Cancer Science最新文献

{"title":"Cell Biology of Cancer Peritoneal Metastasis: Multiclonal Seeding and Peritoneal Tumor Microenvironment","authors":"Hideki Yamaguchi,&nbsp;Makoto Miyazaki","doi":"10.1111/cas.70021","DOIUrl":"10.1111/cas.70021","url":null,"abstract":"<p>Peritoneal metastasis, also known as peritoneal dissemination or carcinomatosis, refers to the spread of cancer to the peritoneum that lines the abdominal and pelvic cavities and covers the abdominal organs. Peritoneal metastasis typically occurs in advanced cancers of abdominal origin, most commonly gastrointestinal and gynecological cancers. Conventional chemotherapy has limited efficacy, and no effective molecular-targeted therapy is currently available for peritoneal metastasis. As a result, peritoneal metastasis is associated with poor outcomes and significantly reduced quality of life in patients with advanced cancers. This is largely due to a limited understanding of the molecular and cellular mechanisms underlying peritoneal metastasis. However, recent studies employing innovative approaches have provided novel insights into the mechanisms of peritoneal metastasis, contributing to the development of novel therapeutic strategies. In this review, we summarize recent findings on the cell biological aspects of peritoneal metastasis and potential therapeutic target molecules. In particular, we emphasize the importance of cancer cell clustering within the abdominal cavity, which drives multiclonal peritoneal seeding. We also focus on the interactions of cancer cells with mesothelial cells and cancer-associated fibroblasts within the peritoneal tumor microenvironment.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1171-1180"},"PeriodicalIF":4.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma tsRNA Signatures Serve as a Novel Biomarker for Bladder Cancer","authors":"Xinyan Xu,&nbsp;Jinbang Chen,&nbsp;Ming Bai,&nbsp;TianYao Liu,&nbsp;Shoubin Zhan,&nbsp;Jiazheng Li,&nbsp;YuanChun Ma,&nbsp;Yulin Zhang,&nbsp;Liming Wu,&nbsp;Zihan Zhao,&nbsp;Siyang Liu,&nbsp;Xi Chen,&nbsp;Feng Fang,&nbsp;Hongqian Guo,&nbsp;Ying Sun,&nbsp;Rong Yang","doi":"10.1111/cas.70003","DOIUrl":"10.1111/cas.70003","url":null,"abstract":"<p>Bladder cancer (BLCA) is one of the most common tumors of the urinary tract. The diagnosis of BLCA is mostly by invasive tests, which are damaging and unsuitable for early screening. Current non-invasive diagnostic modalities are insufficient in sensitivity and specificity. Therefore, novel diagnostic markers are urgently needed to facilitate early detection of bladder cancer. tRNA-derived small RNAs (tsRNAs) are considered to be novel and potentially biologically functional non-coding RNAs (ncRNAs). tsRNAs have been used to help early diagnosis of a variety of tumors. However, whether tsRNAs in BLCA are altered or involved in BLCA progression or regulation remains unclear. Here, we identified a group of up-regulated tsRNAs in BLCA by sequencing tsRNAs in the plasma of BLCA patients and normal controls and further screened two highly correlated tsRNAs with BLCA in the training set and validation set, which were named as tRF-1:28-chrM.Ser-TGA and tiRNA-1:34-Glu-CTC-1-M2. ROC analyses of the expression profiles of these two tsRNAs by the validation set identified a high diagnostic value. We also found that circulating tRF-1:28-chrM.Ser-TGA and tiRNA-1:34-Glu-CTC-1-M2 were specifically expressed and released by BLCA cells and were positively correlated with the degree of disease malignancy. In vitro and in vivo experiments revealed that the two tsRNAs exacerbated BLCA progression and played a role in promoting tumor lipid metabolism. Our study screened two plasma tsRNAs that could serve as valuable early screening and diagnostic biomarkers for BLCA and is also expected to provide potential novel molecular targets for the treatment of BLCA.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1255-1267"},"PeriodicalIF":4.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “PRMT9 Promotes Hepatocellular Carcinoma Invasion and Metastasis via Activating PI3K/Akt/GSK-3β/Snail Signaling”","authors":"","doi":"10.1111/cas.70004","DOIUrl":"10.1111/cas.70004","url":null,"abstract":"<p>H. Jiang, Z. Zhou, S. Jin, K. Xu, H. Zhang, J. Xu, Q. Sun, J. Wang, and J. Xu, “PRMT9 Promotes Hepatocellular Carcinoma Invasion and Metastasis via Activating PI3K/Akt/GSK-3β/Snail Signaling,” <i>Cancer Science</i> 109, no. 5 (2018): 1414–1427, https://doi.org/10.1111/cas.13598.</p><p>Concerns were raised by a third party regarding overlapping image panels within the article (Figures 2D and 5D). The authors admitted to the image compilation error and were able to provide the raw data of the article. The research integrity office of the authors' institute has investigated the concerns and recommended the publication of a correction. The authors confirm that all the experimental results and corresponding conclusions mentioned in the paper remain unaffected and sincerely apologize for this mistake.</p><p><b>FIGURE 5</b> (D) Invasion assays showing that LY294002 inhibits PRMT9-induced cell invasion.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 4","pages":"1155"},"PeriodicalIF":4.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Tumor-derived Prevotella intermedia aggravates gastric cancer by enhancing Perilipin 3 expression”","authors":"","doi":"10.1111/cas.70005","DOIUrl":"10.1111/cas.70005","url":null,"abstract":"<p>Liang W, Zhou Z, Gao Q, et al. Tumor-derived <i>Prevotella intermedia</i> aggravates gastriccancer by enhancing Perilipin 3 expression. Cancer Sci. 2024;115:1141–1153. doi:10.1111/cas.16080.</p><p>In the Abstract section, the text “The abundance of <i>P. intermedia</i> exhibited correlations with tumor differentiation (<i>p</i> = 0.006), perineural invasion (<i>p</i> = 0.004), omentum majus invasion (<i>p</i> = 0.040), and the survival duration of GC patients (<i>p</i> = 0.04<b>2</b>)”. It should instead be “The abundance of <i>P. intermedia</i> exhibited correlations with tumor differentiation (<i>p</i> = 0.006), perineural invasion (<i>p</i> = 0.004), omentum majus invasion (<i>p</i> = 0.040), and the survival duration of GC patients (<i>p</i> = 0.04<b>0</b>)”.</p><p>We apologize for this error.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 4","pages":"1156"},"PeriodicalIF":4.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STAT3 Inhibition Prevents Adaptive Resistance and Augments NK Cell Cytotoxicity to KRASG12C Inhibitors in Nonsmall Cell Lung Cancer","authors":"Zehao Pan,&nbsp;Yuxian Qian,&nbsp;Yajing Wang,&nbsp;Te Zhang,&nbsp;Xuming Song,&nbsp;Hanling Ding,&nbsp;Rutao Li,&nbsp;Yijian Zhang,&nbsp;Zi Wang,&nbsp;Hui Wang,&nbsp;Wenjie Xia,&nbsp;Lei Wei,&nbsp;Lin Xu,&nbsp;Gaochao Dong,&nbsp;Feng Jiang","doi":"10.1111/cas.70017","DOIUrl":"10.1111/cas.70017","url":null,"abstract":"<p>KRAS^G12C inhibitors exhibit conspicuous clinical response in KRAS^G12C-mutant lung cancer, yet adaptive resistance, the rapid onset of intrinsic resistance, dampens their therapeutic success. Rational combination strategies could tackle this challenging problem. A high-throughput screening of a pharmacological library with 423 compounds revealed that napabucasin, a signal transducer and activator of transcription 3 (STAT3) inhibitor, synergistically potentiated the growth inhibition effect of the KRAS^G12C inhibitor sotorasib in sensitive and resistant KRAS^G12C NSCLC cell lines. Functional assays further revealed that the coordinated targeting of KRAS with STAT3 improved the inhibitory effect on tumor growth and augmented the infiltration and activation of natural killer (NK) cells within the tumor microenvironment. Mechanistically, KRAS^G12C inhibition induced compensatory activation of STAT3, contingent on concomitant suppression of downstream ERK signaling, abrogated by napabucasin. Moreover, we unveiled and verified the binding site of phosphorylated STAT3 at the HLA-B promoter, an inhibitor ligand for NK cells. Our study dissected an unknown mechanism of adaptive resistance to KRAS^G12C inhibitors, with the STAT3 activation sustaining the regrowth of tumor cells under KRAS inhibition and up-regulating HLA-B transcription to dampen the cytotoxicity of infiltrated NK cells.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1375-1391"},"PeriodicalIF":4.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: Role of the MUC1-C Oncoprotein in the Acquisition of Cisplatin Resistance by Urothelial Carcinoma","authors":"","doi":"10.1111/cas.70016","DOIUrl":"10.1111/cas.70016","url":null,"abstract":"<p><b>RETRACTION:</b> K. Shigeta, M. Hasegawa, E. Kikuchi, Y. Yasumizu, T. Kosaka, R. Mizuno, S. Mikami, A. Miyajima, D. Kufe and M. Oya, “Role of the MUC1-C Oncoprotein in the Acquisition of Cisplatin Resistance by Urothelial Carcinoma,” <i>Cancer Science</i> 111, no. 10 (2020): 3639–3652, https://doi.org/10.1111/cas.14574.</p><p>The above article, published online on 16 July 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Masanori Hatakeyama; the Japanese Cancer Association; and John Wiley &amp; Sons Australia Ltd. The retraction has been agreed upon due to several instances of duplications of western blot bands observed between Figures 2E and 3B; 4A and 4D; S1b and S3a; and within S1d. The authors commented that this was due to inadvertent errors and provided some data including replacement images. However, the data supplied did not meet acceptable standards for raw data and the editors were not satisfied with the explanation provided. Due to the extent of the errors, the editors have lost confidence in the results and conclusions of this study. The authors disagree with the retraction.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 4","pages":"1154"},"PeriodicalIF":4.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGFR2/3 Gene Alterations and Clinical Outcomes in Advanced/Metastatic Urothelial Cancer in Japan: MONSTAR-SCREEN Database Study","authors":"Nobuaki Matsubara,&nbsp;Takahiro Osawa,&nbsp;Takashige Abe,&nbsp;Mototsugu Oya,&nbsp;Koshiro Nishimoto,&nbsp;Toshiyuki Iwahori,&nbsp;Hiroaki Tsuchiya,&nbsp;Maiko Murota,&nbsp;Masaki Yoshida,&nbsp;Yohei Tatematsu,&nbsp;Yosuke Nakano,&nbsp;Masatoshi Eto,&nbsp;Norio Nonomura","doi":"10.1111/cas.70000","DOIUrl":"10.1111/cas.70000","url":null,"abstract":"<p>Advanced/metastatic urothelial cancer (a/m UC) still has a poor prognosis despite the recent medical advances. Recent studies demonstrated that fibroblast growth factor receptor (<i>FGFR</i>) gene alterations (GAs) may be driver genes for UC; however, the proportion of UC genetic panel testing in Japan remains low. We clarified the proportion of patients with <i>FGFR2/3</i> GAs, treatment patterns, and clinical outcomes in a/m UC patients in Japan. This study was a descriptive epidemiological study using the MONSTAR-SCREEN database, and 138 patients with a/m UC were evaluated. The primary endpoint was the proportion of patients with <i>FGFR2/3</i> GAs. The secondary endpoints included treatment patterns, clinical outcomes, genomic status before and after treatment, etc. The proportion of <i>FGFR</i> GA-positive patients in a/m UC was 11.9%. The most common <i>FGFR</i> mutation variant and fusion gene were S249C (4.4%) and <i>FGFR3-TACC3</i> fusion (3.7%), respectively. Fifty-one patients were tested two or more times; a few changes were observed in the <i>FGFR</i> GA status, regardless of the treatment regimen. Co-occurrence association was observed in <i>FGFR1</i> with <i>TET2</i>, and in <i>FGFR3</i> with <i>CHEK2</i> or <i>MLL2</i>. During the first-, second-, and third-line treatment, median progression-free survival (PFS) of GA-positive patients was 7.3, 2.9, and 6.2 months, while for GA-negative patients, 6.9, 3.1, and 6.9 months, respectively. This study revealed that one in eight a/m UC patients had <i>FGFR2/3</i> GAs, and a few changes were observed in <i>FGFR</i> GA status before and after treatment. Genetic testing will be beneficial for the selection of appropriate treatments after a diagnosis of a/m UC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1424-1432"},"PeriodicalIF":4.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Second Opinion Referrals of Cancer Patients in Japan—A Nationwide Study","authors":"Mieko Takasawa,&nbsp;Norihiro Teramoto,&nbsp;Natsumi Yamashita,&nbsp;Takahiro Higashi","doi":"10.1111/cas.70012","DOIUrl":"10.1111/cas.70012","url":null,"abstract":"<p>Seeking a second opinion (SO) is a patient's right that is essential to appropriate decision-making for their care and treatment. In Japan, however, no previous studies have provided objective data on the nationwide practice of SO among cancer patients. In this study, we investigated SO referrals, including delays in initiating care, using data from nationwide hospital-based cancer registries and 2018–2020 the Diagnosis Procedure Combination (DPC) survey. Among the more than 2.6 million patients diagnosed with cancer, 1.6% received SO referral letters as reimbursement. The referral rates varied based on sex, age, and geographic regions. A total of 52.1% of SO were sought before active treatment of the tumor. Approximately 60% of the patients who sought SO prior to the initial treatment returned to their original provider for treatment. The average period from diagnosis to the start of treatment among those who sought SO was 18 days and 22 days longer for non-small lung cancer and breast cancer, respectively, than among those who did not seek SO. In the future, the risk–benefit of SO referral should be examined, considering both the prognostic impact of treatment delay due to SO and the psychological benefits for the patient gained from SO.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1417-1423"},"PeriodicalIF":4.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-Time, AI-Guided Photodynamic Laparoscopy Enhances Detection in a Rabbit Model of Peritoneal Cancer Metastasis","authors":"Adriana Rivera-Piza,&nbsp;Sung-Ho Lee,&nbsp;Hannah HeeJung Lee,&nbsp;Seungho Lee,&nbsp;Su-Jin Shin,&nbsp;Jaehyuk Kim,&nbsp;Jong-Hyun Park,&nbsp;Jae Eun Yu,&nbsp;Sang Won Lee,&nbsp;Gyuri Park,&nbsp;Brian C. Wilson,&nbsp;Hyoung-Il Kim","doi":"10.1111/cas.70009","DOIUrl":"10.1111/cas.70009","url":null,"abstract":"<p>Accurate diagnosis is essential for effective cancer treatment, particularly in peritoneal surface malignancies, where failure to detect metastatic lesions can mislead the treatment plan. This study assessed the diagnostic accuracy of staging laparoscopy using the integration of artificial intelligence (AI)-guided photodynamic diagnosis (PDD) with the photosensitizer Phonozen, activated at 405 nm in a rabbit model. To create peritoneal carcinomatosis, VX2 cells were inoculated laparoscopically into the peritoneum of female white New Zealand rabbits. Conventional and PDD-guided laparoscopy utilized a customized light source that emitted broad-spectrum white light or 405-nm blue light, respectively. The surgical procedure comprised a tripartite approach: exploration and labeling of suspected nodules under white-light visualization, identification of additional metastatic tumors under blue-excitation fluorescent light, and confirmatory open laparotomy to locate overlooked nodules by palpation. Our results showed that the initial experimental data from 371 nodules in 14 rabbits, comparing conventional diagnostic laparoscopy and PDD, showed increased detection sensitivity from 67% ± 1.9% (conventional) to 98% ± 0.7% (PDD) in the small-size nodule. In the second experimental data set from 265 nodules in 10 rabbits, the addition of a real-time AI algorithm further increased the sensitivity to 100% ± 0.0%. Combining PDD with AI enhances the detection of peritoneal cancer metastasis in staging laparoscopy.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 4","pages":"966-975"},"PeriodicalIF":4.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline Pathogenic Variants and Clinical Outcomes in Asian Patients With Breast Cancer","authors":"Rui Kitadai,&nbsp;Shu Yazaki,&nbsp;Aya Kuchiba,&nbsp;Takashi Yamanaka,&nbsp;Sho Shiino,&nbsp;Chisako Yamauchi,&nbsp;Kenichi Harano,&nbsp;Motonobu Saito,&nbsp;Yosuke Hirotsu,&nbsp;Hisaki Aiba,&nbsp;Teruhiko Yoshida,&nbsp;Ryuji Hamamoto,&nbsp;Chikako Shimizu,&nbsp;Akihiko Shimomura,&nbsp;Yuki Kojima,&nbsp;Tatsunori Shimoi,&nbsp;Yukihide Momozawa,&nbsp;Kazuki Sudo,&nbsp;Masayuki Yoshida,&nbsp;Kuniko Sunami,&nbsp;Megumi Hori,&nbsp;Kota Katanoda,&nbsp;Yoko Shimada,&nbsp;Yuji Yamashita,&nbsp;Takahiro Kogawa,&nbsp;Takeshi Murata,&nbsp;Saori Fujiwara,&nbsp;Yohei Miyagi,&nbsp;Hiroshi Nakagomi,&nbsp;Kazunoshin Tachibana,&nbsp;Masao Omata,&nbsp;Tohru Ohtake,&nbsp;Akihiko Suto,&nbsp;Tatsuya Onishi,&nbsp;Yoichi Naito,&nbsp;Toshinari Yamashita,&nbsp;Kan Yonemori,&nbsp;Takashi Kohno,&nbsp;Kouya Shiraishi","doi":"10.1111/cas.70002","DOIUrl":"10.1111/cas.70002","url":null,"abstract":"<p>Despite the importance of genetic testing for risk assessment and treatment in breast cancer, the prognostic impact of germline pathogenic variants (PVs), especially in Asian populations, is unclear. We assessed the impact of germline PVs in patients with early-stage breast cancer. This study included 7278 Japanese multihospital registry patients. PVs of <i>ATM</i>, <i>BRCA1</i>, <i>BRCA2</i>, <i>CDH1</i>, <i>CHEK2</i>, <i>NBN</i>, <i>NF1</i>, <i>PALB2</i>, <i>PTEN</i>, <i>STK11</i>, and <i>TP53</i> were evaluated. PV and non-PV carriers were matched by age, histology, and stage. Associations between PVs and survival were assessed. The primary outcome was invasive disease-free survival (IDFS). Secondary outcomes included relapse-free survival (RFS), overall survival, and breast cancer-specific survival. We identified 320 (4.4%) patients with <i>BRCA1/2</i> PVs and 79 (1.1%) with PVs other than <i>BRCA1/2</i> (non-<i>BRCA1/2</i>). A total of 360 patients (<i>BRCA1/2</i>, <i>n</i> = 289; non-<i>BRCA1/2</i>, <i>n</i> = 71) were matched to 720 noncarriers. Patients with <i>BRCA1/2</i> PVs had significantly shorter 10-year IDFS (adjusted hazard ratio (aHR) = 2.15; 95% confidence interval (CI), 1.61–2.86; <i>p</i> &lt; 0.001); and RFS (aHR = 1.74; 95% CI, 1.25–2.44; <i>p</i> = 0.001) than noncarriers. Among patients with hormone receptor-positive HER2-negative breast cancer, <i>BRCA1/2</i> PV carriers exhibited significantly shorter 10-year IDFS than noncarriers, even those with stage I/II disease (total, aHR = 2.23; 95% CI, 1.55–3.23; <i>p</i> &lt; 0.001, Stage I/II, aHR = 2.22; 95% CI, 1.43–3.44; <i>p</i> &lt; 0.001). There was no significant difference in 10-year IDFS between the non-<i>BRCA1/2</i> PV carrier and noncarrier groups (aHR = 1.40; 95% CI, 0.67–2.93; <i>p</i> = 0.37). Asian patients with breast cancer carrying germline <i>BRCA1/2</i> PV, even those with a low recurrence risk, have significantly shorter 10-year IDFS than noncarriers.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 4","pages":"1048-1058"},"PeriodicalIF":4.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}