Publisher：Breast Cancer  

In this article the title was incorrectly given as ‘Prognostici of ER-staining patterns and heterogeneity of ER positive HER2 negative breast cancer’ but should have been ‘Prognostic Impact of ER‑staining patterns and heterogeneity of ER positive HER2 negative breast cancer’. The original article has been corrected.

DOI： 10.1007/s12282-025-01729-z

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PubMed

Language：English   Publisher：Breast Cancer  

Background: High 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. Methods: We 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. Results: Patients 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. Conclusions: Patients 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.

DOI： 10.1007/s12282-025-01706-6

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PubMed

DOI： 10.1200/JCO.2025.43.16_suppl.e12535

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DOI： 10.1016/j.breast.2025.104015

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Web of Science

Language：English   Publisher：Japan Surgical Society  

<p><b>INTRODUCTION:</b> Thyroid angiosarcoma (TAS) is an extremely rare and highly aggressive cancer, representing less than 1% of all sarcomas. Typically diagnosed in individuals aged 50–80, with a higher incidence in women, TAS has a poor prognosis due to its tendency to metastasize, leading to a low 5-year survival rate. Due to its rarity, standardized treatment approaches are lacking, often involving a combination of surgery, chemotherapy, and radiation. This report presents TAS in a Japanese male.</p><p><b>CASE PRESENTATION:</b> A 78-year-old male with pre-existing conditions presented with a 30-year history of a slow-growing thyroid tumor that exhibited rapid enlargement 4 months prior to surgery. Initial fine-needle aspiration cytology was no malignancy. Examinations revealed a firm, poorly mobile 10 cm mass in the anterior neck, and left pleural effusion. Notably, papules developed at the aspiration site and progressively enlarged. Preoperative imaging indicated a malignant thyroid tumor, prompting a right thyroid lobectomy with resection of anterior neck muscles and overlying skin. Histological analysis confirmed a highly hemorrhagic angiosarcoma with infiltration into surrounding tissues. Immunohistochemical findings supported the diagnosis of TAS. A comprehensive genomic profiling testing yielded no specific therapeutic recommendations. Paclitaxel therapy was initiated 2 months after surgery, resulting in the shrinking of pulmonary nodules and the decreasing left pleural effusion. The patient subsequently died from septic shock due to a urinary tract infection 5 months after starting chemotherapy, without evidence of cervical recurrence or neutropenia during treatment.</p><p><b>CONCLUSIONS:</b> This case highlights the perioperative management of a rare primary TAS. In the absence of established treatment guidelines, surgical resection followed by paclitaxel administration could be a potential therapeutic strategy to control disease progression. An accumulation of case reports is needed to better understand this aggressive malignancy and to facilitate the development of optimized therapeutic strategies.</p>

DOI： 10.70352/scrj.cr.25-0349

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CiNii Research

Authorship：Corresponding author   Language：English   Publisher：Breast Cancer Basic and Clinical Research  

Background: Although BRCA1 and BRCA2 mutations are known to be associated with different breast cancer (BC) subtypes, real-world evidence on how these genetic differences influence tumor behavior and treatment decisions remains limited, particularly in Japanese patients. With the recent expansion of PARP inhibitor indications in Japan, BRCA testing has become increasingly routine, highlighting the need for clinical data tailored to local populations. Objectives: To compare clinicopathological features, recurrence patterns, and surgical choices between BRCA1- and BRCA2-associated BC in Japanese patients, with a focus on ER-positive tumors. Design: A single-institution retrospective cohort study. Methods: We retrospectively reviewed 417 patients who underwent BRCA1/2 genetic testing at a single Japanese institution between April 2020 and November 2023. Of these, 38 patients (12 BRCA1, 26 BRCA2) had pathogenic variants. We compared clinicopathological features, recurrence patterns, and choices of risk-reducing surgery between BRCA1 and BRCA2 carriers. Results: BRCA1-associated cancers were predominantly triple-negative (75%) and diagnosed at earlier stages (T1 in 83.3%), while BRCA2-associated cancers were mainly ER-positive (69.2%) and more likely to present with multiple lymph node metastases (⩾2 nodes in 42.3%). Although Ki-67 levels were higher in BRCA1 tumors, this was largely subtype-dependent. Notably, ER-positive BRCA tumors showed a trend toward higher recurrence. Preferences for prophylactic surgery also varied by mutation type. Conclusion: This single-institution study highlights clinically meaningful differences between BRCA1- and BRCA2-associated BC in Japanese patients. BRCA2 cancers tended to present with more advanced features, while BRCA1 cancers were more often detected at earlier stage. These findings underscore the value of BRCA testing not only for PARP inhibitor eligibility but also for subtype-specific risk assessment and individualized preventive strategies.

DOI： 10.1177/11782234251399355

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Language：Japanese   Publisher：Japan Association of Breast Cancer Screening  

DOI： 10.3804/jjabcs.34.121

CiNii Research

Language：Japanese   Publisher：Japan Society of Ningen Dock and Preventive Medical Care  

<p>A 48-year-old woman with a 5-year history of annual mammography and ultrasonography screening was found to have a circumscribed mass in the right breast during her routine examination. Simultaneous ultrasound examination revealed a polygonal, internally heterogeneous mass measuring 14.1×11.9×11.9 mm at the right 9 o'clock position, which coincided with the mass. Malignancy was suspected and further examination was performed. During the second examination, a 1.5-cm mass was palpated in the right CD region. Malignancy was diagnosed by cytology. The histopathological diagnosis on vacuum-assisted biopsy was metaplastic carcinoma (matrix-producing type). Surgery was performed at another hospital, including right mastectomy and sentinel lymph node biopsy. The final pathological diagnosis was triple-negative metaplastic carcinoma (cancer associated with cartilage metaplasia) with a disease stage of pT2N0M0, stage IIA.</p><p>In most cases, screening detects luminal breast cancer, which progresses relatively slowly, but in this case, the patient continued to undergo simultaneous annual mammography and ultrasound examinations, which led to the detection of the cancer before symptoms such as lumps appeared. We report this case as illustrating the effectiveness of annual simultaneous examinations in detecting highly malignant breast cancer.</p>

DOI： 10.11320/ndprevmedcare.40.3_563

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CiNii Research

DOI： 10.1016/j.annonc.2024.07.635

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DOI： 10.1016/j.annonc.2024.07.605

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DOI： 10.1016/j.annonc.2024.08.307

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Language：English   Publisher：Japan Epidemiological Association  

<p><b>Background:</b> Reproductive factors, such as age at menarche, are known to be associated with disease risk, but data on trends in these factors in Japan are limited. In this study, we investigated secular trends in reproductive factors and explored their potential association with socioeconomic and historical events.</p><p><b>Methods:</b> We conducted a retrospective analysis of 62,005 Japanese women born between 1890 and 1991 using a survey conducted over 25 years. Trends in reproductive factors were analyzed using linear and joinpoint regression models, and their associations with major historical events involving Japan were evaluated.</p><p><b>Results:</b> We found that the age at menarche showed a significant downward trend (<i>P</i> < 0.001) over the century. Three joinpoints were identified, in 1932 (15.23 years old), 1946 (13.48 years old), and 1959 (12.71 years old), which indicated that average age at menarche decreased by approximately 0.8% per year between 1932 and 1946, and then by 0.4% per year between 1946 and 1959, both of which were statistically significant. However, after 1959, age of menarche remained stable. Analyses of other reproductive factors found significant changes, including a decrease in parity and the number of babies breastfed, and an increase in age at first birth.</p><p><b>Conclusion:</b> Age at menarche showed a long-term downward trend in Japan, with significant change points in annual percent change. Other factors showed secular changes in trends as well. These change points were observed at the same time as historical events, namely wars and economic development, suggesting that socioeconomic and environmental changes at the population level affect reproductive factors in females.</p>

DOI： 10.2188/jea.je20230155

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CiNii Research

Language：English   Publisher：Breast Cancer  

Background: A recent large real-world study conducted in the United States reported the effectiveness of palbociclib plus aromatase inhibitor in HR+/HER2− advanced breast cancer (ABC). However, local clinical practice and available medical treatment can vary between Japan and Western countries. Thus, it is important to investigate Japanese real-world data. This observational, multicenter study (NCT05399329) reports the interim analysis of effectiveness of palbociclib plus ET as first-line or second-line treatment for HR+/HER2− ABC by estimating real-world progression-free survival (rwPFS) and overall survival (OS) in Japanese routine clinical practice. Methods: Real-world clinical outcomes and treatment patterns of palbociclib plus ET were captured using a medical record review of patients diagnosed with HR+/HER2− ABC who had received palbociclib plus ET in the first-line or second-line treatment across 20 sites in Japan. The primary endpoint was rwPFS; secondary endpoints were OS, real-world overall response rate, real-world clinical benefit rate, and chemotherapy-free survival. Results: Of the 677 eligible patients, 420 and 257 patients, respectively, had received palbociclib with ET as first-line and second-line treatments. Median rwPFS (95% confidence interval) was 24.5 months (19.9–29.4) for first-line and 14.5 months (10.2–19.0) for second-line treatment groups. Median OS was not reached in the first-line group and was 46.7 months (38.8-not estimated) for the second-line group. The 36-month OS rates for de novo metastasis, treatment-free interval (TFI) ≥ 12 months, and TFI < 12 months were 80.2% (69.1–87.7), 82.0% (70.7–89.3), and 66.0% (57.9–72.9), respectively. Conclusion: The addition of palbociclib to ET was effective for treating HR+/HER2− ABC in Japanese routine clinical practice.

DOI： 10.1007/s12282-024-01575-5

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Language：English   Publisher：Breast Cancer  

Background: The internet, especially YouTube, has become a prominent source of health information. However, the quality and accuracy of medical content on YouTube vary, posing concerns about misinformation. This study focuses on providing reliable information about hereditary breast cancer on YouTube, given its importance for decision-making among patients and families. The study examines the quality and accessibility of such content in Japanese, where limited research has been conducted. Methods: A nonprofit organization called BC Tube was established in May 2020 to create informative videos about breast cancer. The study analyzed 85 YouTube videos selected using the Japanese keywords “hereditary breast cancer” and “HBOC”, categorized into six groups based on the source of upload: BC Tube, hospitals/governments, individual physicians, public-interest organizations/companies, breast cancer survivors, and others. The videos were evaluated based on various factors, including content length, view counts, likes, comments, and the presence of advertisements. The content was evaluated using the PEMAT and DISCERN quality criteria. Results: BC Tube created high-quality videos with high scores on PEMAT understandability, significantly outperforming other sources. Videos from public-interest organizations/companies received the most views and likes, despite their lower quality. Videos from medical institutions and governments were of superior quality but attracted less attention. Conclusions: Our study emphasizes the importance of promoting accessible, easy-to-understand, and widely recognized medical information online. The popularity of videos does not always correspond to their quality, emphasizing the importance of quality evaluation. BC Tube provides a peer-reviewed platform to disseminate high-quality health information. We need to develop high-quality online health information and encourage the promotion of evidence-based information on YouTube.

DOI： 10.1007/s12282-023-01512-y

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Language：Japanese   Publisher：Japan Association of Endocrine Surgery  

DOI： 10.11226/ojjaes.40.3_140

CiNii Research

Publisher：Gan to Kagaku Ryoho Cancer Chemotherapy  

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Language：Japanese  

PubMed

DOI： 10.1016/j.annonc.2022.05.142

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Language：English   Publisher：Cancer Science  

Approximately 5%–10% of breast cancers are hereditary, caused by germline pathogenic variants (GPVs) in breast cancer predisposition genes. To date, most studies of the prevalence of GPVs and risk of breast cancer for each gene based on cases and noncancer controls have been conducted in Europe and the United States, and little information from Japanese populations is available. Furthermore, no studies considered confounding by established environmental factors and single-nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS) together in GPV evaluation. To evaluate the association between GPVs in nine established breast cancer predisposition genes including BRCA1/2 and breast cancer risk in Japanese women comprehensively, we conducted a case-control study within the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (629 cases and 1153 controls). The associations between GPVs and the risk of breast cancer were assessed by odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models adjusted for potential confounders. A total of 25 GPVs were detected among all cases (4.0%: 95% CI: 2.6–5.9), whereas four individuals carried GPVs in all controls (0.4%). The OR for breast cancer by all GPVs and by GPVs in BRCA1/2 was 12.2 (4.4–34.0, p = 1.74E-06) and 16.0 (4.2–60.9, p = 5.03E-0.5), respectively. A potential confounding with GPVs was observed for the GWAS-identified SNPs, whereas not for established environmental risk factors. In conclusion, GPVs increase the risk of breast cancer in Japanese women regardless of environmental factors and GWAS-identified SNPs. Future studies investigating interactions with environment and SNPs are warranted.

DOI： 10.1111/cas.15312

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Language：Japanese   Publisher：Japan Association of Breast Cancer Screening  

BACKGROUND: Breast awareness is an efficient and effective behavioral pattern against breast cancer, however, its popularity is not yet sufficient. Thus, an effort to raise breast awareness is required. We have established a system for providing breast cancer information through videos on YouTube, and have posted videos on breast awareness. In this study, we compared our videos for breast awareness information in order to clarify the effective way of providing breast awareness information to public.
METHODS: Multiple breast clinicians collaborated to create the videos. We ensured scientific validity by using a peer-review system by independent group of breast clinicians. Patients and public are involved in confirming to ensure explicitness and expression appropriateness. The videos were posted on the YouTube channel “Breast Cancer Encyclopedia”. Among 6 videos for breast awareness information, we compared the number of views and retention rates of these videos from July 2020 to June 2021.
RESULTS: The most frequently viewed video was “A Short Summary of Breast Cancer Symptoms” with 29,000 views and a higher retention rate than the other videos at 47.2%. The video explaining breast awareness itself had 5,000 views and a retention rate of 37.2%.
CONCLUSIONS: The more concise video about the symptoms was viewed more than the video explaining breast awareness. As breast awareness refers to “the process of raising awareness of one's own breasts,” it is essential to establish a concise and accessible platform for viewers to “Think of it as a personal matter” and “Being familiar with the normal consistency of your breasts” so that they understand what's normal and promptly report changes. In addition, it is necessary to continue to improve the contents and methods of providing information in accordance with the times

DOI： 10.3804/jjabcs.31.31

CiNii Research

Language：Japanese   Publisher：Japanese Journal of Clinical Oncology  

Background: Physicians recommend adjuvant therapy to patients based on baseline risk. A common recognition for baseline risk between patients and physicians is critical for successful adjuvant therapy. We prospectively investigated the differences in estimated baseline risk between physicians and patients with early breast cancer. Methods: This analysis was performed at a single institution in Japan. Early breast cancer patients over 18 years old were enrolled after surgery. After explaining the pathological results, physicians asked each patient about an estimated baseline risk. Differences in estimated baseline risk were defined as the baseline risk estimated by patients minus the baseline risk estimated by physicians. The primary endpoint was that the number of patients who estimate baseline risk higher than physicians was higher than those who estimate a lower baseline risk. The secondary endpoints were differences in estimated baseline risk by stage, subtype and the influence of patient factors to differences in estimated baseline risk. Results: From July 2017 to December 2018, 262 patients were enrolled. Among the 262 patients, 190 estimated a higher baseline risk than physicians, 53 estimated a lower baseline risk and 19 estimated the same. Overall, patients estimated a significantly higher baseline risk than physicians (P < 0.001). Differences in estimated baseline risk was significantly smaller in patients who knew the term 'baseline risk' than patients who did not (P = 0.0037). Differences in estimated baseline risk were also significantly smaller in patients with stage II breast cancer than patients with stage I (P = 0.0239). However, there were no statistically significant differences of differences in estimated baseline risk according to other factors. Conclusions: Patients with early breast cancer estimated a significantly higher baseline risk than physicians. Physicians should accurately explain baseline risk to patients for shared decision making.

DOI： 10.1093/jjco/hyab152

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Language：English  

DOI： 10.1097/SLA.0000000000005185

PubMed

Language：English  

DOI： 10.1002/ijc.33478

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Language：English   Publisher：Japan Epidemiological Association  

<p><b>Background:</b> Obesity is a reported risk factor for various health problems. Genome-wide association studies (GWASs) have identified numerous independent loci associated with body mass index (BMI). However, most of these have been focused on Europeans, and little evidence is available on the genetic effects across the life course of other ethnicities.</p><p><b>Methods:</b> We conducted a cross-sectional study to examine the associations of 282 GWAS-identified single nucleotide polymorphisms with three BMI-related traits, current BMI, BMI at 20 years old (BMI at 20), and change in BMI (BMI change), among 11,586 Japanese individuals enrolled in the Japan Multi-Institutional Collaborative Cohort study. Associations were examined using multivariable linear regression models.</p><p><b>Results:</b> We found a significant association (<i>P</i> < 0.05/282 = 1.77 × 10⁻⁴) between BMI and 11 polymorphisms in or near <i>FTO</i>, <i>BDNF</i>, <i>TMEM18</i>, <i>HS6ST3</i>, and <i>BORCS7</i>. The trend was similar between current BMI and BMI change, but differed from that of the BMI at 20. Among the significant variants, those on <i>FTO</i> were associated with all BMI traits, whereas those on <i>TMEM18</i> and <i>HS6SR3</i> were only associated with BMI at 20. The association of <i>FTO</i> loci with BMI remained, even after additional adjustment for dietary energy intake.</p><p><b>Conclusions:</b> Previously reported BMI-associated loci discovered in Europeans were also identified in the Japanese population. Additionally, our results suggest that the effects of each loci on BMI may vary across the life course and that this variation may be caused by the differential effects of individual genes on BMI via different pathways.</p>

DOI： 10.2188/jea.je20190296

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CiNii Research

Language：English  

DOI： 10.1007/s12282-020-01065-4

PubMed

Language：English   Publisher：Cancer Research  

A genetic variant on aldehyde dehydrogenase 2 (ALDH2 rs671, Glu504Lys) contributes to carcinogenesis after alcohol consumption. Somewhat conversely, the ALDH2 Lys allele also confers a protective effect against alcohol-induced carcinogenesis by decreasing alcohol consumption due to acetaldehyde-related adverse effects. Here, we applied a mediation analysis to five case–control studies for head and neck, esophageal, stomach, small intestine, and colorectal cancers, with 4,099 cases and 6,065 controls, and explored the potentially heterogeneous impact of alcohol drinking on digestive tract carcinogenesis by decomposing the total effect of the ALDH2 Lys allele on digestive tract cancer risk into the two opposing effects of the carcinogenic effect (direct effect) and the protective effect (indirect effect mediated by drinking behavior). Alcohol was associated with an increased risk of most digestive tract cancers, but significant direct effects were observed only for upper gastrointestinal tract cancer risk, and varied substantially by site, with ORs (95% confidence interval) of 1.83 (1.43–2.36) for head and neck cancer, 21.15 (9.11–49.12) for esophageal cancer, and 1.65 (1.38–1.96) for stomach cancer. In contrast, a significant protective indirect effect was observed on risk for all cancers, except small intestine cancer. These findings suggest that alcohol is a major risk factor for digestive tract cancers, but its impact as a surrogate for acetaldehyde exposure appears heterogeneous by site. Meanwhile, the behavior-related effect of the ALDH2 Lys allele results in a decreased risk of most digestive tract cancers.

DOI： 10.1158/0008-5472.CAN-19-2685

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Language：English  

DOI： 10.1007/s10549-020-05580-y

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Language：Japanese   Publisher：Breast Cancer Research and Treatment  

Purpose: Lymphedema (LE) decreases the quality of life of breast cancer patients. Objective quantification of PRO may improve the discordance between patient-reported outcomes (PROs) and objective assessments of LE by establishing a standard follow-up for LE. This study determined the prevalence of subjective and objective LE and evaluated the correlation between objective assessment and PRO of LE in primary breast cancer patients undergoing breast and axilla surgery. Methods: Breast cancer patients who underwent sentinel lymph node biopsy (SN) or axillary lymph node dissection (ALND) more than 1 year after surgery were enrolled. We prospectively evaluated LE using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and two objective assessments (arm circumference and bioimpedance) and analyzed their correlations. Results: Between November 2018 and January 2019, 631 patients (SN; n = 415, ALND; n = 216) were enrolled. The median age, body mass index, and duration from surgery was 56 years, 21.9 kg/m², and 3.8 years, respectively. The prevalences of subjective and objective LE were 4.1% and 1.4% in the SN group and 51.8% and 24.1% in the ALND group, respectively. The objective assessments were weakly positively correlated with PRO-CTCAE. Arm circumference measurement correlated better than bioimpedance overall and was most strongly correlated with “frequency” (r = 0.485, p < 0.01). Conclusions: LE occurred in few SN patients. The prevalence of subjective LE was higher than that of objective LE. Arm circumference measurements better reflected PRO than did bioimpedance. These results underscore the limitation of LE detection by subjective or objective methods alone.

DOI： 10.1007/s10549-019-05443-1

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DOI： 10.1038/s41598-019-54839-y

Open Access

PubMed

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DOI： 10.1111/tbj.13473

Open Access

PubMed

Language：English  

DOI： 10.1007/s00595-019-01775-z

PubMed

Language：English  

DOI： 10.1186/s40792-019-0635-4

Open Access

PubMed

Language：Japanese   Publisher：Breast Journal  

Skin-sparing mastectomy (SSM) with immediate reconstruction is standard surgical treatment for early breast cancer with widespread ductal carcinoma in situ (DCIS). The local recurrence rate after SSM is up to 7.0%. We investigated prediction of the pathological margin using contrast-enhanced MRI, and evaluated the cut-off point to obtain the safety margin. We performed SSM with immediate reconstruction in 216 early breast cancer patients with widespread DCIS and/or invasive cancer from January 2014 to December 2015. Forty cases were retrospectively reviewed after excluding those with >15 mm between skin and tumor, determined by preoperative contrast-enhanced MRI, or involving reconstructive surgery for local recurrence, immeasurable lesion by preoperative contrast-enhanced MRI, or neoadjuvant chemotherapy. We defined a positive pathological margin as <1 mm from the cancer nest. We reviewed the distance between skin and tumor by MRI and pathological examination. To identify the cut-off for predicting a positive pathological margin, we performed sensitivity analysis using an ROC curve. The margin-positive rate by pathological examination was 27.5% (n = 11/40), with a moderate correlation of MRI margin and pathological margin (r = 0.44). The best cut-off point for margin positivity was 5 mm of MRI margin, with sensitivity and specificity of 54% and 86%, respectively (P = 0.009). This is the first prediction of pathological margin by preoperative contrast-enhanced MRI in early breast cancer patients with SSM. Care is required for SSM if the MRI margin is less than 5 mm due to pathological margin positivity.

DOI： 10.1111/tbj.13194

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Language：English  

DOI： 10.1007/s10549-018-4898-4

PubMed

Authorship：Lead author  

DOI： 10.1007/s12282-018-0856-6

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DOI： 10.1007/s12282-018-0852-x

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DOI： 10.1007/s12282-018-0850-z

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DOI： 10.1093/jjco/hyy088

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DOI： 10.1007/s12282-016-0742-z

PubMed