Research findings help predict risk of blood clots in women receiving tamoxifen therapy for breast cancer

October 14, 2017

Dana-Farber's Judy Garber, MD, MPH, will present the study's data (Abstract 508) - on behalf of her colleagues at Yale University School of Medicine and more than 30 institutions and medical practices in the Cancer and Leukemia Group B consortium, a clinical research network organized by the National Cancer Institute - during an oral presentation on Sunday, May 15, at 8 a.m., Level 2, Hall A2.

The study involved more than 300 women receiving tamoxifen as "adjuvant" therapy - given after a new breast cancer diagnosis to prevent recurrence. Researchers focused on a blood-clotting protein called Factor V. Previous studies had shown that women with a specific Factor V gene mutation - which gives rise to an abnormal version of the protein, known as Factor V Leiden (FVL) - are at increased risk for blood clots when pregnant or taking oral contraceptives or estrogen replacement therapy.

In the new study, researchers found that women who had blood clots while taking tamoxifen were almost four times as likely to have an FVL mutation as were those who did not have blood clots. The results suggest that testing women in advance for FVL mutations may enable physicians to identify some women who should either use alternatives to tamoxifen or, if good alternatives are not available, use a blood thinner while taking tamoxifen.

"Other factors contributing to blood clot risk must also be considered in the decision to recommend tamoxifen to generally healthy women, including a history of previous blood clots, obesity and planned surgery," says Garber. "But FVL testing can now be used to help make this powerful medication safer for some women who need it for breast cancer treatment or prevention."


To assess the tamoxifen's effects on cardiovascular risk, Bernstein approached researchers at Kaiser Permanente Southern California, a large health maintenance organization with a vast number of women treated for breast cancer. Kaiser Permanente research scientist Ann M. Geiger, Ph.D., and biostatistician Wansu Chen, M.S., collaborated to conduct a nested case-control study among Los Angeles County women who were diagnosed with breast cancer between 1980 and 2000.

Of 11,045 women in the Kaiser Permanente system who were diagnosed with breast cancer over two decades, 134 women experienced their first heart attack-also known as a myocardial infarction-in the years after treatment.

For their analysis, researchers matched each of the 134 women to two other women who had been diagnosed with breast cancer at the same age and during the same year, but who had not suffered a heart attack. The typical breast cancer patient was 67 years old at diagnosis.

Researchers found that use of tamoxifen was not associated with risk of heart attack, either overall or when grouped by duration of use, dose of the drug, or how recently the drug was used.

Breast cancer survivors who smoked, had diabetes or had high blood pressure requiring medication all had higher risk of heart attack. Radiation, too, was associated with higher heart attack risk.

Although the association between radiation and heart attack risk must be further explored, the researchers noted that women with a history of radiation therapy or other potentially heart-damaging therapy for breast cancer "will benefit from ongoing risk factor monitoring and lifestyle modifications to improve cardiovascular health."