Faculty Profiles - Tanioka Maki

Papers - Tanioka Maki

Division display 21 - 40 of about 74 ／ All the affair displays >>

Therapeutic target biomarkers of patient-derived xenograft models of gastric-type cervical adenocarcinoma. International journal

Yuki Kojima, Hiroshi Yoshida, Toshihiro Okuya, Hitomi S Okuma, Tadaaki Nishikawa, Maki Tanioka, Kazuki Sudo, Emi Noguchi, Tatsunori Shimoi, Kenji Tamura, Yasuhito Tanase, Masaya Uno, Mitsuya Ishikawa, Motoko Arakaki, Hitoshi Ichikawa, Shigehiro Yagishita, Akinobu Hamada, Yasuhiro Fujiwara, Kan Yonemori, Tomoyasu Kato

Gynecologic oncology reports 50 101302 - 101302 2023.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Most cervical adenocarcinomas are associated with human papillomavirus (HPV). Gastric-type cervical adenocarcinoma (GAS), an HPV-independent adenocarcinoma, shows an aggressive clinical feature, resulting in a poor prognosis. Resistance to chemotherapy poses a difficulty in managing patients with metastatic GAS. We aimed to establish patient-derived xenografts (PDXs) of tumors from two patients with GAS and evaluated protein biomarkers for drug development using immunohistochemistry. METHODS: Two PDXs were established 78 and 48 days after transplanting the patient's tumor tissues into immunodeficient mice, respectively. PDX and patient's tumor samples were stained for HER2, HER3, PMS2, MSH6, PanTrk, and ARID1A to evaluate biomarkers for therapeutic targets. In addition, whole exome sequencing and RNA sequencing were performed on available samples. RESULTS: The pathological findings in morphological features and immunohistochemical profiles from the established PDXs were similar to those from the patients' surgical tumor specimens. HER3 was overexpressed in the patient's tumors, and the corresponding PDX tumors and HER2 was weakly stained in both types of tumor samples. In all PDX and patient tumor samples, PMS2, MSH6, and ARID1A were retained, and PanTrk was not expressed. In addition, a total of 10 samples, including tumor tissue samples from 8 other GAS patients, were evaluated for HER3 expression scores, all of which were 2 + or higher. CONCLUSIONS: In summary, we evaluated biomarkers for therapeutic targets using newly established PDX models of GAS. Frequent HER3 overexpression and HER2 expression in GAS tumors suggest the possibility of new treatments for patients with GAS by targeting HER3 and HER2.

DOI： 10.1016/j.gore.2023.101302

Proposal for combined macroscopic and microscopic on-site evaluation (cMOSES) of fresh tissue from liver tumor biopsies for histopathological diagnosis and comprehensive genomic panel testing. International journal

Tami Nagatani, Yoji Wani, Soichiro Fushimi, Yu Matsuo, Shiho Murakami, Toshifumi Tada, Shinichiro Nakamura, Hirofumi Inoue, Maki Tanioka, Hiroyuki Okada, Akira Hirasawa

Pathology international 2023.9

A case of ovarian carcinosarcoma with a germline pathogenic variant of BRCA2 involving a perforated appendix with an abscess. International journal

Ayaka Saito, Eiko Yamashita, Urara Sakurai, Akira Hirasawa, Maki Tanioka, Kazuya Tamura, Satoshi Umezawa

The journal of obstetrics and gynaecology research 49 ( 10 ) 2553 - 2557 2023.7

Language：English

We report a case of rare and aggressive ovarian carcinosarcoma with a germline pathogenic BRCA2 variant. A patient with a history of breast cancer who developed an inflammatory ovarian tumor with peritonitis carcinomatosis involving the appendix suffered from cachexia. Following three cycles of weekly paclitaxel and carboplatin chemotherapy, emergency surgery was required owing to sepsis. Bilateral salpingo-oophorectomy, total hysterectomy, appendectomy, and small intestine adhesiolysis were performed. Histologically, the tumor comprised an admixture of carcinomatous and sarcomatous components, with involvement of the appendix, which had caused perforation and abscess formation. The final diagnosis was ovarian carcinosarcoma with a germline pathogenic BRCA2 variant, c.658_659del (p.Val220fs). The patient responded completely to adjuvant chemotherapy. A combination of chemotherapy and surgery might be beneficial to patients with ovarian carcinosarcoma and germline pathogenic BRCA2 variants with a poor general condition. This is the first report of ovarian carcinosarcoma with a germline pathogenic BRCA2 variant that responded favorably to chemotherapy.

DOI： 10.1111/jog.15736

Development of a Detection System for ESR1 Mutations in Circulating Tumour DNA Using PNA-LNA-Mediated PCR Clamping. International journal

Yuki Kojima, Emi Noguchi, Tomomi Yoshino, Shigehiro Yagishita, Shu Yazaki, Hitomi S Okuma, Tadaaki Nishikawa, Maki Tanioka, Kazuki Sudo, Tatsunori Shimoi, Ayaka Kazama, Hiroshi Terasaki, Sachiro Asano, Yasuhiro Fujiwara, Akinobu Hamada, Kenji Tamura, Kan Yonemori

Diagnostics (Basel, Switzerland) 13 ( 12 ) 2023.6

Language：English Publishing type：Research paper (scientific journal)

Although circulating tumour DNA (ctDNA)-based next-generation sequencing (NGS) is a less invasive method for assessing ESR1 mutations that are essential mechanisms of endocrine therapy resistance in patients with oestrogen receptor-positive breast cancer, adequate amounts of DNA are required to assess polyclonal ESR1 mutations. By combining a peptide nucleic acid and locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamping assay, we have developed a novel detection system to screen for polyclonal ESR1 mutations in ctDNA. A validation assay was prospectively performed on clinical samples and compared with the NGS results. The PNA-LNA PCR clamp assay was validated using six and four blood samples in which ESR1 mutations were detected by NGS and no mutations were detected, respectively. The PNA-LNA assay results were comparable with those of NGS. We prospectively assessed the concordance between the PNA-LNA PCR clamp method and NGS. Using the PNA-LNA PCR clamp method, ESR1 mutations were detected in 5 out of 18 samples, including those in which mutations were not detected by NGS due to small amounts of ctDNA. The PNA-LNA PCR clamping method is a highly sensitive and minimally invasive assay for polyclonal ESR1 mutation detection in the ctDNA of patients with breast cancer.

DOI： 10.3390/diagnostics13122040

High mesothelin expression is correlated with non-squamous cell histology and poor survival in cervical cancer: a retrospective study. International journal

Shigemasa Takamizawa, Shu Yazaki, Yuki Kojima, Hiroshi Yoshida, Rui Kitadai, Tadaaki Nishikawa, Tatsunori Shimoi, Kazuki Sudo, Hitomi Sumiyoshi Okuma, Maki Tanioka, Emi Noguchi, Masaya Uno, Mitsuya Ishikawa, Tomoyasu Kato, Yasuhiro Fujiwara, Kan Yonemori

BMC cancer 22 ( 1 ) 1215 - 1215 2022.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Mesothelin (MSLN) is a cell-surface glycoprotein found in various solid tumours. Cancer therapies targeting MSLN have been developed in recent years; however, the available information on MSLN expression in cervical cancer is limited. This study aimed to evaluate MSLN expression in various histological types of cervical cancer and examine its relationship with prognosis. METHODS: This retrospective study included patients with cervical cancer who underwent primary surgery between January 2000 and December 2020 at our institution. MSLN expression was evaluated by immunohistochemistry using clone SP74 and defined as positive if MSLN was expressed at any intensity. High MSLN expression was defined as an intensity of ≥ 2 + in ≥ 30% of tumour cells. The association between MSLN expression and clinicopathological factors was evaluated. RESULTS: Overall, 123 patients were identified, and 140 tumour samples, including 17 paired primary and metastatic samples, were evaluated. Concerning histological type, 67 patients had squamous cell carcinoma (SCC), whereas 56 had non-SCC. MSLN expression was observed in 98.4% (121/123) of primary tumours. High MSLN expression was observed in 63.4% of samples (78/123), but it differed between the histological types (49.2% for SCC vs. 80.4% for non-SCC, p < 0.001). There was a significant correlation between MSLN expression in primary and metastatic lesions (Rs = 0.557, p = 0.015). In patients with common histological types, overall survival (OS) was shorter in the high MSLN expression group than in the low MSLN expression group (hazard ratio, 3.53; 95% confidence interval, 1.16-15.3, p = 0.03). CONCLUSIONS: MSLN was highly expressed in patients with cervical cancer, especially in those with non-SCC. High MSLN expression in the primary lesion was significantly associated with poor OS, and its expression was maintained in metastatic lesions. Our findings indicate that MSLN may be an attractive therapeutic target for cervical cancer. TRIAL REGISTRATION: Retrospectively registered. 2014-393. 1 June 2015.

DOI： 10.1186/s12885-022-10277-0

Integrative prognostic analysis of tumor-infiltrating lymphocytes, CD8, CD20, programmed cell death-ligand 1, and tertiary lymphoid structures in patients with early-stage triple-negative breast cancer who did not receive adjuvant chemotherapy. International journal

Shu Yazaki, Tatsunori Shimoi, Masayuki Yoshida, Hitomi Sumiyoshi-Okuma, Motoko Arakaki, Ayumi Saito, Shosuke Kita, Kasumi Yamamoto, Yuki Kojima, Tadaaki Nishikawa, Maki Tanioka, Kazuki Sudo, Emi Noguchi, Takeshi Murata, Sho Shiino, Shin Takayama, Akihiko Suto, Yuichiro Ohe, Yasuhiro Fujiwara, Kan Yonemori

Breast cancer research and treatment 197 ( 2 ) 287 - 297 2022.11

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Stromal tumor-infiltrating lymphocytes (TILs) are independent prognostic factors in systemically untreated early-stage triple-negative breast cancer (TNBC). Other immune biomarkers including CD8, CD20, programmed cell death-ligand 1 (PD-L1), and tertiary lymphoid structures (TLS) are also reported to be associated with prognosis. However, whether combining other immune biomarkers with TILs would allow for further prognostic stratification is unknown. METHODS: We retrospectively analyzed 125 patients with early-stage TNBC not receiving perioperative chemotherapy. Stromal TILs and TLS were evaluated on hematoxylin-eosin slides. PD-L1 expression was evaluated using the SP142 assay. CD8 and CD20 were assessed by immunohistochemistry and counted by digital pathology. RESULTS: Immune biomarker levels were positively correlated (p < 0.001). Adding CD8 and PD-L1 to multivariable analysis including clinicopathological factors (stage and histological grade) and TILs significantly improved the prognostic model (likelihood ratio χ2 = 9.24, p = 0.01). In Cox regression analysis, high CD8 was significantly associated with better prognosis [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.48-0.98, p = 0.04], and PD-L1 positivity was significantly associated with worse prognosis (HR 4.33, 95%CI 1.57-11.99, p = 0.005). Patients with high CD8/PD-L1 (-) tumors had the most favorable prognosis [5 year invasive disease-free survival (iDFS), 100%], while patients with low CD8/PD-L1( +) tumors had the worst prognosis (5 year iDFS, 33.3%). CONCLUSION: CD8 and PD-L1 levels add prognostic information beyond TILs for early-stage TNBC not receiving perioperative chemotherapy. CD8-positive T cells and PD-L1 may be useful for prognostic stratification and in designing future clinical trials of TNBC.

DOI： 10.1007/s10549-022-06787-x

High expression of folate receptor alpha is associated with poor prognosis in patients with cervical cancer. International journal

Shu Yazaki, Yuki Kojima, Hiroshi Yoshida, Shigemasa Takamizawa, Rui Kitadai, Tadaaki Nishikawa, Tatsunori Shimoi, Kazuki Sudo, Ayumi Saito, Hitomi Sumiyoshi Okuma, Maki Tanioka, Emi Noguchi, Masaya Uno, Mitsuya Ishikawa, Tomoyasu Kato, Yasuhiro Fujiwara, Yuichiro Ohe, Kan Yonemori

Journal of gynecologic oncology 33 ( 6 ) e82 2022.11

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Folate receptor α (FRα) is a membrane protein expressed in various solid tumors but has limited expression in normal cells. Therefore, FRα is an attractive target for cancer treatment. This study aimed to investigate the relationship between FRα expression and the clinicopathological characteristics and survivals of cervical cancer. METHODS: This retrospective study included patients with cervical cancer who underwent primary surgery between 2000 and 2020 at our institution. Immunohistochemical staining of FRα was performed using an anti-folate-binding protein/FBP antibody. FRα-positive staining was defined as ≥5% of tumor staining and FRα-high as ≥50% tumor staining with ≥2+ intensity. The association between FRα expression and survival was assessed using multivariate Cox regression analysis, adjusting for established prognostic factors. RESULTS: Overall, 123 patients were identified, and 140 tumor samples, including 17 paired primary and metastatic samples, were evaluated. As histological types, 67 patients had squamous cell carcinoma (SCC), and 56 patients had non-SCC. All primary tumors were FRα-positive. High FRα expression was observed in 25% of the cases and differed according to histology (SCC vs. non-SCC, 14.9% vs. 37.5%, p=0.004). FRα expression was significantly higher in metastatic tumors than in primary (170 [IQR, 140-205] vs. 125 [IQR, 110-150], p=0.0006). High FRα expression was significantly associated with worse overall survival (hazard ratio, 6.73; 95% confidence interval, 2.21-20.53; p=0.001). CONCLUSION: In cervical cancer, FRα expression was elevated in metastatic tumors and high expression was associated with a worse prognosis. Our study supports the development of FRα-targeted therapy for advanced cervical cancer.

DOI： 10.3802/jgo.2022.33.e82

Phase 1 study of the liposomal formulation of eribulin (E7389-LF): Results from the breast cancer expansion cohort. International journal

Norikazu Masuda, Makiko Ono, Toru Mukohara, Hiroyuki Yasojima, Tatsunori Shimoi, Kokoro Kobayashi, Kenichi Harano, Makiko Mizutani, Maki Tanioka, Shunji Takahashi, Takahiro Kogawa, Takuya Suzuki, Shiori Okumura, Takao Takase, Reiko Nagai, Taro Semba, Zi-Ming Zhao, Min Ren, Kan Yonemori

European journal of cancer (Oxford, England : 1990) 168 108 - 118 2022.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: A liposomal formulation of eribulin, E7389-LF, may provide improved pharmacokinetics and allow increased access to tumour tissues. This expansion of a phase 1 study assessed the safety and efficacy of E7389-LF in patients with human epidermal growth factor receptor type 2-negative metastatic breast cancer. METHODS: Patients received E7389-LF 2.0 mg/m2 every three weeks. Tumour assessments were conducted every six weeks by the investigator by Response Evaluation Criteria in Solid Tumours v1.1. All adverse events were monitored and recorded. Serum biomarker assessments were conducted. RESULTS: Of 28 patients included, 75.0% had hormone receptor-positive breast cancer (HR+ BC) and 25.0% had triple-negative breast cancer (TNBC). The most common grade ≥3 treatment-related treatment-emergent adverse events included neutropenia (67.9%), leukopenia (42.9%), thrombocytopenia (32.1%), and febrile neutropenia (25.0%). Rates of neutropenia and febrile neutropenia were lower among patients who received prophylactic pegfilgrastim. Objective response rate was 35.7% (95% confidence interval [CI]: 18.6-55.9) for all patients and 42.9% (95% CI: 21.8-66.0) for patients with HR+ BC. Median progression-free survival was 5.7 months (95% CI: 3.9-8.3). The median overall survival was 18.3 months (95% CI: 13.2-not estimable). Among the 54 biomarkers assessed, 27, including 5 of 7 vascular markers, were significantly altered by E7389-LF treatment from baseline to any time point. CONCLUSION: E7389-LF was tolerable and favourable antitumour activity was observed, particularly in patients with HR+ BC. Prophylactic pegfilgrastim can be considered in patients at high risk for neutropenia and febrile neutropenia. GOV NUMBER: NCT03207672.

DOI： 10.1016/j.ejca.2022.03.004

Poor Treatment Outcomes with Second-Line Chemotherapy in Advanced Synovial Sarcoma. International journal

Yuki Kojima, Tatsunori Shimoi, Takuji Seo, Shu Yazaki, Toshihiro Okuya, Yohei Ohtake, Hitomi S Okuma, Akihiko Shimomura, Tadaaki Nishikawa, Maki Tanioka, Kazuki Sudo, Emi Noguchi, Kenji Tamura, Akihiko Yoshida, Shintaro Iwata, Eisuke Kobayashi, Akira Kawai, Yasuhiro Fujiwara, Kan Yonemori

Oncology 2022.4

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Synovial sarcoma predominantly affects adolescents and young adults. Doxorubicin with or without ifosfamide therapy is the standard first-line treatment for unresectable or metastatic synovial sarcoma. However, there is no standard second-line chemotherapy regimen. The purpose of the current study was to evaluate the outcomes of second-line chemotherapy for patients with synovial sarcoma. METHODS: We retrospectively evaluated the outcomes of 61 patients with unresectable or metastatic synovial sarcoma who had received first-line chemotherapy at our institution between 1997 and 2017. Patients who received second-line chemotherapy were included in the analysis. Outcomes of the chemotherapy were evaluated. RESULTS: Among the 61 patients treated with first-line chemotherapy, we identified 32 patients who received second-line chemotherapy. Most patients (62.5%) were under 40 years of age. Regarding second-line chemotherapy regimens, 6 (18.8%) patients were treated with doxorubicin with/without ifosfamide, 6 (18.8%) with ifosfamide and etoposide, 4 (12.5%) with docetaxel and gemcitabine, 5 (15.6%) with pazopanib, 2 (6.2%) with trabectedin, and 1 (3.1%) with eribulin. The overall response rate according to the Response Evaluation Criteria in Solid Tumors for all patients was 9.4%. Eleven patients (34.3%) achieved disease-control for > 6 months. The median follow-up duration was 15.2 months. The 1-year progression-free and overall survival rates were 33.1% and 67.1%, respectively. CONCLUSION: Our exploratory study revealed that the response rate of second-line chemotherapy regimens for patients with synovial sarcoma was 9.4%. Therefore, there is an urgent need to develop more active therapeutic regimens for synovial sarcomas.

DOI： 10.1159/000524500

Neutrophil-to-lymphocyte ratio as a prognostic factor for patients with metastatic or recurrent breast cancer treated using capecitabine: a retrospective study. International journal

Shigemasa Takamizawa, Tatsunori Shimoi, Natsuko Satomi-Tsushita, Shu Yazaki, Toshihiro Okuya, Yuki Kojima, Hitomi Sumiyoshi-Okuma, Tadaaki Nishikawa, Maki Tanioka, Kazuki Sudo, Emi Noguchi, Kan Yonemori

BMC cancer 22 ( 1 ) 64 - 64 2022.1

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Eribulin or capecitabine monotherapy is the next cytotoxic chemotherapy option for patients with metastatic or recurrent breast cancer who have previously received an anthracycline or a taxane. However, it is unclear what factors can guide the selection of eribulin or capecitabine in this setting, and prognostic factors are needed to guide appropriate treatment selection. The neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor for eribulin-treated patients, although it is unclear whether it is a prognostic factor for capecitabine-treated patients. Therefore, we analysed the ability of the NLR to predict oncological outcomes among patients who received capecitabine after previous anthracycline or taxane treatment for breast cancer. METHODS: We retrospectively reviewed the medical records of patients with metastatic or recurrent breast cancer who had previously received anthracycline or taxane treatment at the National Cancer Center Hospital between 2007 and 2015. Patients were included if they received eribulin or capecitabine monotherapy as first-line, second-line, or third-line chemotherapy. Analyses of overall survival (OS) and progression-free survival (PFS) were performed according to various factors. RESULTS: Between 2007 and 2015, we identified 125 eligible patients, including 46 patients who received only eribulin, 34 patients who received only capecitabine, and 45 patients who received eribulin and capecitabine. The median follow-up period was 19.1 months. Among eribulin-treated patients, an NLR of <3 independently predicted better OS. Among capecitabine-treated patients, an NLR of <3 independently predicted better PFS but not better OS. In addition, a lymphocyte-to-monocyte ratio of ≥5 was associated with better PFS and OS. CONCLUSIONS: To the best of our knowledge, this is the first study to evaluate whether the NLR is a prognostic factor for capecitabine-treated patients with metastatic or recurrent breast cancer. However, the NLR only independently predicted PFS in this setting, despite it being a useful prognostic factor for other chemotherapies.

DOI： 10.1186/s12885-021-09112-9

Case report: Response to platinum agents and poly (adenosine diphosphate-ribose) polymerase inhibitor in a patient with BRCA1 c.5096G>A (R1699Q) intermediate-risk variant. International journal

Ayumi Saito, Maki Tanioka, Makoto Hirata, Tomoko Watanabe, Yoko Odaka, Tatsunori Shimoi, Kazuki Sudo, Emi Noguchi, Mitsuya Ishikawa, Kan Yonemori

Cancer treatment and research communications 32 100587 - 100587 2022

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: BRCA1 c.5096G>A (p. Arg1699Gln) (hereinafter BRCA1 R1699Q) is classified as a pathogenic genetic variant despite its lower penetrance of breast and ovarian cancers compared to other BRCA1 variants. However, this mutation is currently reported as a 'special interpretation' variant in the BRACAnalysis® because the response to platinum agents and poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors remains unknown in patients with this mutation. CASE PRESENTATION: We present a case of stage IIIc high-grade primary peritoneal cancer in a 69-year-old woman with germline BRCA1 R1699Q variant. She received platinum-containing chemotherapy followed by surgery. Eight months later, the patient experienced recurrence and received six cycles of chemotherapy and olaparib maintenance therapy. However, the disease progressed after only 5 months, and she received another chemotherapy drug. This patient responded slightly to platinum agents and had shorter progression-free survival on olaparib compared with clinical trial data. myChoice® CDx also showed Genomic Instability Score (GIS) was 50. This patient had no other gene mutations which could cause homologous recombination deficiency. CONCLUSION: This is the first report of the clinical outcome of PARP inhibitor and platinum-containing chemotherapy in a patient with a BRCA1 R1699Q variant. Despite BRCA1 mutation and high GIS, used as indicators of drug sensitivity, the recurrent tumor did not respond well to platinum agents and olaparib. BRCA1 R1699Q variant could differ from others in cancer risk and in drug response. Further studies are needed to confirm these observations.

DOI： 10.1016/j.ctarc.2022.100587

Clinical management and outcomes associated with etoposide, doxorubicin, and cisplatin plus mitotane treatment in metastatic adrenocortical carcinoma: a single institute experience

Masaki Uchihara, Maki Tanioka, Yuki Kojima, Tadaaki Nishikawa, Kazuki Sudo, Tatsunori Shimoi, Emi Noguchi, Akiko Miyagi Maeshima, Kan Yonemori

International Journal of Clinical Oncology 26 ( 12 ) 2275 - 2281 2021.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media {LLC}

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive disease that is often diagnosed at an advanced stage. There is no standard treatment for metastatic ACC; EDP-M (etoposide, doxorubicin, and cisplatin plus mitotane) is one treatment option. A randomized controlled trial (FIRM-ACT) evaluating the efficacy of EDP-M showed progression-free survival (PFS) was 5.0 months, overall survival (OS) was 14.8 months, the response rate was 19%, and adrenal insufficiency occurred in 3.4% of patients. However, the efficacy and safety of this regimen in Asia are not fully reported. METHODS: We retrospectively analyzed 43 patients diagnosed with metastatic ACC at the National Cancer Center Hospital between 1997 and 2020. We evaluated PFS, OS, and response in 17 patients who received EDP-M as first-line therapy. RESULTS: The median age at treatment initiation was 45 years (range 18-74). Eight patients (47%) had autonomous hormone production, including six patients with hypercortisolism. The best response of partial response and stable disease was seen in two (12%) and ten (59%) patients, respectively. The median PFS was 6.2 months [95% confidence interval (CI): 4.3-10.0]. The median OS was 15.4 months (95% CI 11.6-not reached). Three patients received only one cycle due to adverse effects associated with hypercortisolism. Grade 3/4 adverse events associated with adrenal insufficiency occurred in three (17%) cases, resulting in EDP-M discontinuation. CONCLUSIONS: The EDP-M regimen had similar PFS to that observed in FIRM-ACT. Adrenal insufficiency was more frequent in the current study, but this could be managed with supportive endocrinological care such as cortisol replacement.

DOI： 10.1007/s10147-021-02021-8

転移性トリプルネガティブ乳癌の予後にエフェクターT細胞遺伝子シグネチャーが及ぼす影響(Prognostic impact of effector T cell gene signature in metastatic triple-negative breast cancer)

谷岡真樹, 吉野友美, 吉田正行, 柳下薫寛, 斎藤亜由美, 矢崎秀, 千葉洋平, 奥屋俊宏, 小島勇貴, 西川忠曉, 須藤一起, 野口瑛美, 下井辰徳, 濱田哲暢, 米盛勧

日本乳癌学会総会プログラム抄録集 29回 17 - 17 2021.7

Independent Validation of the PAM50-Based Chemo-Endocrine Score (CES) in Hormone Receptor-Positive HER2-Positive Breast Cancer Treated with Neoadjuvant Anti-HER2-Based Therapy. International journal

Tomás Pascual, Aranzazu Fernandez-Martinez, Maki Tanioka, M Vittoria Dieci, Sonia Pernas, Joaquin Gavila, Valentina Guarnieri, Javier Cortes, Patricia Villagrasa, Núria Chic, Maria Vidal, Barbara Adamo, Montserrat Muñoz, Gaia Griguolo, Antonio Llombart, Pierfranco Conte, Mafalda Oliveira, Benedetta Conte, Laia Paré, Patricia Galvan, Lisa A Carey, Charles M Perou, Aleix Prat

Clinical cancer research : an official journal of the American Association for Cancer Research 27 ( 11 ) 3116 - 3125 2021.6

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: We do not yet have validated biomarkers to predict response and outcome within hormone receptor-positive/HER2-positive (HR+/HER2+) breast cancer. The PAM50-based chemo-endocrine score (CES) predicts chemo-endocrine sensitivity in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer. Here, we evaluate the relationship of CES with response and survival in HR+/HER2+ breast cancer. EXPERIMENTAL DESIGN: Intrinsic subtype and clinicopathologic data were obtained from seven studies in which patients were treated with HER2-targeted therapy either with endocrine therapy (ET) or with chemotherapy (CTX). CES was evaluated as a continuous variable and categorically from low to high scores [CES-C (chemo-sensitive), CES-U (uncertain), and CES-E (endocrine-sensitive)]. We first analyzed each dataset individually, and then all combined. Multivariable analyses were used to test CES association with pathologic complete response (pCR) and disease-free survival (DFS). RESULTS: A total of 457 patients were included (112 with ET and 345 with CTX). In the combined cohort, CES-C, CES-U, and CES-E were identified in 60%, 23%, and 17% of the patients, respectively. High CES (i.e., CES-E) was associated with a lower probability of achieving pCR independently of clinical characteristics, therapy, intrinsic subtype, and study (adjusted OR = 0.42; P = 0.016). A total of 295 patients were analyzed for DFS with a median follow-up of 66 months. High CES was also associated with better DFS (adjusted HR, 0.174; P = 0.003) independently of pCR, clinical characteristics and intrinsic subtype. In patients with residual disease, the adjusted DFS HR of CES was 0.160 (P = 0.012). CONCLUSIONS: In HER2+/HR+ breast cancer, CES is useful for predicting chemo-endocrine sensitivity and provides additional prognostication beyond intrinsic subtype and clinicopathologic characteristics.

DOI： 10.1158/1078-0432.CCR-20-4102

FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036. International journal

Steven P Angus, Timothy J Stuhlmiller, Gaurav Mehta, Samantha M Bevill, Daniel R Goulet, J Felix Olivares-Quintero, Michael P East, Maki Tanioka, Jon S Zawistowski, Darshan Singh, Noah Sciaky, Xin Chen, Xiaping He, Naim U Rashid, Lynn Chollet-Hinton, Cheng Fan, Matthew G Soloway, Patricia A Spears, Stuart Jefferys, Joel S Parker, Kristalyn K Gallagher, Andres Forero-Torres, Ian E Krop, Alastair M Thompson, Rashmi Murthy, Michael L Gatza, Charles M Perou, H Shelton Earp, Lisa A Carey, Gary L Johnson

NPJ breast cancer 7 ( 1 ) 51 - 51 2021.5

Language：English Publishing type：Research paper (scientific journal)

Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2+ cell line responses to inhibition with lapatinib were analyzed by RNAseq and ChIPseq to characterize transcriptional and epigenetic changes. Motif analysis of lapatinib-responsive genomic regions implicated the pioneer transcription factor FOXA1 as a mediator of adaptive responses. Lapatinib in combination with FOXA1 depletion led to dysregulation of enhancers, impaired adaptive upregulation of HER3, and decreased proliferation. HER2-directed therapy using clinically relevant drugs (trastuzumab with or without lapatinib or pertuzumab) in a 7-day clinical trial designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures. This highlights the importance of the immune response to anti-HER2 antibodies and suggests that inhibiting FOXA1-mediated adaptive responses in combination with HER2 targeting is a potential therapeutic strategy.

DOI： 10.1038/s41523-021-00258-0

Impact of ALK Inhibitors in Patients With ALK-Rearranged Nonlung Solid Tumors. International journal

Yuki Takeyasu, Hitomi S Okuma, Yuki Kojima, Tadaaki Nishikawa, Maki Tanioka, Kazuki Sudo, Tatsunori Shimoi, Emi Noguchi, Ayumu Arakawa, Taisuke Mori, Kuniko Sunami, Takashi Kubo, Takashi Kohno, Yoshida Akihiko, Noboru Yamamoto, Kan Yonemori

JCO precision oncology 5 2021

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Anaplastic lymphoma kinase (ALK) rearrangement is a well-known driver oncogene in non-small-cell lung cancer and has also been identified in other types of tumors. However, there is limited evidence on the clinical response to ALK tyrosine kinase inhibitors (TKIs), such as alectinib and crizotinib, in rare tumors with ALK fusion. We evaluated the therapeutic effect of ALK-TKIs in rare ALK-rearranged tumors. PATIENTS AND METHODS: Between April 2012 and April 2019, clinical outcomes and characteristics of patients with ALK-rearranged nonlung solid tumors who received ALK-TKIs (alectinib and/or crizotinib) outside of clinical trials were reviewed. Expression and/or rearrangement of ALK was evaluated by immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing. The tumor response was assessed according to RECIST (version 1.1). Progression-free survival was estimated from initial ALK-TKI initiation until progression. RESULTS: We identified seven patients (inflammatory myofibroblastic tumors, n = 3; ALK-positive histiocytosis, n = 1; histiocytic sarcoma, n = 1; osteosarcoma, n = 1; and parotid adenocarcinoma, n = 1), with a median age of 17 years. Two rare ALK fusions, namely, CTNNA1-ALK and ITSN2-ALK, were identified. As initial ALK-TKI therapy, five patients received alectinib and two received crizotinib. The objective response rate for the initial ALK-TKI therapy was 85.7% (95% CI, 44 to 97), including two patients who received alectinib and achieved complete response. The median progression-free survival was 8.1 months (range, 1.7 to not estimable). There were no treatment interruptions or dose reductions because of adverse events caused by alectinib. CONCLUSION: This study highlights the potential benefit of ALK-TKIs, especially alectinib, in patients with ALK-rearranged nonlung solid tumors.

DOI： 10.1200/PO.20.00383

Clinical Utility of Circulating Tumor DNA in Advanced Rare Cancers. International journal

Hitomi Sumiyoshi Okuma, Kan Yonemori, Yuki Kojima, Maki Tanioka, Kazuki Sudo, Emi Noguchi, Susumu Hijioka, Keiko Wakakuwa, Ken Kato, Akihiro Hirakawa, Aya Kuchiba, Takashi Kubo, Hitoshi Ichikawa, Akihiko Yoshida, Yasushi Yatabe, Kenichi Nakamura, Hiroyuki Mano, Noboru Yamamoto, Yasuhiro Fujiwara

Frontiers in oncology 11 732525 - 732525 2021

Language：English Publishing type：Research paper (scientific journal)

Purpose: Patients with advanced/relapsed rare cancers have few treatment options. Analysis of circulating tumor DNA in plasma may identify actionable genomic biomarkers using a non-invasive approach. Patients and Methods: Rare cancer patients underwent prospective plasma-based NGS testing. Tissue NGS to test concordance was also conducted. Plasma DNA alterations were assessed for incidence, functional impact, therapeutic implications, correlation to survival, and comparison with tissue NGS. Results: Ninety-eight patients were analyzed. Diseases included soft-tissue sarcoma, ovarian carcinoma, and others. Mean turn-around-time for results was 9.5 days. Seventy-six patients had detectable gene alterations in plasma, with a median of 2.8 alterations/patient. Sixty patients had a likely pathogenic alteration. Five received matched-therapy based on plasma NGS results. Two developed known resistance mutations while on targeted therapy. Patients with an alteration having VAF ≥5% had a significantly shorter survival compared to those of lower VAF. Tissue NGS results from eleven of 22 patients showed complete or partial concordance with plasma NGS. Conclusion: Plasma NGS testing is less invasive and capable of identifying alterations in advanced rare cancers in a clinically meaningful timeframe. It should be further studied as a prospective enrollment assay in interventional studies for patients with rare advanced stage cancers. Clinical Registration: [https://www.umin.ac.jp/ctr/index-j.htm], identifier UMIN000034394.

DOI： 10.3389/fonc.2021.732525

Neoadjuvant chemotherapy promotes the expression of HER3 in patients with ovarian cancer. International journal

Takaaki Mizuno, Yuki Kojima, Kan Yonemori, Hiroshi Yoshida, Yukiko Sugiura, Yohei Ohtake, Hitomi S Okuma, Tadaaki Nishikawa, Maki Tanioka, Kazuki Sudo, Akihiko Shimomura, Emi Noguchi, Tomoyasu Kato, Tatsunori Shimoi, Masaya Uno, Mitsuya Ishikawa, Yasuhiro Fujiwara, Yuichiro Ohe, Kenji Tamura

Oncology letters 20 ( 6 ) 336 - 336 2020.12

Language：English Publishing type：Research paper (scientific journal)

HER3 (erbB3) signaling serves an important role in the development and chemoresistance of ovarian cancer, and is activated by chemotherapy. To evaluate the influence of neoadjuvant chemotherapy and other clinical factors on the expression of HER3, as well as to examine its role as a prognostic marker, the present study evaluated archived tissues from patients who underwent surgery for ovarian cancer between 2011 and 2018 at our hospital. Immunohistochemical staining for HER3 was performed using formalin-fixed paraffin-embedded surgical specimens and biopsy samples. In total, data from 111 patients with sufficient surgically resected tumor samples were extracted. A total of 28 patients with histology type high-grade serous carcinoma (HGSC) had specimens available from both pre-chemotherapy biopsies and post-chemotherapy surgery. High HER3 expression (HER3-high) was observed in 64 patients (58%), whereas low HER3 expression (HER3-low) was observed in 47 patients (42%). Multivariate logistic regression analysis identified neoadjuvant chemotherapy [odds ratio (OR), 7.49; 95% confidence interval (CI), 2.48-22.64; P<0.001) and non-HGSC histology (OR, 5.42; 95% CI, 1.99-14.78; P<0.001) as significant predictive factors for HER3-high. In pre-chemotherapy biopsy specimens, 15 patients were HER3-high and 13 were HER3-low. After chemotherapy, eight of 13 patients with HER3-low exhibited a change in status to HER3-high, with a trend toward poorer progression-free survival compared to that of patients whose status remained HER3-low. In conclusion, HER3 overexpression was revealed to be common among patients with ovarian cancer, especially in those with non-HGSC histology. In addition, HER3 expression may be promoted by chemotherapy. These findings suggested that patients with ovarian cancer are good candidates for emerging HER3-targeting therapies.

DOI： 10.3892/ol.2020.12200

HER3 protein expression as a risk factor for post-operative recurrence in patients with early-stage adenocarcinoma and adenosquamous carcinoma of the cervix. International journal

Takaaki Mizuno, Yuki Kojima, Kan Yonemori, Hiroshi Yoshida, Yukiko Sugiura, Yohei Ohtake, Hitomi S Okuma, Tadaaki Nishikawa, Maki Tanioka, Kazuki Sudo, Akihiko Shimomura, Emi Noguchi, Tomoyasu Kato, Tatsunori Shimoi, Masaya Uno, Mitsuya Ishikawa, Yasuhiro Fujiwara, Yuichiro Ohe, Kenji Tamura

Oncology letters 20 ( 4 ) 38 - 38 2020.10

Language：English Publishing type：Research paper (scientific journal)

Patients with cervical adenocarcinoma (AC) and adenosquamous carcinoma (ASC) have a poorer prognosis than those with squamous cell carcinoma (SCC). Erb-b2 receptor tyrosine kinase 3 (HER3) is a member of the epidermal growth factor receptor family and its expression is associated with unfavorable prognosis in several cancer types, including SCC of the cervix. As there is limited information on the prognostic value of HER3 for AC and ASC of the cervix, the present study aimed to evaluate the expression of HER3 and its impact on post-operative recurrence in patients with AC and ASC of the cervix. This retrospective study included 39 patients with early-stage AC and ASC who underwent primary surgery between January 1997 and December 2017. Immunohistochemical staining for HER3 was performed on formalin-fixed paraffin-embedded surgical specimens. The possible influence of HER3 expression on disease-free survival (DFS) was studied by using multivariate Cox regression with adjustment for established risk factors of post-operative recurrence. High expression of HER3 (HER3-high) was detected in 85.1% of cases of AC (23/27) and in 58.3% of cases of ASC (7/12). The median follow-up duration was 63.1 months and Kaplan-Meier analysis indicated that the 5-year DFS rates of patients with AC and ASC of the cervix were 56.7% in patients with HER3-high and 77.8% in patients with HER3-low (log rank, P=0.20). On multivariate analysis, HER3-high [hazard ratio (HR)=6.32, 95% CI: 1.10-36.26, P=0.039), pelvic lymph node metastasis (HR=7.61, 95% CI: 2.07-28.00, P=0.002) and vascular invasion (HR=4.28, 95% CI: 1.12-16.31, P=0.033) were indicated to be independent predictors of DFS. To date, the present study is the most comprehensive analysis to evaluate the expression of HER3 in patients with early-stage AC and ASC of the cervix. The results suggested that HER3 overexpression may be an independent risk factor for post-operative recurrence. However, these results and the prognostic value of HER3 should be confirmed in a larger sample.

DOI： 10.3892/ol.2020.11899

乳癌発症後に卵巣癌または膵臓癌を重複した患者に関する臨床病理学的検討

佐伯豪士, 谷岡真樹, 千葉洋平, 西川忠暁, 須藤一起, 下井辰徳, 野口瑛美, 米盛勧, 渡辺智子, 村田健, 森實千種, 加藤友康, 河野隆志, 首藤昭彦, 田村研治

日本癌治療学会学術集会抄録集 58回 P - 68 2020.10

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