Search

Tatsunori Shimoi,1 Akihiko Shimomura,1 Tadahiko Shien,2 Yukari Uemura,3 Hiroaki Kato,4 Masahiro Kitada,5 Tatsuya Toyama,6 Tomohiko Aihara,7 Hirofumi Mukai8 1Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan; 2Department of Breast and Endocrine Surgery, Okayama University Hospital, Okayama, Japan; 3Division of Biostatistics, Clinical Research Support Center, Tokyo University Hospital, Tokyo, Japan; 4Department of Thoracic Surgery, Teine Keijinkai Hospital, Sapporo, Japan; 5Department of Surgery, Asahikawa Medical University, Asahikawa, Japan; 6Department of Oncology, Immunology and Surgery, Nagoya City University, Graduate School of Medical Science, Nagoya, Japan; 7Department of Breast Surgery, Keimeikai-Aihara Hospital, Osaka, Japan; 8Department of Breast and Medical Oncology, National Cancer Center Hospital East, Chiba, Japan Background: This is a randomized, multicenter, open-label, Phase II study designed to evaluate the efficacy of everolimus added to continuous aromatase inhibitor (AI) administration in patients who had maintained stable disease or a better response for at least 5 months.Patients and methods: Patients will be randomized to everolimus and standard therapy groups (1:1 ratio). In the everolimus group, patients will receive everolimus in addition to the AI agent. The standard therapy group will continue AI alone treatment. The primary endpoint is progression-free survival. Target accrual is 130 patients with a two-sided type I error rate of 10% and 80% power to detect 35% risk reduction.Conclusion: The Chloe trial will provide important information about the efficacy and safety of adding everolimus to AI in patients with estrogen receptor-positive and human epidermal growth factor 2-negative metastatic breast cancer. Keywords: hormone receptor-positive, breast cancer, aromatase inhibitor, everolimus

Munehiro Kitada,1,2 Yoshio Ogura,2 Daisuke Koya1,2 1Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, 2Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, Japan Abstract: Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes. In addition, db/db mice, KK-Ay mice, Zucker diabetic fatty rats, Wistar fatty rats, Otsuka Long-Evans Tokushima Fatty rats and Goto-Kakizaki rats serve as rodent models of type 2 diabetes. An animal model of diabetic nephropathy should exhibit progressive albuminuria and a decrease in renal function, as well as the characteristic histological changes in the glomeruli and the tubulointerstitial lesions that are observed in cases of human diabetic nephropathy. A rodent model that strongly exhibits all these features of human diabetic nephropathy has not yet been developed. However, the currently available rodent models of diabetes can be useful in the study of diabetic nephropathy by increasing our understanding of the features of each diabetic rodent model. Furthermore, the genetic background and strain of each mouse model result in differences in susceptibility to diabetic nephropathy with albuminuria and the development of glomerular and tubulointerstitial lesions. Therefore, the validation of an animal model reproducing human diabetic nephropathy will significantly facilitate our understanding of the underlying genetic mechanisms that contribute to the development of diabetic nephropathy. In this review, we focus on rodent models of diabetes and discuss the utility and limitations of these models for the study of diabetic nephropathy. Keywords: diabetic nephropathy, rodent model, albuminuria, mesangial matrix expansion, tubulointerstitial fibrosis

Current maritime transportation and shipping is characterized by rapid technological developments effecting the basic concepts of operating ships and even changing traditional paradigms of controlling ships. The e-Navigation concept of the International Maritime Organization (IMO) specifically aims at more comprehensive and reliable support of the human operators on-board and ashore. However, autonomous unmanned ships remote controlled or even autonomously navigating are expected to come soon. In this paper, selected operational aspects of maritime traffic merging conventional and unmanned remote controlled ships in coastal areas are discussed. Furthermore, some preliminary results of experimental simulation studies into a future scenario of maritime traffic are presented and preliminary conclusions in respect to job profiling and training requirements are discussed. [ABSTRACT FROM AUTHOR]

To characterize glucagon-like peptide (GLP)-1 signaling and its effect on renal endothelial dysfunction and glomerulopathy. We studied the expression and signaling of GLP-1 receptor (GLP-1R) on glomerular endothelial cells and the novel finding of protein kinase A-dependent phosphorylation of c-Raf at Ser259 and its inhibition of angiotensin II (Ang II) phospho-c-Raf(Ser338) and Erk1/2 phosphorylation. Mice overexpressing protein kinase C (PKC)β2 in endothelial cells (EC-PKCβ2Tg) were established. Ang II and GLP-1 actions in glomerular endothelial cells were analyzed with small interfering RNA of GLP-1R. PKCβ isoform activation induced by diabetes decreased GLP-1R expression and protective action on the renal endothelium by increasing its degradation via ubiquitination and enhancing phospho-c-Raf(Ser338) and Ang II activation of phospho-Erk1/2. EC-PKCβ2Tg mice exhibited decreased GLP-1R expression and increased phospho-c-Raf(Ser338), leading to enhanced effects of Ang II. Diabetic EC-PKCβ2Tg mice exhibited greater loss of endothelial GLP-1R expression and exendin-4-protective actions and exhibited more albuminuria and mesangial expansion than diabetic controls. These results showed that the renal protective effects of GLP-1 were mediated via the inhibition of Ang II actions on cRaf(Ser259) and diminished by diabetes because of PKCβ activation and the increased degradation of GLP-1R in the glomerular endothelial cells. [ABSTRACT FROM AUTHOR]

Insulin resistance has been associated with the progression of chronic kidney disease in both diabetes and obesity. In order to determine the cellular mechanisms contributing to this, we characterized insulin signaling in renal tubules and glomeruli during diabetic and insulin-resistant states using streptozotocin-diabetic and Zucker fatty-insulin-resistant rats. Compared with nondiabetic and Zucker lean rats, the insulin-induced phosphorylation of insulin receptor substrate-1 (IRS1), Akt, endothelial nitric oxide synthase, and glycogen synthase kinase 3α were selectively inhibited in the glomeruli but not in the renal tubules of both respective models. Protein, but not mRNA levels of IRS1, was decreased only in the glomeruli of streptozotocin-diabetic rats likely due to increased ubiquitination. Treatment with the protein kinase C-β inhibitor, ruboxistaurin, enhanced insulin actions and elevated IRS1 expression. In glomerular endothelial cells, high glucose inhibited the phosphorylation of Akt, endothelial nitric oxide synthase, and glycogen synthase kinase 3α; decreased IRS1 protein expression and increased its association with ubiquitin. Overexpression of IRS1 or the addition of ruboxistaurin reversed the inhibitory effects of high glucose. Thus, loss of insulin's effect on endothelial nitric oxide synthase and glycogen synthase kinase 3α activation may contribute to the glomerulopathy observed in diabetes and obesity. [ABSTRACT FROM AUTHOR]

The TP53 signature is considered a predictor of neoadjuvant chemotherapy (NAC) response and prognostic factor in breast cancer. The objective of this study was to confirm TP53 signature can predict pathological complete response (pCR) and prognosis in cohorts of breast cancer patients who received NAC in prospective studies. Development cohorts (retrospective [n = 37] and prospective [n = 216] cohorts) and validation cohorts (NAC administered prospective study cohorts [n = 407] and retrospective perioperative chemotherapy (PC)-naïve, hormone receptor (HrR)-positive cohort [PC-naïve_HrR+ cohort] [n = 322]) were used. TP53 signature diagnosis kit was developed using the development cohorts. TP53 signature predictability for pCR and the relationship between recurrence-free survival (RFS), overall survival (OS), and the TP53 signature were analyzed. The pCR rate of the mutant (mt) signature group was significantly higher than that of the wild-type (wt) signature group (odds ratio, 5.599; 95 % confidence interval = 1.876-16.705; P = 0.0008). The comparison of the RFS and OS between the HrR+ and HER2- subgroup of the NAC cohort and of the PC-naïve_HrR+ cohort indicated that the RFS and OS benefit of NAC was greater in the mt signature group than in the wt signature group. From post hoc analyses, the RFS and OS benefit from adding capecitabine to FEC+T as NAC might be observed only in the mt signature group. The TP53 signature can predict the pCR after NAC, and the RFS and OS benefit from NAC may be greater in the mt signature group than in the wt signature group., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ST reports honoraria from Ono, Chugai, Yakult Honsha, Taiho, Asahi Kasei Pharma, Eisai, Bristol-Myers Squibb and Eli Lilly; Prof. NM reports grants from Chugai, Eli Lilly, Astra Zeneca, Pfizer, Daiichi-Sankyo, MSD, Eisai, Novartis, Sanofi, Kyowa-Kirin, Nippon-Kayaku, Ono and Gilead Science, and honoraria from Chugai, Pfizer, Astra Zeneca, Eli Lilly and Daiichi-Sankyo, and Representative of a board of directors of JBCRG and Board of Directors of JBCS; MK reports honoraria from Pfizer, Daiichi-Sankyo, Astra Zeneca, Eli Lilly, Taiho, Kyowa-Kirin and Chugai; HI reports grants from Chugai, Daiichi-Sankyo and Astra Zeneca, and consulting fee from Daiichi-Sankyo, Chugai, Astra Zeneca, Eli Lilly, MSD, Pfizer and Gilead Science, and honoraria from Daiichi-Sankyo, Chugai, Astra Zeneca, Eli Lilly, MSD, Pfizer, Taiho and Kyowa-Kirin; TI reports honoraria from Pfizer, Kyowa-Kirin, Chugai, Daiichi-Sankyo, Astra Zeneca and Eli Lilly; TU reports grant from Eli Lilly, and honoraria from Chugai, Eisai, Astra Zeneca and Novartis; SO reports honoraria from Chugai, MSD, Nippon-Kayaku and Eli Lilly; HY reports grants from Eli Lilly and Eiken Kagaku; ET reports honoraria from Daiichi-Sankyo, Eli Lilly and Astra Zeneca; KA reports grants from Chugai, Eisai and Takeda, and consulting fee from Taiho, and honoraria from Chugai, Eisai, Astra Zeneca, Taiho, Novartis, Daiichi-Sankyo, Mochida, Ono, Pfizer, Eli Lilly, Terumo and Becton Dickinson; TT reports grants from Eli Lilly, Chugai, Eisai, Takeda, Kyowa-Kirin, Daiichi-Sankyo and Nippon-Kayaku, and honoraria from Daiichi-Sankyo, Pfizer, Novartis, Astra Zeneca, Chugai and Takeda; YY reports grants from Chugai, Kyowa-Kirin, Eisai, Daiichi-Sankyo, Nippon-Kayaku, Taiho, Takeda, Eli Lilly, Pfizer and Novartis, and honoraria from Astra Zeneca, Chugai, Kyowa-Kirin, Novartis, Eli Lilly, Pfizer, Daiichi-Sankyo, Nippon-Kayaku, Taiho, Eisai, Takeda, MSD, Sysmex and Exact Science, and participation on Advisory Board of Astra Zeneca, Chugai, Novartis, MSD, Eli Lilly, Pfizer and Daiichi-Sankyo, and member of the Board of Directors of JBCS and JBCRG; TY reports grants from Chugai, Taiho, Nippon-Kayaku and Kyowa-Kirin, and honoraria from Chugai, Eisai, Novartis, Taiho, Nippon-Kayaku, Astra Zeneca, Kyowa-Kirin, Pfizer, Eli Lilly and Daiichi-Sankyo; TY reports honoraria from Pfizer, Eli Lilly and Eisai; MT reports grants from Chugai, Takeda, Pfizer, JBCRG assoc., KBCRN assoc., Eisai, Eli Lilly, Daiichi-Sankyo, Astra Zeneca, Astellas, Shimadzu, Yakult, Nippon-Kayaku, AFI technology, Luxonus, Shionogi, GL Science and Sanwa Shurui, and honoraria from Chugai, Takeda, Pfizer, Kyowa-Kirin, Taiho, Eisai, Daiichi-Sankyo, Astra Zeneca, Eli Lilly, MSD, Exact Science, Novartis, Shimadzu, Yakult, Nippon-Kayaku, Devicore Medical Japan and Sysmex, and advisory board of Daiichi-Sankyo, Eli Lilly, BMS, Athenex Oncology, Bertis Terumo and Kansai Medical Net, and a member of the board of directors of JBCRG, KBCRN and OOTR, and chairman of the board of directors of JBCS, and associate editor of British Journal of Cancer, Scientific Reports, Breast Cancer Research and Treatment, Cancer Science, Frontiers in Women's Cancer, Asian Journal of Surgery and Asian Journal of Breast Surgery; TY reports grants from AC Medical, A2 Healthcare, ClinChoice, Japan Tabacco, Japan Media, Medidata Solutions, Ono, Kyowa-Kirin, Tsumura, Daiichi-Sankyo, Otsuka, Eisai, Solasia Pharma, Asahi Intecc, 3H Clinical Trial, Medrio, Nipro, Intellim, Welby, 3H Medi Solution, Baseconnect, Nobori, Puravida Technologies and Hemp Kitchen, and consulting fee from Public Health Research Foundation, EPS, Japan Tabacco, Medidata Solutions, Ono, Kowa, Chugai, Daiichi-Sankyo, Eisai, 3H Clinical Trial, Intellim, Astra Zeneca, Sonire Therapeutics, Seikagaku, Merck, Mebix and Nippon Boehringer Ingelheim, and advisory board of Incyte Bioscience; CI reports grants from Chugai, Asahi Kasei Pharma, Ono, Eli Lilly, Shionogi, Yakult, Otsuka, Sanofi, Merck, Astra Zeneca, Nippon Boehringer Ingelheim, Yansen, MSD, Sonia-Therapy, Taiho, Takeda, Daiichi-Sankyo, Bayer, Nippon-Kayaku, Tsumura, Kyowa-Kirin, Hitachi, Incyte, Ascent, Eisai, PRA Health Science, Novartis and Riken Genesis, and honoraria from Taiho, Merck, Eli Lilly, Bristol-Myers Squibb, Daiichi-Sankyo, Nippon-Kayaku, Nihon-Servier, M3, MSD, Novartis, Astra Zeneca, Ono, Sanofi, Chugai, Terumo, Asahi Kasei Pharma, Pfizer, Bayer, Incyte, Takeda and Kyowa-Kirin. All remaining authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Eribulin prolongs overall survival (OS) of patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), particularly in later chemotherapy (ChT) treatment. However, the health-related quality of life (HRQoL) and efficacy of first or second-line therapy in eribulin-treated patients remain unknown. Using eribulin in the first- or second-line may demonstrate the non-inferiority of HRQoL compared to S-1, an oral 5-fluorouracil derivative, while maintaining OS., Methods: This randomised, controlled, open-label, phase III trial was conducted at 50 hospitals in Japan. Patients were enrolled from June 2016 and October 2019. Patients with HER2-negative MBC once under or no previous ChT were randomly assigned (1:1) to receive eribulin or S-1. HRQoL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) every six weeks until week 24 and every nine weeks until week 42. The primary endpoint was the deterioration defined as more than 10 points worsening of the general health score of QLQ-C30 or death within one year after randomisation. The secondary endpoints included OS. (Trial ID: UMIN000021398)., Findings: Three hundred and two patients were enrolled, with 152 and 148 assigned to the eribulin and S-1 groups, respectively. The questionnaire compliance rate was 85.6%. Risk difference of global health status deterioration through one year was -0.66% (95% CI: -12.47-11.16; non-inferiority P = 0.077) for eribulin compared to S-1 groups. Median time to first deterioration for global health status score was 5.64 (95% CI: 3.51-8.00) and 5.28 months (95% CI: 3.28-7.80) in the eribulin and S-1 groups, respectively. The median OS was 34.7 and 27.8 months, (HR: 0.72, 95% CI: 0.54-0.96; P = 0.026); the median progression-free survival was 7.57 and 6.75 months in the eribulin and S-1 groups, (HR: 0.88, 95% CI: 0.67-1.16; P = 0.35), respectively. No new adverse events occurred., Interpretation: The time of the first clinical deterioration was similar between the two groups and OS significantly increased in eribulin-treated patients., Funding: This study was funded by CSPOR-BC and Eisai CO., Ltd., Competing Interests: KK, TI, KSh, SO, MKi, YT and TA report no coflicts of interest. MT reports honoraria from Astra Zeneca, Daiichi Sankyo, Eisai, Eli Lilly, MSD and Pfizer. YK reports honoraria from Astra Zeneca, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Pfizer and Taiho. NT reports grant and honoraria from Eisai. TY reports honoraria from Astra Zeneca, Chugai, Eisai, Eli Lilly, Kyowa Kirin, MSD and Pfizer. JW reports grant from Eisai and honoraria from Eisai and Taiho. MKa reports honoraria from Eli Lilly and Pfizer. KW reports honoraria from Astra Zeneca, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa Kirin, Novartis, Nippon Kayaku, Pfizer, Shionogi and Taiho. KSa reports honoraria from Eisai and Taiho. HM reports honoraria from Daiichi Sankyo, Taiho and Takeda., (© 2024 The Authors.)

During breast cancer recurrence, drug therapy is planned based on the biological characteristics of the primary tumor. However, the mechanisms underlying these changes have not yet been clarified. A 59-year-old woman underwent breast cancer surgery 23 years previously and received postoperative hormone therapy for 2 years. She had abdominal distention and ascites effusion and was diagnosed with carcinomatous peritonitis due to luminal-type breast cancer after ascites puncture. She received up to the fourth line of treatment. Subsequently, pleural effusion was observed and human epidermal growth factor receptor 2 type breast cancer was diagnosed because of pleurodesis. This case suggests that the cell block diagnostic method based on thoracic and ascites fluid cytology is useful not only for confirming the primary tumor but also for diagnosing the biological characteristics of breast cancer. In the treatment of breast cancer recurrence, it is important to plan the treatment, including aggressive re-biopsy of metastases., Competing Interests: All authors have no competing interests, financial or non-financial., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

An esophagobronchial fistula, an abnormal passageway formed between the esophagus and bronchus, can cause severe respiratory symptoms. This fistula is a complication that can occur during chemoradiotherapy for esophageal and lung cancers; however, to our knowledge, no esophagobronchial fistulas during preoperative chemotherapy for lung cancer have been reported. The patient was a 55-year-old man whose chest computed tomography (CT) revealed a mass on the dorsal bronchus and right side of the esophagus. A transesophageal needle biopsy confirmed the diagnosis of lung adenocarcinoma, and preoperative chemotherapy, which included pembrolizumab, was administered. One week after the first course of chemotherapy, the patient developed a severe cough after drinking water. Chest CT revealed an esophagobronchial fistula, which prompted the discontinuation of the preoperative chemotherapy. Subsequent conservative treatment resulted in no improvement, and the patient was referred to our department. One month thereafter, a two-stage reconstruction of the esophagus was performed via the posterior sternal route. The resected specimen showed no residual tumor in the lungs, and the treatment was determined to result in a complete pathological response. The patient is currently undergoing maintenance therapy with pembrolizumab as a single agent. This is a rare case of esophagobronchial fistula identified during preoperative chemotherapy that included pembrolizumab for lung cancer. In addition to suturing the fistula, filling it with a distal hyoid valve was effective in treating the esophagobronchial fistula., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Yoshino et al.)

Background: Epipericardial fat necrosis (EFN) is a rare disease in which local inflammation and necrosis occur in the adipose tissue surrounding the heart, particularly epicardial fat. Few cases of EFN in which surgical resection was performed have been reported. We report a case of EFN after surgical resection of a right extrapulmonary tumor, in which a malignant disease could not be excluded., Case Presentation: A 75-year-old male patient presented with fever and chest pain. A contrast-enhanced computed tomography scan of the chest revealed a lesion, 53 × 48 mm in size, with mixed fatty density spanning the middle and lower lobes of the right lung. Thoracic magnetic resonance imaging (MRI) revealed a mass with mixed fat and soft tissue density in the same area; the lesion was contiguous with pericardial fatty tissue. The tumor was diagnosed as a liposarcoma or teratocarcinoma based on imaging results; however, the possibility of lung cancer could not be excluded. Finally, EFN was diagnosed based on the postoperative histopathological examination. The patient underwent surgical resection of the suspected right extrapulmonary tumor. The intraoperative findings revealed a mediastinal mass contiguous with pericardial fat located between the middle and lower lobes. Intraoperative pathological examination of the lesion was performed using a needle biopsy; however, no definitive diagnosis was made. The tumor may have invaded the middle lobe of the right lung, and partial resection of the right lower lobe was performed in addition to resection of the middle lobe of the right lung. The patient was followed up every 3 months without adjuvant therapy. No recurrence was reported at 1 year after surgery., Conclusion: EFN should be considered in the differential diagnosis of an extrapulmonary tumor when continuity with the pericardial space is observed on MRI or other imaging studies. Surgical resection is useful in the diagnosis and treatment of EFNs. Preoperative three-dimensional reconstructive imaging and MRI should be used to identify vascular structures and confirm the continuity of the lesion with the surrounding tissues to ensure safe and rapid tumor removal., (© 2024. The Author(s).)

In embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), the expression of an RNA-binding pluripotency-relevant protein, LIN28, and the absence of its antagonist, the tumor-suppressor microRNA (miRNA) let-7, play a key role in maintaining pluripotency. Muse cells are non-tumorigenic pluripotent-like stem cells residing in the bone marrow, peripheral blood, and organ connective tissues as pluripotent surface marker SSEA-3(+). They express pluripotency genes, differentiate into triploblastic-lineage cells, and self-renew at the single cell level. Muse cells do not express LIN28 but do express let-7 at higher levels than in iPSCs. In Muse cells, we demonstrated that let-7 inhibited the PI3K-AKT pathway, leading to sustainable expression of the key pluripotency regulator KLF4 as well as its downstream genes, POU5F1, SOX2, and NANOG. Let-7 also suppressed proliferation and glycolysis by inhibiting the PI3K-AKT pathway, suggesting its involvement in non-tumorigenicity. Furthermore, the MEK/ERK pathway is not controlled by let-7 and may have a pivotal role in maintaining self-renewal and suppression of senescence. The system found in Muse cells, in which the tumor suppressor let-7, but not LIN28, tunes the expression of pluripotency genes, might be a rational cell system conferring both pluripotency-like properties and a low risk for tumorigenicity., (© 2024. The Author(s).)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: The addition of pertuzumab to trastuzumab in neoadjuvant chemotherapy (NAC) for anti-human epidermal receptor 2 (HER2) positive breast cancer has shown a significant improvement in the pathologic complete response (pCR) rate. However, the add-on effect of an anthracycline-based regimen (standard-of-care regimen) remains unclear. In this retrospective, observational study, participants received pertuzumab combination therapy as NAC for HER2-positive primary breast cancer., Methods: This study was conducted from January 1, 2020, to December 31, 2022. Patients who had not received at least three courses of pertuzumab owing to adverse events or those who had received preoperative radiotherapy were excluded., Results: The pCR rate was 35.3% (12/34 patients). The pCR group had a significantly higher percentage of histopathologic grade III (1/11 patients, p=0.030) and a significantly higher percentage of hormone receptor-negative patients (7/12 patients, p=0.015) than the non-pCR group. The non-pCR group had a significantly higher incidence of vascular invasion than the pCR group (7/22 patients, p=0.036). Menopausal status, stage, and ki-67 values were not significantly different between the two groups., Conclusions: This study suggests an unlikely add-on effect of an anthracycline-based regimen for NAC in HER2-positive breast cancer. Moreover, our results support that the pCR rate is high in patients with hormone receptor-negative, HER2-positive breast cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Yoshino et al.)