Understanding Genetic and Genomic Testing in Breast Cancer

Genetic and genomic testing are key in breast cancer risk and treatment, with Dr. Mark Robson explaining their evolving roles at the Miami Breast Cancer Summit.

Genetic and genomic testing play a critical role in understanding breast cancer risk and treatment decisions, according to Dr. Mark Robson, Chief of the Breast Medicine Service and Clinical Geneticist at Memorial Sloan Kettering Cancer Center in New York. During a presentation at the CURE Educated Patient Breast Cancer Summit held during the annual Miami Breast Cancer Conference, he clarified the differences and evolving applications of these tests.

"Genetic testing examines inherited DNA to identify mutations associated with an increased risk of breast cancer, while genomic testing focuses on the DNA of the cancer itself, identifying changes that could influence treatment options," Robson explained.

While the terms are often used interchangeably, he emphasized that genetic testing looks at germline DNA (inherited), whereas genomic testing analyzes somatic DNA (mutations acquired in the tumor).

Implications for Patients and Treatment

Genetic testing can guide personalized treatment decisions. Robson stated, "For example, patients with BRCA mutations may benefit from preventive surgeries, enhanced screening protocols or targeted treatments." Moderate-penetrance gene mutations, such as those in CHEK2 and ATM, also provide valuable risk insights, though their impact is less pronounced than BRCA mutations.

As genetic testing becomes more accessible, its role in patient care continues to expand. Organizations now recommend broader testing criteria, ensuring that more patients who may benefit from genetic insights receive appropriate screening and treatment. The integration of genetic and genomic data is shaping the future of precision medicine in breast cancer, offering more tailored and effective care strategies.

Robson underscored the importance of informed discussions with healthcare providers when considering genetic testing. "While the landscape of genetic research continues to evolve, these advancements are improving early detection, risk assessment and personalized treatment approaches for breast cancer patients and survivors," he said.

Furthermore, Robinson explained that universal testing for actionable genes (BRCA1/2 with our without PALB2) is of low yield in women over 60 who do not meet NCCN guidelines. Most testing in the United States uses multigene panels, with universal testing identifying non-BRCA pathogenic variants in women who do not meet NCCN guidelines. However, most non-BRCA pathogenic variants lack clear treatment implications, and family implications are complicated by an incomplete understanding of risks.

If expanded multigene testing becomes the norm, specialist genetic follow-up, such as cancer genetic counseling, will be crucial for guiding those found to carry pathogenic variants or variants of uncertain significance, especially if the panel includes genes of uncertain clinical significance.

Beyond BRCA-Mutated Genes

While BRCA1 and BRCA2 remain central to hereditary breast cancer risk, additional genes such as TP53, PALB2 and ATM have been identified as risk factors. These genes contribute to a patient’s overall likelihood of developing breast cancer and influence screening and prevention strategies.

Polygenic risk scores, which assess multiple genetic variations contributing to breast cancer risk, are also emerging. "These scores aggregate common genetic variations to estimate a person’s predisposition, providing a more nuanced understanding of inherited cancer risk," Robson explained.

The Evolution of Genetic Testing

The study of hereditary cancer dates back centuries, with early physicians recognizing cancer patterns within families. In the late 20th Century, researchers identified BRCA1 and BRCA2, genes associated with hereditary breast and ovarian cancer. Initially, testing was considered a personal choice rather than a clinical necessity, requiring extensive genetic counseling to address concerns about discrimination and emotional impact.

Since then, research has debunked several early assumptions. "BRCA mutations, once thought to be rare, are more common than previously believed. Moreover, carrying a mutation does not guarantee cancer development," Robson noted.

Scientists also discovered that these mutations have significant treatment implications, leading to targeted therapies such as PARP inhibitors for BRCA-mutant cancers.

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