Genetic/Familial High-Risk Assessment: Breast and Ovarian

Daly, Mary B.; Axilbund, Jennifer E.; Buys, Saundra S.; Crawford, Beth; Farrell, Carolyn; Friedman, Susan J.; Garber, Judy E.; Goorha, Salil; Gruber, Stephen B.; Hampel, Heather; Kaklamani, Virginia; Kohlmann, Wendy; Kurian, Allison W.; Litton, Jennifer K.; Marcom, P. Kelly; Nussbaum, Robert L.; Offit, Kenneth; Pal, Tuya; Pasche, Boris; Pilarski, Robert; Reiser, Gwen; Shannon, Kristen M.; Smith, Jeffrey R.; Swisher, Elizabeth M.; Weitzel, Jeffrey N.

doi:10.6004/jnccn.2010.0043

Cited by 293 publications

(245 citation statements)

References 315 publications

(206 reference statements)

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“…Approximately 10%–15% of all OC patients carry a pathogenic germline aberration in BRCA1 or BRCA2 [Daly et al., 2010; Hennessy et al., 2010; Kanchi et al., 2014]. Loss of heterozygosity (LOH) of the wild‐type allele is the tumor‐initiating second hit in the majority of these patients [Foster et al., 1996; Berchuck et al., 1998].…”

Section: Introductionmentioning

confidence: 99%

NovelBRCA1andBRCA2Tumor Test as Basis for Treatment Decisions and Referral for Genetic Counselling of Patients with Ovarian Carcinomas

et al. 2016

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With the recent introduction of Poly(ADP‐ribose) polymerase inhibitors, a promising novel therapy has become available for ovarian carcinoma (OC) patients with inactivating BRCA1 or BRCA2 mutations in their tumor. To select patients who may benefit from these treatments, assessment of the mutation status of BRCA1 and BRCA2 in the tumor is required. For reliable evaluation of germline and somatic mutations in these genes in DNA derived from formalin‐fixed, paraffin‐embedded (FFPE) tissue, we have developed a single‐molecule molecular inversion probe (smMIP)‐based targeted next‐generation sequencing (NGS) approach. Our smMIP‐based NGS approach provides analysis of both strands of the open reading frame of BRCA1 and BRCA2, enabling the discrimination between real variants and formalin‐induced artefacts. The single molecule tag enables compilation of unique reads leading to a high analytical sensitivity and enabling assessment of the reliability of mutation‐negative results. Multiplex ligation‐dependent probe amplification (MLPA) and Methylation‐specific multiplex ligation‐dependent probe amplification (MS‐MLPA) were used to detect exon deletions of BRCA1 and methylation of the BRCA1 promoter, respectively. Here, we show that this combined approach allows the rapid and reliable detection of both germline and somatic aberrations affecting BRCA1 and BRCA2 in DNA derived from FFPE OCs, enabling improved hereditary cancer risk assessment and clinical treatment of ovarian cancer patients.

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Section: Introductionmentioning

confidence: 99%

NovelBRCA1andBRCA2Tumor Test as Basis for Treatment Decisions and Referral for Genetic Counselling of Patients with Ovarian Carcinomas

et al. 2016

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“…Together with the positive genetic results, female carriers receive a check-up agenda based on international guidelines, typically requiring biannual medical consultations and screenings. [4][5][6][7] Clinical recommendations for women with BRCA1/BRCA2-associated hereditary breast/ovarian cancer syndrome can be summarized as follows: semi-annual clinical breast examinations starting from the age of 25 years; annual breast magnetic resonance imaging and mammograms starting from the age of 25-30 years; semi-annual transvaginal ultrasounds and blood tests (tumor marker CA125) starting from the age of 30 years; risk-reducing salpingo-oophorectomy ideally before the age of 40 years; and prophylactic bilateral mastectomy as an option to be discussed on an individual basis. Thus, at-risk women are encouraged to pursue a lifetime health program in close collaboration with several health-care professionals.…”

Section: Introductionmentioning

confidence: 99%

Challenges in managing genetic cancer risk: a long-term qualitative study of unaffected women carrying BRCA1/BRCA2 mutations

Zufferey

Pagani

Cina

et al. 2015

Genetics in Medicine

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Purpose: Women carrying BRCA1/BRCA2 germ-line mutations have an increased risk of developing breast/ovarian cancer. To minimize this risk, international guidelines recommend lifelong surveillance and preventive measures. This study explores the challenges that unaffected women genetically predisposed to breast/ovarian cancer face in managing their risk over time and the psychosocial processes behind these challenges. Methods:Between 2011 and 2013, biographical qualitative interviews were conducted in Switzerland with 32 unaffected French-and Italian-speaking women carrying BRCA1/BRCA2 mutations. Their mutation status had been known for at least 3 years (mean, 6 years). Data were analyzed through constant comparative analysis using software for qualitative analysis.Results: From the time these women received their positive genetic test results, they were encouraged to follow medical guidelines.Meanwhile, their adherence to these guidelines was constantly questioned by their social and medical environments. As a result of these contradictory pressures, BRCA1/BRCA2 mutation carriers experienced a sense of disorientation about the most appropriate way of dealing with genetic risk. Conclusion:Given the contradictory attitudes of health-care professionals in caring for unaffected BRCA1/BRCA2 mutation carriers, there is an urgent need to educate physicians in dealing with genetically at-risk women and to promote a shared representation of this condition among them.Genet Med advance online publication 11 December 2014

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“…5,6 Identification of women with genetic mutations allows for aggressive surveillance, risk-reduction interventions, and identification of family members who may also be at risk. 7,8 Many PCPs have an inadequate understanding of hereditary breast cancer, risk assessment, shared decision-making, and legal and ethical issues, 9,10 and this results in inappropriate testing: underuse of testing and genetic counseling referral for patients at high risk 9,[11][12][13][14][15][16][17][18] and overuse for those at low risk. 18 Various interventions aimed at increasing patient knowledge have been shown to be effective.…”

Section: Introductionmentioning

confidence: 99%

Impact of a Randomized Controlled Educational Trial to Improve Physician Practice Behaviors Around Screening for Inherited Breast Cancer

et al. 2014

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BACKGROUND: Many primary care physicians (PCPs) are ill-equipped to provide screening and counseling for inherited breast cancer. OBJECTIVE: To evaluate the outcomes of an interactive web-based genetics curriculum versus text curriculum for primary care physicians. DESIGN: Randomized two-group design. PARTICIPANTS: 121 California and Pennsylvania community physicians. INTERVENTION: Web-based interactive genetics curriculum, evaluated against a control group of physicians who studied genetics review articles. After education, physicians interacted with an announced standardized patient (SP) at risk for inherited breast cancer. MAIN MEASURES: Transcripts of visit discussions were coded for presence or absence of 69 topics relevant to inherited breast cancer. KEY RESULTS: Across all physicians, history-taking, discussions of test result implications, and exploration o f e t h i c a l a n d l e g a l i s s u e s w e r e i n c o m p l e t e . Approximately half of physicians offered a genetic counseling referral (54.6 %), and fewer (43.8 %) recommended testing. Intervention physicians were more likely than controls to explore genetic counseling benefits (78.3 % versus 60.7 %, P= 0.048), encourage genetic counseling before testing (38.3 % versus 21.3 %, P= 0.048), ask about a family history of prostate cancer (25.0 % versus 6.6 %, P= 0.006), and report that a positive result indicated an increased risk of prostate cancer for male relatives (20.0 % versus 1.6 %, P= 0.001). Intervention-group physicians were less likely than controls to ask about Ashkenazi heritage (13.3 % versus 34.4 %, P= 0.01) or to reply that they would get tested when asked, "What would you do?" (33.3 % versus 54.1 %, P= 0.03). CONCLUSIONS: Physicians infrequently performed key counseling behaviors, and this was true regardless of whether they had completed the web-based interactive training or read clinical reviews.

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Genetic/Familial High-Risk Assessment: Breast and Ovarian

Cited by 293 publications

References 315 publications

NovelBRCA1andBRCA2Tumor Test as Basis for Treatment Decisions and Referral for Genetic Counselling of Patients with Ovarian Carcinomas

NovelBRCA1andBRCA2Tumor Test as Basis for Treatment Decisions and Referral for Genetic Counselling of Patients with Ovarian Carcinomas

Challenges in managing genetic cancer risk: a long-term qualitative study of unaffected women carrying BRCA1/BRCA2 mutations

Impact of a Randomized Controlled Educational Trial to Improve Physician Practice Behaviors Around Screening for Inherited Breast Cancer

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