A panel of worldwide experts has published recommendations for the management of individuals with an ATM mutation, which increases the risk for breast, pancreatic and prostate cancers.
Sponsored by the American College of Medical Genetics and Genomics, this clinical practice resource was published recently in Genetics in Medicine. Although researchers established decades ago that ataxia-telangiectasia mutated (ATM) heterozygotes are at a moderately increased risk for cancer, there remains a need to provide clear guidance for clinicians on surveillance and management. The resource guide was developed by an international group of experts, based on synthesis of existing peer-reviewed publications and expert opinions.
“It is increasingly becoming important to provide personalized risk estimates and consider risk on a continuum rather than binary. This is especially important for moderate penetrance genes like ATM, where other hormonal and lifestyle, breast density and family history may substantially upgrade or downgrade risks, with possible management considerations,” said the lead author, Tuya Pal, MD, Ingram Professor of Cancer Research, professor of Medicine and associate director for Cancer Health Disparities at Vanderbilt-Ingram Cancer Center.
The clinical surveillance recommendations for specific cancers among ATM heterozygotes include:
Among women
- Breast cancer. Annual breast magnetic resonance imaging (MRI) starting at ages 30 to 35 years and annual mammography starting at age 40 is recommended, based on data from a modeling analysis of ATM heterozygotes which predicted a significant reduction in breast cancer mortality using this regimen. The data on ATM-related breast cancer do not support routine consideration of risk-reducing mastectomy. However, when a female with the mutations has been diagnosed with breast cancer, shared decision making about bilateral mastectomy should be made based on individual estimated risk based on the patient’s age, tumor size, stage, grade, receptor status and family history.
- Ovarian cancer. Generally, the risk threshold to consider salpingo-oophorectomy is not met; however, consideration of family history of ovarian cancer and shared decision making remain important. Screening is not advised since there is no established method to detect ovarian cancer early.
Among men
- Prostate cancer. Prostate-specific antigen testing should begin at age 40 on an annual basis. A digital rectal exam may be useful to guide interpretation of PSA findings.
Among both women and men
- Pancreatic cancer. Surveillance through annual endoscopic ultrasound or MRI cholangiopancreatography may be considered, with great variation in recommendations across countries. Surveillance should be done at medical centers with appropriate expertise. The panel of experts noted that more research is needed to better ascertain clinical guidance and wrote this surveillance should ideally be part of a clinical trial.
The experts also highlighted the need for additional prospective data across diverse populations to refine risk estimates, the importance of providing patients with personalized risk estimates, including 5- and 10-year risks and remaining lifetime risk of breast cancer (i.e., residual risk estimation) based on tools such as CanRisk, as well as the importance of genetic counseling, discussion of biallelic inheritance and partner testing. They also noted that despite FDA approval of PARP inhibitors among men with ATM-associated metastatic castrate-resistant prostate cancer, there is currently a lack of data to demonstrate clinical benefit. They stated that there is no evidence of clinical benefit for targeted therapies with ATM-associated cancers. Consequently, there remain current gaps in data needed to evaluate both established and novel cancer treatments among ATM heterozygotes.
