Comparison of guidelines, BRCAPRO, and genetic counsellors estimates for the identification of BRCA1 and BRCA2 mutations in pancreatic cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15784-e15784
Author(s):  
Robert C Grant ◽  
Spring Holter ◽  
Ayelet Borgida ◽  
Melania Pintile ◽  
Mohammad R Akbari ◽  
...  
Keyword(s):  
Brca Mutation ◽  
Area Under The Curve ◽  
Brca1 And Brca2 ◽  
Degree Relative ◽  
Brca Mutations ◽  
Term Care ◽  
Predictive Values ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
Incident Cases

e15784 Background: Germline BRCA1 and BRCA2 (BRCA) mutation carriers with pancreatic adenocarcinoma (PDAC) are eligible for precision therapy trials and their relatives should undergo genetic testing and tailored cancer prevention. We assessed the performance of strategies to identify BRCA mutation carriers in PDAC. Methods: Incident cases of PDAC were prospectively recruited for BRCA sequencing in a multidisciplinary PDAC clinic. Probands were evaluated according to the National Comprehensive Cancer Network 2017 (NCCN) and the Ontario Ministry of Health and Long-Term Care (MOHLTC) guidelines for BRCA testing. The probability of each proband carrying a BRCA mutation was estimated using BRCAPRO and by surveying genetic counsellors. Guidelines were compared across sensitivity, specificity, and positive and negative predictive values (PPV and NPV). Estimates from BRCAPRO and the genetic counsellors were compared using the area-under-the-curve (AUC) for discrimination and the Hosmer-Lemeshow test for calibration. Results: 22/484 (4.5%) of probands carried a BRCA mutation. The mutation rate was higher in probands with Ashkenazi Jewish ancestry (7/57, p=0.009) or a first-degree relative with breast cancer (8/83, p=0.036). 119 genetic counsellors responded to the survey and each proband was assessed by a mean of 5.9 genetic counsellors. The Table displays the performance of the guidelines. Discrimination was similar for the estimates from genetic counsellors and BRCAPRO (AUC 0.755 and 0.775, respectively, p=0.701). Genetic counsellors generally overestimated (p=0.008), whereas BRCAPRO severely underestimated (p<0.001), the probability that each proband carried a mutation. Conclusions: The NCCN 2017 guidelines and estimates from genetic counsellors accurately identify BRCA mutations in PDAC. The MOHLTC guidelines and BRCAPRO should be updated to account for the association between PDAC and BRCA mutations. [Table: see text]

Therapeutic radiation for breast cancer in BRCA mutation carriers and contralateral breast cancer (CBC) risk

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 611-611
Author(s):  
H. C. Moore ◽  
R. Wesolowski ◽  
T. K. Choueiri ◽  
L. Rybicki ◽  
A. G. Shealy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Treatment ◽  
Brca Mutation ◽  
Negative Group ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Mutation Carriers ◽  
Brca Mutation Carriers

611 Background: BRCA mutation carriers diagnosed with breast cancer are at high risk for contralateral second primary breast cancers. Mutations in BRCA1 and BRCA2 lead to defects in DNA repair. Radiation treatment for breast cancer is felt to increase risk of CBC, but the interaction between BRCA status and local radiation therapy with respect to their effects on CBC is unclear. Methods: Through an IRB approved database registry at the Cleveland Clinic, breast cancer patients tested for BRCA1 and BRCA2 mutations were identified and evaluated for CBC events and radiation treatment history. Patients with inadequate clinical follow-up, those with bilateral synchronous breast cancer and those undergoing bilateral mastectomy within one year of the original breast cancer diagnosis were excluded from the analysis. Chi-square test was used to compare CBC rates with or without prior radiation separately in patients testing positive and those testing negative for BRCA mutations. Results: Of 115 identified breast cancer patients tested for BRCA mutations, 57 met the inclusion criteria. Twenty-one carried BRCA1 or BRCA2 mutations and 36 tested negative for these mutations. Median follow-up for the two groups was 69.5 months (92 months in BRCA positive group and 51.5 months in BRCA negative group). Median age at diagnosis was 45 years (41 years in BRCA positive group and 48.5 in BRCA negative group). Among the 21 carriers, 9 patients (43%) developed CBC while only 3 of 36 patients (8%) testing negative for BRCA mutations developed CBC. Thirteen of 21 mutation carriers (62%) had received radiation treatment for the original cancer: CBC occurred in 3 of 13 (23%) radiated patients and 6 of 8 (75%) patients who had not received radiation (p= 0.02). Among 36 patients with negative BRCA testing, 30 (83%) had received radiation: CBC occurred in 3 of 30 (10%) mutation negative patients who had received prior radiation and in 0 of the 6 patients who had not received radiation (p = 0.42). Conclusions: CBC incidence was higher among BRCA mutation carriers than a control group suspected of having hereditary breast cancer but testing negative for these mutations. The use of radiation in the presence of a BRCA mutation, however, does not appear to further increase the risk for CBC. No significant financial relationships to disclose.

scholarly journals Management Options after Prophylactic Surgeries in Women with BRCA Mutations: A Review

2007 ◽  
Vol 14 (4) ◽  
pp. 330-337 ◽  
Author(s):  
Dawn C. Allain ◽  
Kevin Sweet ◽  
Doreen M. Agnese
Keyword(s):  
Medical Management ◽  
Cancer Susceptibility ◽  
Brca Mutation ◽  
Brca2 Gene ◽  
Brca1 And Brca2 ◽  
Management Options ◽  
Cancer Susceptibility Genes ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Brca Mutation Carriers

Background Although breast cancer is relatively common, only about 5% of cases are due to inheritance of highly penetrant cancer susceptibility genes. The majority of these are caused by mutations in the BRCA1 and BRCA2 genes, which are also associated with an increased risk of ovarian cancer. Increased surveillance, chemoprevention, and prophylactic surgeries are standard options for the effective medical management of mutation carriers. However, optimal management of female carriers who choose to undergo prophylactic surgeries is still poorly understood. Methods The authors provide an overview of the current literature regarding medical management options for women carriers of BRCA1 and BRCA2 gene mutations and the implications for those individuals who have chosen to undergo prophylactic surgeries. Results BRCA mutation carriers who opt for prophylactic surgeries are still at risk for development of malignancy, and appropriate monitoring is warranted. Conclusions There are limited data on the appropriate medical management for BRCA mutation carriers after prophylactic surgeries. However, a management plan can be extrapolated from the general management recommendations for surveillance and other risk-reducing strategies in BRCA-positive individuals.

Fallopian Tube and Primary Peritoneal Carcinomas Associated With BRCA Mutations

2003 ◽  
Vol 21 (22) ◽  
pp. 4222-4227 ◽  
Author(s):  
Douglas A. Levine ◽  
Peter A. Argenta ◽  
Cindy J. Yee ◽  
David S. Marshall ◽  
Narciso Olvera ◽  
...  
Keyword(s):  
Fallopian Tube ◽  
Survival Data ◽  
Statistical Tests ◽  
Brca Mutation ◽  
Ashkenazi Jewish ◽  
Founder Mutations ◽  
Peritoneal Carcinoma ◽  
Brca Mutations ◽  
Mutation Carriers ◽  
Brca Mutation Carriers

Purpose: The aims of this study were to determine the incidence of BRCA mutations among Ashkenazi Jewish patients with fallopian tube carcinoma (FTC) or primary peritoneal carcinoma (PPC), to study the clinicopathologic features of these cancers, and to estimate the risks of these cancers in association with a BRCA mutation. Patients and Methods: A retrospective review at two institutions identified 29 Jewish patients with FTC and 22 Jewish patients with PPC. These patients were genotyped for the three Ashkenazi Jewish BRCA founder mutations (185delAG and 5382insC in BRCA1 and 6174delT in BRCA2). Surgical and pathologic information, family history, and survival data were obtained from hospital records. All statistical tests were two sided. Results: Germline BRCA mutations were identified in five of 29 patients with FTC (17%) and nine of 22 patients with PPC (41%). Mutation carriers had a younger mean age at diagnosis than patients without a mutation (60 v 70 years; P = .002). The overall median survival was 148 months for mutation carriers and 41 months for patients without a mutation (P = .04). For BRCA mutation carriers, the lifetime risks of FTC and PPC were 0.6% and 1.3%, respectively. Conclusion: Substantial proportions of Ashkenazi Jewish patients with FTC or PPC are BRCA mutation carriers. Patients with BRCA-associated FTC or PPC are younger at diagnosis and have improved survival compared with patients without a BRCA mutation. Although the lifetime risks of FTC or PPC for patients with BRCA heterozygotes are greater than those for the general population, the absolute risks seem relatively low.

scholarly journals Tailoring Ovarian Cancer Treatment: Implications of BRCA1/2 Mutations

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 416 ◽  
Author(s):  
Ainhoa Madariaga ◽  
Stephanie Lheureux ◽  
Amit Oza
Keyword(s):  
Ovarian Cancer ◽  
Brca Mutation ◽  
Repair Process ◽  
Resistance Mechanisms ◽  
Tumour Suppressor Genes ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Damage Repair ◽  
Brca Mutation Carriers ◽  
Drug Efflux Pumps

High grade serous ovarian cancer (HGSOC) is the most common epithelial ovarian cancer, harbouring more than 20% germline or somatic mutations in the tumour suppressor genes BRCA1 and BRCA2. These genes are involved in both DNA damage repair process via homologous recombination (HR) and transcriptional regulation. BRCA mutation confers distinct characteristics, including an increased response to DNA-damaging agents, such us platinum chemotherapy and poly-ADP ribose polymerase inhibitors (PARPi). However, several mechanisms of resistance to these agents have been described, including increased HR capacity through reverse BRCA mutations, non-homologous end-joint (NHEJ) repair alterations and drug efflux pumps. Current treatments of ovarian cancer including surgery, chemotherapy, targeted treatment and maintenance strategies, as well as resistance mechanisms will be reviewed, focusing on future trends with respect to BRCA mutation carriers.

Assessment of cancer screening practices after BRCA testing in Michigan.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1557-1557
Author(s):  
Julie Zenger Hain ◽  
Sarah Mange ◽  
Janice Bach ◽  
Debra Duquette ◽  
Jennifer McLosky ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Brca Mutation ◽  
Ca 125 ◽  
Brca Mutations ◽  
Cancer History ◽  
Screening Guidelines ◽  
Screening Practices ◽  
Mutation Carriers ◽  
Post Test ◽  
Brca Mutation Carriers

1557 Background: Women who harbor BRCA1/2 mutations are at increased risk for breast and ovarian cancer and are advised to undergo high risk surveillance and/or preventative surgery. The compliance with screening guidelines in these women is not well known. This study aims to evaluate the uptake and screening practices of women with known deleterious BRCA mutations and BRCA true negatives who received genetic counseling in the state of Michigan. Methods: A telephone survey coordinated by the Michigan Department of Community Health was conducted on pts seen at 8 genetics clinics between 10/07 to 10/09. Each center was staffed by board certified genetics professionals who provided pre and post-test genetic counseling. Pts who were found to carry a deleterious BRCA mutation, or to be negative for a known familial mutation, were queried regarding adherence to NCCN guidelines. Results: 138 of 253 (55%) pts responded to the phone survey, with an elapsed time of 1.7 to 4.6 years from post-test counseling session. Among BRCA mutation carriers over age 25 years with no cancer history or mastectomy, 11 of 21 pts (52%) adhered to MRI screening guidelines, 3 pts (14%) reported two MRIs, and 7 (33%) pts had no MRI screening in the preceding year. 18 of 21 pts (86%) reported having a screening mammogram in the preceding year and the remaining 3 had two or more. 8 of 20 (40%) pts had two clinical breast exams. Of the women who had breast cancer and no mastectomy, 5 of 9 (56%) pts did not have MRI screening. Of the BRCA true negatives with no cancer history, CA-125 or transvaginal ultrasound was performed in 7 (19%) and 8 (20%) of 37 pts, respectively. Conclusions: This study reveals sub-optional compliance with screening guidelines in women who were identified to be carriers of BRCA mutations or those who were true negatives, despite pre and post-test genetic counseling and communication of established management guidelines. Some recommended screening measures were under-utilized in BRCA mutation carriers, and some were over-utilized in the true negatives. Additional interventions are needed to improve adherence to evidence-based screening guidelines aimed at promoting early detection, with an emphasis on appropriate utilization of limited healthcare resources.

Unique genetic characteristics of BRCA mutation carriers in a cohort of Arab American women.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1541-1541 ◽  
Author(s):  
Seerin Viviane Shatavi ◽  
Lindsay Dohany ◽  
Mohammad Muhsin Chisti ◽  
Ishmael A. Jaiyesimi ◽  
Dana Zakalik
Keyword(s):  
Genetic Testing ◽  
Brca Mutation ◽  
Arab American ◽  
Deleterious Mutations ◽  
Brca1 And Brca2 ◽  
American Women ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
Arab American Women ◽  
Exon 11

1541 Background: Worldwide ethnic variations in the distribution of BRCA1 and BRCA2 mutations of breast cancer patients have been recently recognized. This has led to investigations of the epidemiology, genetics and clinical characteristics of BRCA positive individuals within specific populations. This study aims to describe the findings of BRCA genetic testing in a cohort of Arab American women. Methods: A total of 73 women of Arab ancestry were evaluated in the Beaumont Cancer Genetics Program from Jan 2008 to Jan 2013. Criteria for genetic testing included a personal or family history suggestive of Hereditary Breast and Ovarian Cancer Syndrome (HBOC). Patients underwent comprehensive genetic counseling, followed by full sequence analysis for germline mutations in BRCA1 and BRCA2. Results: 63 women of Arab ancestry underwent genetic testing for BRCA1 and BRCA2. 13 (21%) patients were found to be mutation carriers, of whom 10 (16%) of the 63 had deleterious mutations (7 in BRCA2, and 3 in BRCA1), and 3 (5%) had variants of undetermined significance (VUS) in BRCA2. Of the 10 patients with deleterious mutations, 4 (40%) unrelated individuals had the same mutation, 5804del4, in exon 11 of BRCA2. The remaining patients had deleterious mutations in exon 2, exon 20, and exon 13 of BRCA2; one patient had a BRCA1 and BRCA2 mutation (exon 18). 7 of 10 patients with deleterious mutations had a cancer diagnosis, of which 5 had breast cancer, 1 had ovarian cancer, 1 had pancreatic cancer, and 3 were unaffected. Conclusions: This study demonstrates that BRCA mutations (predominantly in BRCA2) were seen in a significant proportion of Arab American women undergoing genetic testing for HBOC. A mutation in BRCA2, 5804del4, was seen in nearly half (4/10) of the carriers of deleterious mutations. This mutation, in exon 11, has not previously been associated with Arab ethnicity and may represent a founder mutation. Knowledge of the genetic spectrum, frequency, and clinical characteristics of BRCA mutation carriers will lead to greater understanding of hereditary cancer in Arab American women.

Comparison of risk-reducing surgery in women with BRCA and non-BRCA ovarian cancer susceptibility genes.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1547-1547
Author(s):  
Zachary Phillip Schwartz ◽  
Mae Zakhour ◽  
Andrew John Li ◽  
Christine S. Walsh ◽  
Bj Rimel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Susceptibility ◽  
Brca Mutation ◽  
Susceptibility Genes ◽  
Brca Mutations ◽  
Cancer Susceptibility Genes ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
History Of ◽  
Risk Reducing

1547 Background: Risk reducing gynecologic surgery (RRSO) is standard of care for women with BRCA mutations. The optimal management for women with non-BRCA ovarian cancer susceptibility mutations remains unclear. We sought to characterize the practice patterns for these women at our two institutions. Methods: Women with germline ovarian cancer susceptibility genes who had a RRSO were identified from 1/2000-1/2019 in an IRB approved study. All patients were asymptomatic with no suspicion for malignancy at time of RRSO. Clinico-pathologic characteristics were extracted from the medical records. Continuous variables were analyzed with Kruskal-Wallis and categorical variables analyzed with chi square and t-tests. Results: 152 BRCA1, 95 BRCA2, and 63 Non-BRCA mutation carriers were identified—50 Lynch (22 MLH1, 13 MSH2, 13 MSH6, 2 PMS2) and 13 Other (6 BRIP1, 2 RAD51C, 5 RAD51D). There was no difference between age at testing, age at RRSO, and interval between testing and RRSO between groups. Genetic counseling was higher in Non-BRCA patients. Family history of ovarian cancer was more common in women with BRCA1 and Other germline mutations compared to BRCA2 and Lynch. Family and personal history of breast cancer was high in all groups except Lynch carriers. Prophylactic mastectomy was seen mostly in BRCA mutation carriers. Concomitant hysterectomy was performed in the majority of women (BRCA1 59%, BRCA2 57%, and Other 62%), with the highest frequency in Lynch carriers (86%, p<.01). Occult cancer was only seen in BRCA mutation carriers: BRCA1 (7%), BRCA2 (2%), Lynch (0%), Other (0%). Conclusions: In this cohort, women with Non-BRCA mutations are managed similarly to women with BRCA mutations. We observed no occult cancers in Non-BRCA patients. The optimal role of surgery as a risk reducing strategy in this group requires further study. [Table: see text]

No association between BRCA mutations and sex ratio in offspring of Pakistani BRCA mutation carriers

2007 ◽  
Vol 107 (1) ◽  
pp. 155-156 ◽  
Author(s):  
Muhammad U. Rashid ◽  
Diana Torres ◽  
Anbreen Zaidi ◽  
Farah Rasheed ◽  
Faisal Sultan ◽  
...  
Keyword(s):  
Sex Ratio ◽  
Brca Mutation ◽  
Brca Mutations ◽  
Mutation Carriers ◽  
Brca Mutation Carriers

scholarly journals Biological Role and Clinical Implications of microRNAs in BRCA Mutation Carriers

2021 ◽  
Vol 11 ◽  
Author(s):  
Chiara Tommasi ◽  
Benedetta Pellegrino ◽  
Daniela Boggiani ◽  
Angelica Sikokis ◽  
Maria Michiara ◽  
...  
Keyword(s):  
Brca Mutation ◽  
Scientific Evidence ◽  
Clinical Implications ◽  
Brca Mutations ◽  
Small Noncoding Rnas ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Modifiable Factors ◽  
Brca Mutation Carriers

Women with pathogenic germline mutations in BRCA1 and BRCA2 genes have an increased risk to develop breast and ovarian cancer. There is, however, a high interpersonal variability in the modality and timing of tumor onset in those subjects, thus suggesting a potential role of other individual’s genetic, epigenetic, and environmental risk factors in modulating the penetrance of BRCA mutations. MicroRNAs (miRNAs) are small noncoding RNAs that can modulate the expression of several genes involved in cancer initiation and progression. MiRNAs are dysregulated at all stages of breast cancer and although they are accessible and evaluable, a standardized method for miRNA assessment is needed to ensure comparable data analysis and accuracy of results. The aim of this review was to highlight the role of miRNAs as potential biological markers for BRCA mutation carriers. In particular, biological and clinical implications of a link between lifestyle and nutritional modifiable factors, miRNA expression and germline BRCA1 and BRCA2 mutations are discussed with the knowledge of the best available scientific evidence.

Prolonged survival among women with BRCA germline mutations and advanced endometrial cancer: a case series

2008 ◽  
Vol 18 (3) ◽  
pp. 546-549 ◽  
Author(s):  
J. S. KWON ◽  
J. LENEHAN ◽  
M. CAREY ◽  
P. AINSWORTH
Keyword(s):  
Endometrial Cancer ◽  
Brca Mutation ◽  
Sarcomatoid Carcinoma ◽  
Case Series ◽  
Serous Carcinoma ◽  
Population Database ◽  
Brca Mutations ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
Papillary Serous Carcinoma

It is unclear if BRCA mutation carriers diagnosed with advanced endometrial cancer have a better prognosis compared to sporadic cases. From a population database of BRCA1 and 2 mutation carriers in Southwestern Ontario, Canada, we identified three women with advanced-stage endometrial cancer. They were 57, 59, and 64 years of age, and of English/Scottish, Ashkenazi Jewish, and English heritage, respectively. They had different mutations in BRCA1 (Q1240X:C3837T; 68_69delAG; 1961delA). One had a sarcomatoid carcinoma and two had uterine papillary serous carcinoma. All had stage IVB disease, with surgery followed by adjuvant chemotherapy and/or radiotherapy. Follow-up has ranged from 3.3 to 14.6 years. They are still alive and well with no evidence of recurrent disease. This observation raises the question as to whether BRCA mutations may be associated with a better prognosis in patients with advanced endometrial cancer

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