Universal hereditary cancer genetic testing: Expanding possibilities for cancer care

Evidence suggests genetic testing guidelines may miss a subset of patients with hereditary cancer

Over the years, medical research has transformed the way we approach cancer care. We’ve seen incredible progress in understanding and treating cancer, including the benefits of hereditary cancer genetic testing to inform prevention and early detection strategies.

Although hereditary cancer genetic testing is increasingly available, a review article in the Journal of Clinical Oncology Precision Oncology (JCO-PO) titled “Universal Germline Genetic Testing for Hereditary Cancer Syndromes in Patients with Solid Tumor Cancer” noted that genetic testing guidelines miss many patients with genetic variants that are known to cause cancer.¹

In this post, we will explore the article’s key findings and highlight the potential benefits of universal hereditary cancer genetic testing (called “germline genetic testing”). Additionally, we will discuss testing implications for patients with solid tumor cancers and how hereditary cancer genetic testing can impact their care and help inform if family members may be at risk.

What is universal hereditary cancer genetic testing, and why is it needed? 

Universal hereditary cancer testing is a comprehensive approach in which all individuals diagnosed with cancer are offered hereditary cancer genetic testing to determine whether they have inherited DNA changes associated with hereditary cancer syndromes. Traditional hereditary cancer genetic testing approaches often target specific genes associated with a particular type of cancer and limit testing to patients by age of diagnosis, stage of cancer, or family history. In contrast, universal hereditary cancer genetic testing aims to capture more at-risk patients by offering testing to all patients with cancer.

Inherited genetic variants can significantly increase an individual’s risk of developing cancer over their lifetime. Universal hereditary cancer genetic testing has the potential to identify underlying hereditary cancer syndromes that may otherwise go unrecognized. Early identification of these variants can inform personalized treatment decisions and enable targeted surveillance and risk-reduction strategies for patients and their at-risk family members.

Helping identify missed opportunities 

Traditional cancer testing guidelines have been proven effective at identifying individuals with the highest chance of having a hereditary cancer syndrome. However, current guidelines can miss patients with clinically actionable inherited genetic variants who do not meet existing testing criteria.¹

Historically, guidelines recommended hereditary cancer genetic testing for patients with solid tumor cancers who meet specific criteria. 

These typically include: 

• Young age at cancer diagnosis
• Strong family history of cancer
• Multiple primary cancers
• Specific tumor characteristics that suggest a potential genetic basis 

Relying solely on guideline-based testing may overlook patients with disease-causing genetic variants, leaving them, and family members may also be affected, unaware of their genetic predisposition to cancer.¹ These genetic changes, known as pathogenic variants (PVs), play a central role in hereditary cancer syndromes and can meaningfully influence treatment decisions and prevention strategies.

The power of genetic testing 

In one large multi-institutional study, a multi-gene panel was used to perform genetic testing on all patients with cancer, regardless of existing guideline criteria. 2 Findings revealed that 1 in 8 patients with a solid tumor had a germline PV identified, and 48% of these patients would have been missed by testing guidelines at the time of the study.²

Additionally, the study showed that 1 in 4 patients with high-penetrance variants, meaning those associated with a higher likelihood of developing cancer, had changes to their cancer management recommendations.²

By identifying PVs, healthcare providers gain valuable insights into an individual’s cancer risks and can tailor care plans accordingly. For example, knowledge of hereditary cancer syndromes may prompt increased surveillance, risk-reducing surgeries, or targeted therapies.

Hereditary cancer genetic testing can also provide crucial information for patients and their families, allowing them to make informed decisions about their health, including lifestyle modifications.

Testing, therefore, enables patients and their providers to take proactive steps to help reduce risks, improve health outcomes, and enhance patient well-being.

The importance of family variant testing 

While hereditary cancer genetic testing for patients is essential, extending testing to their blood relatives is equally crucial and has an important role in identifying individuals before a potential cancer diagnosis. Family variant testing involves testing family members to determine whether they carry the same genetic variant as their relative who has undergone hereditary cancer genetic testing. If a family member is found to carry the same genetic variant, their own care and management may be impacted.¹ 

Unfortunately, the study noted a low uptake of family variant testing; only 18% of patients with PVs had relatives undergo testing, despite offering it at no additional cost. 2 Healthcare providers can encourage wider adoption of family variant testing to provide comprehensive risk assessment for individuals and their families and inform appropriate preventive measures.

Evolving guidelines and what’s next? 

The publication of this article and the universal hereditary cancer testing studies it highlights have already influenced changes in genetic testing guidelines. ² Medical organizations increasingly recognize the importance of identifying PVs early and are working on updating their recommendations to include broader testing.

By incorporating the studies’ findings, updated guidelines would aim to capture a broader range of patients who may benefit from hereditary cancer genetic testing. This response would reflect a commitment to improving patient care through evidence-based practices and staying at the forefront of medical advancements.

Testing all patients with solid tumor cancers using hereditary cancer multi-gene panels can transform patient care by enabling more targeted treatment, earlier detection, and proactive risk management for both patients and their families.² 

The publication further demonstrates the impact of universal hereditary cancer testing across multiple cancer types.² Expanding the use of this important tool will help providers and patients unlock valuable genetic information that can guide more personalized cancer care decisions.