Clotting mutation linked to increased TE risk among tamoxifen users
MedWire News: Women who experience a thromboembolic event (TE) while taking tamoxifen for early breast cancer are nearly five times more likely to carry the Factor V Leiden (FVL) gene mutation than women who do not develop a thromboembolism, US researchers report.
Both tamoxifen use and the clotting factor mutation FVL are independent risk factors for TEs but it was not known whether carrying the FVL mutation increases the risk for TEs among women taking tamoxifen, explain Judy Garber (Dana-Farber Cancer Institute, Boston, Massachusetts) and colleagues.
To investigate, Garber and team compared 124 women who experienced a TE while taking adjuvant tamoxifen for early breast cancer with 248 controls who took adjuvant tamoxifen but did not experience TE and were matched for age at diagnosis.
The researchers found that a significantly greater proportion of patients with TE had the FVL mutation, compared with controls, at 18.5% versus 4.8%. This meant that patients with TE were 4.66 times more likely to carry the FVL mutation than controls.
The result differs from previous studies in high-risk women taking tamoxifen to prevent breast cancer that found no associated risk for TEs nor an increased presence of FVL mutations.
In multivariable analysis, the FVL mutation was significantly associated with the likelihood of experiencing TE while taking adjuvant tamoxifen (odds ratio=4.73). A personal history of TE and smoking were also significantly associated with the risk for TE.
"These data may prove useful to women who must decide between tamoxifen and an effective, essentially non-thrombogenic, alternative adjuvant therapy for breast cancer, such as aromatase inhibitors for postmenopausal women, and gonadotropin-releasing hormone analogs or oophorectomy for premenopausal women," conclude Garber and co-authors in the Journal of the National Cancer Institute.
In an accompanying editorial, Jack Cuzick, from Queen Mary University of London in the UK, said that the reason for the association between the FVL mutation and TEs among breast cancer patients treated with tamoxifen as opposed to taking it preventively "remains a mystery."
He concluded: "Continued follow-up and research on the relationship between the FVL mutation and tamoxifen, especially in the prevention setting, will be the only way to clarify these apparently contradictory findings.”
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010
By Laura Dean