Beyond BRCA: Using Genetics to Assess Risk of VTE in Patients With Breast Cancer

ALLIE CASEY
Friday, November 04, 2016
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Judith S. Brand, PhD

Judith S. Brand, PhD

Genetic testing is an ever-expanding field in oncology, helping to personalize treatment and predict patients at a higher risk for cancer. Genetic testing can also be used to determine a patient’s potential risk for developing certain complications of cancer treatment, and knowing a patient’s risk is an important factor when deciding whether to take preventive measures that could result in serious side effects.
 
A recent study found that chemotherapy status and genetic susceptibility could be used to stratify the risk of venous thromboembolism (VTE) in patients receiving chemotherapy for their breast cancer—a serious and potentially fatal complication.

Stratifying Risk for Venous Thromboembolism
Preventive treatment for VTE includes low molecular weight heparin, but because of the risk of bleeding with the anticoagulant, it is not recommended for patients who are undergoing chemotherapy. Being able to risk-stratify patients to target those who are at highest risk for developing VTE would enable clinicians to be more selective and effective in deciding when to administer thromboprophylaxis.

This study by researchers at the Karolinska Institute in Stockholm, Sweden, examined 4261 women who were diagnosed with primary invasive breast cancer between the years 2001 and 2008 and monitored them through 2012. Patients were stratified based on potential risk of VTE, taking chemotherapy status and genetic susceptibility into account.

During a median follow-up period of 7.6 years, a total of 276 patients had experienced a VTE event.
 
To determine genetic susceptibility, researchers used a polygenic risk score (PRS). The PRS considered 9 genetic variants, including factor V Leiden, a mutation in one of the clotting factors in the blood. The researchers classified patients with a PRS in the top 5% to have high genetic susceptibility.

Although the Mayo Clinic reports that most people with factor V Leiden do not develop abnormal blood clots, among those who do, it can create long-term, potentially life-threatening health problems.

Researchers reported the total cumulative incidence of VTE in 1 year for patients who were both receiving chemotherapy and had high genetic susceptibility was 9.5%, whereas patients who were not receiving chemotherapy and had a lower genetic susceptibility had a 1.3% total cumulative incidence of VTE (P < .001).

The study discovered that both chemotherapy and genetic susceptibility acted independently on the risk of VTE.

VTE Risk Higher In Older Patients After Chemo
Additionally, the impact of a higher PRS was more pronounced in older patients; the cumulative incidence of VTE was 25% in patients who had chemotherapy, a high genetic susceptibility, and were aged 60 years or older.

“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,” Judith S. Brand, PhD, a postdoctoral researcher at Karolinska Institute and lead author of the study, said in a statement.

“Because older patients demonstrated a stronger genetic effect and higher VTE incidence, this group requires special attention in future risk stratification efforts,” she added.

In the future, Brand suggested studies that are larger scale, with more patients who are older, had chemotherapy, and a high genetic susceptibility. This would allow future researchers to make more precise risk estimates. Brand also recommended further testing of thromboprophylaxis and its risks and benefits in patients with cancer at high-risk for VTE.
Brand J, Hedayati E, Humphreys K, et al. Chemotherapy, genetic susceptibility, and risk of venous thromboembolism in breast cancer patients. Clin Cancer Res. 2016;22(21):5249-5255.

Talk about this article with nurses and others in the oncology community in the General Discussions Oncology Nursing News discussion group.
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