Breast Cancer Health Center

Tamoxifen: Risk of Rare Second Breast Cancer?

Researcher's Perspective

"Any sort of treatment has risks and benefits, and the benefits for tamoxifen are very clear, particularly with respect to reducing mortality. It also reduces the risk of recurrences," Li says.

Li counts increased risk of stroke and endometrial cancer among tamoxifen's known risks, and he says ER-negative cancer may be another risk.  

But Li isn't calling for any change in how tamoxifen is used in breast cancer patients, or for taking tamoxifen for less than five years, because overall, the benefits still win out.

"The randomized trials looking at tamoxifen have very convincingly shown that full benefit of the drug is only obtained when it's used for five years," Li says. "I don't think they should change the recommendation that women should use it for the full five years."

Li also emphasizes that ER-negative breast cancers are rare, and that the study wasn't designed to show a woman's absolute risk of developing an ER-negative breast cancer.

"This is a relatively rare type of second cancer. In our study, only 25% were of this type," Li says. "So for the vast majority of cancers, [tamoxifen] is lowering the risk of second cancers. But for the smaller subset, this 25%, it's increasing the risk."

The study doesn't prove that tamoxifen caused any cancers, though Li's team weighed many other factors in analyzing the data.

Li and colleagues aren't sure how tamoxifen might raise ER-negative breast cancer risk, but they speculate that targeting ER-positive cells may allow ER-negative cells to take center stage. The researchers plan to study that further and to check to see if the findings also apply to another class of estrogen-related breast cancer drugs called aromatase inhibitors.

Second Opinion

Vogel, with The American Cancer Society, wasn't involved in the study, and he doesn't question the data analysis. But he notes that most women don't take tamoxifen beyond five years, and he's concerned that people may come away with the wrong impression.

"This should not be controversial, and actually, it's not new. This has been suggested before," Vogel says.

"But certainly none of the data has suggested that we stop using tamoxifen or change the way we apply it. ... The net benefit for tamoxifen is huge."