Methods for Assessing Familial Breast Cancer Risk Depend on Study Purpose

A study, published in Cancer, found that the choice of method for assessing familial breast cancer risk should depend on the purpose of the study, with the accumulative method being the most convenient in practice and the least favored for risk prediction, the static method being suitable for etiological impact and risk attribution studies, and the dynamic method being better suited for risk stratification studies. 

Given this finding, the researchers suggested that studies aiming at risk stratification and the identification of high-risk women for early preventive interventions, such as personalized cancer prevention and risk-adapted screening strategies, should consider the timing of breast cancer events in family members, especially if they have early-onset or premenopausal breast cancer. 

“Because each of these methods required a different set of variables in the data collection phase, the results of the current study can help clinicians and investigators know which information should be collected from study patients, on the basis of which a valid risk prediction tool can be developed,” the authors wrote.

Using a nationwide cohort study of 5,099,172 women, the researchers evaluated the effect of incorporating the timing of cancer diagnosis events into the assessment of familial risks of breast cancer in first-degree and second-degree relatives. Family history was assessed using 3 approaches, including as a static variable (ever having a relative with breast cancer), as accumulative history, and as a dynamic variable (time-dependent variable). 

For women aged <50 years, the familial risk was found to be mostly higher when family history was evaluated as a dynamic variable compared with using a static or accumulative family history. For example, the cumulative risk of receiving a breast cancer diagnosis until age 50 years for women with a history of breast cancer in 1 first-degree relative was 2.6% (95% CI, 2.5-2.7) using the static method, 2.4% (95% CI, 2.3-2.4) using the accumulative method, and 3.1% (95% CI, 3.0-3.2) using the dynamic method. 

Moreover, relative risk in women aged <50 years with a breast cancer diagnosis in a sister was 1.40-fold (95% CI, 1.31-fold to 1.48-fold) using the static method, 1.66-fold (95% CI, 1.57-fold to 1.76-fold) using the accumulative method, and 2.28-fold (95% CI, 2.07-fold to 2.51-fold) using the dynamic method. 

“A woman’s risk of breast cancer may vary over time due to aging and lifestyle factors. Of course, the inherited risk of breast cancer due to a genetic predisposition does not change by every cancer diagnosis in the family,” the authors wrote. “However, this information can be used for better breast cancer risk predictions in real life without genetic testing or after a negative genetic test.”

According to the study, approximately 15% of all breast cancers are diagnosed among women who have a family history of the disease. Further, women with a family history of breast cancer are at a 2 to 4 times increased risk of breast cancer depending on the number of affected relatives the age at which the relatives were diagnosed. 

Reference:

Mukama T, Kharazmi E, Sundquist K, Sundquist J, Brenner H, Fallah M. Familial Risk of Breast Cancer by Dynamic, Accumulative, and Static Definitions of Family History. Cancer. doi:10.1002/cncr.32815.