British Journal of Cancer最新文献

{"title":"BRCA-mutated breast cancer: the unmet need, challenges and therapeutic benefits of genetic testing","authors":"Banu Arun, Fergus J. Couch, Jean Abraham, Nadine Tung, Peter A. Fasching","doi":"10.1038/s41416-024-02827-z","DOIUrl":"10.1038/s41416-024-02827-z","url":null,"abstract":"Mutations in the BRCA1 and/or BRCA2 genes (BRCAm) increase the risk of developing breast cancer (BC) and are found in ~5% of unselected patients with the disease. BC resulting from a germline BRCAm (gBRCAm) has distinct clinical characteristics along with increased sensitivity to DNA-damaging agents such as poly(ADP-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapies, and potentially decreased sensitivity to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. Given the evolving treatment landscape for gBRCAm BC in early and advanced disease settings, timely determination of gBRCAm status is fundamental to facilitate the most effective treatment strategy for patients. However, many patients with gBRCAm are not identified due to suboptimal referral rates and/or a low uptake of genetic testing. We discuss current evidence for a differential response to treatment in patients with gBRCAm in early and advanced BC settings, including outcomes with PARP inhibitors, platinum-based chemotherapies, and CDK4/6 inhibitors, as well as ongoing treatment innovations and the potential of these treatment approaches. Current genetic testing strategies are also examined, including the latest guidelines on who and when to test for gBRCAm, as well as challenges to testing and how these may be overcome.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 9","pages":"1400-1414"},"PeriodicalIF":6.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02827-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating miRNA panels as a novel non-invasive diagnostic, prognostic, and potential predictive biomarkers in non-small cell lung cancer (NSCLC)","authors":"Maryam Abdipourbozorgbaghi, Adrienne Vancura, Ramin Radpour, Simon Haefliger","doi":"10.1038/s41416-024-02831-3","DOIUrl":"10.1038/s41416-024-02831-3","url":null,"abstract":"Non-small cell lung cancer (NSCLC) is characterised by its aggressiveness and poor prognosis. Early detection and accurate prediction of therapeutic responses remain critical for improving patient outcomes. In the present study, we investigated the potential of circulating microRNA (miRNA) as non-invasive biomarkers in patients with NSCLC. We quantified miRNA expression in plasma from 122 participants (78 NSCLC; 44 healthy controls). Bioinformatic tools were employed to identify miRNA panels for accurate NSCLC diagnosis. Validation was performed using an independent publicly available dataset of more than 4000 NSCLC patients. Next, we correlated miRNA expression with clinicopathological information to identify independent prognostic miRNAs and those predictive of anti-PD-1 treatment response. We identified miRNA panels for lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) diagnosis. The LUAD panel consists of seven circulating miRNAs (miR-9-3p, miR-96-5p, miR-147b-3p, miR-196a-5p, miR-708-3p, miR-708-5p, miR-4652-5p), while the LUSC panel comprises nine miRNAs (miR-130b-3p, miR-269-3p, miR-301a-5p, miR-301b-5p, miR-744-3p, miR-760, miR-767-5p, miR-4652-5p, miR-6499-3p). Additionally, miR-135b-5p, miR-196a-5p, miR-31-5p (LUAD), and miR-205 (LUSC) serve as independent prognostic markers for survival. Furthermore, two miRNA clusters, namely miR-183/96/182 and miR-767/105, exhibit predictive potential in anti-PD-1-treated LUAD patients. Circulating miRNA signatures demonstrate diagnostic and prognostic value for NSCLC and may guide treatment decisions in clinical practice.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 8","pages":"1350-1362"},"PeriodicalIF":6.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02831-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical utility of BRCA and ATM mutation status in circulating tumour DNA for treatment selection in advanced pancreatic cancer","authors":"Kentaro Sudo, Yoshiaki Nakamura, Makoto Ueno, Masayuki Furukawa, Nobumasa Mizuno, Yasuyuki Kawamoto, Naohiro Okano, Kumiko Umemoto, Akinori Asagi, Masato Ozaka, Koushiro Ohtsubo, Satoshi Shimizu, Nobuhisa Matsuhashi, Shinji Itoh, Toshihiko Matsumoto, Taroh Satoh, Hiroyuki Okuyama, Masahiro Goto, Hiroko Hasegawa, Yoshiyuki Yamamoto, Justin I. Odegaard, Hideaki Bando, Takayuki Yoshino, Masafumi Ikeda, Chigusa Morizane","doi":"10.1038/s41416-024-02834-0","DOIUrl":"10.1038/s41416-024-02834-0","url":null,"abstract":"Identification of homologous recombination deficiency (HRD) remains a challenge in advanced pancreatic cancer (APC). We investigated the utility of circulating tumour DNA (ctDNA) profiling in the assessment of BRCA1/2 and ATM mutation status and treatment selection in APC. We analysed clinical and ctDNA data of 702 patients with APC enroled in GOZILA, a ctDNA profiling study using Guardant360. Inactivating BRCA1/2 and ATM mutations were detected in 4.8% (putative germline, 3.7%) and 4.4% (putative germline, 0.9%) of patients, respectively. Objective response (63.2% vs. 16.2%) and PFS (HR 0.55, 95% CI 0.32–0.93) on platinum-containing chemotherapy were significantly better in patients with putative germline BRCA1/2 (gBRCA) mutation than those without. In contrast, putative gBRCA mutation had no impact on the efficacy of gemcitabine plus nab-paclitaxel. In 2 patients treated with platinum-containing therapy, putative BRCA2 reversion mutations were detected. Three of seven patients with somatic BRCA mutations responded to platinum-containing therapy, while only one of four with putative germline ATM mutations did. One-third of somatic ATM mutations were in genomic loci associated with clonal haematopoiesis. Comprehensive ctDNA profiling provides clinically relevant information regarding HRD status. It can be a practical, convenient option for HRD screening in APC.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 7","pages":"1237-1245"},"PeriodicalIF":6.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early detection of pancreatic cancer by comprehensive serum miRNA sequencing with automated machine learning","authors":"Munenori Kawai, Akihisa Fukuda, Ryo Otomo, Shunsuke Obata, Kosuke Minaga, Masanori Asada, Atsushi Umemura, Yoshito Uenoyama, Nobuhiro Hieda, Toshihiro Morita, Ryuki Minami, Saiko Marui, Yuki Yamauchi, Yoshitaka Nakai, Yutaka Takada, Kozo Ikuta, Takuto Yoshioka, Kenta Mizukoshi, Kosuke Iwane, Go Yamakawa, Mio Namikawa, Makoto Sono, Munemasa Nagao, Takahisa Maruno, Yuki Nakanishi, Mitsuharu Hirai, Naoki Kanda, Seiji Shio, Toshinao Itani, Shigehiko Fujii, Toshiyuki Kimura, Kazuyoshi Matsumura, Masaya Ohana, Shujiro Yazumi, Chiharu Kawanami, Yukitaka Yamashita, Hiroyuki Marusawa, Tomohiro Watanabe, Yoshito Ito, Masatoshi Kudo, Hiroshi Seno","doi":"10.1038/s41416-024-02794-5","DOIUrl":"10.1038/s41416-024-02794-5","url":null,"abstract":"Pancreatic cancer is often diagnosed at advanced stages, and early-stage diagnosis of pancreatic cancer is difficult because of nonspecific symptoms and lack of available biomarkers. We performed comprehensive serum miRNA sequencing of 212 pancreatic cancer patient samples from 14 hospitals and 213 non-cancerous healthy control samples. We randomly classified the pancreatic cancer and control samples into two cohorts: a training cohort (N = 185) and a validation cohort (N = 240). We created ensemble models that combined automated machine learning with 100 highly expressed miRNAs and their combination with CA19-9 and validated the performance of the models in the independent validation cohort. The diagnostic model with the combination of the 100 highly expressed miRNAs and CA19-9 could discriminate pancreatic cancer from non-cancer healthy control with high accuracy (area under the curve (AUC), 0.99; sensitivity, 90%; specificity, 98%). We validated high diagnostic accuracy in an independent asymptomatic early-stage (stage 0-I) pancreatic cancer cohort (AUC:0.97; sensitivity, 67%; specificity, 98%). We demonstrate that the 100 highly expressed miRNAs and their combination with CA19-9 could be biomarkers for the specific and early detection of pancreatic cancer.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 7","pages":"1158-1168"},"PeriodicalIF":6.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02794-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What kind of tumour rupture requires adjuvant therapy?","authors":"Gaku Chiguchi, Haruhiko Cho","doi":"10.1038/s41416-024-02812-6","DOIUrl":"10.1038/s41416-024-02812-6","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 7","pages":"1109-1110"},"PeriodicalIF":6.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Development and validation of a circulating microRNA panel for the early detection of breast cancer","authors":"Ruiyang Zou, Sau Yeen Loke, Yew Chung Tang, Heng-Phon Too, Lihan Zhou, Ann S. G. Lee, Mikael Hartman","doi":"10.1038/s41416-024-02800-w","DOIUrl":"10.1038/s41416-024-02800-w","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 6","pages":"1107-1107"},"PeriodicalIF":6.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02800-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of post-operative iron biomarkers in colorectal cancer: population-based patient cohort","authors":"Tafirenyika Gwenzi, Petra Schrotz-King, Sophie C. Anker, Ben Schöttker, Michael Hoffmeister, Hermann Brenner","doi":"10.1038/s41416-024-02814-4","DOIUrl":"10.1038/s41416-024-02814-4","url":null,"abstract":"Post-operative anaemia is linked to iron deficiency. We investigated the prognostic value of post-operative iron biomarkers in colorectal cancer (CRC). Ferritin, transferrin, iron, and transferrin saturation (TS%) were measured from blood collected at a single time-point post-surgery in 2769 CRC patients. Associations between iron biomarkers with cancer-specific survival (CSS) and overall survival (OS) were assessed using Cox regression with hazard ratios (HR), stratified by post-operative time of blood collection (<1-month/≥1-month). After a median follow-up of 9.5 years, 52.6% of patients had died. For iron biomarkers assessed <1-month post-surgery, higher compared to normal TS% was associated with shorter CSS (HR [95% CI] = 2.36 [1.25–4.46]), and higher iron levels with better OS (upper vs. median tertile: HR [95% CI] = 0.79 [0.65–0.97]). When assessed ≥1-month post-surgery, elevated ferritin was associated with poor CSS (high vs. normal: HR [95% CI] = 1.44 [1.10–1.87]), and low TS% with worse CSS (low vs. normal: HR [95% CI] = 1.60 [1.24–2.06]). Similar but weaker associations were observed for OS. Monitoring of serum ferritin and TS% beyond 1-month post-surgery may be relevant for risk stratification of patients with operable CRC. Future studies should validate our findings.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 7","pages":"1195-1201"},"PeriodicalIF":6.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02814-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pursuit of the optimal therapeutic approach and intensity for children with bilateral Wilms tumour","authors":"Andrew J. Murphy","doi":"10.1038/s41416-024-02806-4","DOIUrl":"10.1038/s41416-024-02806-4","url":null,"abstract":"Investigators from the International Society of Paediatric Oncology Renal Tumour Study Group (SIOP-RTSG) report on outcomes of children with bilateral Wilms tumour treated on the SIOP 2001 study. They demonstrate that vincristine and actinomycin-D induction chemotherapy is sufficient in a subset of children, but most required additional agents during their treatment.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 6","pages":"970-971"},"PeriodicalIF":6.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02806-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intention to have blood-based multi-cancer early detection (MCED) screening: a cross-sectional population-based survey in England","authors":"Ninian Schmeising-Barnes, Jo Waller, Laura A. V. Marlow","doi":"10.1038/s41416-024-02822-4","DOIUrl":"10.1038/s41416-024-02822-4","url":null,"abstract":"Trials assessing the clinical utility of blood-based multi-cancer early detection (MCED) tests are underway. Understanding public attitudes towards MCED screening is essential if these tests are to be used. We aimed to quantify MCED screening intention and potential barriers and facilitators to uptake. Adults aged 50–77 (n = 958) completed an online survey. The primary outcome was intention to have MCED screening if offered. Psychological variables including barriers and facilitators were assessed. We used logistic regressions to explore associations between socio-demographics and psychological factors and intention. 93.8% of participants said they would ‘definitely’ or ‘probably’ have MCED screening if offered. Intention was significantly associated with previous screening participation and general cancer attitudes but not with socio-demographic factors. Participants were more likely to be intenders if they had higher health motivation, and perceived greater benefits of blood tests. Participants were less likely to be intenders if they perceived greater disadvantages of blood tests, more practical barriers, were more worried about the outcome and more concerned about a positive result. MCED screening intention was high. The lack of socio-demographic variation suggests equitable interest in this type of screening; however, future research should consider how intention translates to uptake.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 7","pages":"1202-1211"},"PeriodicalIF":6.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02822-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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: Serum microRNA expression profile: miR-1246 as a novel diagnostic and prognostic biomarker for oesophageal squamous cell carcinoma","authors":"Nobuyoshi Takeshita, Isamu Hoshino, Mikito Mori, Yasunori Akutsu, Naoyuki Hanari, Yasuo Yoneyama, Norimasa Ikeda, Yuka Isozaki, Tetsuro Maruyama, Naoki Akanuma, Aki Komatsu, Mari Jitsukawa, Hisahiro Matsubara","doi":"10.1038/s41416-024-02820-6","DOIUrl":"10.1038/s41416-024-02820-6","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 6","pages":"1106-1106"},"PeriodicalIF":6.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02820-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}