Genetic counseling processes and outcomes among prostate cancer patients (ProGen).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS343-TPS343 ◽  
Author(s):  
Donna Rachel Vatnick ◽  
Sandjida Aktar ◽  
Jill E. Stopfer ◽  
Lindsay Kipnis ◽  
Samantha K. Culver ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Genetic Counseling ◽  
Genetic Testing ◽  
Cancer Risk ◽  
Mismatch Repair ◽  
Metastatic Prostate Cancer ◽  
Germline Mutations ◽  
Mismatch Repair Genes ◽  
Repair Genes

TPS343 Background: Prostate cancer (PC) is among the leading causes of cancer mortality in males. Recent studies found 8-12% of advanced PC cases may be hereditary. Germline mutations have been reported in BRCA1/2, other DNA repair genes including ATM, CHEK2, PALB2 and DNA mismatch repair genes. Genetic testing can inform treatment decisions including drug targeting, such as PARP inhibitors for men with BRCA mutations, and checkpoint inhibitors for those with pathogenic mutations in mismatch repair genes2. Discovering a pathogenic mutation associated with increased cancer risk also prompts dissemination of this information to family, where subsequent testing can lead to risk stratification and impactful opportunities for cancer screening and prevention. It is critical that men with high risk and potentially lethal prostate cancer routinely be offered genetic testing as a component of their cancer care. Genetic counseling services are limited, and more efficient services are needed. Methods: We are investigating video education prior to genetic testing compared with in-person pretest counseling with a licensed genetic counselor (GC). ProGen is an ongoing randomized trial evaluating two distinct models of cancer genetics service delivery in 450 PC cases over a two-year period. The study is conducted in collaboration with Ambry Genetics utilizing a 67-gene cancer panel. The primary aim is analysis of the proportion and type of germline mutations identified. Secondary aims include testing uptake by arm, evaluation of distress, knowledge, satisfaction with testing services, family communication, and impact on cancer care. Results are communicated by telephone with a GC. Inclusion criteria are: potentially lethal PC (metastatic, localized with Gleason score ≥8, rising/persistent PSA after local therapy), early diagnosis (≤ 55 years), prior malignancy, and/or family history potentially indicating a hereditary cancer risk. Enrollment is 74% completed at a single institution. (NCT03328091). 1 Pritchard CC, et al. Inherited DNA‐repair gene mutations in men with metastatic prostate cancer. NEJM. 2016;375:443 2 Mateo J, et al. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. NEJM . 2015;373(18):1697-1708 Clinical trial information: NCT03328091.

The role of germline mutations in the BRCA1/2 and mismatch repair genes in men ascertained for early-onset and/or familial prostate cancer

2015 ◽  
Vol 15 (1) ◽  
pp. 111-121 ◽  
Author(s):  
Sofia Maia ◽  
Marta Cardoso ◽  
Paula Paulo ◽  
Manuela Pinheiro ◽  
Pedro Pinto ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mismatch Repair ◽  
Early Onset ◽  
Germline Mutations ◽  
Mismatch Repair Genes ◽  
Repair Genes

Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5568-5568
Author(s):  
Elisa Marie Ledet ◽  
Ellen Jaeger ◽  
Whitley Hatton ◽  
Marcus W. Moses ◽  
Alexandra Sokolova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Dna Repair ◽  
African American ◽  
Family History ◽  
Metastatic Prostate Cancer ◽  
Germline Mutations ◽  
Dna Repair Genes ◽  
Brca Mutations ◽  
Repair Genes

5568 Background: The relevance of germline mutations in metastatic prostate cancer is well established; however, comparison of germline genetics in African American (AA) versus Caucasian (CA) men with metastatic prostate cancer (PCa) is limited. Methods: Germline data from self-identified AA and CA metastatic PCa patients (pts) were collected from 5 academic cancer centers. Various commercial cancer-specific germline testing panels were used to evaluate 12-86 genes. Pathogenic (P) or likely pathogenic (LP) mutations, and variants of unknown significance (VUS), were reported according to ACMG guidelines. Self-reported family history (FH) was annotated for 99% of pts. Statistical analyses included Chi-squared and Fischer’s exact tests. Results: A total of 821 metastatic PCa pts were assessed: 152 AAs and 669 CAs. For P/LP alterations, AAs had a frequency of 11.2% (17/152) as compared to a frequency of 14.6% (98/669) in CAs (p = 0.302). AA pts were more likely to have a VUS than CA pts, 61% vs 43% respectively (OR = 2.09, 95%CI [1.45, 2.99], p < 0.001). BRCA mutations were similar between races, but AA were more likely to have a BRCA1 P/LP alteration (OR = 6.00, 95% CI [1.33, 27.09], p = 0.025). AA pts were less likely to have a P/LP alteration in a non-BRCA gene (OR = 0.34, 95% CI [0.15, 0.80], p = 0.013). Among DNA repair genes, there were no significant difference between AA and CA pts (p = 0.574); however, there was a trend toward AA pts having fewer P/LP alteration in a non-BRCA DNA repair genes (OR = 0.26, 95% CI [0.06, 1.08], p = 0.071). In pts with >1 first degree relative (FDR) with ovarian cancer, P/LP germline alterations were more likely in CAs (OR = 2.33, 95% CI [1.05, 5.17], p = 0.043); but there were no significant differences in AAs (p = 0.098). Those with >2 FDRs with PCa were more likely to have a P/LP change in CAs (OR = 2.32, 95% CI [1.04, 5.15], p = 0.043), but there were no difference in AAs (p = 0.700). In pts with ≥2 FDRs with breast cancer, P/LP germline alterations were more likely in both AAs (OR = 9.36, 95% CI [1.72, 50.84], p = 0.019) and CAs (OR = 3.92, 95% CI [1.79, 8.59], p = 0.001). Conclusions: We did not observe a difference in the overall frequency of germline P/LP alterations between AA and CA men with metastatic PCa but VUSs were more common in AA men. These AA men have an overall frequency of BRCA mutations similar to CA men; however, BRCA1 mutations were more prevalent in these AAs. Non-BRCA P/LP mutations are significantly less frequent in AA pts. A positive family history of >2 FDRs with breast cancer was associated with P/LP alterations in both AA and CA pts.

Germline mutations in DNA repair genes in a large series of unselected Chinese prostate cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17523-e17523
Author(s):  
Yu Wei ◽  
Yao Zhu ◽  
Junlong Wu ◽  
Dingwei Ye ◽  
Hao Zeng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Genetic Testing ◽  
Family History ◽  
High Risk ◽  
Cancer Patients ◽  
Germline Mutations ◽  
Dna Repair Genes ◽  
History Of ◽  
Repair Genes

e17523 Background: Germline DNA repair gene (DRG) mutations has emerged as a potential determinant of cancer risk and therapeutic response in PCa. Despite substantial advances in delineating the germline mutation in DRGs among Caucasian population, the prevalence of mutations in DRGs are largely unknown among a large series of unselected prostate cancer patients in Chinese population. Methods: We enrolled 1003 prostate cancer patients from three different hospitals in China, unselected for family history of cancer or age at diagnosis. All patients received germline genetic testing using a clinician-selected multi-gene panel. The 18 DNA repair genes and HOXB13, which has established or emerging potential clinical actionability in PCa, were analyzed in our study. Results: A total of 94 (9.7%) deleterious germline mutations were identified among the 1003 unselected prostate cancer patients. Of these, 5.6% patients carried a BRCA1 or BRCA2 mutations (5.2% in BRCA2 and 0.4% in BRCA1), 3.6% patients carried other DRG mutations (including 10 genes) and 0.5% patients carried HOXB13 mutations. Besides, variants with uncertain significance (VUS) were found in approximately 45% patients. We also divided 633 metastatic PCa patients into 542 de novo metastastic PCa and 91 recurrent metastastic PCa and found mutation frequencies did not differ between these two groups (9.0% vs 11.6%, p = 0.6). Patients with younger age of onset or family history of cancers were more likely to harbour germline mutations in DRGs. However, the rate of germline mutations were still at a high level for patients more than 70 years old (6.7%) and patients without family history of cancers (7.5%). There is no statistically significant difference in the mutation frequencies between patients with metastasis and without metastasis (7.5% vs 9.2%, p = 0.4), which may be because 85% patients without metastasis in our cohort were in high to very high risk group or have lymph node metastasis. Conclusions: To our knowledge, our study reported the largested series of Chinese PCa patients who received germline genetic testing. Our study provided a rationality for germline genetic testing criteria from high risk to metastastic PCa regardless of family history considering the high proportion. In addition, we recommended a multigene panel covering 13 genes ( ATM, BRCA1, BRCA2, CHEK2, FANCA, HOXB13, MSH2, MSH6, NBN, PALB2, RAD51C, RAD51D, TP53) in China. Nevertheless, the high prevalence of VUS (45%) in Chinese PCa patients warrant further efforts.

scholarly journals Population-Based Study of the Association of Variants in Mismatch Repair Genes with Prostate Cancer Risk and Outcomes

2010 ◽  
Vol 19 (1) ◽  
pp. 258-264 ◽  
Author(s):  
Wendy J. Langeberg ◽  
Erika M. Kwon ◽  
Joseph S. Koopmeiners ◽  
Elaine A. Ostrander ◽  
Janet L. Stanford
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Mismatch Repair ◽  
Prostate Cancer Risk ◽  
Population Based ◽  
Mismatch Repair Genes ◽  
Population Based Study ◽  
Repair Genes

scholarly journals Determining the frequency of de novo germline mutations in DNA mismatch repair genes

2011 ◽  
Vol 48 (8) ◽  
pp. 530-534 ◽  
Author(s):  
A. K. Win ◽  
M. A. Jenkins ◽  
D. D. Buchanan ◽  
M. Clendenning ◽  
J. P. Young ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
De Novo ◽  
Dna Mismatch Repair ◽  
Germline Mutations ◽  
Mismatch Repair Genes ◽  
Dna Mismatch ◽  
Dna Mismatch Repair Genes ◽  
Repair Genes

scholarly journals Biallelic germline mutations of mismatch-repair genes

Cancer ◽  
2007 ◽  
Vol 109 (11) ◽  
pp. 2349-2356 ◽  
Author(s):  
Jan-Werner Poley ◽  
Anja Wagner ◽  
Monique M. C. P. Hoogmans ◽  
Fred H. Menko ◽  
Carli Tops ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Germline Mutations ◽  
Mismatch Repair Genes ◽  
Repair Genes

Mismatch Repair Genes and EPCAM germline mutations in patients with gastric or colorectal cancer with suspected of Lynch syndrome.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e13623-e13623 ◽  
Author(s):  
Nora Manoukian Forones ◽  
Fernanda Tereza Lima ◽  
Renan Paulo Martin ◽  
Leonardo Martins ◽  
Patricia Valera Lima Teixeira ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Germline Mutations ◽  
Mismatch Repair Genes ◽  
Repair Genes

Streamlining the genetics pipeline to increase testing for patients at risk for hereditary prostate cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1590-1590
Author(s):  
Barry Tong ◽  
Hala Borno ◽  
Eric Jay Small ◽  
Fern Alagala ◽  
Amie Blanco ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Testing ◽  
High Risk ◽  
Metastatic Prostate Cancer ◽  
Genetic Counselor ◽  
Germline Mutations ◽  
Genetic Counselors ◽  
High Risk Population ◽  
Risk Population ◽  
Positive Results

1590 Background: Metastatic prostate Cancer (mPCa) is increasingly recognized as a heritable disease and germline genetic testing has increasingly become a part of standard of care. At the University of California at San Francisco (UCSF) Genitourinary (GU) Medical Oncology clinic, approximately 850 new patients with mPCa are seen annually. A feasibility pilot Genetic Testing Station (GTS) was developed to expand access to genetic testing among this high-risk population. GTS is facilitated by Genetic Counselor Assistants (GCA) under the supervision of genetic counselors. Methods: This is a feasibility pilot of a GTS model among patients with mPCa. In this model, all patients with mPCa are offered a same day GTS visit with a GCA. At the GTS, the patient receives pre-test education via videos developed by genetic counselors. The patient provides informed consent, a family history, and a saliva sample for Invitae’s 87-gene panel. All positive results trigger a genetic counselor visit while non-positive results either receive a letter or a genetic counselor visit (in person or via telehealth). To evaluate the model, testing frequency and laboratory turnaround time (TAT) was assessed before and after the pilot. Results: In the first four months of the GTS pilot (10/14/2019 – 02/10/2020), 94 patients were referred and received genetic testing. Eight germline positives were identified (BRCA2, CHEK2, HOXB13 MSH6, RECQL4). The average TAT was 8 days. 9.3% of patients were found to have pathogenic mutations through the prostate GTS which is comparable to previously published rates of germline mutations in metastatic prostate cancer patients. In a 4-month time frame the prior to the intervention (10/01/2018-1/31/2019), 26 genetic testing orders were placed. The average laboratory TAT in this prior process was 17 days. Rates of positive germline mutations in the prior model was 8.6%. Conclusions: The GTS is a feasible method to increase access to germline genetic testing among a high-risk population. It may reduce barriers to testing and facilitate real-time discussion of treatment and prevention strategies with patients and family members. As a result, we will continue to operate the GTS. This model provides a framework for scaling access for and cascade testing in other high-risk patient groups.

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