Dr Zakalik on the Role of Genetic Testing to Guide Breast Cancer Treatment

Dana Zakalik, MD, professor, corporate director, Nancy and James Grosfeld Cancer Genetics Center, William Beaumont Medical School, Oakland University, Beaumont Health, discusses the critical role of genetic testing in managing breast cancer and assessing risk in high-risk individuals.

Genetic testing has shown efficacy in identifying hereditary cancer syndromes, with approximately 10% of breast cancer cases linked to inherited mutations, Zakalik explains. This includes high-penetrance mutations in genes such as BRCA1 and BRCA2, which significantly elevate breast cancer risk, she says. Additionally, other high-penetrance genes like TP53 and CDH1 are associated with conditions such as Li-Fraumeni syndrome and hereditary diffuse gastric cancer, respectively, and contribute to an increased predisposition to breast and other cancers, Zakalik notes.

The recognition of moderate-penetrance mutations, including CHEK2 and ATM, further highlights the importance of comprehensive genetic testing, she adds, emphasizing that understanding a patient’s genetic profile can inform tailored surveillance and risk-reduction strategies.

One of the most impactful advances in breast cancer management has been the use of targeted therapies for genetically predisposed patients, Zakalik continues. PARP inhibitors, which are particularly effective in BRCA1- and BRCA2-associated breast cancers, have shown promising results in both early-stage and advanced disease settings, she explains.

Ongoing research is evaluating the efficacy of PARP inhibitors in other genetic contexts, including PALB2-associated breast cancer, with early data suggesting potential benefit, she adds. These targeted therapies underscore the value of genetic insights in guiding treatment, Zakalik states, noting that tailored approaches can optimize outcomes for genetically high-risk patients.

Genetic testing not only aids in identifying individuals who may benefit from specific therapies but also facilitates preventive strategies for those with elevated risk, Zakalik elaborates. For instance, the identification of a high-risk gene mutation can lead to more frequent screenings, risk-reducing surgeries, or other preventive interventions, which may help lower the likelihood of cancer development. Furthermore, genetic testing supports surveillance for secondary cancers in patients with known mutations, such as contralateral breast cancer, ensuring proactive management across the care continuum, she notes.

Zakalik concludes that as genetic testing continues to evolve, its role in breast cancer management will likely expand, providing a powerful tool to personalize care, enhance early detection, and optimize therapeutic choices for both patients with established disease and those at high hereditary risk.