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Although adjuvant (post-surgery) tamoxifen (Nolvadex®) provides important benefits in the treatment of hormone receptor-positive breast cancer, it may increase a woman’s risk of developing an estrogen receptor (ER)-negative breast cancer in the opposite breast. These results were published in Cancer Research.

A majority of breast cancers are ER–positive, meaning they are stimulated to grow by the female hormone estrogen. Depriving ER-positive breast cancers of estrogen can slow their growth. Tamoxifen is an anti-estrogen that has long been a mainstay of hormonal therapy for breast cancer.

Several studies have shown that adjuvant (post-surgery) treatment with tamoxifen for five or more years significantly reduces the risk of breast cancer recurrence among women with early breast cancer. Tamoxifen also reduces the risk of developing a second ER-positive cancer in the opposite breast. Less information has been available, however, about the effect of tamoxifen on the risk of developing an ER-negative second breast cancer.

To explore patterns in second breast cancers among women who did and did not use tamoxifen, researchers conducted a study among 1,103 breast cancer survivors who had been diagnosed with an ER-positive breast cancer between the ages of 40 and 70.

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The study focused on second cancers in the contralateral breast (the breast that did not have the original cancer).

  • Compared with women who did not receive hormonal therapy, women who received adjuvant tamoxifen for at least five years were 60% less likely to develop an ER-positive second breast cancer but four times more likely to develop an ER-negative second breast cancer.

An increase in the risk of ER-negative second cancers is a concern because this type of cancer tends to be more aggressive. It should be noted, however, that only 52 of the 367 second cancers were ER-negative. Furthermore, because this was an observational study (not a randomized clinical trial), the results cannot be considered definitive.

In a prepared statement, Dr. Christopher Li, the lead author of the study, concluded: “It is clear that estrogen-blocking drugs like tamoxifen have important clinical benefits and have led to major improvements in breast cancer survival rates. However, these therapies have risks, and an increased risk of ER negative second cancer may be one of them. 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.”

Reference: Li CI, Daling JR, Porter PL, Tang M-TC, Malone KE. Adjuvant hormonal therapy for breast cancer and risk of specific subtypes of contralateral breast cancer. Cancer Research [early online publication]. August 25, 2009.