Another Adverse Effect of Tamoxifen
Nolvadex Increases Risk for Aggressive Cancer in the Opposite Breast
Sep 5, 2009
In the United States, Nolvadex (tamoxifen) is the most commonly used endocrine modulator for all stages of estrogen receptor (ER)-positive breast cancers.
While it reduces recurrence of ER-positive cancers, tamoxifen carries some serious side effects, including stroke, blood clots, osteoporosis, and endometrial (uterine) cancer.
Now, researchers have demonstrated that the drug also increases a woman’s risk for developing more aggressive, ER-negative breast cancers that are harder to treat. (Shari Roan. A danger emerges in long-term tamoxifen use. Los Angeles Times: Health. August 25, 2009)
Tamoxifen has been used to treat breast cancers in American women since 1977. It was initially approved for the treatment of patients with advanced breast cancer; over the succeeding years the drug has found applications for other populations of cancer patients as well.
How Does Tamoxifen Work?
- Most breast cancers are ER-positive (75%). This means that the cancers’ cells have estrogen receptors on their surfaces.
- An estrogen receptor acts like a switch that, when turned on by an estrogen molecule, stimulates the cancer to grow faster.
- ER-positive tumors grow more aggressively and spread faster when the estrogen in a woman’s bloodstream attaches to more of the cancer’s receptors.
- Tamoxifen is a selective estrogen-receptor modulator (SERM). SERMs work by occupying estrogen receptors on the surfaces of cancer cells and preventing circulating estrogen from turning the switch to the “on” position (it’s like trying to turn on a light switch when someone else’s hand is covering it).
- If the “switch” in ER-positive cancers can’t be turned on by estrogen, the cancer is far less likely to grow and spread.
- Through this mechanism, tamoxifen prevents the recurrence of already-treated ER-positive cancers and helps to prevent the development of new ones.
Why do Tamoxifen and Other SERMs Cause Problems?
Unfortunately, SERMs also occupy estrogen receptors in other tissues of the body, such as bone or the endometrial tissue of the uterus. In these other sites, SERMs either block the activity of circulating estrogen—just like they do in breast cancer cells—or they exert a weak estrogen-like effect.
It is this variable level of ER stimulation that causes most of tamoxifen’s side effects.
While the precise reason that tamoxifen increases the risk for more aggressive cancers is unknown, that risk appears to be real and substantial. Dr. Christopher Li, leader of the research team at Fred Hutchinson Cancer Research Center, reported that tamoxifen use is associated with a 60% reduction in the risk of developing a second ER-positive cancer in the opposite breast. However, if the drug is used for more than 5 years—a not uncommon scenario—the chances of developing an aggressive, ER-negative tumor in the opposite breast are increased by 440%. (Li C, et al. Adjuvant Hormonal Therapy for Breast Cancer and Risk of Hormone Receptor–Specific Subtypes of Contralateral Breast Cancer. Cancer Res. 2009;69[17]:6865-70)
Should Women with Breast Cancer Avoid Tamoxifen?
The incidence of breast cancer in American women has been decreasing since 2001. In large part, this is due to a cessation of the wholesale practice of prescribing hormone replacement therapy for menopausal symptoms and other conditions.
However, refinements in adjuvant treatment are credited with helping to decrease mortality from breast cancer, too. Tamoxifen and other estrogen-blocking drugs have proven themselves to be valuable in this respect.
According to Dr. Li, the new finding “…should not discourage women from taking tamoxifen to prevent a second (ER-positive) cancer.”
As always, the risks and benefits of any medical treatment must be carefully weighed within the context of an open and informative environment.
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