Dr Maxwell on Cancer Risk for Males Carrying Germline BRCA Mutations

Kara N. Maxwell, MD, PhD, assistant professor of medicine (hematology-oncology), Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, discusses the risk of developing cancer for males carrying germline 

In research published in JAMA Oncology, Maxwell and colleagues found that despite males being equally as likely to harbor germline 

 mutations, a lower proportion of males undergo cancer genetic testing compared with the female population.

Maxwell begins by highlighting the increased risk of various cancers for males who harbor BRCA mutations. She explains that the risk of breast cancer over the course of a lifetime for a male carrying a 

 mutation is approximately 5%, and she notes that this represents a significant increase compared with the general male population, where the risk is approximately 0.1%. Although the 5% risk for males carrying germline 

 mutations is lower than the 60% to 80% risk of developing breast cancer for female carries, this elevated risk in males underscores the need for awareness and potential screening strategies, Maxwell says.

 mutations face increased risks for pancreatic and prostate cancers. The risk for these cancers is higher for those carrying 

 mutations; however, Maxwell says that the increased risk for carries of either mutation is clinically significant. She notes that the risk of pancreatic cancer in those with 

 mutations is estimated to be between 3% and 5%, affecting both male and female patients equally. This highlights the necessity for vigilance and potential early detection strategies in male carriers, she says.

 mutations, the highest cancer risk is prostate cancer, with a lifetime risk potentially reaching up to 50%, Maxwell continues. This contrasts with the somewhat lower prostate cancer risk observed in 

 carriers, she adds. The wide range in risk estimates for prostate cancer in males harboring 

 mutations reflects the variability and the current limitations in data regarding specific cancer risks in this population, Maxwell explains.

Additionally, Maxwell highlights the challenges in understanding the full spectrum of cancer risks for male carriers of 

 mutations due to the limited data currently available. She underscores the importance of ongoing research to better quantify these risks and inform clinical management.

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Kara N. Maxwell, MD, PhD, discusses the risk of cancer for males carrying BRCA mutations.



Dr Maxwell on Real-World Germline Variant Rates in Prostate Cancer

Kara N. Maxwell, MD, PhD, assistant professor, medicine (hematology-oncology), Department of Medicine, Perelman School of Medicine, University of Pennsylvania, discusses 

key takeaways from a real-world investigation of germline mutation rates

 in patients with metastatic prostate cancer.

A recent study focusing on patients with metastatic prostate cancer has revealed that the real-world prevalence of DNA repair pathogenic germline variants is lower than the rate reported in prior literature. The patient cohort in this analysis included those who underwent genetic testing either through a point-of-care model at the Basser Center of Penn Medicine or through cancer genetics practices at the VA Philadelphia Health Care and VA Greater Los Angeles Health Care.

The increasing number of patients with metastatic prostate cancer, particularly in the oligometastatic setting, means that radiation oncologists and urologists are encountering more of these cases, Maxwell explains. Therefore, it is crucial for healthcare providers managing patients with metastatic prostate cancer to proactively discuss the option of genetic testing with their patients, she reports.

Maxwell emphasizes that although a patient may not present with a genetic alteration, understanding how to identify and treat these alterations can significantly inform the selection of future treatment options, such as PARP inhibitors. Moreover, the implications of genetic findings extend beyond individual patients, potentially guiding family health decisions and screening practices, she states.

Implementing genetic testing in clinical practice should be a priority, Maxwell continues, adding thatthis can be done efficiently and can yield valuable information for both treatment planning and familial risk assessment. The support for this research from the Basser Center for BRCA at the University of Pennsylvania underscores its importance. As the director of the Men & BRCA Program, Maxwell concludes that she is enthusiastic about how this research can enhance genetic testing rates and improve knowledge of disease among all men with cancer.

Kara N. Maxwell, MD, PhD, discusses key takeaways from a real-world investigation of germline mutation rates in patients with metastatic prostate cancer.

Dr Maxwell on the Accessibility of Genetic Testing in Metastatic Prostate Cancer

Kara N. Maxwell, MD, PhD, assistant professor, medicine (hematology-oncology), Department of Medicine, Perelman School of Medicine, University of Pennsylvania, 

the accessibility of genetic testing in the community setting

 for patients with metastatic prostate cancer.

In a study of patients with metastatic prostate cancer, researchers found that the real-world rates of DNA repair pathogenic germline variants were lower than previously reported. Furthermore, these rates did not show significant differences according to racial characteristics. The analysis focused on patients who underwent genetic testing through a point-of-care model at the Basser Center of Penn Medicine or through cancer genetics practices at either the VA Philadelphia Health Care or VA Greater Los Angeles Health Care.

To improve the implementation and accessibility of genetic testing, especially in community settings, several strategies can be adopted, Maxwell begins. First, there is a general awareness about genetic testing, indicating progress in this area, according to Maxwell. However, the VA setting has shown that individual nurses often bear a significant workload to facilitate genetic testing for patients. Designating a specific person whose sole responsibility is to assist patients in navigating genetic testing can greatly enhance testing efficiency and effectiveness within an oncology practice, she says. This approach is becoming more feasible as the costs of genetic testing have decreased over time, Maxwell notes.

Additionally, the Basser Center has developed a video for pre-test genetic counseling, and a similar resource was created for the VA in collaboration with the Prostate Cancer Foundation, Maxwell continues. These educational tools are crucial, as they help prepare patients for the testing process, Maxwell says. Just as prostate-specific antigen scans are routinely performed when a man is diagnosed with localized prostate cancer and bone scans are conducted for metastatic prostate cancer, genetic testing should also become a standard part of the diagnostic process, she expands.

By integrating genetic testing into the routine diagnostic workflow, health care providers can ensure patients receive comprehensive care that includes an assessment of their genetic risk factors, Maxwell concludes.

Kara N. Maxwell, MD, PhD, discusses the accessibility of genetic testing in the community setting for patients with metastatic prostate cancer.

Kara N. Maxwell, MD, PhD, discusses strategies to optimize the utility of genetic testing to better inform decision-making in prostate cancer treatment.

Dr Maxwell on Strategies to Optimize Genetic Testing in Metastatic Prostate Cancer

Kara N. Maxwell, MD, PhD, assistant professor of medicine (hematology-oncology), Department of Medicine, Perelman School of Medicine, University of Pennsylvania, discusses how findings from a study evaluating the real-world rates of pathogenic germline variants in patients with metastatic prostate cancer may optimize the use of genetic testing to inform treatment decision-making.

This prospective study analyzed pathogenic germline variants in 3 cohorts of patients with metastatic prostate cancer. Patients had either received genetic testing through a point-of-care model at the Basser Center of Penn Medicine, or through cancer genetics practice at the VA Philadelphia health care or VA Greater Los Angeles health care.

 demonstrate consistent rates of pathogenic germline variants associated with prostate cancer across diverse patient populations, irrespective of racial differences. Notable discrepancies were observed in variants of uncertain significance, correlating with the racial diversity of each cohort. Moreover, the incidence of DNA repair pathologic germline variants in this study was lower than what prior research had suggested.

Overall, the study underscores the importance of genetic testing in metastatic prostate cancer, particularly given the lower rates of high-yield genetic findings in this patient population, Maxwell emphasizes. Despite the clinical relevance of genetic testing, rates remain low in men with metastatic prostate, pancreatic, and male breast cancers, indicating a critical need to optimize testing strategies, Maxwell states. In response, efforts are underway to implement streamlined genetic testing approaches, such as point-of-care models seen at institutions like the Basser Center of Penn Medicine or nurse-embedded models within the VA system, she details. These innovative strategies aim to increase testing accessibility and efficiency, ensuring that all patients with metastatic prostate cancer have access to genetic testing that can inform personalized treatment decisions, Maxwell explains.

Moving forward, future trials and initiatives within the Basser Center at Penn Medicine are focused on advancing genetic testing approaches to enhance uptake and utilization among metastatic prostate cancer patients and their healthcare providers, Maxwell reports. By promoting wider adoption of genetic testing in clinical practice, researchers aim to improve patient outcomes and advance precision medicine in the management of metastatic prostate cancer, she concludes.

Dr Maxwell on Strategies to Optimize Genetic Testing in Metastatic Prostate Cancer  

Dr Maxwell on a Study of Genetic Testing in Metastatic Prostate Cancer

Kara N. Maxwell, MD, PhD, assistant professor of medicine (hematology-oncology), Department of Medicine, Perelman School of Medicine, University of Pennsylvania, discusses a study of genetic testing results for patients with metastatic prostate cancer.

The study included cohorts of patients with metastatic prostate cancer in a point-of-care model at Basser Center of Penn Medicine, as well as patients from a cancer genetics practice at the Corporal Michael Crescenz VA Medical Center in Philadelphia. Maxwell and colleagues sought to evaluate the rates of pathogenic germline variants in the context of broader, more diverse patient populations.

Various institutions have implemented different models to streamline genetic testing processes, Maxwell says. Notably, some have integrated nurses into oncology programs to facilitate this testing.

Findings presented at the 2024 AACR Annual Meeting showed that despite differences in the racial breakdowns of each cohort of patients, the prevalence of pathogenic germline variants associated with prostate cancer remained consistent across the cohorts, Maxwell explains. This finding underscores the uniformity of mutation rates across diverse racial groups, challenging previous assumptions regarding racial disparities in genetic mutation prevalence, she continues.

However, difference in rates of variants of uncertain significance were observed, correlating with the racial diversity of each cohort. This suggests that although pathogenic mutation rates appeared to remain consistent, the significance and interpretation of genetic variants may differ among populations, Maxwell explains. Nonetheless, the study underscores the importance of genetic testing for all patients with metastatic prostate cancer and its potential to inform personalized treatment approaches.

By analyzing a cohort of 1000 individuals with metastatic prostate cancer, the study provides a comprehensive population-level perspective on genetic testing, Maxwell says. These data can help enrich the understanding of mutation prevalence beyond traditionally high-risk populations, offering insights into broader demographic representations, she concludes.

Kara Maxwell, MD, PhD discusses a study of genetic testing results in metastatic prostate cancer. 

Kara N. Maxwell, MD, PhD

Articles

Dr Maxwell on Cancer Risk for Males Carrying Germline BRCA Mutations

Dr Maxwell on Real-World Germline Variant Rates in Prostate Cancer

Dr Maxwell on the Accessibility of Genetic Testing in Metastatic Prostate Cancer

Dr Maxwell on Strategies to Optimize Genetic Testing in Metastatic Prostate Cancer

Dr Maxwell on a Study of Genetic Testing in Metastatic Prostate Cancer