Once again, we have an example of when the news isn’t exactly news.
A study reported today in the journal Cancer Research says that treatment to prevent breast cancer recurrence with the drug tamoxifen increases the risk of a woman developing a second, more aggressive of breast cancer in the opposite breast over 400%.
That’s the headline. But the fact is we have basically known that since 2001, and frankly the way we treat women with breast cancer has changed considerably in between the two reports. So the practical implications of the article aren’t new information, and the unfortunate unintended consequence is that many women with breast cancer may become unnecessarily alarmed.
Women with breast cancer are frequently put on preventive therapy to avoid a recurrence or spread of their cancer. That treatment can include hormone-related medicines, such as tamoxifen or drugs called aromatase inhibitors, and may also include chemotherapy drugs which frequently have to be given intravenously.
We know these treatments—which may also include radiation therapy–are very effective in reducing the risk of cancer returning in the breast where it was diagnosed, as well as in the opposite breast and in more distant location.
In this current study, the researchers examined medical records of women diagnosed with breast cancer from the
The goal of the study was to look at how often these women developed a second cancer in the opposite breast (women with cancer of one breast are at greater risk of developing a second cancer in the opposite breast), and whether or not that cancer was hormone sensitive (the cancer in the first breast had to be hormone sensitive, or otherwise the woman would not have been placed on taxmoxifen).
They found—as expected—that the women on taxmoxifen had a 40% decrease in the risk of developing a hormone-sensitive breast cancer in the opposite breast in they had taken tamoxifen for five or more years. However, if the women took the tamoxifen for five years or more, then the researchers report that the risk of developing a second hormone-negative breast cancer—which is likely more aggressive than a hormone-sensitive breast cancer—increased 440%.
But here is where it gets tricky:
If you look at the number of cases of hormone-sensitive breast cancer avoided with tamoxifen compared to the increase in hormone-insensitive breast cancers, you find out the number avoided far outweighs the number increased. And that doesn’t mean the women who developed these second cancers died from their disease. It simply means those were the cancers diagnosed, and then treated.
And then there is the question of how precise and predictable the numbers really are.
Take that 440% number. That means the women who took tamoxifen had 440% greater chance of developing a more aggressive, hormone insensitive tumor compared to women who did not take the drug.
But wait a moment…
In statistics, there is something we call the “confidence interval.” In simple terms, it means if you kept repeating the same experiment in different populations or with more women in the same population, what is the chance you would come up with the same result? What are the possible other numbers that may show up?
In this study, the confidence intervals for that 440% number vary from 1.03 (a 3% increased risk) up to 19 (a 1900% risk). In our world, that is what we call “not very tight.” That 1.03 number—in reality—just gets you over the line of what we call statistical significance.
Much of this discussion would be academic if not for a couple of other issues.
First, this research was focused on women who were supposed to be post-menopausal, even though there were a number of subjects that were between 40 and 50. In today’s practice, most of these women are not treated with tamoxifen. Instead, they receive an aromatase inhibitor, and this study says nothing about their risk. Most of the women who get preventive treatment with tamoxifen today are pre-menopausal breast cancer patients.
Secondly, this really isn’t new news. It is a further refinement of a study previously reported—in 2001. That study, which was written up on cancer .org when it was published had almost the exact same result, although at that time more women were being started on tamoxifen as a preventive treatment since we didn’t have as clear evidence that aromatase inhibitors were more effective in post-menopausal women. In that study, the increased risk was 4.9 times greater for an ER negative tumor on women who had taken tamoxifen.
But I probably would have left this whole issue of “alarm” alone, were it not for a press release that promoted the study.
Here’s the headline:
Long-term tamoxifen use increases risk of an aggressive, hard to treat type of second breast cancer
Study finds a more than four-fold increased risk of ER negative second cancers
Sounds pretty scary, but in fact it’s not new news.
The study is fine, and the results are what the results are. But for women out there who are taking tamoxifen, it will inevitably cause them distress and panic and they certainly don’t need more of that.
Especially when we have played this song before.
By the way, here is what we recommended 8 years ago:
“Tamoxifen now has over 25 years of widespread use throughout the world, and it has clearly been documented as saving many, many thousands of lives from breast cancer,” says Eyre (Dr. Harmon Eyre, our chief medical officer at the time). “Additionally, it has been documented to prevent many, many contralateral cancers of the breast in women who have had breast cancer, and it now prevents breast cancer in women who are at high risk from the disease,” he emphasizes.
Patients and doctors will continue to benefit from using tamoxifen under appropriate circumstances, Eyre says, while exercising the cautions appropriate to a drug carrying some serious side effects.
“I believe that better drugs that have fewer side effects will eventually replace it,” he suggests; “however, the use of tamoxifen should not be changed at the present time based on this one study.”
And here is what my colleague Victor Vogel, MD, who is our National Vice President for Research—and is an expert on this issue—had to say today:
“The other very important point to make is that tamoxifen reduces the risk of recurrence in half, and also cuts the risk of dying by half among women who take it for only five years. That fact should not be lost: the benefits of tamoxifen among women who take it for five years are significant. Even if a woman were to take it for longer than five years and increase her risk of an ER-negative contralateral breast cancer, there would still be positive net benefit. Tamoxifen also reduces the risk of contralateral, ER-positive breast cancer by 50 percent, a fact that is not sufficiently emphasized in this article, in my opinion.
“So this study, while identifying a small risk only among women who take more than five years of therapy, does not sufficiently identify the benefits of taking up to five years of therapy. Women should not stop taking tamoxifen as a result of this study. Postmenopausal women should ask their doctors to switch them to an aromatase inhibitor (AI) if they are taking tamoxifen, and an AI should be used as first line therapy in postmenopausal women being treated for early breast cancer. Premenopausal women should still receive five years of tamoxifen and switch to an aromatase inhibitor when they are postmenopausal. These women will not be at increased risk for an ER-negative contralateral breast cancer.”
It is time to move on. And in the process, let’s not scare people with news that is not new.