Investigating the immunological function of alpha-2-glycoprotein 1, zinc-binding in regulating tumor response in the breast cancer microenvironment.

BACKGROUND: Alpha-2-glycoprotein 1, zinc-binding (ZAG), a secreted protein encoded by the AZGP1 gene, is structurally similar to HLA class I. Despite its presumed immunological function, little is known about its role in tumor immunity. In this study, we thus aimed to determine the relationship between the expression of AZGP1/ZAG and the immunological profiles of breast cancer tissues at both the gene and protein level. METHODS: Using a publicly available gene expression dataset from a large-scale breast cancer cohort, we conducted gene set enrichment analysis (GSEA) to screen the biological processes associated with AZGP1. We analyzed the correlation between AZGP1 expression and immune cell composition in breast cancer tissues, estimated using CIBERSORTx. Previously, we evaluated the infiltration of 11 types of immune cells for 45 breast cancer tissues using flow cytometry (FCM). ZAG expression was evaluated by immunohistochemistry on these specimens and analyzed for its relationship with immune cell infiltration. The action of ZAG in M1/M2 polarization models using primary cultures of human peripheral blood mononuclear cells (PBMC)-derived macrophage (Mφ) was analyzed based on the expression of M1/M2 markers (CD86, CD80/CD163, MRC1) and HLA class I/II by FCM. RESULTS: AZGP1 expression was negatively correlated with multiple immunological processes and specific immune cell infiltration including Mφ M1 using GSEA and CIBERSORTx. ZAG expression was associated with decreased infiltration of monocytes/macrophages, non-classical monocytes, and myeloid-derived suppressor cells in tumor tissues assessed using FCM. In in vitro analyses, ZAG decreased the expression of CD80, CD163, MRC1, and HLA classes I/II in the M1 polarization model and the expression of CD163 and MRC1 in the M2 polarization model. CONCLUSION: ZAG is suggested to be a novel immunoregulatory factor affecting the Mφ phenotype in breast cancer tissues.

Association between obtaining injury prevention information and maternal and child health services during COVID-19.

BACKGROUND: Coronavirus disease 2019 disrupted the delivery of public maternal and child health services to caregivers of preschool children, leading to decreased opportunities for injury prevention education. We aim to 1) explore the timing, content, and methods of providing injury prevention information desired by pregnant women and mothers and 2) identify mothers who experienced difficulty in obtaining injury prevention information owing to reduced maternal and child health services. METHODS: From March 24 to 29, 2022, we conducted a population-based cross-sectional study and web-based survey. Of the registered monitors of the internet research company Rakuten Insight, 675 mothers raising their first child aged 0-2 during the COVID-19 period (February 2020 to March 2022) were included in the analysis. RESULTS: Over half of the mothers wanted injury prevention information throughout their pregnancy. They preferred receiving information through traditional face-to-face services provided by local governments, such as antenatal classes or checkups. However, 34.1% of mothers said they did not obtain the information they needed; this was particularly true of unemployed mothers, had children aged 0-1, and had children with illnesses requiring hospital visits. CONCLUSIONS: Mothers who could not obtain injury prevention information were originally disadvantaged mothers concerning access to information. The decrease in maternal and child health services may have widened this information gap. These findings can inform recommendations for caregivers, particularly those susceptible to information gaps during emergencies, and offer insights into future injury prevention education strategies.

Predictors of parenting difficulties at the 18-month health checkups: A retrospective study using administrative data from infant health checkups.

OBJECTIVE: This study aimed to identify predictors of parenting difficulties at 18 months from the results of the 4-, 6-7-, and 9-10-month infant health checkups among caregivers who had not experienced difficulties at 4 months. DESIGN AND SAMPLES: This retrospective study used data from infant health checkups conducted in a city in Tokyo from November 2019 to October 2021. The participants were caregiver-child dyads of children who had undergone four checkups. Low birthweight, preterm, and multiple birth infants, and caregivers who experienced difficulties at 4 months were excluded. MEASUREMENTS: Data included caregiver, child-rearing environment, and child factors at the 4-, 6-7-, and 9-10-month checkups and caregivers' self-reported parenting difficulties at the 18-month checkup. RESULTS: Of the 555 caregivers, 48 (8.6%) experienced parenting difficulties at 18 months. Logistic regression analyses showed that mothers' physical condition (4 months), children being male, abnormal child growth (4 months), less than 10th percentile for children's height (6-7 and 9-10 months), and abnormal examination results (6-7 months) were significantly associated with parenting difficulties at 18 months. CONCLUSIONS: To prevent child abuse, public health nurses should consider the identified factors to detect and support caregivers with emerging parenting difficulties.

Expression of hormone receptors is associated with specific immunological profiles of the breast cancer microenvironment.

BACKGROUND: Elucidating the unique immunoregulatory mechanisms in breast cancer microenvironment may help develop new therapeutic strategies. Some studies have suggested that hormone receptors also have immune regulatory functions, but their mechanisms are not fully understood. In this study, we have comprehensively analyzed the relationship between the expressions of estrogen (ER), progesterone (PgR), and androgen receptors (AR), and the immunological profile in breast cancer. METHODS: Using publicly available gene expression profile datasets, METABRIC and SCAN-B, the associations between the expressions of hormone receptors and the immune cell compositions in breast cancer tissue, estimated by CIBERSORTx algorithm, were analyzed. We histologically evaluated tumor-infiltrating lymphocytes (hTIL), PD-L1 (hPD-L1) expression, and the infiltration of 11 types of immune cells by flow cytometry (FCM) for 45 breast cancer tissue samples. The relationships between them and the expressions of ER, PgR, and AR of tumor tissues, evaluated immunohistochemically, were analyzed. RESULTS: Expressions of ESR1, PGR, and AR were negatively correlated with overall immune composition. Expressions of ER and AR, but not that of PgR, were inversely associated with hTIL and hPD-L1 expression. FCM analysis showed that the expressions of ER and AR, but not that of PgR, were associated with decreased total leukocyte infiltration. Both CIBERSORTx and FCM analysis showed that ER expression was associated with reduced infiltration of macrophages and CD4+ T cells and that of AR with reduced macrophage infiltration. CONCLUSION: Hormone receptor expression correlates with specific immunological profiles in the breast cancer microenvironment both at the gene and protein expression levels.

Identification of MicroRNAs Associated with Histological Grade in Early-Stage Invasive Breast Cancer.

This study aimed to identify microRNAs associated with histological grade using comprehensive microRNA analysis data obtained by next-generation sequencing from early-stage invasive breast cancer. RNA-seq data from normal breast and breast cancer samples were compared to identify candidate microRNAs with differential expression using bioinformatics. A total of 108 microRNAs were significantly differentially expressed in normal breast and breast cancer tissues. Using clinicopathological information and microRNA sequencing data of 430 patients with breast cancer from The Cancer Genome Atlas (TCGA), the differences in candidate microRNAs between low- and high-grade tumors were identified. Comparing the expression of the 108 microRNAs between low- and high-grade cases, 25 and 18 microRNAs were significantly upregulated and downregulated, respectively, in high-grade cases. Clustering analysis of the TCGA cohort using these 43 microRNAs identified two groups strongly predictive of histological grade. miR-3677 is a microRNA upregulated in high-grade breast cancer. The outcome analysis revealed that patients with high miR-3677 expression had significantly worse prognosis than those with low miR-3677 expression. This study shows that microRNAs are associated with histological grade in early-stage invasive breast cancer. These findings contribute to the elucidation of a new mechanism of breast cancer growth regulated by specific microRNAs.

Confusions and responses of managerial public health nurses during the COVID-19 pandemic in Japan.

OBJECTIVE: This study aimed to elucidate the experiences of public health nurses (PHNs) in Japan during the first wave of COVID-19. DESIGN AND SAMPLE: Twelve PHNs in charge of responding to COVID-19 in X-city within Tokyo metropolis in Japan participated in this case study. MEASUREMENTS: Data were collected through self-administered questionnaires and semi-structured interviews on PHNs' experiences from January 2020 to May 2020. RESULTS: Initially, only infectious disease control division (IDCD) PHNs experienced confusion due to the rapidly increased workload. Managerial PHNs attempted to explain the need for a dispatch system for the IDCD, using available statistical data from other managerial members, within one's maximum understanding of this unprecedented situation. Without having a clear and forward-looking understanding regarding the purpose and reasons for dispatching, some dispatched PHNs had concerns and frustrations; they did not view the COVID-19 pandemic as a disaster. In the never-ending, exhausting work, PHNs managed to modify the provision of conventional services to residents. CONCLUSIONS: Despite experiencing confusion, PHNs worked to continuously provide community services, re-considering the meaning of public health nursing. Prioritizing the work and shifting tasks to other professionals at an early stage of the pandemic may prevent organizational dysfunction.

Prefectural public health nurses' support in human resource development of municipal public health nurses in Japan.

Objective　This study aimed to explore the support extended by prefectural public health nurses (PHNs) toward the human resource development (HRD) of municipal PHNs in Japan.Methods　We performed a qualitative descriptive study involving nine prefectural PHNs from April 2019 to May 2020. The data were collected through semi-structured interviews using an interview guide, described qualitatively, coded, and then categorized.Results　Five categories were extracted. "Clarifying the needs and problems related to HRD and daily PHN activities in the municipalities," "Creating an environment where all municipal PHNs have equal opportunities for off-the-job training," and "Helping municipal PHNs recognize the meaning of practice and develop an evaluation perspective" were extracted from the prefectural government PHNs and prefectural health center (HC) PHNs. "Clarifying problems and future prospects to encourage the growth of PHNs" and "Creating an environment where the significance and value of the activities of PHNs are recognized within the organization and HRD can easily take place" were extracted from the HC PHNs.Conclusion　Much of the HRD support provided by the prefectural PHNs to the municipal PHNs was analogous to the PHN activities provided to the community and residents. To promote HRD effectively, prefectural PHNs should apply their individual care skills to the HRD of municipal PHNs.

Oncological safety of immediate breast reconstruction with skin- or nipple-sparing mastectomy: the value of tumor-to-dermis distance measured by preoperative ultrasonography.

BACKGROUND: Immediate breast reconstruction with skin-sparing (SSM) or nipple-sparing mastectomy (NSM) has become a common procedure. In this study, we evaluated the distance between breast tumor and skin in a series of patients undergoing IBR as it relates to oncologic safety, namely, the incidence of recurrence. METHODS: The distance of the tumor to the dermis, rather than the outer layer of skin, was the key parameter of our preoperative ultrasound measurements. Our data set comprised the cases of 171 patients and 181 breasts with breast cancer that had undergone two-stage breast reconstruction by expander. The median age of the patients was 47 years (25-75 years). The overall median follow-up period was 47.1 months (8.8-125.3 months). Eighty-five breasts underwent IBR with SSM/NSM; the others underwent conventional mastectomy. RESULTS: Among the total of 181 reconstructed breast mounds, the locoregional recurrence rate was 1.1% (2 breasts) with no cases of skin flap recurrence or skin flap necrosis. The tumor-to-dermis distance of cases with skin preservation (NSM/SSM) was significantly less than that of cases with conventional mastectomy (3.8 ± 2.7 mm vs 5.2 ± 2.4 mm). In cases with invasive carcinoma, all cases whose tumor-to-dermis distance was less than 2 mm underwent resection of the skin immediately overlying the tumor. CONCLUSIONS: Our results suggested that a 2-mm distance between the dermis and tumor on ultrasound evaluation is sufficient for the use of this tissue as a skin flap in SSM/NSM procedures. Our study indicated that immediate breast reconstruction with SSM/NSM can be an oncologically safe surgical option for breast cancer. However, we recommend that resection of the skin overlying the tumor be performed in cases with invasive breast cancer in which the tumor-to-dermis distance is less than 2 mm. TRIAL REGISTRATION: Patients in this study were retrospectively registered. This study design was approved by our Clinical Ethics Committee (No 1297) ( http://ciru.dept.showa.gunma-u.ac.jp/guidance/storage-sample/list.html ).

FDG uptake reflects breast cancer immunological features: the PD-L1 expression and degree of TILs in primary breast cancer.

BACKGROUND: High F18-fluorodeoxyglucose (FDG) uptake has been reported to be a predictor of poor prognosis in patients with breast cancer. We investigated the relationship between FDG uptake and immunological factors, including the data of programmed cell death-ligand 1 (PD-L1), CD8, and tumor-infiltrating lymphocytes (TILs). METHODS: Breast cancer tissues of 97 patients who underwent surgery without preoperative therapy were examined. The grade of stromal TILs was immunohistochemically evaluated using the criteria of the International TILs Working Group in breast cancer. PD-L1 positivity and CD8 positivity were immunohistochemically evaluated. The FDG uptakes were evaluated based on the standardized uptake value max (SUVmax). The relationships between SUVmax and TIL grade and expression of PD-L1 and CD8 were investigated. RESULTS: Among the 97 patients, 41 (42.3%) had a high SUVmax in their primary tumor, based on the SUVmax cut-off value 3 yielded by receiver operating characteristic curves. PD-L1 was positive in 17 patients (17.5%). Our analyses revealed that large tumor size, high nuclear grade, high degree of TILs and positive expression of PD-L1 were significantly associated with high SUVmax in the primary tumor. There were significant associations between SUVmax and the degree of TILs (r = 0.428, p < 0.001) and between SUVmax and the PD-L1 positivity (r = 0.413, p < 0.001). All cases with a high degree of TILs showed high CD8 expression. CONCLUSION: Our results indicate that the FDG uptake may be predictive of immunological features including TILs and PD-L1 expression in breast cancer patients. Additional research is necessary to further evaluate FDG-PET as a biomarker of immune checkpoint therapy in breast cancer.

Epigenetic regulation of MdMYB1 is associated with paper bagging-induced red pigmentation of apples.

MAIN CONCLUSION: Paper-bagging treatment can transform non-transcribed MdMYB1 - 2 and MdMYB1 - 3 alleles into transcribed alleles through epigenetic regulations, resulting in the red pigmentation of a normally non-red apple cultivar 'Mutsu.' Anthocyanin biosynthesis in apples is regulated by MdMYB1/A/10, an R2R3-Type MYB gene. 'Mutsu,' a triploid apple cultivar harboring non-transcribed MdMYB1-2 and MdMYB1-3 alleles, retains green skin color under field conditions. However, it can show red/pink pigmentation under natural or artificial ultraviolet-B (UV-B) light exposure after paper-bagging and bag removal treatment. In the present study, we found that in 'Mutsu,' paper bagging-induced red pigmentation was due to the activation of non-transcribed MdMYB1-2/-3 alleles, which triggered the expression of downstream anthocyanin biosynthesis genes in a UV-B-dependent manner. By monitoring the epigenetic changes during UV-B-induced pigmentation, no significant differences in DNA methylation and histone modifications in the 5' upstream region of MdMYB1-2/-3 were recorded between the UV-B-treated fruit skin (red) and the fruit skin treated only by white light (green). In contrast, bag treatment lowered the DNA methylation in this region of MdMYB1-2/-3 alleles. Similarly, higher levels of histone H3 acetylation and trimethylation of H3 tail at lysine 4, and lower level of trimethylation of H3 tail at lysine 27 were observed in the 5' upstream region of MdMYB1-2/-3 in the skin of the fruit immediately after bag removal. These results suggest that bagging treatment can induce epigenetic changes, facilitating the binding of trans factor(s) to MdMYB1-2/-3 alleles, resulting in the activation of these MYBs after bag removal.

An apple B-box protein, MdCOL11, is involved in UV-B- and temperature-induced anthocyanin biosynthesis.

MAIN CONCLUSION: Our studies showed that an apple B-box protein, MdCOL11, the homolog of AtBBX22, is involved in UV-B- and temperature-induced anthocyanin biosynthesis in apple peel. Anthocyanin is responsible for the red pigmentation in apple peel and a R2R3 MYB gene, MdMYBA/1/10, a homolog of MdMYBA, controls its accumulation. Arabidopsis PAP1 is under the control of a series of upstream factors involved in light signal transduction and photomorphogenesis, such as ELONGATED HYPOCOTYL 5 (HY5) and B-box family (BBX) proteins. In this study, we identified and characterized the homolog of Arabidopsis BBX22 in apple, designated as MdCOL11. Overexpression of MdCOL11 in Arabidopsis enhanced the accumulation of anthocyanin. In apples, MdCOL11 was differentially expressed in all tissues, with the highest expression in petals and the lowest expression in the xylem. Transcripts of MdCOL11 noticeably accumulated at the ripening stage, concomitant with increases in the expressions of anthocyanin biosynthesis-related genes. In an in vitro treatment experiment, MdCOL11 was upregulated in an ultra-violet (UV)-B- and temperature-dependent manner, together with the inductions of anthocyanin biosynthesis-related genes and anthocyanin accumulation in apple peel. Furthermore, a dual-luciferase assay indicated that (1) MdCOL11 regulated the expression of MdMYBA and (2) MdCOL11 was a target of MdHY5. Taken together, our results suggest that MdCOL11 is involved in MdHY5-mediated signal transduction and regulates anthocyanin accumulation in apple peel, which sheds new light on anthocyanin accumulation in apples.

Efficacy of Mirogabalin for Taxane-associated Chemotherapy-induced Peripheral Neuropathy in Perioperative Chemotherapy for Early Breast Cancer.

BACKGROUND/AIM: Treatment with taxanes can result in chemotherapy-induced peripheral neuropathy (CIPN). We investigated the efficacy and safety of mirogabalin for the treatment of CIPN in patients who had been administered perioperative chemotherapy including taxane-based agents for breast cancer. PATIENTS AND METHODS: We retrospectively analyzed the case of 43 patients with early breast cancer who received a taxane as perioperative chemotherapy and were administered mirogabalin at the diagnosis of CIPN. RESULTS: Thirty-six patients (83.7%) had grade 1 CIPN and the other seven patients (16.3%) had grade 2 CIPN. The median mirogabalin dose was 10 mg (5-30 mg). CIPN improved from grade 1 to 0 in 12 patients (27.9%) and from grade 2 to 1 in one patient (2.3%); 13 (30.2%) patients thus had an objective therapeutic response. There were no cases in which chemotherapy was reduced or discontinued due to CIPN. Adverse events were evaluated by Common Terminology Criteria for Adverse Events and included five cases of dizziness (11.7%), three of somnolence (7.0%), and two of nausea (4.7%), all of which were grade ≤2. There were no cases of serious (grade ≥3) adverse effects. CONCLUSION: Mirogabalin may be effective and safe for treating CIPN of patients who receive a taxane in a perioperative breast cancer setting.

Developing an Educational Program for Ultrasound Hip Screening during Newborn and Infant Home Visits: A Protocol Paper.

Ultrasound hip screening is suitable for the early identification of developmental dysplasia of the hip (DDH). Newborn and infant home visits are good opportunities for hip screening in the community, but studies focusing on nurse-led screenings are lacking. Based on a pre-post design, this study aims to develop and evaluate an ultrasound training program to improve nurses' assessment skills in detecting DDH cases during newborn and infant home visits. Said educational program will include e-learning, hands-on seminars, and clinical training. The primary outcome will be the success rate of imaging standard planes (standardized images for hip assessment) in clinical training. The secondary outcomes will include knowledge test results, objective structured clinical examination scores, time required for imaging, and inter-rater reliability between nurses and physicians. The educational program will address the issue of missed and late detection of DDH cases in resource-limited communities. This study will demonstrate the feasibility of procedures and the effectiveness of the educational program in 2024. The protocol was registered in the University Hospital Medical Information Network Clinical Trial Registry before starting the study (no. UMIN000051929, 16 August 2023).

Cancer-associated fibroblast spatial heterogeneity and EMILIN1 expression in the tumor microenvironment modulate TGF-ß activity and CD8+ T-cell infiltration in breast cancer.

Rationale: The tumor microenvironment (TME) and its multifaceted interactions with cancer cells are major targets for cancer treatment. Single-cell technologies have brought major insights into the TME, but the resulting complexity often precludes conclusions on function. Methods: We combined single-cell RNA sequencing and spatial transcriptomic data to explore the relationship between different cancer-associated fibroblast (CAF) populations and immune cell exclusion in breast tumors. The significance of the findings was then evaluated in a cohort of tumors (N=75) from breast cancer patients using immunohistochemistry analysis. Results: Our data show for the first time the degree of spatial organization of different CAF populations in breast cancer. We found that IL-iCAFs, Detox-iCAFs, and IFNγ-iCAFs tended to cluster together, while Wound-myCAFs, TGFß-myCAFs, and ECM-myCAFs formed another group that overlapped with elevated TGF-ß signaling. Differential gene expression analysis of areas with CD8+ T-cell infiltration/exclusion within the TGF-ß signaling-rich zones identified elastin microfibrillar interface protein 1 (EMILIN1) as a top modulated gene. EMILIN1, a TGF-ß inhibitor, was upregulated in IFNγ-iCAFs directly modulating TGFß immunosuppressive function. Histological analysis of 75 breast cancer samples confirmed that high EMILIN1 expression in the tumor margins was related to high CD8+ T-cell infiltration, consistent with our spatial gene expression analysis. High EMILIN1 expression was also associated with better prognosis of patients with breast cancer, underscoring its functional significance for the recruitment of cytotoxic T cells into the tumor area. Conclusion: Our data show that correlating TGF-ß signaling to a CAF subpopulation is not enough because proteins with TGF-ß-modulating activity originating from other CAF subpopulations can alter its activity. Therefore, therapeutic targeting should remain focused on biological processes rather than on specific CAF subtypes.

Screening of UV-B-induced genes from apple peels by SSH: possible involvement of MdCOP1-mediated signaling cascade genes in anthocyanin accumulation.

Suppression subtractive hybridization (SSH) was employed to identify candidate genes involved in red coloration in apple peel with the ultraviolet (UV)-B-treated 'Mutsu'. After reverse Northern blotting verification, nearly 80 clones were successfully sequenced. Large portions of the expressed sequence tags (ESTs) are well characterized anthocyanin biosynthesis-related genes, such as chalcone synthase (11A5), flavonol synthase (12F3), anthocyanidin synthase (11H5) and UDP-glycosyl transferase (14A12) whose presence proved the success of SSH. Eight ESTs were selected for quantitative real-time polymerase chain reaction analysis and their expressions were all elevated in 'Induction', further confirming the reliability of the SSH library. One EST, 11F4 (CONSTITUTIVE PHOTOMORPHOGENIC 1: COP1) with putative function in light signal relay was further analyzed in 'Mutsu' and 'Tsugaru', along with MdHY5 (ELONGATED HYPOCOTYL 5: the downstream target of COP1), MdMYB22 (a possible flavonol-specific activator under the regulation of HY5, belonging to the SG7/PRODUCTION OF FLAVONOL GLYCOSIDES family) and MdMYBA. Results showed that MdCOP1, MdHY5, MdMYB22 and MdMYBA were all UV-B inducible genes and anthocyanin accumulation occurred after their increased expressions. Moreover, their expressions and anthocyanin content were enhanced under UV-B plus 17°C treatment. The presence of G box, a known consensus binding site of HY5, in the MdMYBA promoter region implicated that it could be regulated by MdHY5, which was verified by the result of the yeast one-hybrid analysis. Our data suggested that UV-B irradiation would induce the utmost upstream light signaling factor, MdCOP1, which activates MdHY5 signaling by binding to the promoter regions of MdMYBs, and finally leads to the red coloration of apple peels.

Community-Based Hip Screening for Up to Four-Month-Old Infants and Health Guidance for Their Caregivers in Japan: A Nation-Wide Survey.

Early detection of developmental dysplasia of the hip (DDH) in children is crucial. Due to COVID-19, maternal and child health services have been suspended temporarily, increasing the risk of late detection of DDH. This study aimed to reveal Japan's current situation regarding community hip screening for newborns and infants and to provide health guidance for caregivers regarding DDH. A web-based, nationwide cross-sectional survey was conducted between February and March 2023 (n = 1737). One public health nurse overseeing maternal and child health per municipality responded to the 2022 municipality hip screening system. Among the 436 municipalities that responded (response rate: 25.1%), 97.5% implemented hip screening within 4 months, and approximately 60% performed it during newborn home visits, while only 2.3% conducted hip ultrasound screening. Perfect checking of the risk factors for DDH during newborn home visits and training opportunities for home visitors must be improved. Educational programs regarding DDH for home visitors and caregivers are needed to prevent the late diagnosis of DDH. Furthermore, collaboration between pediatric orthopedic surgeons and nurses is crucial for developing effective community-based hip-screening systems by bridging the evidence and practice gap in the early detection of DDH.

Characteristics of Patients With Metastatic Breast Cancer Who Survived more than 10 Years.

BACKGROUND/AIM: Despite advances in the treatment of breast cancer, metastatic breast cancer (MBC) remains difficult to cure, and few MBC patients survive 10 years after receiving a breast cancer metastasis diagnosis. We collected the cases of patients with MBC who survived >10 years post-metastasis diagnosis and assessed the patients' characteristics. PATIENTS AND METHODS: We retrospectively analyzed the cases of 245 consecutive patients diagnosed with MBC between January 2005 and December 2012 at our institution. Among them, 167 patients with confirmed survival of >10 years (i.e., long-term survival) or confirmed death at ≤10 years post-metastasis diagnosis were enrolled. RESULTS: There were 22 patients with MBC who survived >10 years. Regarding the cancer subtypes, 11 patients (50%) with long-term survival were HER2-positive. Seven of the 11 patients with HER2-positive MBC have been without recurrence although anti-HER2 therapy was discontinued. Triple-negative breast cancer (TNBC) was most common in the patients who survived ≤5 years but was not present in the >10-year survival group. In the HER2-negative cases, more cases in the long-term survival group were treated with local therapy (34.4% in the <5-year survival group, 43.8% in the 5-10-year group, and 72.7% in the >10-year group). CONCLUSION: MBC patients who survive >10 years after being diagnosed with metastasis are more likely to be HER2-positive and treated with local therapy. This suggests the efficacy of anti-HER2 therapy, and, conversely, clarifies unmet needs in TNBC and luminal-type MBC. The usefulness of local therapy was also supported by our findings.