Sherry Lynn Denton, NP, MSN, MHA; Bernard Michael Gburek, MD
Arizona Urology Specialists, United Group/OneOncology, Scottsdale
KEYWORDS:
Prostatic neoplasms; genetic testing; germ-line mutation; genes, BRCA2; pedigree
Abstract
Prostate cancer has a substantial hereditary component, particularly in patients with high-risk or metastatic disease or a family history of cancer. We present the case of a 78-year-old man diagnosed with low-volume Gleason 4+5=9, nonmetastatic prostate cancer, who was found to have BRCA2 mutation. His family has a history of prostate cancer, breast cancer, and other malignancies. He was the first in his family to undergo genetic testing, but his findings prompted other family members to pursue testing. Some family members who also tested positive made life-altering decisions following the discovery. This case underscores the importance of a thorough family history and integrating genetic testing into the care of patients with prostate cancer to guide treatment and inform family members of their risk.
Prostate cancer is the second-most diagnosed cancer and the most common cause of cancer-related death in men globally, with approximately 1 in 8 men being diagnosed with prostate cancer in their lifetime.1 The American Cancer Society predicts 313 780 new cases of prostate cancer will be diagnosed in the United States in 2025, which is 15% of all new cancer cases.1 Between 2018 and 2022, the rate of new prostate cancer cases was 120.2 per 100 000 people. The age-adjusted diagnosis rate for new prostate cancer cases rose an average of 1.8% each year between 2013 and 2022, but death rates fell an average of 0.6% each year between 2014 and 2023, likely because of earlier detection and advances in prostate cancer treatment over the past 15 years.1
Approximately 5% to 15% of men with prostate cancer have hereditary factors that contribute to their disease. Germline genetic testing evaluates for mutations inherited from a parent. Somatic variations are important drivers of prostate cancer behavior, but these variations occur only sporadically and can be detected through analysis of the tumor itself or through liquid biopsies. For this reason, patients with metastatic prostate cancer should be tested both for germline mutations and for somatic variations.2 Germline genetic testing has been standard of care in breast and ovarian cancer for more than 30 years, but only over the past 10 years has it emerged as an important factor in the treatment of prostate cancer.
Here we report the case of a 78-year-old White man who was diagnosed with prostate cancer in 2019. At initial presentation, his prostate-specific antigen (PSA) value was 5.9 and digital rectal examination was normal. He was diagnosed based on findings from a transrectal ultrasound–guided biopsy. His pathology demonstrated 1 core of Gleason 4+5=9 prostatic adenocarcinoma, 4 cores of Gleason 3+3=6 prostatic adenocarcinoma, and 2 cores of high-grade prostatic intraepithelial neoplasia. His staging included computed tomography scans of the abdomen and pelvis as well as a bone scan, all of which were negative for metastatic disease.
The patient underwent intensity-modulated radiation therapy and a 2-year course of androgen-deprivation therapy with leuprolide acetate. His last leuprolide acetate injection was in June 2021. His PSA value was 0.2 on November 28, 2022. He is currently stable with nonmetastatic prostate cancer and is not on any treatment.
The patient is in good health, although his medical history is notable for sleep apnea, rheumatoid arthritis, kidney stones, and benign prostatic hyperplasia. He is under surveillance for a history of bladder cancer, which was diagnosed in 2006. While providing his family history, the patient reported 4 brothers with prostate cancer. Therefore, genetic testing was completed using a multigene panel, with results demonstrating a BRCA2 mutation.
This positive BRCA2 mutation status is made more interesting because the patient is part of a large family (he is 1 of 13 siblings). Although his family history is notable for multiple cancer diagnoses, our patient was the first to be tested for genetic mutations. His parents are deceased, and neither his mother nor his father was tested. Both parents lived to be in their 80s, however, and neither was diagnosed with cancer.
In this pedigree (Figure 1) and for the sake of simplicity, we excluded some siblings who were not relevant to the case. This large family has a history of cancer over generations, with at least 13 family members having been diagnosed with cancer. To date, 12 of the family members who have been tested for genetic mutations have tested positive. Three of the women in this family who tested positive but had not been diagnosed with cancer chose to undergo risk-reduction surgeries. Decisions to have prophylactic mastectomies and salpingooophorectomies are life changing and impactful to a woman and her future. The family’s pedigree is by no means complete, however, and it is likely that more family members will be affected, in this or future generations.
The BRCA1 and BRCA2 genes are widely considered the principal biomarkers for the genetic study of hereditary breast and ovarian cancers. Most people are not aware, however, that there is an association in patients affected with hereditary prostate cancer, as well.2 Studies have shown that germline mutations are seen in approximately 15% of patients with prostate cancer, with BRCA2 mutations the most commonly found, at 12% to 18%.3 Germline mutations are an independent factor in prostate cancer diagnosis at a younger age (ie, younger than 55 years of age) and can cause more aggressive disease, with a higher risk of recurrence after initial treatment. Hereditary prostate cancer has the highest heritability of any major cancer in men.4
Figure 1. Pedigree of the patient in this case report Circles = female; squares = male; diamonds = unknown sex; crosses = deceased; red = breast cancer; blue = prostate cancer; green = other cancer; + = tested positive for BRCA2; ‒ = tested negative for BRCA2; blank = has not been tested; roman numerals = family generation.
The National Comprehensive Cancer Network 2025 guidelines for prostate cancer recommend germline testing for BRCA1, BRCA2, HOXB13, and TP53.5 Criteria for testing include risk group, pathology, and family history. Testing should be undertaken in individuals with a personal history of prostate cancer at any age with5
metastatic or node-positive prostate cancer;
very high-risk or high-risk disease;
Ashkenazi Jewish ancestry; and
family history with
– 1 or more close relatives with any of the following:
· Breast cancer diagnosed before age 50 years
· Male breast cancer
· Ovarian cancer
· Pancreatic cancer
· Metastatic, node-positive, or very high-risk or high-risk prostate cancer
– 3 or more close blood relatives with prostate cancer (any grade) and/or breast cancer on the same side of the family, including the patient with prostate cancer.
Knowing a patient's genetic makeup can guide treatment and help family members, both male and female, make decisions about earlier cancer screening and prophylactic treatment options.
The results from the IMPACT study (ClinicalTrials.gov identifier NCT00261456) suggest annual PSA screening for carriers of BRCA1/BRCA2 mutations aged 40 to 69 years. Clinicians should consider prostate biopsies at a lower PSA level (3.00 µg/L [3 ng/mL]) in these individuals.6
First-degree relatives of a person with a BRCA2 mutation have a 50% chance of inheriting that mutation and therefore are at increased risk of developing associated cancers. This information, along with genetic counseling, helps the family make informed decisions about early cancer screening, starting a family, and prophylactic treatment options. Cascade testing—the process of informing family members of the genetic mutation, followed by other family members being tested—enables family members to take steps to prevent disease or find and treat disease early. The clinical significance of this testing is clear in the pedigree of our patient, who has 6 family members in generation IV who tested positive for the BRCA2 mutation.
Germline BRCA2 mutations increase the risk of high-risk prostate cancer 8.6-fold in men younger than 65 years of age, but the BRCA2 mutation puts people at higher risk of certain other cancers, as well.2 Men with BRCA2 mutations are at 6.8% higher risk of male breast cancer, for example. For male and female patients alike, there is a 7% increased risk of pancreatic cancer, and these individuals are at elevated risk of melanoma. Women with BRCA2 mutation are at an 84% increased risk of breast cancer and at a 27% increased risk of ovarian cancer.7
The number of people in this family affected by cancer is astounding. The discovery of a BRCA2 mutation in 1 family member, our patient, has changed the course of some of these family members’ lives. To date, at least 11 members have tested positive for the BRCA2 mutation (Figure 1). Four female family members chose to have serious prophylactic surgeries based on their BRCA2 status. These surgeries are meant for cancer risk reduction because women with BRCA2 mutations are at high risk of breast and other cancers. No doubt more members of this family will be tested for genetic mutations as they come of age. This case emphasizes the importance of taking a thorough family history from every patient diagnosed with prostate cancer. Early identification of hereditary cancer syndromes not only guides individual treatment decisions but, as demonstrated in this case, provides critical opportunities for cancer risk reduction in at-risk relatives. This case highlights how genetic testing in individuals with prostate cancer can transform the landscape of care for entire families across generations.
American Cancer Society. Cancer Facts & Figures 2025. American Cancer Society; 2025.
National Cancer Institute. Genetics of Prostate Cancer (PDQ®)—Health Professional Version. Updated January 3, 2025. Accessed August 17, 2025. https://www.cancer.gov/types/prostate/hp/prostate-genetics-pdq
Vietri MT, D’Elia G, Caliendo G, et al. Hereditary prostate cancer: genes related, target therapy and prevention. Int J Mol Sci. 2021;22(7):3753. doi:10.3390/ijms22073753
Congregado B, Rivero I, Osmán I, Sáez C, Medina López R. PARP inhibitors: a new horizon for patients with prostate cancer. Biomedicines. 2022;10(6):1416. doi:10.3390/biomedicines10061416
McHugh J, Bancroft E, Kote-Jarai Z, Eeles R. Prostate cancer: genetics in practice now and in the future. Hered Cancer Clin Pract. 2025;23(1):11. doi:10.1186/s13053-025-00310-1
Mikropoulos C, Eeles RA. IMPACT study: targeted prostate cancer screening. Oncologist. 2013;18(8):e28. doi:10.1634/theoncologist.2013-0221
Myriad Genetics. Gene table. Accessed March 25, 2025. https://myriad.com/gene-table
Published: October 5, 2025.
Conflict of Interest Disclosures: S. L. Denton and B. M. Gburek have no conflict of interest to disclose.
Funding/Support: There was no funding for this case report.
Author Contributions: Both authors had full access to the data and were involved in developing and approving the case study.
Data Availability Statement: The data that support the findings of this case study are available from the corresponding author upon reasonable request.
Citation: Denton SL, Gburek BM. Germline genetic testing: a case study of a patient with prostate cancer and a BRCA2 mutation and implications for the family. Rev Urol. 2025;24(3):e123-e127.
Corresponding author: Sherry Denton, NP, MSN, MHA, Arizona Urology Scpecialists, 17300 N Perimeter Dr, No. 220, Scottsdale, AZ 85260 (sherry.denton@arizonauro.com)
