John Murphy, MDLinx | November 30, 2017
Breast cancer patients are at approximately twice the risk of mortality shortly after a venous thromboembolism (VTE). But in patients who survive an initial VTE, the risk is less certain—and may not even be increased at all, according to UK researchers in a recently published meta-analysis in BMC Cancer.
The association between breast cancer and VTE is already known. Breast cancer patients have a three- to four-fold greater risk of developing VTE compared to similar patients without breast cancer. Numerous studies (including one from these researchers) have also shown that this risk is even higher in certain breast cancer patients—as much as 5-fold greater in patients given tamoxifen and 10-fold greater for those on chemotherapy, the researchers noted.
For this study, the investigators sought to determine whether VTE increases the risk of mortality in breast cancer patients—and if so, by what extent.
“To our knowledge, this is the first attempt to systematically evaluate all available data exploring whether or not among women with breast cancer the risk of mortality is raised following development of a VTE,” wrote senior author Matthew J. Grainge, PhD, and colleagues from University of Nottingham Medical School, Nottingham, UK.
Using the Clinical Practice Research Datalink—a population-based, electronic health dataset including about 8% of the UK population—Dr. Grainge and co-authors identified 13,202 patients with breast cancer: 611 who were diagnosed with VTE between 1997 and 2006 and 12,591 who did not develop VTE.
The researchers calculated hazard ratios (HR) to compare mortality between the two groups according to two very specific time frames. First, they found that VTE was associated with increased mortality in breast cancer patients when follow-up began at cancer diagnosis (HR: 2.42; 95% CI: 2.13-2.75). This was the short-term mortality analysis.
However, when follow-up was considered to begin at 6 months after cancer diagnosis—and the VTE event occurred during that time—the researchers observed that mortality risk was not significantly increased (HR: 1.22; 95% CI: 0.93-1.60). This was the long-term mortality analysis.
“Our two distinct approaches to analysis enabled us to assess the effect of a VTE on short-term and long-term mortality separately,” noted Dr. Grainge and colleagues.
Next, the researchers pooled these data with seven other studies on this topic. Using the short-term mortality analysis, they determined that the pooled HR was 2.35 (95% CI: 2.17-2.55). When using the long-term mortality analysis, the pooled HR was 1.69 (95% CI: 1.12-2.55).
“We have previously shown with this cohort that VTE events in women with breast cancer are likely to occur either during or immediately following chemotherapy or in the first month following surgery,” Dr. Grainge and co-authors noted.
“In the case where a woman with breast cancer is fortunate enough to survive her initial thrombotic event, the influence on long-term prognosis is more difficult to establish, with a suggestion from this current study that mortality is not raised at all once cancer stage and underlying health status are taken into account,” they added.
But why does short-term mortality risk increase in breast cancer patients?
The first explanation for the high short-term mortality is simply the result of having a thrombotic event, in which fatality occurs in about 1% of all patients following a deep vein thrombosis and in more than 20% following a pulmonary embolism, the researchers noted.
“A further explanation for the detrimental impact of VTE on cancer survival relates to complex mechanisms underlying the symbiotic relationship between coagulation and tumor factors,” they wrote. “It is hypothesized that VTE, even at the subclinical level of biochemical hypercoagulability, may have a role in promoting cancer growth and metastases and be associated with a more aggressive tumor behavior.”
Further research along these lines may one day show that VTE could potentially be used a marker for severe and more aggressive forms of cancers, Dr. Grainge and colleagues speculated.
This study was supported by Cancer Research UK.