 98 patients, 3 had high TMB (>19 mutations/mb), 31 had intermediate TMB (6-19 mutations/mb), 63 had low TMB (1-5 mutations/mb) and 1 were unable to be determinated. The average was 6.7 mutations/mb. The most frequent alteration is TP53 (54.5 %), PIK3CA (39.4 %) and ERBB2 (29.3 %). 87 patients (87.8 %) detected the alterations leading to some therapeutic options based on genetic profiling. 25 patients with metastases had taken genetic testing for BRCA1/2 germline mutation (gBRCA1/2mut), which isnamed BRACAnalysis. In all of 5 patients who had gBRCA1/2muts the same spot mutations were also detected with F1CDx. In 2 of 20 patients had negative gBRCA1/2mut, somatic BRCA1/2muts were newly detected with F1CDx. In 9 of the other patients had not taken the genetic testing, somatic BRCA1/2muts were founded. 18 tumors with HER2/Immunohistochemical staining (IHC) =3+ were judged as ERBB2 amplification, 3 tumors with HER2/IHC=2+ and HER2/FISH positive as low amplification, and 18 tumors with HER2/IHC=2+ and HER2/FISH negative as no amplification. Moreover, there are were 3 patients who newly confirmed ERBB2 amplification and 4 patients who confirmed ERBB2 mutations in this study. Conclusions: The multiplex cancer genetic testing could help identify actionable alterations for the breast cancer patients. NGS results may add some new therapeutic options to standard therapies. Citation Format: Hitomi Kawaji, Makoto Kubo, Nami Yamashita, Yurina Harada, Akiko Shimazaki, Saori Hayashi, Kanako Kurata, Mai Yamada, Kazuhisa Kaneshiro, Masaya Kai, Eiji Baba, Yoshinao Oda, Masafumi Nakamura. A prospective evaluation of comprehensive tumor profiling busing a targeted Next-generation sequencing for Japanese breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-09-12.

[background] In general, TNBC has a high distant metastasis rate and is highly aggressive. Despite good response to chemotherapy, it has a poorer prognosis compared to other subtypes. There is a need to develop new treatments for the selection of appropriate treatments. At present, treatments using an immune check point blockade are attracting attention, and the evaluations as biomarkers of and, PD-1 / PD-L1 expression on immune cells for therapeutic effects and prognosis in TNBC are controversial. In order to select patients with TNBC for who immunotherapy is likely to be effective, new biomarkers need to be explored. [Purpose] Our aim is to investigate the possibility as a biomarker of PD-L1 expression on immune cells(PD-L1/IC) in TNBC. We also assess the relationship among PD-L1/IC, PD-L1 expression on tumor cells(PD-L1/TC) and TIL. [Methods] This study included 248 patients with primary TNBC who underwent resection without neoadjuvant chemotherapy at Kyushu University Hospital(Fukuoka, Japan) and related hospitals between January 2004 and December 2014. [Results] PD-L1/IC was positive in 129 cases (52.0%) of 248 TNBCs. Although there was no significant difference in RFS and OS between the positive and negative groups, PD-L1/IC-positive and TIL-High group showed the best prognosis, considering the combination whether PD-L1/IC was positive or negative, and TIL was high or low. PD-L1/IC was significantly correlated with PD-L1/TC(p [Conclusion] In TNBC, the relationship between PD-L1/IC and prognosis is still not clear, but in IMpassion130 trial, PD-L1/IC is a predictive marker for the effect of Atezolizumab. PD-L1/IC has potential as an immune biomarker in TNBCs. This study also found that PD-L1/IC was related to the therapeutic effect of anthracycline. PD-L1/IC may be a predictive marker of the efficacy of various treatments. Citation Format: Yurina Harada, Makoto Kubo, Hitomi Mori, Masaya Kai, Mai Yamada, Kanako Kurata, Hitomi Kawaji, Kazuhisa Kaneshiro, Saori Hayashi, Akiko Shimazaki, Takafumi Morisaki, Rin Yamaguchi, Nobuyuki Arima, Reiki Nishimura, Masayuki Okido, Masafumi Nakamura. PD-L1 expression of tumor infiltrating immune cells has potential as a biomarker in triple-negative breast cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-21.

BackgroundIt is important to identify biomarkers for triple-negative breast cancers (TNBCs). Recently, pembrolizumab, an immune checkpoint inhibitor (ICI) for programmed cell death 1 (PD-1), was approved as a treatment strategy for unresectable or metastatic tumor with high-frequency microsatellite instability (MSI-H) or mismatch repair deficiency, such as malignant melanoma, non-small cell lung cancer, renal cell cancer and urothelial cancer. In addition, results from clinical trials suggested that ICI was a promising treatment for TNBCs with accumulated mutations. However, the frequency of MSI in Japanese TNBCs still remains unclear. We aimed to analyze the presence of MSI-H in TNBCs as a biomarker for ICI therapy.MethodsIn this study, we retrospectively evaluated the MSI of 228 TNBCs using an innovative method, MSI Analysis System Version 1.2 (Promega), consisting of 5 microsatellite markers: BAT-26, NR-21, BAT-25, MONO-27 and NR-24 without a normal tissue control.ResultsAmong 228 tumors, 222 (97.4%) were microsatellite stable, 4 (1.7%) low-frequency MSI and 2 (0.9%) MSI-H, respectively. Two MSI-H tumors were potentially aggressive pathologically as indicated by nuclear grade 3 and high Ki-67 (> 30%), and were classified as basal-like and non-BRCA-like, but were not consistent regarding tumor-infiltrating lymphocytes, CD8 and PD-L1 expression.ConclusionsAlthough we found that MSI-H was uncommon (0.9%) in TNBCs, potential targets for ICIs exist in TNBCs. Therefore, MSI-H breast cancer patients should be picked up using not only conventional methods but also platforms for comprehensive genomic profiling.

Background/aim With advances in anti-HER2 treatment and improved prognoses of HER2-positive breast cancer, the American Society of Clinical Oncology and the American Society of Pathologists (ASCO/CAP) have revised the HER2 diagnostic guidelines several times. We examined how to respond clinically to the revisions of the interpretation of the immunohistochemistry (IHC) method. Patients and methods We re-evaluated 254 patients diagnosed as HER2 IHC equivocal, who underwent fluorescence in situ hybridization (FISH) before and after the IHC diagnostic criteria update in 2013. Results Twenty of 131 (15.3%) IHC equivocal cases by the ASCO/CAP 2007 guideline were IHC score 3+ and one of 20 (0.76%) was negative for FISH. Five of 123 (4.1%) IHC equivocal cases by the ASCO/CAP 2013 guideline were negative for IHC as per the 2007 guideline and four were positive for FISH. Conclusion After revision of the ASCO/CAP 2013 guideline, 3.3% of HER2-negative cases before the revision should have received anti-HER2 treatment.

Background:Microsatellite instability (MSI) is a phenotype resulting from defect in mismatch repair genes. The Food and Drug Administration approved anti-programmed death 1 (PD-1) immune checkpoint inhibitor for any solid tumor with MSI-high (MSI-H). Some tumors had good response to PD-1 blockade and it is a promising treatment for a part of refractory breast cancers. Our goal was to determine the frequency of MSI in triple negative breast cancer (TNBC), one of the most clinically aggressive subtypes. Patients and Methods:This study included 228 patients with primary TNBC underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Genomic DNA was extracted from formalin-fixed and paraffin-embedded tissue. Tumor and control DNA were amplified by polymerase chain reaction at the following 5 microsatellite markers: NR-21, BAT-26, BAT-25, NR-24, MONO-27. We classified the tumors as microsatellite stable(MSS), MSI-low or MSI-H. Results: The mean age of patients was 59 years (range: 30-89) and all were women. T1 tumors were 57.9% and N0 were 67.5%. Meanwhile, the tumors with nuclear grade 3 were 66.2% and high Ki-67 (> 30%) were 66.7%. Among the 228 tumors, 222 tumors (97.4%) revealed MSS, of which 6 (2.6%) revealed MSI and 2 (0.9%) were MSI-H. Among the MSI tumors, T and N factor were showed as follows: T1: 2 tumors, T2: 3 tumors, T3: 1 tumor, N0: 5 tumors and N1: 1 tumor. Of two MSI-H tumors, one showed T1N0 and another showed T2N0. The both of them showed nuclear grade 3, high Ki-67 (> 30%) and had common following instable markers: NR-21, BAT-26 and BAT-25. Conclusions: Our results demonstrated that the frequency of MSI-H was 0.9% (2/228). MSI might not be useful as a biomarker for immune check point inhibitors. MSI should be combined with another biomarker such as tumor mutational burden in TNBC. Citation Format: Kurata K, Kubo M, Mori H, Kawaji H, Motoyama Y, Kuroki L, Yamada M, Kaneshiro K, Kai M, Nakamura M. Microsatellite instability in triple negative breast cancers [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-06-11.

Objectives Non-surgical treatment is an acceptable approach for managing appendiceal abscess in adults. However, it is only applicable for selected patients, and conversion to surgery is mandatory for failed conservative treatment. This study aimed to determine the predictive factors for unsuccessful outcomes. Methods Of 594 patients with acute appendicitis, 34 (5.7%) diagnosed with appendiceal abscess were initially treated conservatively. Patients were divided into two groups: the conservative group, which was successfully treated with antibiotics and percutaneous abscess drainage, and the conversion group, which comprised patients who had surgical conversion despite conservative treatment. Risk factors for the conversion group were investigated by comparing clinical and radiological parameters between the two groups. Results Eight (23.4%) patients were converted to surgical management at an average of 5.5 days of non-surgical treatment. An abscess size greater than 40 mm and a lower rate of improvement in the white blood cell (WBC) count were significant factors for predicting conversion in multivariate analysis. The conversion group had a long operative time and high morbidity and operative conversion rates (change of proposed initial operation). Early conversion to operation group, i.e., less than 5 days of treatment, contributed to a significantly shorter hospital stay, lower hospital cost, and relatively shorter operative time (p = 0.02, p = 0.04, and p = 0.11, respectively). Conclusions Contributing factors in predicting unsuccessful outcomes for non-surgical treatment include an abscess size greater than 40 mm and a low rate of improvement in WBC count on the first day of antibiotic treatment.

Background: Many analyzes regarding immunotherapies using checkpoint blockade has made it clear that tumor infiltrating lymphocytes (TILs) plays an important role in treating cancers with high levels of somatic mutations such as triple-negative breast cancer (TNBC). We reported the relationship between TILs and PD-L1 expression, and revealed that high-TILs/positive-PD-L1 expression population in TNBC was associated with better prognosis (Oncotarget 2017). However, its molecular mechanism is still unclear. Meanwhile, T-box transcription factor 21 (T-bet) which regulates effecter T-cells activation is derived by stimulation of T-cell receptor and IL-12. Activated T-cells work as antitumor lymphocytes by enhancing the production of cytokines such as INFγ. We focused on T-bet and examined the function of activated T-cells. Patients and Methods: This study included 242 patients with primary TNBC who underwent resection without neoadjuvant chemotherapy at our three hospitals between January 2004 and December 2014. The immunohistochemistry scoring for CD8 and T-bet expression on TILs was defined as ≥30 per 0.00625mm2. PD-L1 positivity was defined as ≥1% of tumor cells staining positive for PD-L1. Results: Of the 242 TNBC, CD8 on TILs was expressed as positive in 127 (52.5%) tumors, T-bet on TILs was expressed as positive in 67 (27.7%) tumors, and PD-L1 expression on tumor cells was expressed as positive in 99 (40.9%) tumors. T-bet expression was significantly correlated with CD8 expression (P Conclusion: OS was significantly longer among patients with high T-bet expressing TNBC. These results may validate the significance of T-bet as a biomarker for various immunotherapies in TNBC. Citation Format: Mori H, Kubo M, Kai M, Kurata K, Kawaji H, Kaneshiro K, Motoyama Y, Kuroki R, Yamada M, Nishimura R, Okido M, Oda Y, Nakamura M. Transcription factor T-bet and PD-L1 expression in tumor microenvironment of triple-negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-22.

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 mm2. 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

The role of the resection of primary tumour in stage IV breast cancer is unclear. Systemic therapy is recommended to prolong the survival and improve the quality of life (QOL). However, even if the systemic therapy is effective to control distant metastasis, sometimes the local lesion worsens, especially in the aggressive subtypes such as HER2-positive breast cancer. In uncontrollable tumours, the wound bed can bleed, weep and get infected, leading to dismal QOL. Our study describes two cases of patients with HER2-positive stage IV breast cancer who underwent palliative mastectomy which resulted in improvement of QOL. Local tumour control through palliative mastectomy can be beneficial for symptomatic aggressive patients with HER2-positive breast cancer to improve their QOL.

Kyushu University Hospital has been designated as a Core Hospital for Cancer Genomic Medicine since February 2018. Our institution promotes cancer genomic medicine collaborating with 16 Cooperative Hospitals for Cancer Genomic Medicine among Kyushu, Chugoku, and Shikoku region. From November 2018 to March 2019, a total of 120 solid tumor cases has been examined by clinical sequencing tests and the results have been intensively evaluated and discussed in the expert panel meetings. One of the features of our institution is an employment of multiple clinical sequencing tests for different purposes and that the concordance of each test is assessed. In our institution, a cancer genomic outpatient, which enhanced genetic counseling division, has been started and a new hospital information system for cancer genomic medicine was developed. This hospital information system integrates the result of a cancer genome sequence report and physicians can refer to the progress and results of clinical sequencing test in real time. Current progress and issues of cancer genomic medicine in Kyushu University Hospital will be presented.

Background Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes in breast cancer and has a worse prognosis than others. Tumor infiltrating lymphocytes (TIL) are considered to be a prognostic factor in TNBC. Cytotoxic T cells (CTL) produce cytokines and cytotoxic substances such as perforin and granzyme B, and attack target cells. We have previously shown that combination of PD-L1 expression and TIL is useful as a functional indicator of tumor immune activation. Granzyme B released from CTL induces apoptosis by passing through pores formed by perforin on the cell membrane of target cells. We focused on the cytotoxic substance granzyme B and explored functional of TIL. Methods This study included 228 patients with primary TNBC who underwent resection without neoadjuvant chemotherapy at Kyushu University Hospital (Japan), between January 2004 and December 2014. We retrospectively analyzed granzyme B, CD8, PD-L1 expression assessed by immunohistochemistry and TIL in 228 TNBCs. Granzyme B was evaluated in TIL, ≥ 3% was defined as high expression, and Results Among the 228 tumors, granzyme B expression was classified as high in 106 (46.5%), low in 122 (53.5%). Granzyme B-high is correlated with high levels of TIL (p = 0.004), CD8 expression of T cell (p = 0.016) and PD-L1 of tumor cells (p Conclusions Granzyme B is an important substance of cytotoxic pathway and has been possible to be an indicator of TIL activation. Legal entity responsible for the study Masafumi Nakamura. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.