In a study reported in the Journal of Clinical Oncology, Veenstra et al found that pathogenic variants (PVs) in ATM, CHEK2, or PALB2 were not associated with significant differences in mortality from breast, colorectal, or pancreatic cancer compared with the absence of such PVs.
Study Details
The study involved data from patients diagnosed between 2013 and 2019 in SEER registries in California and Georgia who were linked to germline genetic testing results. Multivariable models of cancer mortality were fit—for each cancer, the reference group was the average hazard across all genetically tested patients with that particular diagnosis. Random effects models were also used as a regularization approach to reduce overfitting.
Key Findings
The analysis included a total of 70,272 patients with breast cancer who had undergone testing (48,473 hormone receptor–positive, HER2-negative; 9,957 HER2-positive; 11,842 triple-negative), 5,822 with colorectal cancer, and 1,861 with pancreatic cancer. Mean follow-up was 3.9 years.
Patients with ATM, CHEK2, or PALB2 PVs had no significant differences in breast, colorectal, or pancreatic cancer mortality vs those without these PVs. Patients with ATM PVs in triple-negative breast cancer had higher mortality in the fixed effects models (hazard ratio [HR] = 3.7, 95% confidence interval [CI] = 1.8–7.8) but not in random effects models (HR = 1.2, 95% CI = 0.8–1.6); as related by the investigators, the fixed effects estimate was based on a small number of observations and likely reflected overfitting.
Patients with BRCA1/2 PVs had lower triple-negative breast cancer mortality in both models (fixed HR = 0.6, 95% CI = 0.5–0.9; random HR = 0.7, 95% CI = 0.6–0.8). Patients with Lynch syndrome gene PVs had lower colorectal cancer mortality in both models (fixed HR = 0.5, 95% CI = 0.4–0.8; random HR = 0.7, 95% CI = 0.5–0.9).
The investigators concluded: “Patients with ATM, CHEK2, or PALB2 PVs had similar breast, colorectal, and pancreatic cancer mortality to the average genetically tested patient with their cancer type.”
Allison W. Kurian, MD, of Stanford University School of Medicine, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute and others. For full disclosures of the study authors, visit ascopubs.org.
