Venous thromboembolism is a serious—and sometimes fatal—complication of cancer and chemotherapy treatment. Since breast cancer is one of the most common cancers, it accounts for a large number of cancer-related cases of venous thromboembolism. Routine thromboprophylaxis, however, is not recommended for patients undergoing chemotherapy due to the increased risk of bleeding. Because venous thromboembolism is highly heritable, genetic markers are promising candidates for the identification of high-risk patients who could potentially benefit from thromboprophylactic measures.
To assess the effects of chemotherapy and genetic susceptibility on the risk of venous thromboembolism in patients with breast cancer, Judith S. Brand, PhD, of the Karolinska Institutet, and colleagues launched a population-based study of over 4,000 patients with breast cancer and found that genetic testing may have clinical potential for venous thromboembolism risk stratification in the chemotherapy setting, especially in older patients with breast cancer. The study was published in Clinical Cancer Research.
The researchers analyzed data from 4,261 women, ages 25 to 75, with breast cancer in the Stockholm-Gotland region of Sweden enrolled in the Libro-1 study, a cohort study aimed at identifying risk and prognostic factors for breast cancer. All of the patients were identified through the Stockholm Breast Cancer Register and were diagnosed with primary invasive breast cancer between 2001 and 2008 and followed until 2012.
Risk stratification by chemotherapy and genetic susceptibility (a polygenic risk score, including nine established venous thromboembolism loci) was assessed using Kaplan-Meier and flexible parametric survival analyses, adjusting for patient, tumor, and treatment characteristics.
The researchers found that 276 patients experienced a venous thromboembolism event during a median follow-up of 7.6 years. Patients receiving chemotherapy [hazard ratio [HR] = 1.98; 95% confidence interval [CI] = 1.40–2.80] and patients in the highest 5% of the polygenic risk score (HR = 1.90; 95% CI = 1.24–2.91] were at increased risk of developing venous thromboembolism.
Chemotherapy and polygenic risk score acted independently on venous thromboembolism risk, and the 1-year cumulative incidence in patients carrying both risk factors was 9.5%, compared with 1.3% in patients not having these risk factors (P < .001). Stratified analyses by age showed that the risk-increasing effect of polygenic risk score was stronger in older patients (P interaction = .04), resulting in an excess risk among genetically susceptible patients receiving chemotherapy aged ≥ 60 years (1-year cumulative incidence = 25.0%).
“Breast cancer patients receiving chemotherapy are not routinely being examined for venous thromboembolism prevention in today’s clinical practice,” said Dr. Brand, a postdoctoral researcher in the Department of Medical Epidemiology and Biostatistics at the Karolinska Institutet in Stockholm, Sweden, in a statement. “Our study demonstrates that information on genetic susceptibility can be used to identify patients at high risk of developing [venous thromboembolism]. Combined with other clinical risk factors and biomarkers, these findings will guide future studies evaluating routine [venous thromboembolism] risk assessment in chemotherapy outpatients and prophylaxis for those at highest risk. Because older patients demonstrated a stronger genetic effect and higher [venous thromboembolism] incidence, this group requires special attention in future risk-stratification efforts.”
Funding for this study was provided by the Swedish Research Council, the Swedish Cancer Society, and Forte—Swedish Research Council for Health, Working Life, and Welfare.