At the present time, and while there is no specific evidence related to ATM (c.7271T>G) pathogenic variant carriers, these guidelines are based on those that apply to the management of breast cancer risk in female BRCA2 pathogenic variant carriers.
Bilateral risk reducing mastectomy reduces breast cancer risk by at least 90%rr (depending on the operation performed). Statistically significant survival benefit associated with bilateral risk-reducing mastectomy compared with surveillance is yet to be demonstrated.
MRI+MMG is the preferred screening technique due to its high sensitivity. MRI detects tumours which are smaller and more likely to be node-negative than mammography. MRI has a recall rate (requiring further investigation and/or biopsy) of 15% for initial screening, which decreases with subsequent rounds of screening to <10%.
There is no evidence to date that early detection of breast cancer is associated with a better prognosis and survival in ATM pathogenic variant carriers. Despite this lack of evidence, surveillance is strongly recommended for women who decide not to have risk reducing surgery.
Selective oestrogen receptor modulators (SERM), such as tamoxifen, have been shown to reduce the risk of oestrogen receptor-positive breast cancer in women identified to be at increased risk. Pathogenic variants in ATM are associated with an increased risk of ER positive breast cancer.rr In a meta-analysis, SERM reduced breast cancer incidence by 38% (HR 0.62 with 95% CI, 0.56–0.69) compared with placebo in women at increased risk with the risk reduction extending beyond the treatment period.r
To date studies have not included enough ATM pathogenic variant carriers to determine if it is effective for primary prevention in this population.
In view of the potential side effects, risk-reducing medications should be discussed with an experienced medical professional to determine the relevant risks and benefits in an individual pathogenic variant carrier. See COSA – Medications to lower the risk of breast cancer: clinician guide.
There is currently no effective surveillance that detects early pancreatic cancer. Refer to Australian Pancreatic Cancer Genome Initiative website for up-to-date screening trials.
There is currently no evidence of efficacy of prostate cancer screening in ATM pathogenic variant carriers.
There are mixed reports regarding the effects of radiation on heterozygous ATM pathogenic variant carriers. However, radiation therapy at conventional doses is not contraindicated in ATM pathogenic variant heterozygous carriers and should be considered and delivered if required clinically.