AACR: Genetic testing could help identify
breast cancer patients with high risk of experiencing venous
thromboembolism (VTE), a serious and potentially fatal complication that
can occur during cancer treatment, according to results of a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research.
“The
risk for venous thromboembolism (the formation of blood clots in a
vein) is increased in cancer patients, particularly in those receiving
chemotherapy,” explained the study’s lead author, Judith S. Brand, PhD, a postdoctoral researcher in the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet in
Stockholm, Sweden. “As one of the most common cancers, breast cancer
accounts for a large number of cancer-associated VTE cases.”
Brand
said VTE is preventable through thromboprophylaxis with low molecular
weight heparin, an anticoagulant drug. However, this regimen is not
routinely recommended in patients undergoing chemotherapy due to side
effects such as bleeding.
In this study, Brand and colleagues
sought to identify the individual and joint effects of chemotherapy and
genetic susceptibility on VTE risk. The study included 4,261 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 polygenic risk score (PRS) based on nine genetic variants
(including the factor V Leiden mutation), with the top 5 percent
classified as having high genetic susceptibility.
The study found
that the one-year cumulative incidence of VTE was 9.5 percent in the
breast cancer patients who received chemotherapy and had high genetic
susceptibility, compared with 1.3 percent in the patients who did not
receive chemotherapy and had lower genetic susceptibility.
The
study discovered that chemotherapy and genetic susceptibility
independently increased the risk of VTE and that the impact of genetic
susceptibility was most pronounced in older patients: In patients aged
60 or older who underwent chemotherapy and had a high genetic
susceptibility, the 1-year cumulative incidence of VTE was 25 percent.
“Breast
cancer patients receiving chemotherapy are not routinely being examined
for VTE prevention in today’s clinical practice. Our study demonstrates
that information on genetic susceptibility can be used to identify
patients at high risk of developing VTE,” Brand said.
“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,” she added.
Brand said a limitation of
the 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. Brand added that
further research is needed to assess the safety and potential benefit of
thromboprophylaxis in high-risk cancer patients.