Most women with a CHEK2 gene truncating pathogenic variant will be at moderately increased risk of breast cancer.r For women with a CHEK2 gene truncating pathogenic variant and family history of breast cancer, risk should be formally assessed using a validated risk prediction tool such as CanRisk.r High-risk management only applies when the estimated 5-year incidence of breast cancer in a woman with a CHEK2 gene truncating pathogenic variant exceeds the highest risk experienced by women in the general population (currently estimated to be 2.2% in the USA).r
Risk-reducing mastectomy is not recommended for women at moderate risk of breast cancer. Consider risk-reducing mastectomy for women assessed as high risk of breast cancer. Bilateral risk-reducing mastectomy reduces cancer risk by at least 90% (depending on the operation performed) in BRCA1 or BRCA2 pathogenic variant carriers.rr
Breast screening is generally recommended when the 5-year relative risk exceeds the 5-year relative risk for a woman at age 50 years, when population screening commences.r This occurs at age 40 years for women with CHEK2 gene truncating pathogenic variants and no strong family history.r Annual mammography is both cost effective and clinically effective in reducing breast cancer predicted mortality.
Screening plans should be individualised for CHEK2 carrier women where a validated risk prediction tool (e.g. CanRisk) places them at high risk, and should include annual MRI or mammogram.
Selective oestrogen receptor modulators (SERM), such as tamoxifen and raloxifene, have been shown to reduce the risk of oestrogen receptor-positive breast cancer in women identified to be at increased risk.r To date studies have not included enough CHEK2 gene 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.
Increased risk of other cancer types has been suggested (including cancer of lung, colon, papillary thyroid, prostate, and testicular germ cell tumours) but more research is required as data are conflicting. Screening and advice should be based on the family history of these cancers.r