Hereditary Cancer in Clinical Practice最新文献

{"title":"Decisional conflict in women with a BRCA1 or BRCA2 pathogenic variant who have not elected for risk-reducing salpingo-oophorectomy.","authors":"Kelly A Metcalfe, Anita Y Kinney, Steven A Narod, Aletta Poll, Susan Armel, Lucia Lombardi, Farideh Tavangar, Tuya Pal","doi":"10.1186/s13053-025-00329-4","DOIUrl":"10.1186/s13053-025-00329-4","url":null,"abstract":"<p><strong>Objective: </strong>To identify predictors of decisional conflict among women with a BRCA pathogenic variant (PV) who were eligible for risk reducing salpingo-oophorectomy (RRSO) who had not made a decision to have surgery at least one year after receiving genetic test results.</p><p><strong>Methods: </strong>Women with a BRCA1 or BRCA2 PV between the ages of 35 and 70 years old, who had not elected for RRSO at least 12 months after receipt of genetic test results, were administered self-report questionnaires investigating demographic variables, decisional conflict (Decisional Conflict Scale), cancer-related distress (Impact of Event Scale) and cancer risk perception. Decisional conflict scores were generated and a multivariable linear regression was conducted to identify variables associated with decisional conflict.</p><p><strong>Results: </strong>A sample of 107 women completed questionnaires. Overall, 44 participants (41%) had a high decisional conflict score (greater than 37.5) related to the RRSO decision. Higher education (β = 11.40, 95% C.I: 0.59, 22.20; p = 0.039), non-white race (β = 11.12, 95% C.I: 0.66, 21.57; p = 0.037), and having children (β = 22.89, 95% C.I: 10.07, 35.71; p < 0.001) were significantly associated with higher decisional conflict. Lower decisional conflict was significantly associated with genetic testing more than 3 years prior (β = -13.14, 95% C.I: -23.27, -2.99; p = 0.012).</p><p><strong>Conclusions: </strong>Many women with a BRCA PV who have not elected for RRSO are experiencing high levels of decisional conflict related to the decision regarding RRSO. Interventions that target decisional conflict are needed to increase the uptake of RRSO which will result in a reduction of the risk of ovarian cancer in women with BRCA1 or BRCA2 PV.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":" ","pages":"2"},"PeriodicalIF":2.4,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12895950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skin cancer risk in hereditary mixed cancer syndromes.","authors":"Veera Nikkola, Anna Alakoski, Jukka-Pekka Mecklin, Toni T Seppälä, Jussi Nikkola, Kashmintan Schrader","doi":"10.1186/s13053-025-00326-7","DOIUrl":"10.1186/s13053-025-00326-7","url":null,"abstract":"<p><p>Hereditary cancer syndromes are genetic conditions that increase an individual's risk for multiple cancer types, often due to mutations that affect critical cellular processes such as DNA repair and cell cycle regulation. Skin cancers, including malignant melanoma (MM), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and related precancerous lesions may be underrecognized in some hereditary cancer syndromes, as suggested by underlying biological mechanisms and their underreporting in studies. In this narrative review, we examine the skin cancer risks associated with the most prevalent hereditary cancer syndromes, including Li-Fraumeni syndrome (LFS), Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), ATM-associated hereditary cancer syndrome, CHEK2-associated hereditary cancer syndrome, BRIP1-associated cancer predisposition, and hereditary leiomyomatosis and renal cell carcinoma (HLRCC). This review consolidates existing evidence and suggests that mixed cancer syndromes, especially LFS, LS, and HBOC but also pathogenic ATM and CHEK2 variants may predispose individuals to skin cancers, warranting tailored screening and preventive measures. On the basis of emerging evidence, we recommend dermatologic evaluation and individualized UV protection strategies for patients with reviewed hereditary cancer syndromes to reduce skin cancer risk and enhance early detection.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":" ","pages":"1"},"PeriodicalIF":2.4,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12777409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145662615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and healthcare burden of neurofibromatosis type 1 in Saudi Arabia: a single centre experience.","authors":"Mohammed A Almuqbil, Maha Al Ammari, Nada S Al Dhayyan, Seena Thomas Kaithathara, Mohamed Al Balwi","doi":"10.1186/s13053-025-00325-8","DOIUrl":"https://doi.org/10.1186/s13053-025-00325-8","url":null,"abstract":"<p><strong>Background: </strong>Neurofibromatosis type 1 (NF1; 613113) is a hereditary neurocutaneous disorder that causes tumors in the nervous system, significantly impacting the quality of life (QoL). It is characterized by diverse clinical manifestations, including café-au-lait macules (CALMs), axillary or inguinal freckling, Lisch nodules, skeletal abnormalities, and various types of neurofibromas. Plexiform neurofibromas (PN), a common complication of NF1, are often inoperable and prone to recurrence. The study aimed to describe the clinical characteristics and healthcare burden of NF1, including those with PN and those receiving Selumetinib therapy, in Saudi Arabia.</p><p><strong>Methods: </strong>This retrospective observational study was conducted at the National Guard Health Affairs King Abdulaziz Medical City in Saudi Arabia. Patient medical records were retrospectively reviewed from January 2016 to January 2024. We included all patients diagnosed with NF1 who fulfilled the National Institutes of Health (NIH) diagnostic criteria in 2021 or had a confirmed pathogenic NF1 variant on genetic testing.</p><p><strong>Results: </strong>A total of 60 patients with NF1 were included; 55.2% of them were females. CALMs were the most common cardinal criteria, affecting 80% of the patients. Among NF1 patients, 12 had PN (20%). Only four patients received Selumetinib therapy. Genetic testing was performed in 39 patients, revealing pathogenic NF1 variants in 29 (74.4%). Pain medications were used by eight patients (13.3%). NF-1-related pain negatively impacted patients' attention (24%), outdoor activities (24%), and social interactions with friends (20%). Among NF1 patients, 28 (46.7%) required hospitalization, twelve ER visits were conducted by seven (11.7%) NF1 patients, and outpatient services were utilized by nearly all NF1 patients (96.7%), with 1076 outpatient visits. The overall financial burden was high, with NF1 patients incurring $64.5 million, PN patients $13.5 million, and PN patients treated with Selumetinib $3.7 million.</p><p><strong>Conclusion: </strong>This study highlights the clinical and healthcare challenges of NF1 and PN in Saudi Arabia, emphasizing the need for a multidisciplinary approach that combines medical, psychological, and financial support. The limited access to Selumetinib represents a gap. Increasing treatment accessibility and financial support are key to improving the outcomes and QoL.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"27"},"PeriodicalIF":2.4,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12659344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145642819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of MLH1, MSH2, and MSH6 large genomic rearrangements to Pakistani colorectal cancer patients.","authors":"Humaira Naeemi, Noor Muhammad, Asif Loya, Muhammed Aasim Yusuf, Muhammad Usman Rashid","doi":"10.1186/s13053-025-00327-6","DOIUrl":"10.1186/s13053-025-00327-6","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is the fourth most common cancer in Pakistan and poses significant public health challenges. While the majority of CRC cases are sporadic, ~ 5-10% are hereditary, linked to germline pathogenic variants (PVs) in mismatch repair genes (MLH1, MSH2, MSH6, PMS2) and other susceptibility genes (APC, EPCAM). In Pakistan, small-range PVs in MLH1 and MSH2 account for 34.5% of hereditary nonpolyposis colorectal cancer (HNPCC)/suspected-HNPCC and 1.1% of non-HNPCC cases. However, the contribution of large genomic rearrangements (LGRs) in MLH1, MSH2, MSH6, and the 3' end of EPCAM remains uncharacterized.</p><p><strong>Methods: </strong>We comprehensively screened 199 Pakistani CRC patients (HNPCC/suspected-HNPCC:18 and non-HNPCC:181), previously tested negative for small-range PVs in MMR genes. LGRs in MLH1, MSH2, MSH6, and the 3' end of EPCAM were analyzed using multiplex ligation-dependent probe amplification (MLPA). Deletion breakpoints were characterized using long-range polymerase chain reaction (PCR) and Sanger sequencing.</p><p><strong>Results: </strong>Five distinct MSH2 deletions (5' upstream, exons 1-3, exons 1-6, exon 7, and exon 11) were identified in 11.1% (2/18) of HNPCC/suspected-HNPCC and 3.3% (6/181) of non-HNPCC cases. A recurrent 5' upstream deletion was identified in four unrelated patients, including one suspected-HNPCC and three non-HNPCC cases. Other deletions were identified in patients with variable family histories of cancer. No LGRs were detected in MLH1, MSH6, or the 3' end of EPCAM. Notably, 87.5% of patients with MSH2 LGRs belonged to Punjabi ethnicity.</p><p><strong>Conclusions: </strong>Our findings demonstrate that MSH2 LGRs occur at a notable frequency among Pakistani CRC patients, with a recurrent 5' upstream deletion representing a potential Punjabi founder variant. Inclusion of this deletion into targeted genetic testing panels may enhance diagnostic yield and improve risk stratification for CRC in Pakistan.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"26"},"PeriodicalIF":2.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12628528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145551899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genetic puzzle of FAP: exploring novel diagnostic approaches for APC/MUTYH-negative case.","authors":"Natalia Grot, Marek Kazimierczyk, Marcin Szuman, Marta Kaczmarek-Ryś, Alicja Kryszczyńska, Iga Dziechciowska, Monika Knaur, Andrzej Hnatyszyn, Szymon Hryhorowicz, Andrzej Pławski","doi":"10.1186/s13053-025-00318-7","DOIUrl":"10.1186/s13053-025-00318-7","url":null,"abstract":"<p><p>Multiple polyposis syndromes include Familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome (PJS), Juvenile polyposis syndrome (JPS), PTEN hamartoma tumor syndrome (PHTS), MUTYH-associated polyposis (MAP), NTHL1-associated polyposis (NAP), Polymerase proofreading-associated polyposis (PPAP), and MBD4-associated polyposis. Common to these syndromes is the presence of polyps in the large intestine and very high risk of developing colorectal cancer (CRC), which can reach up to 100% in the case of FAP. The development of FAP is associated with pathogenic variants of the APC gene. However, pathogenic variants are not always detected in patients with FAP, which poses a significant clinical challenge for both patients and their families, who may be at increased risk for developing the disease. A second strong predisposition to CRC is MAP, characterized by biallelic pathogenic variants in the MUTYH gene, with a phenotype similar to FAP. This mini review focuses on potential approaches to improve the diagnosis of patients in whom pathogenic variants in the APC and MUTYH genes are not detected by routine testing.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"25"},"PeriodicalIF":2.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12595752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145472466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular markers associated with elevated colorectal cancer risk: a mini review.","authors":"Marcin Szuman, Marek Kazimierczyk, Natalia Grot, Marta Kaczmarek-Ryś, Alicja Kryszczyńska, Iga Dziechciowska, Monika Knaur, Andrzej Hnatyszyn, Szymon Hryhorowicz, Andrzej Pławski","doi":"10.1186/s13053-025-00319-6","DOIUrl":"10.1186/s13053-025-00319-6","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the third most common cancer worldwide, with 70% of cases attributed to sporadic mutations and the remaining linked to inherited genetic predispositions. This mini-review focuses on low-penetrance genetic variants that modestly influence CRC risk, categorizing them by mutation type - single nucleotide polymorphisms (SNPs) and non-SNP variants. Missense mutations in genes such as TP53, APC, CHEK2, and MUTYH are highlighted for their varying associations with CRC risk across populations. Additionally, silent mutations, untranslated region variants, and promoter modifications, such as those in PLA2G2A, XPA, and DNMT3B, are discussed for their potential, albeit modest, roles in CRC predisposition. Non-SNP variants, including deletions and insertions in genes like CHEK2, NOD2, GSTM1, and GSTT1, are explored for their frameshift effects and influence on CRC susceptibility. The review underscores the complexity of CRC risk, shaped by genetic, environmental, and lifestyle factors, and advocates for comprehensive, population-specific research to enhance genetic counseling and advance personalized medicine in CRC prevention and treatment.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"24"},"PeriodicalIF":2.8,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12587527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumour spectrum, distinguishing features and management recommendations for NTHL1-associated tumour syndrome: a systematic review.","authors":"Weilun Gao, Chuyi Liao, Daniel D Buchanan, Finlay Macrae, Richarda M de Voer","doi":"10.1186/s13053-025-00323-w","DOIUrl":"10.1186/s13053-025-00323-w","url":null,"abstract":"<p><p>BACKGROUND AND AIM: To systematically describe the genotypes and phenotypes of NTHL1-associated tumour syndrome (NATS) cases reported in the literature. METHODS: A systematic review of literature across Medline, Embase and Web of Science was carried out by two independent reviewers. Studies reporting individuals with germline biallelic NTHL1 likely pathogenic/pathogenic variants (PVs) were identified and collected for statistical analysis. RESULTS: In total, 24 studies reported 77 individuals with germline biallelic NTHL1 PVs (51.9% female) from 54 families with 81.8% (63/77) of cases developing at least one cancer [median age at first cancer diagnosis 47 years; range 19–68 years]. The c.244 C > T, p.(Gln82*) PV occurred in 50/54 (92.6%) probands with 31 of these being homozygous and 19 having this PV in compound heterozygosity with another PV. Colorectal cancer occurred in 39/77; (50.6%), with the median age at diagnosis 50 years; range 31–73 years followed by breast cancer 25/77; (32.5%), with median age at diagnosis 47 years; range 36–68 years. Other phenotypes were central nervous system neoplasia, skin, gynecological, urothelial and hematological cancers. Colonic polyposis (≥ 10 polyps of any histology) was observed in 39/70 (55.7%) cases reported to have colonoscopy. In probands, colorectal cancer was the most common indication for genetic testing (38/54; 70.4%) followed by colorectal and breast cancer (8/54; 14.8%). The presence of COSMIC mutational signature SBS30 in a cancer genome may indicate the presence of biallelic NTHL1 deficiency. CONCLUSION: The prevalence of colorectal-, breast, endometrial cancers and meningiomas in this series highlights the importance of surveillance. Findings of this systematic review should inform guidelines for screening and diagnosis. COSMIC mutational signature 30 may assist in defining the tumour spectrum and assessing the pathogenicity of variants of unknown significance. Prospective studies on cancer development in NATS cases, with broader ascertainment, are recommended to further characterize of the cancer spectrum and penetrance. </p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"23"},"PeriodicalIF":2.8,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lynch syndrome caused by SINE-VNTR-Alu-F retrotransposon insert in MSH6 confirmed after 20 years of testing: a case report and literature review.","authors":"Wenche Sjursen, Eva Kathrine Svaasand, Bodil Gilde, Anuradha Ravi, Katinka Madtzog Korseth, Ashish Kumar Singh, Jostein Johansen, Olaug Kristin Rødningen, Sofie Geck Sevatdal, Siv Anita Hegre, Maren Fridtjofsen Olsen, Kristine Misund","doi":"10.1186/s13053-025-00324-9","DOIUrl":"10.1186/s13053-025-00324-9","url":null,"abstract":"<p><strong>Background: </strong>Lynch syndrome is due to error in DNA mismatch repair (MMR) genes caused by germline pathogenic variants. For some families highly suspicious of Lynch syndrome, the diagnosis may not be confirmed.</p><p><strong>Case presentation: </strong>We present a family where Lynch syndrome has been suspected for 20 years. Although haplotyping and tumor analyses suggested Lynch syndrome, newer sequencing methods such as whole-genome sequencing and long-read sequencing, were needed to detect the underlying genetic cause of their cancer predisposition. We identified a > 3kbp retrotransposon (RT) insertion in MSH6 to be the causative germline variant. Further, we reviewed the literature for RT events in Lynch syndrome families and found a total of 40 RT cases, making up about 0.5% of Lynch cases. Two-third of the RTs were shorter ALU-elements (< 500 bp).</p><p><strong>Conclusions: </strong>Although RTs insertions do not seem to be a common cause of Lynch syndrome, the number might be underestimated because of the difficulties in detecting these variants with well-established methods like Sanger sequencing and NGS target sequencing.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"22"},"PeriodicalIF":2.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12523002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic characterization of patients with colorectal cancer.","authors":"Marwa Mahdouani, Drenushe Zhuri, Fulya Dusenkalkan, Hakan Gurkan, Sinem Yalcintepe","doi":"10.1186/s13053-025-00322-x","DOIUrl":"10.1186/s13053-025-00322-x","url":null,"abstract":"<p><strong>Background: </strong>Hereditary colorectal cancer (CRC) predisposition syndromes account for 5-10% of all diagnosed CRC cases. Lynch syndrome (LS), Familial Adenomatous Polyposis (FAP), and MUTYH-associated polyposis (MAP) are well-characterized hereditary syndromes known to contribute to colorectal cancer predisposition. However, other inherited genetic factors beyond these established conditions remain underexplored. Recent advancements in next-generation sequencing (NGS) have facilitated the identification of germline pathogenic variants (gPV) in cancer predisposition genes, enhancing diagnostic and management strategies for hereditary CRC syndromes. Using this technology, this study aimed to investigate the genetic causes of CRC in 23 Turkish patients belonging to 23 different families.</p><p><strong>Methods: </strong>Patients with a personal or familial history of colorectal cancer (CRC) or polyposis were selected from a cohort of 54 individuals examined between 2019 and 2022. Genetic testing was performed using the TruSight^® Cancer and Qiaseq panels on the Illumina NextSeq next-generation sequencing (NGS) platform.</p><p><strong>Results: </strong>A total of 23 variants were identified, including 10 pathogenic or likely pathogenic variants, 5 of which were novel. These germline pathogenic/likely pathogenic variants were detected in the key genes MLH1, MSH6, PMS2, and APC, which are associated with LS and FAP. Variants were also found in other genes, including FANCC, CHEK2, ATM, and MUC16. Additionally, 13 variants of uncertain significance (VUS) were identified, 5 of which were novel. These VUS were detected in the genes MUTYH (linked to MAP), ATR, XRCC3, PALB2, ATM, SYNE1, RAD51D, NF1, ABRAXAS1, ERBB2, FGFR, and CHEK2, necessitating further investigation to determine their potential role in CRC predisposition.</p><p><strong>Conclusion: </strong>These findings highlight the utility of NGS in identifying germline variants linked to hereditary CRC syndromes and emphasize the need for functional studies to assess the pathogenicity of VUS.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"21"},"PeriodicalIF":2.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medullary breast cancer and germline BRCA1 mutations: a possible criterion for genetic testing.","authors":"Adriana I Apostol, David Lim, Steven A Narod","doi":"10.1186/s13053-025-00321-y","DOIUrl":"10.1186/s13053-025-00321-y","url":null,"abstract":"<p><p>Medullary breast cancer is a rare subtype of invasive breast cancer, representing from 0.2% to 6% of all breast carcinomas, with a higher proportion among women with triple-negative breast cancer and among those with a BRCA1 mutation. This review article aims to investigate the frequency of medullary breast cancer among all breast cancers and to assess its association with BRCA1 mutations. We surveyed studies involving patients diagnosed with breast cancer that report both the histology of the breast cancer as well as the presence of BRCA1 mutations. Among women with medullary breast cancer, the proportion of cases that carry a BRCA1 mutation ranges from 3% up to 35.3%, depending on the study. Among BRCA1-mutated breast cancers, the proportion that are medullary ranges from 8 to 20%. Given the notable association between medullary breast cancer and BRCA1 mutations, we propose to consider medullary breast cancer as a criterion for genetic testing in order to improve the identification of a larger number of carriers, thereby enhancing screening and prevention strategies.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"20"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}