Hereditary Cancer in Clinical Practice最新文献

{"title":"Significant detection of new germline pathogenic variants in Australian Pancreatic Cancer Screening Program participants.","authors":"Krithika Murali,&nbsp;Tanya M Dwarte,&nbsp;Mehrdad Nikfarjam,&nbsp;Katherine M Tucker,&nbsp;Rhys B Vaughan,&nbsp;Marios Efthymiou,&nbsp;Allison Collins,&nbsp;Allan D Spigelman,&nbsp;Lucinda Salmon,&nbsp;Amber L Johns,&nbsp;David B Williams,&nbsp;Martin B Delatycki,&nbsp;Thomas John,&nbsp;Alina Stoita","doi":"10.1186/s13053-021-00190-1","DOIUrl":"10.1186/s13053-021-00190-1","url":null,"abstract":"<p><strong>Background: </strong>The Australian Pancreatic Cancer Screening Program (APCSP) offers endoscopic ultrasound surveillance for individuals at increased risk of pancreatic ductal adenocarcinoma (PDAC) with all participants requiring assessment by a Familial Cancer Service before or after study enrolment.</p><p><strong>Methods: </strong>Individuals aged 40-80 years (or 10 years younger than the earliest PDAC diagnosis) were eligible for APCSP study entry if they had 1) ≥ two blood relatives with PDAC (at least one of first-degree association); 2) a clinical or genetic diagnosis of Hereditary Pancreatitis or Peutz-Jeghers syndrome irrespective of PDAC family history; or 3) a known PDAC predisposition germline pathogenic variant (BRCA2, PALB2, CDKN2A, or Lynch syndrome) with ≥one PDAC-affected first- or second-degree relative. Retrospective medical record review was conducted for APCSP participants enrolled at the participating Australian hospitals from January 2011 to December 2019. We audited the genetic investigations offered by multiple Familial Cancer Services who assessed APCSP participants according to national guidelines, local clinical protocol and/or the availability of external research-funded testing, and the subsequent findings. Descriptive statistical analysis was performed using Microsoft Excel.</p><p><strong>Results: </strong>Of 189 kindreds (285 participants), 50 kindreds (71 participants) had a known germline pathogenic variant at enrolment (BRCA2 n = 35, PALB2 n = 6, CDKN2A n = 3, STK11 n = 3, PRSS1 n = 2, MLH1 n = 1). Forty-eight of 136 (35%) kindreds with no known germline pathogenic variant were offered mutation analysis; 89% was clinic-funded, with increasing self-funded testing since 2016. The relatively low rates of genetic testing performed reflects initial strict criteria for clinic-funded genetic testing. New germline pathogenic variants were detected in five kindreds (10.4%) after study enrolment (BRCA2 n = 3 kindreds, PALB2 n = 1, CDKN2A n = 1). Of note, only eight kindreds were reassessed by a Familial Cancer Service since enrolment, with a further 21 kindreds identified as being suitable for reassessment.</p><p><strong>Conclusion: </strong>Germline pathogenic variants associated with PDAC were seen in 29.1% of our high-risk cohort (55/189 kindreds; 82/285 participants). Importantly, 10.4% of kindreds offered genetic testing were newly identified as having germline pathogenic variants, with majority being BRCA2. As genetic testing standards evolve rapidly in PDAC, 5-yearly reassessment of high-risk individuals by Familial Cancer Services is warranted.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"33"},"PeriodicalIF":1.7,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39329156","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":"Expanding the phenotype of E318K (c.952G > A) MITF germline mutation carriers: case series and review of the literature.","authors":"Leandro Jonata Carvalho Oliveira,&nbsp;Aline Bobato Lara Gongora,&nbsp;Fabiola Ambrosio Silveira Lima,&nbsp;Felipe Sales Nogueira Amorim Canedo,&nbsp;Carla Vanessa Quirino,&nbsp;Janina Pontes Pisani,&nbsp;Maria Isabel Achatz,&nbsp;Benedito Mauro Rossi","doi":"10.1186/s13053-021-00189-8","DOIUrl":"https://doi.org/10.1186/s13053-021-00189-8","url":null,"abstract":"<p><strong>Background: </strong>The microphthalmia-associated transcription factor gene (MITF) belongs to the MYC supergene family and plays an important role in melanocytes' homeostasis. Individuals harboring MITF germline pathogenic variants are at increased risk of developing cancer, most notably melanoma and renal cell carcinoma.</p><p><strong>Case presentation: </strong>We describe a cohort of ten individuals who harbor the same MITF c.952G > A (p.Glu 318Lys), or p.E318K, germline pathogenic variant. Six carriers developed at least one malignancy (4 cases of breast cancer; 1 cervical cancer; 1 colon cancer; 1 melanoma; 1 ovarian/fallopian tube cancer). A significant phenotypic heterogeneity was found among these individuals and their relatives. Breast cancer was, overall, the most frequent malignancy observed in this case series, with 13 occurrences of 60 (21.67 %) total cancer cases described among the probands and their relatives.</p><p><strong>Conclusions: </strong>Our retrospective analysis data raise the hypothesis of a possible association of the MITF p.E318K pathogenic variant with an increased risk of breast cancer.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"32"},"PeriodicalIF":1.7,"publicationDate":"2021-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13053-021-00189-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39206357","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":"Evaluation and comparison of hereditary Cancer guidelines in the population.","authors":"Jordon B Ritchie, Cecelia Bellcross, Caitlin G Allen, Lewis Frey, Heath Morrison, Joshua D Schiffman, Brandon M Welch","doi":"10.1186/s13053-021-00188-9","DOIUrl":"10.1186/s13053-021-00188-9","url":null,"abstract":"<p><strong>Background: </strong>Family health history (FHx) is an effective tool for identifying patients at risk of hereditary cancer. Hereditary cancer clinical practice guidelines (CPG) contain criteria used to evaluate FHx and to make recommendations for genetic consultation. Comparing different CPGs used to evaluate a common set of FHx provides insight into how well the CPGs perform, the extent of agreement across guidelines, and how well they identify patients who should consider a cancer genetic consultation.</p><p><strong>Methods: </strong>We compare the American College of Medical Genetics and Genomics (ACMG) and the National Comprehensive Cancer Networks (NCCN) (2019) CPG criteria for FHx collected by a chatbot and evaluated by ontologies and web services in a previous study. Collected FHx met criteria from seven groups: Gene Mutation, Breast and Ovarian, Li-Fraumeni syndrome (LFS), Colorectal and Endometrial, Relative Meets Criteria, ACMG Only Criteria, and NCCN Testing. CPG Criteria were coded and matched across 12 ACMG sub-guidelines and 6 NCCN sub-guidelines for comparison purposes.</p><p><strong>Results: </strong>The dataset contains 4915 records, of which 2221 met either ACMG or NCCN criteria and 2694 did not. There was significant overlap-1179 probands met both ACMG and NCCN criteria. The greatest similarities were for Gene Mutation and Breast and Ovarian criteria and the greatest disparity existed among Colorectal and Endometrial criteria. Only 156 positive gene mutations were reported and of the 2694 probands who did not meet criteria, 90.6% of them reported at least one cancer in their personal or family cancer history.</p><p><strong>Conclusion: </strong>Hereditary cancer CPGs are useful for identifying patients at risk of developing cancer based on FHx. This comparison shows that with the aid of chatbots, ontologies, and web services, CPGs can be more efficiently applied to identify patients at risk of hereditary cancer. Additionally this comparison examines similarities and differences between ACMG and NCCN and shows the importance of using both guidelines when evaluating hereditary cancer risk.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"31"},"PeriodicalIF":1.7,"publicationDate":"2021-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39193649","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":"Ultrasound guided needle biopsy of axilla to evaluate nodal metastasis after preoperative systemic therapy in cohort of 106 breast cancers enriched with BRCA1/2 pathogenic variant carriers.","authors":"Baiba Līcīte, Arvīds Irmejs, Jeļena Maksimenko, Pēteris Loža, Genādijs Trofimovičs, Edvīns Miklaševičs, Jurijs Nazarovs, Māra Romanovska, Justīne Deičmane, Reinis Irmejs, Gunta Purkalne, Jānis Gardovskis","doi":"10.1186/s13053-021-00187-w","DOIUrl":"10.1186/s13053-021-00187-w","url":null,"abstract":"<p><strong>Background: </strong>Aim of the study is to evaluate the role of ultrasound guided fine needle aspiration cytology (FNAC) in the restaging of node positive breast cancer after preoperative systemic therapy (PST).</p><p><strong>Methods: </strong>From January 2016 - October 2020 106 node positive stage IIA-IIIC breast cancer cases undergoing PST were included in the study. 18 (17 %) were carriers of pathogenic variant in BRCA1/2. After PST restaging of axilla was performed with ultrasound and FNAC of the marked and/or the most suspicious axillary node. In 72/106 cases axilla conserving surgery and in 34/106 cases axillary lymph node dissection (ALND) was performed.</p><p><strong>Results: </strong>False Positive Rate (FPR) of FNAC after PST in whole cohort and BRCA1/2 positive subgroup is 8 and 0 % and False Negative Rate (FNR) - 43 and 18 % respectively. Overall Sensitivity - 55 %, specificity- 93 %, accuracy 70 %.</p><p><strong>Conclusion: </strong>FNAC after PST has low FPR and is useful to predict residual axillary disease and to streamline surgical decision making regarding ALND both in BRCA1/2 positive and negative subgroups. FNR is high in overall cohort and FNAC alone are not able to predict ypCR and omission of further axillary surgery. However, FNAC performance in BRCA1/2 positive subgroup is more promising and further research with larger number of cases is necessary to confirm the results.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"30"},"PeriodicalIF":1.7,"publicationDate":"2021-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39161783","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":"Deciding the operation type according to mismatch repair status among hereditary nonpolyposis colorectal cancer patients: should a tailored approach be applied, or does one size fit all?","authors":"Chun-Kai Liao,&nbsp;Yueh-Chen Lin,&nbsp;Yu-Jen Hsu,&nbsp;Yih-Jong Chern,&nbsp;Jeng-Fu You,&nbsp;Jy-Ming Chiang","doi":"10.1186/s13053-021-00186-x","DOIUrl":"https://doi.org/10.1186/s13053-021-00186-x","url":null,"abstract":"<p><strong>Background: </strong>Although extended colectomy (EC) was recommended for HNPCC patients, previous studies did not show significantly improved overall survival. Immunohistochemical (IHC) stain of mismatch repair (MMR) gene protein expression is now a feasible and reliable test clinically. Therefore, we tried to investigate whether we could use MMR IHC stain to select operation types in HNPCC patients.</p><p><strong>Patients and methods: </strong>Between 1995 and 2013, 186 HNPCC patients were collected. Status of MMR protein expression, perioperative clinic-pathological variables and post-operative follow up status were analyzed by multivariate analyses.</p><p><strong>Results: </strong>Sixty-five percent (121 of 186) patients of these HNPCC patients demonstrated loss of at least one MMR protein. There were several significant differences existing between deficient MMR (dMMR) and proficient MMR (pMMR) subgroups in terms of clinic-pathological characteristics. With the average follow-up duration of 93.9 months, we observed significantly high risk of developing metachronous CRC between SC and EC subgroups (crude rate 8.5% vs. 0%, p = 0.035). However, no significant difference was observed among the presence of extra-colonic tumors (12.4% vs. 5.8%, p = 0.284). The positive and negative prediction rate of metachronous CRC in dMMR subgroup was 12.8 and 87.2% while 1.9 and 98.1% in the pMMR subgroup. Survival outcomes were significantly affected by MMR status and resection types by multivariate analysis. Significantly better OS in dMMR subgroup (HR = 0.479, 95% CI: 0.257-0.894, p = 0.021) comparing with pMMR subgroup was observed. However, significant improved DFS (HR = 0.367, 95% CI: 0.172-.0787, p = 0.010) but not significant for OS (HR = 0.510, 95% CI: 0.219-1.150, p = 0.103) for EC subgroup compared with SC subgroup. Differences existing among different subgroups by combing extent of resection and MMR status. In dMMR subgroup, SC, compared with EC, demonstrated significantly worse DFS by multivariate analyses (HR = 3.526, 95% CI: 1.346-9.236, p = 0.010) but not for OS (HR = 2.387, 95% CI: 0.788-7.229, p = 0.124), however, no significantly differences of OS and DFS in pMMR subgroup between SC and EC were found.</p><p><strong>Conclusions: </strong>Significantly better overall survival and higher rate of metachronous CRC exist in dMMR subgroup of HNPCC patients comparing with pMMR subgroup. Extended colectomy significantly improved DFS and was thus recommended for dMMR subgroup but not pMMR subgroup of HNPCC patients.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"29"},"PeriodicalIF":1.7,"publicationDate":"2021-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39121159","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":"A novel germline mutation in hMLH1 in three Korean women with endometrial cancer in a family of Lynch syndrome: case report and literature review.","authors":"Youn-Joon Jung,&nbsp;Hye Ryoun Kim,&nbsp;Mi Kyung Kim,&nbsp;Eun-Ju Lee","doi":"10.1186/s13053-021-00185-y","DOIUrl":"https://doi.org/10.1186/s13053-021-00185-y","url":null,"abstract":"<p><strong>Background: </strong>Endometrial cancer is often the sentinel cancer in women with Lynch syndrome, among which endometrioid endometrial cancer is the most common. We found a Korean case of uterine carcinosarcoma associated with Lynch syndrome. And we reviewed 27 Korean women with endometrial cancer associated with Lynch syndrome already released in case report so far.</p><p><strong>Case presentation: </strong>The proband, a 45-year-old Korean woman received treatment for endometrioid adenocarcinoma. Her older sister and niece were treated for endometrioid adenocarcinoma and carcinosarcoma, respectively. Family history met the Amsterdam II criteria and immunohistochemical analysis revealed a loss of MLH1 and PMS2. They all harbored a previously unreported germline likely pathogenic variant in c.1367delC in MLH1. They underwent staging operations including total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymph node dissection, and washing cytology. All three women were healthy without evidence of relapse for over 4 years.</p><p><strong>Conclusion: </strong>This report indicates a novel germline c.1367delC variant in MLH1, and presents a Korean case of uterine carcinosarcoma associated with Lynch syndrome. Furthermore, the c.1757_1758insC variant in MLH1 was suggested as a founder mutation in Lynch syndrome in Korean women.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"28"},"PeriodicalIF":1.7,"publicationDate":"2021-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13053-021-00185-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39058538","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":"Correction to: Overview on population screening for carriers with germline mutations in mismatch repair (MMR) genes in China.","authors":"Min Zhang,&nbsp;Tianhui Chen","doi":"10.1186/s13053-021-00184-z","DOIUrl":"https://doi.org/10.1186/s13053-021-00184-z","url":null,"abstract":"","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"27"},"PeriodicalIF":1.7,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13053-021-00184-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39004014","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":"Overview on population screening for carriers with germline mutations in mismatch repair (MMR) genes in China.","authors":"Min Zhang,&nbsp;Tianhui Chen","doi":"10.1186/s13053-021-00182-1","DOIUrl":"https://doi.org/10.1186/s13053-021-00182-1","url":null,"abstract":"<p><p>DNA mismatch repair (MMR) genes play an important role in maintaining genome stability. Germline mutations in MMR genes disrupt the mismatch repair function and cause genome instability. Carriers with MMR germline mutations are more likely to have MMR deficiency and microsatellite instability (MSI) than non-carriers and are prone to develop colorectal cancer (CRC) and extracolorectal malignancies, known as Lynch syndrome (LS). MMR gene testing for suspected mutation carriers is a reliable method to identify the mutation types and to discover mutation carriers. Given that carriers of MMR germline mutations have a higher risk of LS-related cancers (LS-RC) and a younger age at onset than non-carriers, early surveillance and regular screening of relevant organs of carriers are very important for early detection of related cancers. This review mainly focuses on the general status of MMR carriers, the approaches for early detection and screening, and the surveillance of MMR mutation carriers in China. Population screening of MMR germline mutation carriers in China will be helpful for early detection, early diagnosis and treatment of MMR mutation carriers, which may improve the 5-year survival, and reduce mortality and incidence rate in the long term.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"26"},"PeriodicalIF":1.7,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13053-021-00182-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38936234","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":"CD36 polymorphisms and the age of disease onset in patients with pathogenic variants within the mutation cluster region of APC.","authors":"T Connor,&nbsp;M McPhillips,&nbsp;M Hipwell,&nbsp;A Ziolkowski,&nbsp;C Oldmeadow,&nbsp;M Clapham,&nbsp;P G Pockney,&nbsp;E Lis,&nbsp;T Banasiewicz,&nbsp;A Pławski,&nbsp;R J Scott","doi":"10.1186/s13053-021-00183-0","DOIUrl":"https://doi.org/10.1186/s13053-021-00183-0","url":null,"abstract":"<p><strong>Background: </strong>Familial adenomatous polyposis (FAP) is an autosomal dominant condition that predisposes patients to colorectal cancer. FAP is the result of a loss of APC function due to germline pathogenic variants disrupting gene expression. Genotype-phenotype correlations are described for FAP. For example attenuated forms of the disease are associated with pathogenic variants at the 5' and 3' ends of APC whilst severe forms of the disease appear to be linked to variants occurring in the mutation cluster region (MCR) of the gene. Variants occurring in the MCR are phenotypically associated with hundreds to thousands of adenomas carpeting the colon and rectum and patients harbouring changes in this region have a high propensity to develop colorectal cancer. Not all patients who carry pathogenic variants in this region have severe disease which may be a result of environmental factors. Alternatively, phenotypic variation observed in these patients could be due to modifier genes that either promote or inhibit disease expression. Mouse models of FAP have provided several plausible candidate modifier genes, but very few of these have survived scrutiny. One such genetic modifier that appears to be associated with disease expression is CD36. We previously reported a weak association between a polymorphism in CD36 and a later age of disease onset on a relatively small FAP patient cohort.</p><p><strong>Methods: </strong>In the current study, we enlarged the FAP cohort. 395 patients all carrying pathogenic variants in APC were tested against three CD36 Single Nucleotide Polymorphisms (SNP)s (rs1049673, rs1761667 rs1984112), to determine if any of them were associated with differences in the age of disease expression.</p><p><strong>Results: </strong>Overall, there appeared to be a statistically significant difference in the age of disease onset between carriers of the variant rs1984112 and wildtype. Furthermore, test equality of survivor functions for each SNP and mutation group suggested an interaction in the Log Rank, Wilcoxon, and Tarone-Ware methods for rs1049673, rs1761667, and rs1984112, thereby supporting the notion that CD36 modifies disease expression.</p><p><strong>Conclusions: </strong>This study supports and strengthens our previous findings concerning CD36 and an association with disease onset in FAP, AFAP and FAP-MCR affected individuals. Knowledge about the role CD36 in adenoma development may provide greater insight into the development of colorectal cancer.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"25"},"PeriodicalIF":1.7,"publicationDate":"2021-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13053-021-00183-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38932222","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":"Impact of national guidelines on use of BRCA1/2 germline testing, risk management advice given to women with pathogenic BRCA1/2 variants and uptake of advice.","authors":"Bettina Meiser,&nbsp;Rajneesh Kaur,&nbsp;April Morrow,&nbsp;Michelle Peate,&nbsp;W K Tim Wong,&nbsp;Emily McPike,&nbsp;Elisa Cops,&nbsp;Cassandra Nichols,&nbsp;Rachel Austin,&nbsp;Miriam Fine,&nbsp;Letitia Thrupp,&nbsp;Robyn Ward,&nbsp;Finlay Macrae,&nbsp;Janet E Hiller,&nbsp;Alison H Trainer,&nbsp;Gillian Mitchell","doi":"10.1186/s13053-021-00180-3","DOIUrl":"https://doi.org/10.1186/s13053-021-00180-3","url":null,"abstract":"<p><strong>Background: </strong>This nationwide study assessed the impact of nationally agreed cancer genetics guidelines on use of BRCA1/2 germline testing, risk management advice given by health professionals to women with pathogenic BRCA1/2 variants and uptake of such advice by patients.</p><p><strong>Methods: </strong>Clinic files of 883 women who had initial proband screens for BRCA1/2 pathogenic variants at 12 familial cancer clinics between July 2008-July 2009 (i.e. before guideline release), July 2010-July 2011 and July 2012-July 2013 (both after guideline release) were audited to determine reason given for genetic testing. Separately, the clinic files of 599 female carriers without a personal history of breast/ovarian cancer who underwent BRCA1/2 predictive genetic testing and received their results pre- and post-guideline were audited to ascertain the risk management advice given by health professionals. Carriers included in this audit were invited to participate in a telephone interview to assess uptake of advice, and 329 agreed to participate.</p><p><strong>Results: </strong>There were no significant changes in the percentages of tested patients meeting at least one published indication for genetic testing - 79, 77 and 78% of files met criteria before guideline, and two-, and four-years post-guideline, respectively (χ = 0.25, p = 0.88). Rates of documentation of post-test risk management advice as per guidelines increased significantly from pre- to post-guideline for 6/9 risk management strategies. The strategies with the highest compliance amongst carriers or awareness post-release of guidelines were annual magnetic resonance imaging plus mammography in women 30-50 years (97%) and annual mammography in women > 50 years (92%). Of women aged over 40 years, 41% had a risk-reducing bilateral mastectomy. Amongst women aged > 40 years, 75% had a risk-reducing salpingo-oophorectomy. Amongst women who had not had a risk-reducing bilateral mastectomy, only 6% took risk-reducing medication. Fear of side-effects was cited as the main reasons for not taking these medicines by 73% of women.</p><p><strong>Conclusions: </strong>Guidelines did not change the percentages of tested patients meeting genetic testing criteria but improved documentation of risk management advice by health professionals. Effective approaches to enhance compliance with guidelines are needed to improve risk management and quality of care.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"24"},"PeriodicalIF":1.7,"publicationDate":"2021-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13053-021-00180-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25592859","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}