Image by Andre E.X. Brown
Genetic testing could help identify breast cancer patients with a high risk of developing venous thromboembolism (VTE), according to a study published in Clinical Cancer Research.
The study showed that patients who received chemotherapy, had a higher genetic susceptibility for VTE according to a polygenic risk score (PRS), or had both of these risk factors were more likely to develop VTE than patients without these risk factors.
In addition, researchers found the impact of genetic susceptibility was most pronounced in older patients.
“The risk for [VTE] is increased in cancer patients, particularly in those receiving chemotherapy,” said study author Judith S. Brand, PhD, of Karolinska Institutet in Stockholm, Sweden.
“As one of the most common cancers, breast cancer accounts for a large number of cancer-associated VTE cases.”
Dr Brand and her colleagues sought to identify the individual and joint effects of chemotherapy and genetic susceptibility on VTE risk. They studied 4261 women in the Stockholm region diagnosed with primary invasive breast cancer between 2001 and 2008, and followed until 2012.
Risks were stratified based on chemotherapy status and genetic susceptibility, as determined by a PRS based on 9 established VTE loci, with the top 5% classified as having high genetic susceptibility.
The median follow-up was 7.6 years, and 276 patients experienced a VTE during that time.
The researchers found that receiving chemotherapy and having high genetic susceptibility independently increased the risk of VTE. The hazard ratio was 1.98 for patients receiving chemotherapy and 1.90 for patients in the highest 5% of the PRS.
The 1-year cumulative incidence of VTE was 9.5% among patients who both received chemotherapy and had high genetic susceptibility, compared with 1.3% in the patients who did not have either of these risk factors (P<0.001).
The researchers also found that patient age played a role in VTE risk. The team said the risk-increasing effect of the PRS was stronger in older patients (P interaction = 0.04).
In patients age 60 or older who underwent chemotherapy and had a high genetic susceptibility, the 1-year cumulative incidence of VTE was 25%.
“Breast cancer patients receiving chemotherapy are not routinely being examined for VTE prevention in today’s clinical practice,” Dr Brand said. “Our study demonstrates that information on genetic susceptibility can be used to identify patients at high risk of developing VTE.”
“Combined with other clinical risk factors and biomarkers, these findings will guide future studies evaluating routine VTE risk assessment in chemotherapy outpatients, and prophylaxis for those at highest risk. Because older patients demonstrated a stronger genetic effect and higher VTE incidence, this group requires special attention in future risk stratification efforts.”
Dr Brand added that a limitation of this study is the small number of older patients who had chemotherapy and a high genetic susceptibility. She said larger-scale studies would be necessary to provide more precise risk estimates. And further research is needed to assess the safety and potential benefit of thromboprophylaxis in high-risk cancer patients.
