Papers - Hayashida, Tetsu

Mindfulness-Based Cognitive Therapy for Psychological Distress, Fear of Cancer Recurrence, Fatigue, Spiritual Well-Being, and Quality of Life in Patients With Breast Cancer-A Randomized Controlled Trial.

Park S, Sato Y, Takita Y, Tamura N, Ninomiya A, Kosugi T, Sado M, Nakagawa A, Takahashi M, Hayashida T, Fujisawa D

Journal of pain and symptom management 60 ( 2 ) 381 - 389 2020.08

Joint Work,  ISSN  0885-3924

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Increased frequency of ESR1 mutation in metastatic breast cancer by dosing selective estrogen receptor modulator followed by aromatase inhibitor.

Takeshima K, Hayashida T, Maeda H, Nakashoji A, Yokoe T, Seki T, Takahashi M, Kitagawa Y

Oncology letters 20 ( 2 ) 1231 - 1238 2020.08

Joint Work,  ISSN  1792-1074

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A novel diagnostic system to evaluate epidermal growth factor receptor impact as a prognostic and therapeutic indicator for lung adenocarcinoma.

Takakuwa K, Mogushi K, Han M, Fujii T, Hosoya M, Yamanami A, Akita T, Yamashita C, Hayashida T, Kato S, Yamaguchi S

Scientific reports 10 ( 1 ) 6214 2020.04

Joint Work

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Evaluation of the Japanese Version of the Cancer Survivors' Unmet Needs Scale.

Komatsu H, Yagasaki K, Sato Y, Arao H, Yamamoto S, Hayashida T

Asia-Pacific journal of oncology nursing 7 ( 2 ) 167 - 173 2020.04

Joint Work,  ISSN  2347-5625

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Identification of a Modified HOXB9 mRNA in Breast Cancer.

Nakashoji A, Hayashida T, Kawai Y, Kikuchi M, Watanuki R, Yokoe T, Seki T, Takahashi M, Miyao K, Yamaguchi S, Kitagawa Y

Journal of oncology 2020   6065736 2020

Joint Work,  ISSN  1687-8450

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A first Japanese case of neuroendocrine prostate cancer accompanied by lung and brain metastasis with somatic and germline BRCA2 mutation.

Kosaka T, Hongo H, Aimono E, Matsumoto K, Hayashida T, Mikami S, Nishihara H, Oya M

Pathology international 69 ( 12 ) 715 - 720 2019.12

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1320-5463

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THUMP domain containing 2 protein possibly induces resistance to cisplatin and 5-fluorouracil in in vitro human esophageal squamous cell carcinoma cells as revealed by transposon activation mutagenesis.

Hayashi M, Kawakubo H, Fukuda K, Mayanagi S, Nakamura R, Suda K, Hayashida T, Wada N, Kitagawa Y

The journal of gene medicine 21 ( 12 ) e3135 2019.12

Joint Work,  ISSN  1099-498X

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Intensive optimization and evaluation of global DNA methylation quantification using LC-MS/MS.

Nakagawa T, Wakui M, Hayashida T, Nishime C, Murata M

Analytical and bioanalytical chemistry 411 ( 27 ) 7221 - 7231 2019.10

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1618-2642

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Magnetically Promoted Rapid Immunofluorescence Staining for Frozen Tissue Sections

Onishi T., Matsuda S., Nakamura Y., Kuramoto J., Tsuruma A., Sakamoto S., Suzuki S., Fuchimoto D., Onishi A., Chikaki S., Kaneko M., Kuwahata A., Sekino M., Yasuno H., Hanyu N., Kurita T., Takei H., Sakatani T., Taruno K., Nakamura S., Hayashida T., Jinno H., Kusakabe M., Handa H., Kameyama K., Kitagawa Y.

Journal of Histochemistry and Cytochemistry (Journal of Histochemistry and Cytochemistry)  67 ( 8 ) 575 - 587 2019.08

Research paper (scientific journal), Joint Work, Accepted,  ISSN  00221554

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© The Author(s) 2019. Current immunohistochemistry methods for diagnosing abnormal cells, such as cancer cells, require multiple steps and can be relatively slow compared with intraoperative frozen hematoxylin and eosin staining, and are therefore rarely used for intraoperative examination. Thus, there is a need for novel rapid detection methods. We previously demonstrated that functionalized fluorescent ferrite beads (FF beads) magnetically promoted rapid immunoreactions. The aim of this study was to improve the magnetically promoted rapid immunoreaction method using antibody-coated FF beads and a magnet subjected to a magnetic field. Using frozen sections of xenograft samples of A431 human epidermoid cancer cells that express high levels of epidermal growth factor receptor (EGFR) and anti-EGFR antibody-coated FF beads, we reduced the magnetically promoted immunohistochemistry procedure to a 1-min reaction and 1-min wash. We also determined the optimum magnetic force for the antibody reaction (from 7.79 × 10−15 N to 3.35 × 10−15 N) and washing (4.78 × 10−16 N), which are important steps in this technique. Furthermore, we stained paraffin-embedded tissue arrays and frozen sections of metastatic breast cancer lymph nodes with anti-pan-cytokeratin antibody-coated FF beads to validate the utility of this system in clinical specimens. Under optimal conditions, this ultra-rapid immunostaining method may provide an ancillary method for pathological diagnosis during surgery. (J Histochem Cytochem 58:XXX–XXX, 2010).

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Optimal use of anthracycline-free perioperative chemotherapy in HER2-positive breast cancer patients

Watanuki R., Hayashida T., Kawai Y., Kikuchi M., Nakashoji A., Yokoe T., Toyota T., Seki T., Takahashi M., Kitagawa Y.

International Journal of Clinical Oncology (International Journal of Clinical Oncology)  24 ( 7 ) 807 - 814 2019.07

Research paper (scientific journal), Joint Work, Accepted,  ISSN  13419625

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© 2019, Japan Society of Clinical Oncology. Purpose: In adjuvant settings of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, anthracycline-based chemotherapy followed by taxane and trastuzumab is a standard regimen. Recent studies have reported the use of anthracycline-free adjuvant chemotherapy in selected HER2-positive breast cancer patients. We conducted a single-center retrospective study to identify the characteristics of HER2-positive breast cancer patients for whom anthracyclines can be safely omitted. Methods: A total of 238 women were diagnosed with HER2-positive breast cancer and treated with neoadjuvant and/or adjuvant chemotherapy between January 1, 2008 and December 31, 2015 at Keio University Hospital. They were divided in two cohorts: an “anthracycline” cohort of 112 anthracycline-treated women and a “no anthracycline” cohort of 126 anthracycline-untreated women. Survival outcomes were estimated by Kaplan–Meier method. Results: The 3-year disease-free survival rates in the no-anthracycline and anthracycline cohorts were 91.3% and 93.1%, respectively (P = 0.692). After using a statistical method with inverse probability of treatment weighting to minimize the selection bias, no significant differences were observed between the two cohorts (adjusted hazard ratio for disease-free survival: 1.042; P = 0.909). Stratified by tumor size, no significant differences were observed between the two cohorts in the cT1N0 and cT2N0 subsets (P = 0.516 and P = 0.579, respectively). The recurrence rate was low among patients who achieved pathological complete response after receiving neoadjuvant chemotherapy with or without anthracyclines. Conclusion: Our study suggests that anthracyclines can be safely omitted in selected patients with HER2-positive breast cancer, who have cT1N0 or cT2N0 and achieved pathological complete response after receiving neoadjuvant chemotherapy.

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Effectiveness of Antiemetic Regimens for Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: A Systematic Review and Network Meta-Analysis

Yokoe T., Hayashida T., Nagayama A., Nakashoji A., Maeda H., Seki T., Takahashi M., Takano T., Abe T., Kitagawa Y.

Oncologist (Oncologist)  24 ( 6 ) e347 - e357 2019.06

Research paper (scientific journal), Joint Work, Accepted,  ISSN  10837159

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© AlphaMed Press 2018 Background: It is important to control chemotherapy-induced nausea and vomiting (CINV) to maintain dose intensity and patients' quality of life. The National Comprehensive Cancer Network guidelines suggest combination therapy of antiemetic agents. The growing number of antiemetic regimens, and in particular the growing use of regimens containing antagonists to the Nk-1 receptor (NK1RAs) and the antipsychotic drug olanzapine (OLZ), call for the re-evaluation of the optimal regimen for CINV. This study assessed the efficacy and safety of antiemetic regimens for highly emetogenic chemotherapy, using Bayesian network meta-analysis. Methods: Randomized trials that compared different antiemetic regimens were included. We strictly followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The main outcomes were the odds ratio (OR) for overall complete response (absence of vomiting). We conducted network meta-analysis within a Bayesian model to combine the direct and indirect evidence. Safety was assessed from the trial description. All statistical tests were two-sided. Results: We systematically reviewed 27 randomized control trials (13,356 participants), which compared 12 different antiemetic regimens: serotonin-3 receptor antagonist (5HT3), 5HT3 + dexamethasone (Dex), palonosetron (PAL), PAL + Dex, PAL at 0.75 mg (PAL0.75), PAL0.75 + Dex, NK1RA + 5HT3 + Dex, NK1RA + PAL + Dex, an oral combination of netupitant and palonosetron (NEPA) + Dex, OLZ + 5HT3 + Dex, OLZ + PAL + Dex, and OLZ + NK1RA + 5HT3 + Dex. An NK1RA + 5HT3 + Dex regimen and an NK1RA + palonosetron + Dex regimen gave a higher complete response (CR) rate than the reference regimen, 5HT3 + Dex (OR, 1.75; 95% credibility interval [95% CrI], 1.56–1.97, and OR, 2.25; 95% CrI, 1.66–3.03, respectively). A regimen containing NEPA was more effective in producing CR than conventional regimens without NEPA or olanzapine. Further analysis, based on the surface under the cumulative ranking probability curve, indicated that olanzapine-containing regimens were the most effective in producing CR. Conclusion: Our meta-analysis supports the conclusion that olanzapine-containing regimens are the most effective for CINV of highly emetogenic chemotherapy. We confirmed that NK1RA + PAL + Dex is the most effective of conventional regimens. Substituting olanzapine for an Nk-1 receptor antagonist may offer a less costly and more effective alternative for patients. Implications for Practice: Nausea and vomiting during chemotherapy often pose difficulties for patients and doctors, making it hard to continue the proper therapy and to maintain the quality of life. This article gives insights into the optimal choice of medicine to treat nausea during chemotherapy. The findings reported here provide readers with a robust efficacy ranking of antinausea medicine, which can be used as a reference for the best possible treatment. Furthermore, the 70% less costly drug, olanzapine, is suggested to be equally effective to aprepitant in reducing nausea and vomiting. The possibility of offering a cost-effective treatment to a wider range of the population is discussed.

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Establishment of a model of sentinel lymph node metastasis using immunodeficient swine

Kurihara T., Matsuda S., Nakamura Y., Suzuki S., Fuchimoto D., Onishi A., Saeki K., Nakagawa T., Fujiwara R., Kamata M., Kuramoto J., Kameyama K., Sekino M., Kusakabe M., Hayashida T., Jinno H., Kitagawa Y.

Scientific reports (Scientific reports)  9 ( 1 ) 7923 2019.05

Research paper (scientific journal), Joint Work, Accepted

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Lymph node metastasis occurs via the migration of cancer cells through the lymphatic system. Sentinel lymph node (SLN) biopsy is a common diagnostic strategy. SLNs have been studied using healthy rodents and large animals without metastasis. Here we used immunodeficient swine to establish a model of lymph node metastasis. We used RAG2-knockout immunodeficient swine. A431 human epithelial carcinoma cells expressing green fluorescent protein were injected subcutaneously into the posterior sides of the auricle, forelimb and hindlimb of knockout swine. Indigo carmine dye was injected subcutaneously 8 weeks after tumour cell transplantation. SLNs were extracted, observed using a stereoscopic fluorescence microscope and analysed histologically using haematoxylin and eosin staining, and immunohistochemistry. Lymphoid follicles were found in wild-type swine, and a few aggregated lymphocytes and immature lymphoid follicles were observed in knockout swine. Fluorescence in the lymph nodes indicated metastasis of tumour cells to the lymph nodes. Tumour cells replaced lymph node architectures, showed high-grade nuclear atypia and formed irregular tumour nests. Our model may be useful for the preclinical validation of diagnostic methods and minimally invasive treatment of metastatic cancer.

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Experimental and clinicopathological analysis of HOXB9 in gastric cancer

Kato F., Wada N., Hayashida T., Fukuda K., Nakamura R., Takahashi T., Kawakubo H., Takeuchi H., Kitagawa Y.

Oncology Letters (Oncology Letters)  17 ( 3 ) 3097 - 3102 2019.03

Research paper (scientific journal), Joint Work, Accepted,  ISSN  17921074

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© 2019, Spandidos Publications. All rights reserved. The association between homeobox (HOX)B9 expression and tumor malignancy was identified recently. It was reported that HOXB9 induced tumor angiogenesis, and associated with poor prognosis in patients with breast and colon cancer. On the other hand, regional lymph nodes are the most common site of tumor spread, and lymph node metastasis is a major prognostic factor in gastric cancer. It was hypothesized that HOXB9 promotes tumor lymphangiogenesis and induces tumor progression, invasion and metastasis in gastric cancer. The aim of the present study was to evaluate the correlation between HOXB9 expression, prognosis and clinicopathologic factors in patients with gastric cancer, and to assess the contribution of HOXB9 expression to tumor cell lymphangiogenesis in vitro. HOXB9 expression was evaluated by immunohistochemistry in resected tumor tissues from 58 patients with gastric cancer, and the association between prognosis and clinicopathologic factors was determined. HOXB9 gene was overexpressed in human gastric cancer TMK-1 cells and the effect of HOXB9 overexpression on the expression of vascular endothelial growth factor (VEGF)-C, VEGF-D and VEGF receptor (R)-3 was determined. It was demonstrated that the depth of tumor invasion, the number of node metastases, lymphatic invasion and vascular invasion were significantly associated with HOXB9 expression. Overall survival was decreased in patients with HOXB9 expression. The mRNA expression of VEGF-D but not of VEGF-C and VEGFR-3 was increased in HOXB9-overexpressing TMK-1 cells compared with control cells. In conclusion, HOXB9 expression was positively correlated with gastric cancer progression and lymphangiogenesis marker expression. HOXB9 may be associated with lymphogenic metastasis.

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Clinicopathologic features of hormone-receptor-positive breast cancer patients with late recurrence

Murata T., Jinno H., Takahashi M., Shimoda M., Hayashida T., Kameyama K., Kitagawa Y.

Breast Journal (Breast Journal)  25 ( 1 ) 9 - 15 2019.01

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1075122X

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© 2018 Wiley Periodicals, Inc. The number of long-term breast cancer survivors with a risk of late recurrence is increasing. Hormone-receptor-positive patients have greater risks of late recurrence. Although several studies demonstrated that extended adjuvant endocrine therapy reduces the incidence of late recurrence, it remains unclear which hormone-receptor-positive patients have greater risks of late recurrence. Hormone-receptor-positive breast cancer patients were retrospectively selected from the prospective database of primary breast cancer patients treated at Keio University Hospital from January 1989 to December 2003. Late recurrence was defined as initial recurrence after 5 years from the initial surgery. We evaluated the clinicopathologic features of breast cancer patients with late recurrence. At a median follow-up of 10.9 years (range, 5.1-23.8), 371 patients had no recurrence, 90 had early recurrence (within 5 years), and 83 had late recurrence. Multivariate analysis revealed that >4 involved lymph nodes were significant risk factors for late recurrence (P <.001), whereas 1-3 positive nodes were not. Endocrine therapy significantly reduced the incidence of late recurrence (P <.001). After menopause, adjuvant therapy with aromatase inhibitors resulted in longer disease-free survival than tamoxifen (10-year disease-free survival: 97.6% vs 89.7%, P =.0955). High nodal involvement was significantly correlated with late recurrence in hormone-receptor-positive breast cancer patients. Hormone-receptor-positive breast cancer patients who receive adjuvant endocrine therapy with tamoxifen alone might be candidates for extended endocrine therapy.

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Fatty acid β-oxidation-dependent and -independent responses and tumor aggressiveness acquired under mild hypoxia

Wakui M., Kawai K., Mizushima T., Nishime C., Serizawa A., Suemizu H., Asakura K., Yamauchi Y., Hayashida T., Suematsu M., Murata M.

Anticancer Research (Anticancer Research)  39 ( 1 ) 191 - 200 2019.01

Research paper (scientific journal), Joint Work, Accepted,  ISSN  02507005

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© 2019 International Institute of Anticancer Research. All Rights Reserved. Background/Aim: The present study assessed whether and how tumor cells undergoing hypoxia contribute to disease progression after moving to areas with different oxygen conditions. Materials and Methods: Human colorectal carcinoma HCT116 cells cultured under mild hypoxia were subjected to in vivo experiments using transfer to immunodeficient murine recipients and to in vitro experiments using pharmacological inhibition of fatty acid β-oxidation (FAO). Results: Bone involvement and hepatic metastases were accelerated in transfer models of hypoxically cultured HCT116 cells. Hypoxic HCT116 cells exhibited FAO-dependent glycogen synthesis. FAO-dependent and -independent induction of gene expression also occurred under hypoxia. The distribution of glucose transporter 1 expression compared with heme oxygenase 1 expression in HCT116 cell spheroids seemed consistent with differential dependence of hypoxic expression of these molecules on FAO. Conclusion: These results provide insights into the contribution of hypoxia to tumor progression and the relevance of FAO.

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Salivary metabolomics with alternative decision tree-based machine learning methods for breast cancer discrimination

Murata T., Yanagisawa T., Kurihara T., Kaneko M., Ota S., Enomoto A., Tomita M., Sugimoto M., Sunamura M., Hayashida T., Kitagawa Y., Jinno H.

Breast Cancer Research and Treatment (Breast Cancer Research and Treatment)  177 ( 3 ) 591 - 601 2019

Research paper (scientific journal), Joint Work, Accepted,  ISSN  01676806

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© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Purpose: The aim of this study is to explore new salivary biomarkers to discriminate breast cancer patients from healthy controls. Methods: Saliva samples were collected after 9 h fasting and were immediately stored at − 80 °C. Capillary electrophoresis and liquid chromatography with mass spectrometry were used to quantify hundreds of hydrophilic metabolites. Conventional statistical analyses and artificial intelligence-based methods were used to assess the discrimination abilities of the quantified metabolites. A multiple logistic regression (MLR) model and an alternative decision tree (ADTree)-based machine learning method were used. The generalization abilities of these mathematical models were validated in various computational tests, such as cross-validation and resampling methods. Results: One hundred sixty-six unstimulated saliva samples were collected from 101 patients with invasive carcinoma of the breast (IC), 23 patients with ductal carcinoma in situ (DCIS), and 42 healthy controls (C). Of the 260 quantified metabolites, polyamines were significantly elevated in the saliva of patients with breast cancer. Spermine showed the highest area under the receiver operating characteristic curves [0.766; 95% confidence interval (CI) 0.671–0.840, P < 0.0001] to discriminate IC from C. In addition to spermine, polyamines and their acetylated forms were elevated in IC only. Two hundred each of two-fold, five-fold, and ten-fold cross-validation using different random values were conducted and the MLR model had slightly better accuracy. The ADTree with an ensemble approach showed higher accuracy (0.912; 95% CI 0.838–0.961, P < 0.0001). These prediction models also included spermine as a predictive factor. Conclusions: These data indicated that combinations of salivary metabolomics with the ADTree-based machine learning methods show potential for non-invasive screening of breast cancer.

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IgG4-related mastopathy: A case report and literature review

Yokoe T., Hayashida T., Kikuchi M., Watanuki R., Nakashoji A., Maeda H., Toyota T., Seki T., Takahashi M., Iwasaki E., Mikami S., Kameyama K., Kitagawa Y.

Clinical Case Reports (Clinical Case Reports)  6 ( 8 ) 1549 - 1553 2018.08

Research paper (scientific journal), Joint Work, Accepted,  ISSN  2050-0904

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© 2018 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd. IgG4-related sclerosing disease (IgG4-RD) occasionally involves breast entity, which is often difficult to distinguish from malignant tumor, as both radiologically resembles. We report a case of a breast mass diagnosed as IgG4-related mastopathy (IgG4-RM) through needle biopsy, which responded well to glucocorticoid therapy. Unnecessary excision should be avoided.

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Antitumor effect of lapatinib and cytotoxic agents by suppression of E2F1 in HER2-positive breast cancer

Matsumoto A., Hayashida T., Takahashi M., Jinno H., Kitagawa Y.

Molecular Medicine Reports (Molecular Medicine Reports)  18 ( 1 ) 958 - 964 2018.07

Research paper (scientific journal), Joint Work, Accepted,  ISSN  17912997

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Copyright © Spandidos Publications 2017. All rights reserved. The human epidermal growth factor receptor 2 (HER2)-targeting agent, lapatinib, combined with oral fluoropyrimidine capecitabine, has been previously demonstrated to be an effective treatment option for patients with trastuzumab-resistant HER2-positive metastatic breast cancer. To investigate the molecular mechanisms associated with the interactions between lapatinib and capecitabine, the effect of treatment with lapatinib and phosphatidylinositol-4,5-bispho-sphate 3-kinase (PI3K) inhibitors on the expression of E2F transcription factor 1 (E2F1) and thymidylate synthase (TS), which is associated with an increased response to 5-fluorouracil (5-FU)-based chemotherapy, was determined in HER2-positive breast cancer cells. The results of reverse transcription-quantitative polymerase chain reaction demonstrated that administration of lapatinib and PI3K inhibitors decreased the mRNA expression of TS and E2F1, a transcription factor that promotes TS gene expression, in SKBR3 and T47D cell lines. Furthermore, treatment with lapatinib and PI3K inhibitors also suppressed the mRNA expression of ribonucleotide reductase M1 subunit (RRM1), an important determinant of gemcitabine resistance, and DNA topoisomerase II-? (TOP2A), a molecular target of anthracyclines, in SKBR3 and T47D cell lines. Western blot analysis further demonstrated that the phosphorylation of Akt was inhibited by lapatinib, and the results of the MTT assay revealed that the combination of lapatinib with either 5-FU or gemcitabine demonstrated synergistic antitumor effects, whereas a combinatory treatment of lapatinib with epirubicin, a typical anthracycline drug, exhibited antagonistic antitumor effects in HER2-positive breast cancer cells. These results indicate that the synergistic antitumor effects exhibited by combinatory treatment of lapatinib with capecitabine may be induced via the suppression of E2F1-mediated TS expression.

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Phase II trial of eribulin mesylate as a first- or second-line treatment for locally advanced or metastatic breast cancer: A multicenter, single-arm trial

Hayashida T., Jinno H., Mori K., Sato H., Matsui A., Sakurai T., Hattori H., Takayama S., Wada M., Takahashi M., Seki H., Seki T., Nagayama A., Matsumoto A., Kitagawa Y.

BMC Cancer (BMC Cancer)  18 ( 1 ) 701 2018.06

Research paper (scientific journal), Joint Work, Accepted

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© 2018 The Author(s). Background: Eribulin mesylate is currently indicated as a sequential monotherapy to be administered after two chemotherapeutic regimens, including anthracycline and taxane treatments, for treatment of metastatic breast cancer. This open-label, multicenter phase II study was designed to evaluate the efficacy and safety of eribulin as a first- or second-line treatment for patients with metastatic breast cancer. Methods: The primary objective was to determine the overall response rate. Secondary objectives were to evaluate progression-free survival and the safety profile. Patients were scheduled to receive eribulin mesylate 1.4 mg/m 2 intravenously on days 1 and 8 of a 21-day cycle. Patients received the study treatment unless disease progression, unacceptable toxicity, or a request to discontinue from the patient and/or investigator eventuated. Results: Between December 2012 and September 2015, 32 patients with metastatic breast cancer were enrolled at 10 participating clinical institutions in Japan, and toxicity and response rates were evaluated. The overall response rate was 43.8% (95% confidence interval [CI] 26.5-61.0). The clinical benefit and tumor control rates were 56.3% (95% CI 39.0-73.5) and 78.1% (95% CI 63.8-92.5), respectively. Median progression-free survival was 8.3 months (95% CI 7.1-9.4). A subgroup analysis did not identify any factors affecting the efficacy of eribulin. The most common adverse events were neutropenia (71.9%), alopecia (68.7%), and peripheral neuropathy (46.9%). As a first- or second-line therapy, eribulin showed sufficient efficacy for metastatic breast cancer compared with taxane and capecitabine treatment in previous clinical trials. The safety profile of eribulin was acceptable. Conclusions: Eribulin may be another option for first-line chemotherapeutic regimens for metastatic breast cancer.

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The updated network meta-analysis of neoadjuvant therapy for HER2-positive breast cancer

Nakashoji A., Hayashida T., Yokoe T., Maeda H., Toyota T., Kikuchi M., Watanuki R., Nagayama A., Seki T., Takahashi M., Abe T., Kitagawa Y.

Cancer Treatment Reviews (Cancer Treatment Reviews)  62   9 - 17 2018.01

Research paper (scientific journal), Joint Work, Accepted,  ISSN  03057372

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© 2017 Elsevier Ltd Background We previously described a systematic assessment of the neoadjuvant therapies for human epidermal growth factor receptor-2 (HER2) positive breast cancer, using network meta-analysis. Accumulation of new clinical data has compelled us to update the analysis. Methods Randomized trials comparing different anti-HER2 regimens in the neoadjuvant setting were included, and odds ratio for pathologic complete response (pCR) in seven treatment arms were assessed by pooling effect sizes. Direct and indirect comparisons using a Bayesian statistical model were performed. All statistical tests were two-sided. Results A database search identified 993 articles with 13 studies meeting the eligibility criteria, including three new studies with lapatinib (lpnb). In an indirect comparison, dual anti-HER2 agents with CT achieved a better pCR rate than other arms. The credibility intervals of CT + tzmb + lpnb arm were largely reduced compared to our former report, which we added sufficient clinical evidence by this update. Values of surface under the cumulative ranking (SUCRA) suggested that CT + tzmb + pzmb had the highest probability of being the best treatment arm for pCR, widening the difference between the top two dual-HER2 blockade arms compared to our former report. The overall consistency with our first report enhanced the credibility of the results. Conclusion Network meta-analysis using new clinical data firmly establish that combining two anti-HER2 agents with CT is most effective against HER2-positive breast cancer in the neoadjuvant setting. New pzmb related trials are required to fully determine the best neoadjuvant dual-HER2 blockade regimen.

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