Long-term tamoxifen use among breast cancer survivors is associated with a more than fourfold increased risk of ER-negative cancer in the contralateral breast, according to the investigators at Seattle's Fred Hutchinson Cancer Research Center.

Comparing breast cancer patients who received tamoxifen to those who did not in 1,103 subjects, researchers found that while the drug was associated with a 60% reduction in ER-positive secondary breast cancer, the risk of ER-negative secondary went up by 440%.

"This is of concern, given the poorer prognosis of ER-negative tumors, which are also more difficult to treat," said lead author Christopher Li, MD, PhD. "Still, the benefits of this therapy are well established and doctors should continue to recommend hormonal therapy for breast cancer patients who can benefit from it" (Cancer Res online, August 24, 2009). These findings confirm preliminary research by Dr. Li's group, which was the first to suggest a link between long-term tamoxifen use and an increased risk of ER-negative second cancers (J Natl Cancer Inst 93:1008-1013, 2001).

The current study is the first to determine if tamoxifen use among survivors influences their risk of a second cancer, Dr. Li said.