"BRCA1" from_date:2012

resubmission. BRCA = BReast CAncer gene; BRCAwt = BReast CAncer gene wild type; ER = estrogen receptor; HER2 = human epidermal growth factor receptor 2; HR = hormone receptor; MBC = metastatic breast cancer; PR = progesterone receptor; SLN = sentinel lymph node biopsy; TNBC = triple negative breast cancer 13 8. Comparator The nominated comparator was unchanged in the resubmission and remained ‘no test Germline BRCA mutation test to detect BRCA1 or BRCA2 mutations in patients with HER2- negative high risk early breast cancer to determine eligibility for PBS-listed olaparib treatment 1 Medical Services Advisory Committee (MSAC) Public Summary Document Application No.1716 – Germline BRCA mutation test to detect BRCA1 or BRCA2 mutations in patients with HER2-negative high risk early breast cancer

: Table 1.7, p30 of the submission. BRCA = breast cancer gene, HER2 = human epidermal growth factors receptor 2, MBS = Medicare Benefits Schedule. α Multigene recurrence risk assays such OncotypeDX 21 gene tests are not currently MBS-listed. EndoPredict has been recommended for public funding by MSAC (MSAC Application 1408.1) The proposed high-risk population for olaparib differed from the population and endocrine therapy, if HR-positive. 10 Figure 1 Proposed clinical treatment algorithm Abbreviations: BRCA, BReast CAncer gene; BRCAwt, BReast CAncer gene wild type; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; MBC, metastatic breast cancer; MBS, Medicare Benefits Schedule; PR, progesterone receptor; SLN, sentinel lymph node biopsy; TNBC, triple negative

Testing of tumour tissue or blood to detect somatic or germline BRCA1 or BRCA2 gene mutations, in a patient with newly diagnosed, advanced (FIGO stage III-IV) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response ( 1 Public Summary Document Application No. 1554 – Amendment to MBS item 73295 to allow testing for somatic BRCA mutation to allow patient Benefits Schedule (PBS) listing of olaparib (Lynparza) to include newly diagnosed advanced BRCA-mutated high grade epithelial ovarian, fallopian tube or primary peritoneal cancer in response (complete or partial) to first-line platinum-based chemotherapy  an amendment of Medicare Benefits Schedule (MBS) item 73343 to include first-line tumour BRCA1 BRCA2 testing at diagnosis of advanced ovarian cancer

estimates and recommendationsAfter reviewing all available evidence, our experts identify that for CRC there is a 1.5-fold increased risk for BRCA1 carriers, and no increased risk in BRCA2 carriers. The modest increased colorectal cancer risk inBRCA1carriers is insufficient to recommend earlier or more intensive screening;BRCA carriers with family history of CRC or symptoms should be managed according Expert guidance on screening for colorectal and pancreatic cancer in BRCA1 and BRCA2 carriers Expert guidance on screening for colorectal and pancreatic cancer in BRCA1 and BRCA2 carriers - American Gastroenterological AssociationAGA Family of Websites: Gastro.orgAGA Family of Websites: Gastro.orgLogin here Create AccountLogin Gastro.org * AGA Journals * AGA University * AGA Research

123 sBRCAm Included Study 19, NOVA, ARIEL3, SOLO2 PFS: 0.24 (0.13, 0.46) PFS: 0.27 (0.09, 0.33) BRCA = breast cancer gene 1 and 2; DB=double blind; gBRCAm = germline BRCA pathological or likely pathological variant; CI = confidence interval; HGEOC = high grade epithelial ovarian cancer; HGSOC = high grade serous ovarian cancer; HR = hazard ratio; MC = multicentre; OS = overall survival; PFS with platinum-sensitive HGEOC PFS: 0.27 (0.17, 0.41) PFS: 0.58 (0.36, 0.92) BRCA = breast cancer gene 1 and 2; BRCAm = BRCA pathological or likely pathological variant; BRCAwt = BRCA wild type; CI = confidence interval; DB=double blind; HR = hazard ratio; MC = multicentre; OS=overall survival; PFS=progression-free survival; R=randomised Source: Constructed during the evaluation. Comparative analytical

Rucaparib versus chemotherapy for treatment of relapsed ovarian cancer with deleterious BRCA1 or BRCA2 mutation (ARIEL4): final results of an international, open-label, randomised, phase 3 trial. In the ARIEL4 trial of rucaparib versus standard-of-care chemotherapy in patients with relapsed BRCA-mutated ovarian carcinoma, the primary endpoint was met, showing improved investigator-assessed aged 18 or older with BRCA1 or BRCA2-mutated ovarian carcinoma and had received at least two previous chemotherapy regimens. Patients had to have evaluable disease as per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) criteria and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (2:1) using an interactive response technology

Using species richness calculations to model the global profile of unsampled pathogenic variants: Examples from BRCA1 and BRCA2. There have been many surveys of genetic variation in BRCA1 and BRCA2 to identify variant prevalence and catalogue population specific variants, yet none have evaluated the magnitude of unobserved variation. We applied species richness estimation methods from ecology to estimate "variant richness" and determine how many germline pathogenic BRCA1/2 variants have yet to be identified and the frequency of these missing variants in different populations. We also estimated the prevalence of germline pathogenic BRCA1/2 variants and identified those expected to be most common. Data was obtained from a literature search including studies conducted globally that tested

Germline mutations in BRCA1 and BRCA2 among Brazilian women with ovarian cancer treated in the Public Health System. Germline mutations in BRCA1 and BRCA2 genes are among the main causes of hereditary ovarian cancer. Identifying these mutations may reduce cancer risk, facilitate early detection, and enable personalized treatment. However, genetic testing is limited in the Brazilian Public Health System, and data regarding germline mutations in many regions are scarce. Therefore, the study aimed to investigate the prevalence of germline mutations in BRCA1 and BRCA2 in women with ovarian cancer treated in the Public Health System in Pernambuco, Brazil. A cross-sectional study was conducted in the Hereditary Cancer Program from two reference oncological centers in Pernambuco. Women (n = 45

Pathogenic variant detection rate varies considerably in male breast cancer families and sporadic cases: minimal additional contribution beyond BRCA2, BRCA1 and CHEK2. Male breast cancer (MBC) affects around 1 in 1000 men and is known to have a higher underlying component of high and moderate risk gene pathogenic variants (PVs) than female breast cancer, particularly in . However, most studies

and all-cause mortality among women with a BRCA1 or BRCA2 sequence variation. In this international, longitudinal cohort study of women with BRCA sequence variations, information on bilateral oophorectomy was obtained via biennial questionnaire. Participants were women with a BRCA1 or BRCA2 sequence variation, no prior history of cancer, and at least 1 follow-up questionnaire completed. Women were Bilateral Oophorectomy and All-Cause Mortality in Women With BRCA1 and BRCA2 Sequence Variations. Preventive bilateral salpingo-oophorectomy is offered to women at high risk of ovarian cancer who carry a pathogenic variant in BRCA1 or BRCA2; however, the association of oophorectomy with all-cause mortality has not been clearly defined. To evaluate the association between bilateral oophorectomy

BRCA1, BRCA2, and Associated Cancer Risks and Management for Male Patients: A Review. Half of all carriers of inherited cancer-predisposing variants in BRCA1 and BRCA2 are male, but the implications for their health are underrecognized compared to female individuals. Germline variants in BRCA1 and BRCA2 (also known as pathogenic or likely pathogenic variants, referred to here as BRCA1/2 PVs ) are well known to significantly increase the risk of breast and ovarian cancers in female carriers, and knowledge of BRCA1/2 PVs informs established cancer screening and options for risk reduction. While risks to male carriers of BRCA1/2 PVs are less characterized, there is convincing evidence of increased risk for prostate cancer, pancreatic cancer, and breast cancer in males. There has also been

MRI Surveillance and Breast Cancer Mortality in Women With BRCA1 and BRCA2 Sequence Variations. Magnetic resonance imaging (MRI) surveillance is offered to women with a pathogenic variant in the BRCA1 or BRCA2 gene who face a high lifetime risk of breast cancer. Surveillance with MRI is effective in downstaging breast cancers, but the association of MRI surveillance with mortality risk has not been well defined. To compare breast cancer mortality rates in women with a BRCA1 or BRCA2 sequence variation who entered an MRI surveillance program with those who did not. Women with a BRCA1 or BRCA2 sequence variation were identified from 59 participating centers in 11 countries. Participants completed a baseline questionnaire between 1995 and 2015 and a follow-up questionnaire every 2 years

Large-scale copy number alterations are enriched for synthetic viability in BRCA1/BRCA2 tumors. Pathogenic BRCA1 or BRCA2 germline mutations contribute to hereditary breast, ovarian, prostate, and pancreatic cancer. Paradoxically, bi-allelic inactivation of BRCA1 or BRCA2 (bBRCA1/2) is embryonically lethal and decreases cellular proliferation. The compensatory mechanisms that facilitate in the setting of bBRCA1/2 mutations. We found that bBRCA1/2 tumors harbor recurrent large-scale genomic deletions significantly more frequently than histologically matched controls (n = 238 cytobands in breast and ovarian cancers). Within the deleted regions, we identified 277 BRCA1-related genes and 218 BRCA2-related genes that had reduced expression and increased proliferation in bBRCA1/2 but not in wild

Parp-inhibitors in the therapeutic landscape of breast cancer patients with BRCA1 and BRCA2 pathogenic germline variants: An Italian consensus paper and critical review. The introduction of PARP inhibitors has revolutionized the management and treatment of patients with pathogenic germline variants of BRCA1/2 who have developed breast cancer. The implementation of PARP inhibitors in clinical . The Panel unanimously agreed on various issues, including the timing, techniques, and patient characteristics for BRCA1/2 genetic testing, andthe appropriate placement of PARP inhibitors in the treatment algorithm for both early and advanced breast cancer. Nevertheless, some areas of divergence became evident, particularly regarding the use of axillary surgery for therapeutic purposes and the application

Exploring the impact of BRCA1 and BRCA2 mutation type and location on Olaparib maintenance therapy in platinum-sensitive relapsed ovarian Cancer patients: A single center report. In patients with platinum-sensitive relapsed ovarian cancer (PSROC) harboring pathogenic/likely pathogenic variants (PV) in BRCA1 and BRCA2 genes, olaparib maintenance monotherapy (OMT) is a viable option. Our study -generation sequencing (NGS). PFS and OS were significantly shorter in PSROC patients with PV in BRCA1 compared to those with PV in BRCA2 (PFS:14.0 vs. 38.8 months, p = 0.007, OS: 21.8 vs. 62.0 months, p = 0.011). Notably, there was a significant difference in PFS based on the intragenic location of BRCA1 PV, with shorter PFS in patients with 1st/2nd relapse, harboring PV in BRCA1 RING domain compared

Evidence-based recommendations for gene-specific ACMG/AMP variant classification from the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel. The ENIGMA research consortium develops and applies methods to determine clinical significance of variants in hereditary breast and ovarian cancer genes. An ENIGMA BRCA1/2 classification sub-group, formed in 2015 as a ClinGen external expert panel , evolved into a ClinGen internal Variant Curation Expert Panel (VCEP) to align with Food and Drug Administration recognized processes for ClinVar contributions. The VCEP reviewed American College of Medical Genetics and Genomics/Association of Molecular Pathology (ACMG/AMP) classification criteria for relevance to interpreting BRCA1 and BRCA2 variants. Statistical methods were used to calibrate evidence

Breast cancer after ovarian cancer in BRCA1 and BRCA2 pathogenic variant heterozygotes: lower rates for 5-years post chemotherapy. The identification of germline BRCA1/BRCA2 pathogenic variants (PV) infer high remaining lifetime breast/ovarian cancer risks, but there is paucity of studies assessing breast cancer risk after ovarian cancer diagnosis. We reviewed the history of breast cancer in 895 PV heterozygotes (BRCA1=541). Cumulative annual breast cancer incidence was assessed at 2,5,10 and >10 years following ovarian cancer diagnosis date. Breast cancer annual rates were evaluated in 701 assessable women with no breast cancer at ovarian diagnosis (BRCA1=425). Incidence was lower at 2years (1.18%) and 2-5years (1.13%), but rose thereafter for BRCA1 with incidence post 10years in excess

Featuring BRCA1 and BRCA2 germline mutational landscape from Asturias (North Spain). The singular BRCA1/2 mutational landscape of Asturias is updated 10 years after the first study. We analyzed BRCA1 and BRCA2 pathogenic variants in 1653 index cases. In total, 238 families were identified to carry a pathogenic variant, 163 families in BRCA1 and 75 families in BRCA2. This yielded a prevalence rate of 14.4%. Seven recurrent variants were found accounting for 55% of the cases. Among them, three are widely distributed (BRCA1 c.211A>G, c.470_471del and c.3331_3334del) and four had been reported as novel in Asturias: two in BRCA1 (c.1674del and c.2901_2902dup) and two in BRCA2 (c.2095C>T and c.4040_4035delinsC). A common haplotype was established for all recurrent variants indicating a shared

Novel Cancer Prevention Strategies in Individuals With Hereditary Cancer Syndromes: Focus on BRCA1, BRCA2, and Lynch Syndrome. Germline pathogenic variants (PVs) in the and genes confer elevated risks of breast, ovarian, and other cancers. Lynch syndrome (LS) is associated with increased risks of multiple cancer types including colorectal and uterine cancers. Current cancer risk mitigation

Incidence of Peritoneal Cancer Following Oophorectomy among BRCA1 and BRCA2 Mutation Carriers. To estimate the incidence of primary peritoneal cancer following preventive bilateral oophorectomy in women with a BRCA1 or BRCA2 mutation. A total of 6,310 women with a BRCA1 or BRCA2 mutation who underwent a preventive bilateral oophorectomy were followed for a mean of 7.8 years from oophorectomy -five women developed primary peritoneal cancer (n = 45 in BRCA1, 8 in BRCA2, and 2 in women with a mutation in both genes). Their mean age at oophorectomy was 48.9 years. The annual risk of peritoneal cancer was 0.14% for women with a BRCA1 mutation and was 0.06% for women with a BRCA2 mutation. The 20-year cumulative risk of peritoneal cancer from the date of oophorectomy was 2.7% for BRCA1 carriers