Family history and germline alterations in metastatic prostate cancer patients.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 231-231
Author(s):  
Whitley Hatton ◽  
Ellen Jaeger ◽  
Marcus W. Moses ◽  
Alexa Zaheri ◽  
Patrick Cotogno ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Metastatic Prostate Cancer ◽  
Family Members ◽  
Prostate Cancer Risk ◽  
Pathogenic Mutation ◽  
Cancer Center ◽  
Cancer Type ◽  
Pathogenic Mutations ◽  
History Of

231 Background: Recent literature has highlighted the importance of germline genetic testing in metastatic prostate cancer (PCa)patients (pts). This retrospective study evaluated family history (FH), evaluate treatment outcomes in metastatic patients with pathogenic germline mutations, and compared family history in Caucasian (CA) and Africans Americans (AA). Methods: At Tulane Cancer Center, 428 metastatic PCa pts had germline testing in at least 79 genes. Comprehensive family histories were obtained in all. Analysis of prevalent FH, including breast, ovarian, prostate, and pancreatic cancers was assessed for all metastatic pts. Statistical analyses including chi square were performed. Results: 64 (64/428; 14.9%) pts had at least one or more pathogenic mutations, while 166 (166/428; 38.7%) had were normal. The remaining 199 (199/428; 46.4%) of pts had a variant of uncertain significance (VUS). Pts with a DNA repair pathogenic mutation were more likely to have >2 family members affected by cancer, regardless of cancer type or degree of relationship (p=0.0047); 6 pts without any family history of cancer had a pathogenic mutation. In CA, the presence of either a breast or PCa family history was associated with pathogenic germline findings (p=.022/.0367) However, in AAs neither breast nor prostate cancer predicted pathogenic germline alterations. Conclusions: The correlation between family history of breast and PCa cancer in CA pts with pathogenic mutations is notable as is the finding of >2 family members with cancer predicting germline pathogenic alterations. With AA pathogenic pts, there was no correlation of family history of breast and PCa, which highlights the need to learn more about the genetic factors which influence AA prostate cancer risk.[Table: see text]

DNA repair germline pathogenic mutation associations with treatment duration and family history in prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 245-245
Author(s):  
James Vu ◽  
Marcus Marie Moses ◽  
Lahiru Ranasinghe ◽  
Patrick Cotogno ◽  
Charlotte Manogue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Dna Repair ◽  
Family History ◽  
Treatment Outcomes ◽  
Treatment Duration ◽  
Pathogenic Mutation ◽  
Germline Mutations ◽  
Cancer Type ◽  
History Of

245 Background: Germline mutation testing for metastatic prostate cancer patients creates a potential opportunity to personalize targeted therapies to improve treatment outcomes. The goal of this study was to characterize cancer family history, and evaluate treatment outcomes, in mCRPC patients with DNA repair pathogenic germline alterations. Methods: A retrospective study of metastatic PCa patients at Tulane Cancer Center identified 246 patients undergoing germline testing using panels (30-80 genes) (Color.com or Inviate.com). Clinical annotations included family history, life-extending treatments, and treatment duration. Statistical analyses including chi-square and Wilcoxon Rank Sum. Results: In the 246 patients tested for germline mutations, 27 patients (11.0%) had ≥1 DNA repair germline pathogenic mutation (BRCA2 = 11, BRCA1 = 3, CHEK2 = 5, ATM = 3, NBN = 1, PMS2 = 2, MSH2 = 1, PALB2 = 1) while 219 patients (89.0%) possessed no pathogenic mutation in these genes. Patients with a DNA repair pathogenic mutation were more likely to have > 2 family members affected by cancer, regardless of cancer type or degree of relationship (p = 0.04). In the DNA repair population, 5 pathogenic patients had no family history of cancer (18.5%, n = 5). Patients were more likely to have a germline alteration if they had 1 or more first degree relatives affected with breast cancer (p = 0.00001). Median lines of life-extending treatments to date between the pathogenic and non-pathogenic population were equal at 2. There were no significant differences in treatment duration for abiraterone (p = 0.49), enzalutamide (p = 0.99), docetaxel (p = 0.28), cabazitaxel (p = 0.53), carboplatin+docetaxel (p = 0.41), or radium-223 (p = 0.59) between the two groups. Conclusions: In this study, DNA repair pathogenic germline mutations did not affect treatment durations or lines of therapy but these studies are underpowered. The relationship between a family history of breast cancer and a DNA repair pathogenic mutation has not previously been reported.

scholarly journals Multi-cohort modeling strategies for scalable globally accessible prostate cancer risk tools

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Johanna Tolksdorf ◽  
Michael W. Kattan ◽  
Stephen A. Boorjian ◽  
Stephen J. Freedland ◽  
Karim Saba ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Family History ◽  
Cancer Risk ◽  
Risk Prediction ◽  
Prostate Biopsy ◽  
Prostate Cancer Risk ◽  
High Grade ◽  
Prediction Tools ◽  
History Of

Abstract Background Online clinical risk prediction tools built on data from multiple cohorts are increasingly being utilized for contemporary doctor-patient decision-making and validation. This report outlines a comprehensive data science strategy for building such tools with application to the Prostate Biopsy Collaborative Group prostate cancer risk prediction tool. Methods We created models for high-grade prostate cancer risk using six established risk factors. The data comprised 8492 prostate biopsies collected from ten institutions, 2 in Europe and 8 across North America. We calculated area under the receiver operating characteristic curve (AUC) for discrimination, the Hosmer-Lemeshow test statistic (HLS) for calibration and the clinical net benefit at risk threshold 15%. We implemented several internal cross-validation schemes to assess the influence of modeling method and individual cohort on validation performance. Results High-grade disease prevalence ranged from 18% in Zurich (1863 biopsies) to 39% in UT Health San Antonio (899 biopsies). Visualization revealed outliers in terms of risk factors, including San Juan VA (51% abnormal digital rectal exam), Durham VA (63% African American), and Zurich (2.8% family history). Exclusion of any cohort did not significantly affect the AUC or HLS, nor did the choice of prediction model (pooled, random-effects, meta-analysis). Excluding the lowest-prevalence Zurich cohort from training sets did not statistically significantly change the validation metrics for any of the individual cohorts, except for Sunnybrook, where the effect on the AUC was minimal. Therefore the final multivariable logistic model was built by pooling the data from all cohorts using logistic regression. Higher prostate-specific antigen and age, abnormal digital rectal exam, African ancestry and a family history of prostate cancer increased risk of high-grade prostate cancer, while a history of a prior negative prostate biopsy decreased risk (all p-values < 0.004). Conclusions We have outlined a multi-cohort model-building internal validation strategy for developing globally accessible and scalable risk prediction tools.

scholarly journals Family history of prostate cancer and prostate cancer risk in the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study

2008 ◽  
Vol 123 (5) ◽  
pp. 1154-1159 ◽  
Author(s):  
Jiyoung Ahn ◽  
Roxana Moslehi ◽  
Stephanie J. Weinstein ◽  
Kirk Snyder ◽  
Jarmo Virtamo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Cancer Prevention ◽  
Prostate Cancer Risk ◽  
Beta Carotene ◽  
Alpha Tocopherol ◽  
History Of ◽  
Atbc Study

scholarly journals First-degree family history of breast cancer is associated with prostate cancer risk: a systematic review and meta-analysis

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zheng-Ju Ren ◽  
De-Hong Cao ◽  
Qin Zhang ◽  
Peng-Wei Ren ◽  
Liang-Ren Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Systematic Review ◽  
Family History ◽  
Cancer Risk ◽  
Meta Analysis ◽  
Prostate Cancer Risk ◽  
History Of

Abstract 2543: A family affair: Prostate cancer risk and family history of breast or prostate cancer

2016 ◽  
Author(s):  
Lauren E. Barber ◽  
Travis A. Gerke ◽  
Sarah C. Markt ◽  
Giovanni Parmigiani ◽  
Lorelei A. Mucci
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
History Of

scholarly journals Dutasteride and Prostate Cancer Risk: Does Family History of Prostate and/or Breast Cancers Influence the Number Needed to Treat? Results from REDUCE

2014 ◽  
Vol 2 (2) ◽  
pp. 31-36
Author(s):  
Jean-Alfred Thomas II ◽  
Leah Gerber ◽  
Robert J. Hamilton ◽  
Adriana C. Vidal ◽  
Daniel M. Moreira ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Number Needed To Treat ◽  
Breast Cancers ◽  
History Of

Prostate cancer risk in U.S. blacks and whites with a family history of cancer

1995 ◽  
Vol 60 (3) ◽  
pp. 361-364 ◽  
Author(s):  
Richard B. Hayes ◽  
Jonathan M Liff ◽  
Linda M. Pottern ◽  
Raymond S. Greenberg ◽  
Janet B. Schoenberg ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Family History Of Cancer ◽  
History Of ◽  
Blacks And Whites ◽  
History Of Cancer

FIRST-DEGREE FAMILY HISTORY OF PROSTATE CANCER AND CARRIER STATUS OF PROSTATE CANCER RISK ALLELES

2009 ◽  
Vol 181 (4S) ◽  
pp. 49-49
Author(s):  
Joshua J Meeks ◽  
Brian T Helfand ◽  
Stacy Loeb ◽  
Donghui Kan ◽  
Angela J Fought ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Carrier Status ◽  
Risk Alleles ◽  
History Of

scholarly journals Family History of Prostate Cancer, Body Size, and Prostate Cancer Risk

2006 ◽  
Vol 163 (suppl_11) ◽  
pp. S112-S112
Author(s):  
J Ahn ◽  
R Moslehi ◽  
S Weinstein ◽  
K Snyder ◽  
J Virtamo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Body Size ◽  
Family History ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
History Of

scholarly journals Metastatic prostate cancer: clinical aspects and treatment limitations in a university hospital center in Senegal

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Cyrille Ze Ondo ◽  
Abdoulaye Ndiath ◽  
Alioune Sarr ◽  
Amath Thiam ◽  
Babacar Sine ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Family History ◽  
Metastatic Prostate Cancer ◽  
Specific Antigen ◽  
University Hospital ◽  
Clinical Aspects ◽  
Castration Resistance ◽  
African Countries ◽  
History Of

Abstract Background Prostate cancer is most often diagnosed at the metastatic stage in many sub-Saharan African countries. The objective of our study is to analyze the management of metastatic prostatic adenocarcinoma based on epidemiological, clinical, therapeutic and evolutionary aspects in developing country context. Methods Retrospective study collecting 276 patients from January 1st, 2012 to December 31st, 2019 in Aristide Le Dantec University Hospital in Dakar, Senegal. Parameters studied: age, family history of prostate cancer, reasons for consultation, total Prostate Specific Antigen (PSA), anatomic pathology examination, extension assessment, treatment, nadir PSA, castration resistance, and overall survival. Results The average age was 71.4 years. A family history of prostate cancer was noted in 21 patients. Spinal pain was the most noted reason for consultation. The average total PSA level was 1967.1 ng/ml. The majority of patients had moderately differentiated prostate cancer. Bone metastases were the most common. All patients had androgen suppression. A tumor cytoreduction was performed in 89 patients. The average nadir PSA was 193 ng/ml as early as the sixth month. The time to onset of castration resistance ranged from 6 to 30 months. Abiraterone acetate was used in seven patients and docetaxel in 43 patients. The overall survival of the patients was 19.8 ± 1.2 months. Conclusion Metastatic prostate cancer was most often symptomatic at the time of diagnosis. Second-line treatments were rarely used during castration resistance. Overall survival was low.

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