Tamoxifen: Risk of Rare Second Breast Cancer?

A new study links long-term use of the breast cancer drug
tamoxifen to a rare but aggressive form of breast cancer , but experts say the
findings shouldn't stop breast cancer patients from taking tamoxifen.

"We don't think that it overall changes the risk-benefit equation, in that
women who are eligible to take this drug probably should still take it because
of its proven benefit," researcher Christopher Li, MD, PhD, an associate member
of the Fred Hutchinson Cancer Research Center in Seattle, tells WebMD.

"I think the worst thing that could happen, on a public health basis, with
this paper is for patients and their doctors to look at this and say, 'Oh, this
is a reason not to take tamoxifen.' Nothing could be further from the truth,
for the reason that it obviously has enormous benefit," says Victor Vogel, MD,
MHS, the American Cancer Society's national vice president for research.

Here's a look at the study Li and Vogel are talking about -- and why they
stand by tamoxifen's use in breast cancer patients with "ER positive" breast
cancer.

Most breast cancers are "
ER positive ," or estrogen receptor-positive. That means they grow when
exposed to the hormone estrogen. Tamoxifen and other breast cancer hormone
therapies thwart ER-positive breast cancer cells. 

"ER negative" breast cancers, on the other hand, are rarer, tend to be more
aggressive, and are more difficult to treat. They're not treated by tamoxifen
or another class of estrogen-related breast cancer drugs called aromatase
inhibitors, because ER-negative breast tumors aren't sensitive to estrogen.

Tamoxifen Study

Li's team studied data on nearly 1,100 Seattle-area women aged 40-79 who
were treated for ER-positive breast cancer between 1990 and 2005. The group
included 367 women who developed breast cancer in their other breast at least
six months after their first diagnosis.

Li and colleagues interviewed all of the women and checked their medical
records, noting any use of tamoxifen or other hormone therapies to help prevent
breast cancer's return, and how long those drugs were used.

Most of the women took tamoxifen -- aromatase inhibitors are newer drugs and
weren't available during many of the years studied. And most of the women
didn't have another cancer develop in their other breast.

Women who used tamoxifen or other breast cancer hormone therapies were 60%
less likely to develop an ER-positive cancer in their other breast, compared to
those who never took tamoxifen.

But women who used tamoxifen for five or more years were about four times
more likely than women who never used breast cancer hormone therapies to
develop an ER-negative tumor in their other breast.

Tamoxifen use for less than five years wasn't linked to ER-negative breast
cancer risk. The study didn't include any women taking tamoxifen to try to
prevent a first 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."

By Miranda Hitti
Reviewed by Louise Chang
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