Prevalence of pathogenic germline variants in DNA repair by race, age, and ethnicity in men with prostate cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5062-5062
Author(s):  
Alexandria Mara ◽  
Jason Zhu ◽  
Yuan Wu ◽  
Tom Callis ◽  
Shan Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Advanced Prostate Cancer ◽  
Final Analysis ◽  
The United States ◽  
National Study ◽  
Germline Variants ◽  
Variant Of Uncertain Significance ◽  
Race Ethnicity ◽  
Germline Testing

5062 Background: Patients with advanced prostate cancer (PC) frequently harbor pathogenic or likely pathogenic (P/LP) germline variants (GVs) in mismatch repair (MMR) and homologous repair (HR) enzymes which have clinical and treatment implications. However, whether the prevalence of such GVs differ by race, ethnicity, family history, or age is unknown in men with PC. Methods: This is a retrospective analysis of germline DNA from men with PC in the United States, tested by Invitae. Baseline characteristics including self-identified race, ethnicity, family history (FH), and age were recorded. Race and ethnicity were analyzed by 3 cohorts: non-Ashkenazi Caucasian Americans (CA), non-Ashkenazi African Americans (AA), and Ashkenazi Jewish Americans (AJ). Chi-square testing was performed to identify significant differences across these categories between the three cohorts, with respect to combined and individual pathogenic MMR (MSH2/6, MLH1, PMS2, and MUTYH) and HR genes (BRCA1/2, ATM, CHEK2, RAD51D, and PALB2). Results: 3057 men were included in the final analysis: 2248 (74%) men were CA, 229 (7%) were AA, and 210 (7%) were AJ. Of these, 2665 (87%) men had a FH of PC and 463 (15%) had a P/LP GV. In addition, 1068 (35%) were found to have a variant of uncertain significance, and 35 (1.6%) had the HOXB13 G84E variant. There were no significant differences in the overall prevalence of MMR (CA 1.5% vs AA 0.9% vs AJ 1.4%, p = 0.89) or HR genes (CA 7.8% vs AA 7.9% vs AJ 10.5%, p = 0.37) by race/ethnicity. With respect to individual genes, AJ had a higher prevalence of pathogenic BRCA1 alterations (AJ 3.3% vs CA 0.8% vs AA 1.7%, p = 0.0034) and CHEK2 alterations (AJ 4.3% vs CA 2.8% vs AA 0.4%, p = 0.02). There were no significant differences in the prevalence of individual or specific classes of GVs between those with or without a self-reported FH of prostate or breast/ovarian cancers. There was also no association between prevalence of HR genes and age at germline testing (p = 0.40). Conclusions: This national study found that the overall prevalence of pathogenic GVs in MMR and HR genes do not differ by race, ethnicity, or age at the time of testing, and suggests that all men with advanced prostate cancer should be offered germline testing.

Diagnostic yield of germline genetic testing following tumor testing in prostate cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1591-1591
Author(s):  
Kingshuk Das ◽  
Stephen E Lincoln ◽  
Nhu Ngo ◽  
Daniel Esteban Pineda Alvarez ◽  
Shan Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Cancer Patients ◽  
Diagnostic Yield ◽  
Significant Proportion ◽  
Consecutive Series ◽  
Primary Malignancy ◽  
Germline Variants ◽  
Nccn Guidelines ◽  
Germline Testing

1591 Background: NCCN guidelines recommend germline testing for patients with localized or advanced prostate cancer meeting family history or clinical/pathologic criteria. However, the guidelines for somatic molecular analysis generally consider advanced disease only, primarily to inform therapy. As the analytical and clinical specifications of both testing modalities differ accordingly, we examined the results of germline testing following prior somatic testing. Methods: We reviewed somatic and germline variants in an otherwise unselected consecutive series of patients who: (a) had a current or previous diagnosis of prostate cancer; (b) had undergone tumor sequencing; and (c) were referred for germline testing. Indications for germline testing included: potential germline origin of somatic test result, treatment or surgical planning, personal or family history, and patient concern. Results: 208 patients met study criteria of whom 81 (39%) harbored a pathogenic germline variant (PGV) in a cancer predisposition gene. Certain genes were more likely to harbor germline variants, and 98% (81) of PGVs were potentially actionable (Table). 9.6% of PGVs were not reported by somatic testing, reflecting analytical limitations of the somatic testing. Of note, 11 patients (14%) had PGVs identified after diagnosis of a subsequent primary malignancy. Conclusions: The high PGV rate of 39% was unexpected, given reported rates of 11.8% in patients with metastatic prostate cancer and 6% in high-risk localized disease (NCCN)--even considering potential clinician ascertainment bias. This finding, the potential clinical utility of 98% of PGVs identified, the significant proportion unreported by somatic testing, and the fraction of patients diagnosed with a PGV after a subsequent malignancy all suggest that germline testing is an underutilized tool in the care of prostate cancer patients and their families. [Table: see text]

Prostate Cancer

2018 ◽  
Author(s):  
Kathryn M. Wilson ◽  
Lorelei Mucci
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Family History ◽  
Prostate Specific Antigen ◽  
Advanced Prostate Cancer ◽  
Advanced Disease ◽  
African Ancestry ◽  
Specific Antigen ◽  
Dietary Factors ◽  
Increased Risk

Prostate cancer is among the most commonly diagnosed cancers among men, ranking second in cancer globally and first in Western countries. There are marked variations in incidence globally, and its incidence must be interpreted in the context of diagnostic intensity and screening. The uptake of prostate-specific antigen screening since the 1990s has led to dramatic increases in incidence in many countries, resulting in an increased proportion of indolent cancers that would never have come to light clinically in the absence of screening. Risk factors differ when studying prostate cancer overall versus advanced disease. Older age, African ancestry, and family history are established risk factors for prostate cancer. Obesity and smoking are not associated with risk overall, but are associated with increased risk of advanced prostate cancer. Several additional lifestyle factors, medications, and dietary factors are now emerging as risk factors for advanced disease.

MP78-17 FACTORS ASSOCIATED WITH INITIAL THERAPY FOR REGIONALLY ADVANCED PROSTATE CANCER IN THE UNITED STATES

2014 ◽  
Vol 191 (4S) ◽  
Author(s):  
Thomas Jang ◽  
Neal Patel ◽  
Shunhua Shen ◽  
Michael Karellas ◽  
Robert DiPaola ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
United States ◽  
Advanced Prostate Cancer ◽  
The United States ◽  
Initial Therapy ◽  
Factors Associated

Racial and age specific differences in localized and metastatic prostate cancer incidence: 1988-2013.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 211-211
Author(s):  
Marc Dall'Era ◽  
Ralph deVere White ◽  
Danielle Rodgriguez ◽  
Rosemary Donaldson Cress
Keyword(s):  
Prostate Cancer ◽  
Cancer Incidence ◽  
Metastatic Prostate Cancer ◽  
Prostate Cancer Screening ◽  
The United States ◽  
Incidence Rates ◽  
Localized Prostate Cancer ◽  
Prostate Cancer Incidence ◽  
Race Ethnicity ◽  
The Impact

211 Background: The United States Preventive Services Task Force (USPSTF) recommended against routine PSA based prostate cancer screening in all men in 2012. This led to dramatic reductions in screening and rates of localized disease across all clinical risk groups. We sought to study the impact of this on rates of metastatic disease, specifically by patient race and age. Methods: We analyzed new prostate cancer incidence by stage at diagnosis between 1988-2013 within the Cancer Registry of Greater California. We further stratified cases by four major race/ethnicity groups (non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic and non-Hispanic Asian/PI (API)) and age. Incidence rates were calculated and compared per 100,000 and age-adjusted to the 2000 US Standard Population. Joinpoint regression was used to detect changes in incidence and to calculate the average percent change (APC). Results: Adjusted rates of remote prostate cancer incidence for NHW men increased slightly in the most recent decade (+0.28%) after steady declines in previous years with the inflection point occurring in 2002, however this was not statistically significant. In contrast, incidence of remote prostate cancer continued to decline for NHB (-2.73%), Hispanic (-2.04%), and API (-1.45%) men. The greatest increase of +1.1% a year since 2002 was observed for NHW men under age 65. The incidence of localized prostate cancer declined for all race/ethnicity groups over the most recent time period and also declined in all age groups. After remaining relatively flat since 1992, incidence of localized prostate cancer among NHW men declined by over 8% per year starting in 2007 compared with a more gradual decline of -3.52% a year since 2000 for NHB, and more recent declines of -14.41% and -16.64% for Hispanic and API men, respectively. Incidence of regional stage cancer also declined in all groups, but less dramatically. Conclusions: Incidence rates of newly metastatic prostate cancer have not significantly changed since PSA screening declined in the US although we noted a slight upward trend primarily for younger, white men since 2002.

Germline pathologic mutations and cancer family history in prostate cancer patients.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 378-378
Author(s):  
Marcus Marie Moses ◽  
Elisa Ledet ◽  
Emma M. Ernst ◽  
Patrick Cotogno ◽  
Joshua Schiff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
San Francisco ◽  
Treatment Options ◽  
Distant Metastases ◽  
Cancer Center ◽  
Chi Square ◽  
Variant Of Uncertain Significance ◽  
Pathogenic Variants ◽  
Uncertain Significance

378 Background: Prostate cancer (PCa) patients (pts) with metastases and/or strong family history (FH) of cancer (Ca) are at higher risk of a germline mutation. The identification of alterations in PCa pts may be important for risk stratification as well as personalizing treatment options. The goal of this study was characterization of FH and pathogenic variants (PV) detected in PCa pts, with both localized and metastatic disease. Methods: 300 PCa pts from Tulane Cancer Center underwent germline testing. 265 Caucasian (C) and 35 African-Americans (AA) were tested and met the NCCN criteria for testing and/or had distant metastases (mets). Germline genetic testing was done via commercial panels (30-80 genes) (Invitae. San Francisco, Ca). PCa pts had extensive FH screening. Clinical annotation included age at diagnosis (dx), race, and presence of mets at any time. Chi square tests were used to compare clinical correlates and PVs. Results: Of the 300 pts tested, 182 pts (60.6%) had mets and 118 (39.4%) did not. 41 pts (13.6%) had ≥ 1 germline pathogenic variant (PV) and 161 pts (53.6%) had ≥ 1 germline variant of uncertain significance (VUS). PVs were detected in BRCA2 (n = 10), MUTYH (n = 8), CHEK2 (n = 6), BRCA1 (n = 4), ATM (n = 4), TP53 (n = 3), PMS2 (n = 2), BLM (n = 2), MITF (n = 2), NBN (n = 1), and RAD51D (n = 1). MUTYH and MITF are not known to be linked to prostate cancer. There was no significant relationships in FH PCa and FH non-PCa in regard to likelihood of a PV (p = .86 and p = .18). Of the 300 pts tested, 136 pts (45.3%) had PCa FH, 131 pts (43.6%) had breast Ca FH, 61 pts (20.3%) had lung Ca FH, 61 pts (20.3%) had colon Ca FH, 37 pts (12.3%) had pancreatic Ca FH, and 32 pts (10.6%) had ovarian Ca FH. 45.6% of C men (n = 121) and 42.8% of AA men (n = 15) had PCa FH. Pts with a non-PCa FH (n = 255) were 1.37 times more likely to develop mets (p = .01168). The median age of dx were 61 for PV pts, 62 for VUS pts, and 61 for negative pts (non-significant). 21/182 pts with mets (11.5%) had a PV; 8/182 (4.4%) pts with mets had a BRCA2 PV. Conclusions: In metastatic patients, FH of prostate cancer alone cannot predict those with PV. The most common Cas observed in these pts were breast, lung, colon and pancreatic. A larger cohort is needed to fully characterize and understand the co-segregation of PCa with other Cas.

MP14-15 INCREASE IN THE INCIDENCE OF ADVANCED PROSTATE CANCER IN THE UNITED STATES

2017 ◽  
Vol 197 (4S) ◽  
Author(s):  
Jonathan Shoag ◽  
Art Sedrakyan ◽  
Joshua Halpern ◽  
Wei-Chun Hsu ◽  
Jim Hu
Keyword(s):  
Prostate Cancer ◽  
United States ◽  
Advanced Prostate Cancer ◽  
The United States

scholarly journals Redefining Hormone Sensitive Disease in Advanced Prostate Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Xiaoyu Hou ◽  
Thomas W. Flaig
Keyword(s):  
Prostate Cancer ◽  
Hormonal Therapy ◽  
Advanced Prostate Cancer ◽  
The United States ◽  
Castration Resistant ◽  
Hormonal Resistance ◽  
Hormone Sensitive ◽  
Hormone Resistant Prostate Cancer ◽  
Term Management

Prostate cancer is the most common cancer among men in the United States. For decades, the cornerstone of medical treatment for advanced prostate cancer has been hormonal therapy, intended to lower testosterone levels, known as Androgen Deprivation Therapy (ADT). The development of hormone-resistant prostate cancer (now termed castration-resistant prostate cancer:CRPC) remains the key roadblock in successful long-term management of prostate cancer. New advancements in medical therapy for prostate cancer have added to the hormonal therapy armamentarium. These new therapeutic agents not only provide a survival benefit but also show potential for reversing hormonal resistance in metastatic CRPC, and thus redefining hormonally sensitive disease.

scholarly journals Early national dissemination of abiraterone and enzalutamide for advanced prostate cancer in Medicare Part D.

2017 ◽  
Vol 35 (8_suppl) ◽  
pp. 35-35
Author(s):  
Megan Veresh Caram ◽  
Tudor Borza ◽  
Hye-Sung Min ◽  
Jennifer J. Griggs ◽  
David Christopher Miller ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
United States ◽  
Regional Variation ◽  
Advanced Prostate Cancer ◽  
Medicare Part D ◽  
The United States ◽  
Medicare Part ◽  
Part D ◽  
Hospital Referral ◽  
Early National

35 Background: Abiraterone and enzalutamide are oral medications approved by the Food & Drug Administration in 2011 and 2012 to treat men with advanced castration-resistant prostate cancer. Most men with advanced prostate cancer are over age 65 and thus eligible for Medicare Part D. We conducted a study to better understand the early dissemination of these drugs across the United States using national Medicare Part D data. Methods: We evaluated the number of prescriptions for abiraterone and enzalutamide by provider specialty and hospital referral region (HRR) using Medicare Part D and Dartmouth Atlas data. We categorized HRRs by abiraterone and enzalutamide prescriptions, adjusted for prostate cancer incidence, and examined factors associated with regional variation using multilevel regression models. Results: Among all providers who wrote prescriptions for abiraterone or enzalutamide in 2013 (n=2121), 87.5% were medical oncologists, 3.3% urologists, and 9.2% were listed as other provider specialties. Among those who prescribed either drug, 5% of providers were responsible for 75% of the claims for abiraterone, and 7% were responsible for 75% of the claims for enzalutamide. Some HRRs demonstrated low-prescribing rates despite average medical oncology and urology physician workforce density. Conclusions: The majority of prescriptions written for abiraterone and enzalutamide through Medicare Part D in 2013 were written by a minority of providers with marked regional variation across the United States. Better understanding the early national dissemination of these effective but expensive drugs can help inform strategies to optimize introduction of new, evidence-based advanced prostate cancer treatments.

scholarly journals Epidemiological Determinants of Advanced Prostate Cancer in Elderly Men in the United States

2019 ◽  
Vol 13 ◽  
pp. 117955491985511 ◽  
Author(s):  
Jinani Jayasekera ◽  
Eberechukwu Onukwugha ◽  
Christopher Cadham ◽  
Sarah Tom ◽  
Donna Harrington ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Health Services ◽  
Health Behavior ◽  
Cancer Diagnosis ◽  
Advanced Prostate Cancer ◽  
The United States ◽  
Preventive Health ◽  
Prostate Cancer Diagnosis ◽  
Individual Level ◽  
Preventive Health Behavior

In this study, we examined the effects of individual-level and area-level characteristics on advanced prostate cancer diagnosis among Medicare eligible older men (ages 70+ years). We analyzed patients from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2000-2007) linked to US Census and County Business Patterns data. Cluster-adjusted logistic regression models were used to quantify the effects of individual preventive health behavior, clinical and demographic characteristics, area-level health services supply, and socioeconomic characteristics on stage at diagnosis. The fully adjusted model was used to estimate county-specific effects and predicted probabilities of advanced prostate cancer. In the adjusted analyses, low intensity of annual prostate-specific antigen (PSA) testing and other preventive health behavior, high comorbidity, African American race, and lower county socioeconomic and health services supply characteristics were statistically significantly associated with a higher likelihood of distant prostate cancer diagnosis. The fully adjusted predicted proportions of advanced prostate cancer diagnosis across 158 counties ranged from 3% to 15% (mean: 6%, SD: 7%). County-level socioeconomic and health services supply characteristics, individual-level preventive health behavior, demographic and clinical characteristics are determinants of advanced stage prostate cancer diagnosis among older Medicare beneficiaries; other health care-related factors such as family history, lifestyle choices, and health-seeking behavior should also be considered as explanatory factors.

Sign in / Sign up

Export Citation Format

Share Document