
Invitae Study Furthers Argument Supporting Hereditary Cancer Testing for all Breast Cancer Patients
Invitae, a leading genetic testing company, has released the findings of a collaborative study on the benefits of universal hereditary cancer genetic testing in all breast cancer patients within a rural population. Conducted in partnership with The Outer Banks Hospital (TOBH) in North Carolina from 2019 to 2022, this study analyzed the implementation of universal hereditary cancer genetic testing, following the guidelines established by the American Society of Breast Surgeons (ASBrS) in 2019. The results underscore the clinical advantages of universal hereditary cancer genetic testing, and could provide further support for guideline bodies, most notably the National Comprehensive Cancer Network (NCCN), to update guidelines supporting broader testing.
The study offered hereditary cancer genetic testing to all patients diagnosed with breast cancer, with 91.4% choosing to undergo testing. These patients received results that could inform their healthcare care continuum. Notably, 52.4% of patients met the criteria outlined by the NCCN, while 45.8% did not meet these criteria. NCCN guidelines assess family and personal history of cancer to determine if someone is a good candidate for testing. The National Comprehensive Cancer Network (NCCN) recommends genetic testing for breast cancer patients under 50, those with triple-negative breast cancer under 60, males with breast cancer, individuals with bilateral or second primary breast cancer, or those with a history of ovarian cancer. Additional family history criteria include a relative with early-onset breast cancer, ovarian cancer, or more than two relatives with certain cancers. These guidelines, though, are complex and often result in under-identification of potential candidates for genetic testing, with just one in five eligible patients getting referred. Efforts to simplify and expand genetic testing guidelines are emerging globally to ensure more mutation carriers are identified.
Among the patients who underwent testing, 13% were found to have a pathogenic (disease-causing) germline variant (PGV) in one of 15 genes. Significantly, the frequency of PGVs did not differ between patients who met the NCCN criteria and those who did not. However, the in-criteria patients had a larger proportion of high-risk variants, consistent with previous findings. This study reinforces the recent recommendation from the ASBrS for universal testing for all breast cancer patients as the standard of care, challenging the current restrictions set by NCCN criteria. Other studies have come to similar conclusions supporting broader testing for women with breast cancer.
Identifying genetic mutation carriers among breast cancer patients holds significance for several reasons. One key factor is that specific systemic therapies can be more effective in this population. For instance, poly (ADP-ribose) polymerase inhibitors have shown particular effectiveness in metastatic breast tumors with DNA-repair defects like those found in BRCA1/2 mutation carriers. Similarly, cisplatin, a DNA replication-disrupting agent, has demonstrated activity in BRCA1/2-mutated patients due to their impaired DNA repair mechanisms. Consequently, ongoing clinical trials are exploring patient-specific treatment regimens tailored to BRCA mutation carriers. As cancer treatment evolves towards personalized or precision medicine, the identification of genetic mutation carriers becomes increasingly crucial. Another reason for genetic testing in breast cancer patients is the heightened risk of second primary breast cancer, both in the same and opposite breast, for germline genetic mutation carriers with remaining breast tissue. Therefore, enhanced post-treatment surveillance, involving annual mammograms/tomosynthesis and magnetic resonance imaging (MRI), is recommended for these individuals. In contrast, women at average risk without genetic mutations typically require only an annual bilateral mammogram.
Dr. Robert Nussbaum, Chief Medical Officer at Invitae, emphasized the importance of this study, stating, “This study demonstrates the feasibility of implementing universal hereditary cancer genetic testing for patients with breast cancer in rural community practices. The results reiterate in a real-world setting that genetic testing changes management and treatment plans for these patients, improving patient care.”