BackgroundImmediate breast reconstruction (IBR) has become increasingly recognized in Japan as an important component of breast cancer care, improving patients’ quality of life after mastectomy. While the adoption of IBR is growing, the reconstruction rate in Japan remains lower than in Western countries. To clarify the current practice and challenges, the Japanese Breast Cancer Society (JBCS) conducted a nationwide survey.MethodsWe conducted a comprehensive web-based questionnaire survey among all JBCS-certified institutions between December 2020 and February 2021. The survey assessed institutional capabilities, surgical techniques, decision-making criteria for BR, and the integration of adjuvant therapy.ResultsA total of 429 institutions responded, with 72.5% offering BR and 61.7% capable of providing immediate reconstruction. Nipple-sparing mastectomy (NSM) was performed at 73.7% of institutions offering reconstruction. Multidisciplinary conferences with plastic surgeons were held at 70.5% of institutions. Approximately 30% of institutions discontinued IBR if sentinel lymph node metastases were detected intraoperatively, and 62.8% avoided recommending IBR for patients likely to require postoperative radiation therapy. In 94% of institutions, BR did not cause delays in the administration of adjuvant chemotherapy. However, 15% of institutions modified their radiation therapy approach in reconstructed patients. Additionally, 27% of physicians still believed that BR could negatively affect prognosis.ConclusionsThe survey confirmed that IBR is widely performed and feasible in Japan. However, institutional differences, limited access to plastic surgeons, and persistent misconceptions remain significant barriers. Strengthening multidisciplinary collaboration and establishing standardized guidelines will help improve BR rates and patient outcomes in Japan.

BackgroundA cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) is a current standard first-/second-line treatment for hormone receptor (HR)-positive, HER2-negative advanced/metastatic breast cancer (AMBC). We aimed to provide real-world evidence regarding CDK4/6i therapy in this population.MethodsIn this multicenter observational study, data from patients who had started CDK4/6i therapy between January 1, 2019, and December 31, 2021, as first-/second-line treatment for AMBC were used; real-world progression-free survival (rwPFS), chemotherapy-free survival, and overall survival were analyzed using the Kaplan–Meier method. Additionally, data were analyzed by separating patients with treatment-free interval (TFI) < 12 months (deemed resistant to ET) from the first-line treatment group (hereafter, the exclusive first-line treatment group).ResultsData from 745 patients were analyzed. Compared with palbociclib, abemaciclib was used in younger patients and those with expected poor prognosis. Median rwPFS was 36.8, 17.8, and 31.4 months in patients with de novo stage IV disease, TFI < 12 months, and TFI ≥ 12 months, respectively, in the first-line treatment group, and 17.4 months in the second-line treatment group. In the exclusive first-line treatment group, median rwPFS of the subsequent treatment after initial CDK4/6i plus ET was < 7 months, regardless of the type of subsequent treatment; prognosis was especially poor in those who were switched to chemotherapy.ConclusionsThe real-world survival outcomes found in this study for patients receiving first-/second-line CDK4/6i therapy were consistent with those of randomized phase 3 studies. As outcomes of subsequent treatment after initial CDK4/6i plus ET remain insufficient, further improvement in treatment is necessary.

PurposeTo clarify particularly how febrile neutropenia-related hospitalization (FNH) affects patients’ daily lives, by analyzing real-world data on FNH among patients with early breast cancer (EBC) receiving perioperative chemotherapy in Japan.MethodsThis retrospective nationwide large-scale database study was conducted using anonymized claims data from 2010 to 2020. The patients with EBC who had available surgical records were included. Men, those aged < 18 years, and those who had not available chemotherapy records were excluded. FNH was defined as hospitalization during perioperative chemotherapy for EBC, with administration of intravenous antibacterial drugs and a diagnosis of FN, sepsis, infection, or fever.ResultsThe analysis population included 33,310 EBC patients with a mean age of 56.9 years, who received a total of 267,535 perioperative chemotherapy cycles. FNH occurred in 1,910 patients (5.73%) and 2144 chemotherapy cycles (0.80%). Median duration of FNH was 6.0 days. Fourth-generation cephalosporins were the most used intravenous antibacterial drugs (50.42%). Median duration of intravenous antibacterial drugs administration was 4.0 days. Therapeutic granulocyte-colony stimulating factor (G-CSF) was used in 1285 patients (67.28%). Median cost for FNH was estimated to be 189 thousand yen in 1,474 chemotherapy cycles with FNH, in which patients received intravenous antibacterial drugs administration for 3–8 days.ConclusionThis nationwide real-world data analysis revealed the incidence, duration, treatment patterns, and medical cost of FNH in patients with EBC receiving perioperative chemotherapy in Japan. These findings indicate that FNH imposes a considerable burden on patients’ daily lives, including time and financial impacts, contributing to the implementation of appropriate shared decision-making for primary G-CSF prophylaxis.

BackgroundThe Medical Imaging Projection System (MIPS) projects fluorescence ICG images on the surgical field. In this study, we aimed to assess sentinel lymph node (SLN) identification by the MIPS in patients with and without neoadjuvant chemotherapy (NAC) administration and compare the utility of the MIPS with the radioisotope (RI) method.MethodsWe retrospectively reviewed medical records of patients with primary breast cancer who underwent SLN biopsy using the MIPS at Kyoto University Hospital between April 2020 and December 2024. The primary endpoint was the identification rate of SLNs. The secondary endpoints included the number of positive SLNs and SLNs detected per patient.ResultsThe analysis included 470 procedures (448 patients), of which 56 (11.9%) were conducted after NAC. The identification rate of SLNs by the MIPS was 99.6% (95% confidence interval [CI], 98.5–99.9) in all procedures and 98.2% (95% CI, 90.6–99.7) after NAC. The median number of SLNs identified per patient was 3 (range, 2–4) by the MIPS and 2 (range, 1–3) by the RI method (P < 0.001). No significant difference was observed in the number of SLNs between patients who received NAC and those who did not (3 vs 3, P = 0.84). Seventy-eight positive SLNs were excised, all of which were accurately identified by the MIPS.ConclusionsThis study suggested that the identification rate of SLNs by the MIPS was high regardless of the presence or absence of preceding systemic chemotherapy.

BackgroundFor breast cancer patients, postoperative lymphedema and upper limb movement disorders are serious complications that absolutely reduce their quality of life (QOL). To evaluate this serious complication, we used “Quick Dash” or “FACT-B”, which can assess a patient's physical, social, emotional, and functional health status. To evaluate their breast cancer surgery-related dysfunction correctly, “FACT-B + 4” was created by adding four questions about “arm swelling'' and “tenderness”. We have translated it into Japanese according to international translation guidelines.MethodsAt the beginning, we contacted FACT headquarters that we would like to create a Japanese version of FACT-B + 4. They formed the FACIT Trans Team (FACIT) following international translation procedures, and then, we began translating according to them. The steps are 1: perform “Forward and Reverse translations” to create a “Preliminary Japanese version”, 2: request the cooperation of 5 breast cancer patients and “conduct a pilot study” and “questionnaire survey”, and 3: amendments and final approval based on pilot study results and clinical perspectives.ResultIn Step1, FACIT requested faithful translation of the words, verbs, and nouns from the original text. In Step2, patients reported that they felt uncomfortable with the Japanese version words such as “numb'' and “stiffness'' and felt that it might be difficult to describe their symptoms accurately. In Step3, we readjusted the translation to be more concise and closer to common Japanese language, and performed “Step1” again to ensure that the translation definitely retained the meaning of the original.ConclusionA Japanese version of FACT has existed until now, but there was no Japanese version of FACT-B + 4, which adds four additional items to evaluate swelling and pain in the upper limbs. This time, we have created a Japanese version that has been approved by FACT.

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by limited targeted therapies and high recurrence rates. While immune checkpoint inhibitors (ICIs) have shown promise, their efficacy as monotherapy is limited. Clinically, ICIs demonstrate significant benefit primarily when combined with chemotherapy, particularly in the neoadjuvant setting for early-stage TNBC, which yields superior outcomes compared to adjuvant therapy. This review elucidates the tumor immunological principles underlying these observations. We discussed how the suppressive tumor microenvironment (TME), progressive T cell exhaustion, and associated epigenetic scarring constrain ICI monotherapy effectiveness. Crucially, we highlight the immunological advantages of the neoadjuvant approach: the presence of the primary tumor provides abundant antigens, and intact tumor-draining lymph nodes (TDLNs) act as critical sites for ICI-mediated priming and expansion of naïve and precursor exhausted T cells. This robust activation within TDLNs enhances systemic anti-tumor immunity and expands the T cell repertoire, a process less effectively achieved in the adjuvant setting after tumor resection. These mechanisms provide a strong rationale for the improved pathological complete response (pCR) rates and event-free survival observed with neoadjuvant chemoimmunotherapy, as demonstrated in trials like KEYNOTE-522. We further explore the implications for adjuvant therapy decisions based on treatment response, the challenges of ICI resistance, the need for predictive biomarkers, management of immune-related adverse events (irAEs), and future therapeutic directions. Understanding the dynamic interplay between chemotherapy, ICIs, T cells, and the TME, particularly the role of TDLNs in the neoadjuvant context, is essential for optimizing immunotherapy strategies and improving outcomes for patients with TNBC.

BackgroundConsidering past research in Europe and the USA, the conditions for medical insurance coverage of BRCA1/2 genetic testing (GT) in Japan have been established as follows: 1. Breast cancer onset at 45 years or younger age; 2. Triple-negative breast cancer (TNBC) onset at 60 years or younger age; 3. Onset of two or more primary breast cancers; 4. Family history of breast cancer, ovarian cancer, or pancreatic cancer up to the third degree; 5. Male breast cancer, 6. Ovarian, fallopian, or peritoneal cancers. However, data to determine the importance and extent of each factor in the current conditions are insufficient. Consequently, this study aimed to assess the validity of insurance coverage conditions in Japan, elucidate the relationship between these conditions, and explore the possibility of proposing new indicators.MethodsA total of 5987 breast cancer patients were enrolled from 92 centers participating in the HBOC consortium and the JOHBOC registry project. Of these, 5904 patients were analyzed after excluding 48 male breast cancer patients due to insufficient numbers for analysis and 35 patients whose age at breast cancer onset was unknown or unregistered. We compared 1,091 cases in which pathogenic variants (PVs) (BRCA1(B1s): 543, BRCA2(B2s): 548) were detected with 4580 cases in which no variants (non-Vs) were detected. Variants of uncertain significance (VUS: 233 cases) were not classified as either PVs or non-Vs for subsequent analysis. We investigated the validity of each condition under which an HBOC diagnosis could be considered for medical insurance coverage.ResultsRegardless of the insurance coverage conditions, the detection rate of pathogenic variants (DRPV) of all analyzed cases was 19.2%. The DRPV under the insurance coverage conditions for GT—‘Age of breast cancer onset ≤ 45 years,’ ‘TNBC onset at ≤ 60 years,’ ‘ ≥ 2 primary breast cancers,’ ‘Patients with breast cancer concurrent with ovarian cancer,’ and ‘ ≥ 1 family history of breast or ovarian cancer up to the third degree’—was 25.4%, 31.6%, 24.6%, 48.8%, and 25.6%, respectively. Those within the insurance coverage group showed a pathogenic variant detection rate of 21.1%, compared to only 5.6% outside of the coverage. Our analysis indicates that medical insurance coverage conditions effectively identify candidates for GT. Furthermore, when examining the number of conditions met and the positivity rate, the positivity rate was 11.2%, with only one condition met. This rate increases exponentially as more conditions are met, underscoring the importance of multiple matching conditions. Additionally, those with comorbid ovarian cancer or a family history of ovarian cancer are more likely to have a pathogenic variant. Additionally, we reevaluated cases who did not meet the medical insurance conditions. TNBC occurrence was significantly associated with B1s, even when restricted to onset age ≥ 61 years. Familial history of prostate cancer also significantly associated with B2s.ConclusionThis study determined that the Japanese medical insurance coverage conditions effectively identified candidates eligible for GT. Consequently, it is imperative to disseminate information to all patients with breast cancer covered by insurance, emphasizing the opportunity for GT, particularly if they have ovarian cancer complications or a family history of ovarian cancer.

BackgroundATPase copper transporting beta (ATP7B) functions as a copper-transporting ATPase that ejects copper from cells. Although high expression of ATP7B has been reported to increase cisplatin resistance, its role in breast cancer (BC) remains unclear. This study aimed to elucidate the function of ATP7B in BC cells and its significance in patients with BC.MethodsThe mRNA and protein expression levels of ATP7B were evaluated in BC and non-cancerous mammary cell lines. Polymerase chain reaction (PCR) array analysis was conducted to determine the correlation between ATP7B and 84 cancer-related genes. ATP7B knockdown was performed using small interfering RNA, and cell proliferation, invasiveness, and migration were analyzed. The associations between the mRNA and protein expression of ATP7B and clinicopathological factors were also investigated in 156 patients with BC.ResultsATP7B was found to be highly expressed in estrogen receptor-positive and human epidermal growth factor receptor 2-positive BC cell lines. PCR array analysis revealed a significant correlation between the expression level of ATP7B and those of cadherin 1, estrogen receptor 1, and MET proto-oncogene. ATP7B knockdown significantly increased the proliferation, invasiveness, and migration of MDA-MB-361 and MDA-MB-415 cells. Patients with high ATP7B expression at the mRNA and protein levels experienced favorable prognoses. In addition, ATP7B expression level was identified as an independent prognostic factor in multivariate analysis.ConclusionsATP7B is involved in promoting anti-cancer activities of tumor suppressors in BC cells across different subtypes and is considered a prognostic marker for BC.

BackgroundHigh tumor mutational burden (TMB-H) is an established biomarker for a favorable response to immune checkpoint inhibitors. However, tumor mutational burden (TMB) in invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) has not been sufficiently investigated.MethodsWe collected data of patients with ILC or IDC from the Center for Cancer Genomics and Advanced Therapeutics database between June 2019 and August 2023. Furthermore, we examined the clinicopathological factors and TMB status.ResultsPatients with ILC (n = 170) had a median TMB score of 4.00 mut/Mb (interquartile range, 2.00–7.14 mut/Mb), whereas those with IDC (n = 2598) had a score of 3.90 mut/Mb (2.00–6.00 mut/Mb). TMB-H was more common in patients with ILC than in those with IDC (18.2% vs. 10.1%, P < 0.001), particularly in the ER+ /HER2− subtype. Multivariate analysis revealed that the pathological diagnosis of ILC (P = 0.006), tissue samples collected from metastatic sites (P < 0.001), and older age (50 years, P < 0.001) were independent factors for TMB-H.ConclusionsPatients with ILC were more likely to have TMB-H than those with IDC. The findings of this study would be invaluable in selecting treatment strategies for patients with ILC.

The Japanese Breast Cancer Society initiated the breast cancer registry in 1975 and migrated the registry to the National Clinical Database-Breast Cancer Registry (NCD-BCR) in 2012. This annual report presents 2021 data on the NCD-BCR. We analyzed data from 98,540 breast cancer (BC) cases registered in 2021. In 2021, 99.4% of BC cases were females with a median age of 61. Most (57.5%) were diagnosed at early stages (Stage 0 or I). Breast-conserving surgery was performed in 42.8% of cases. Sentinel lymph node biopsy was performed in 67.8%, followed by radiotherapy in 71.0% of those post-conserving surgery. Regarding postoperative systemic therapy, 63.1% received endocrine therapy, 28.2% received chemotherapy, and 14.9% received molecular-targeted therapy. ER positivity was observed in 75.2%, HER2 in 13.6%, and Ki67 ≥30% in 29.1% of cases. The median age of premenopausal cases was 46 (interquartile range, 42–49) years and the median BMI was 21.5 (19.7–24.2) kg/m2 whereas the median age of postmenopausal cases was 69 (61–76) years and the median BMI was 23.0 (20.6–25.9) kg/m2. In premenopausal cases, cases with normal BMI were more likely to be found at checkups without subjective symptoms and in the early stage than those with high BMI. The tendency of ER, PgR, HER2, and Ki67 status on BMI differed by menopause status; premenopausal cases with a lower BMI showed higher proportions of ER- and PgR-positive cancer and lower proportions of cancer with high Ki67. These nationwide descriptive statistics would help clinical explanation and further research on breast cancer.