Tamoxifen: Truly A Miracle Drug
What is it?
Tamoxifen (trade name Nolvadex-R) is produced by Zeneca
Pharmaceuticals as an anti-breast cancer drug. Tamoxifen is a
drug in pill form that is taken orally. It has been used for the past 20
years to treat patient who suffer from advanced breast cancer.
Recently, it has gained popularity as an additional form of therapy
after primary treatment of early stage breast cancer. Tamoxifen
has recently been studied in conjunction with the prevention of
breast cancer, as well as the treatment of melanoma and other
types of cancer.
How does it work?
Tamoxifen acts as an "anti-estrogen" in the body. Since estrogen
promotes the growth of breast cancer cells, Tamoxifen slows or
stops the growth of breast cancer cells that are already present in
the body. It is also used to prevent the development of cancer in
the opposite breast. Although Tamoxifen acts as an
"anti-estrogen" in breast tissue, it in fact acts like estrogen in other
body systems. This leads women who take Tamoxifen to
experience many of the same benefits as women who undergo
estrogen replacement therapy. These benefits include lowering of
blood cholesterol levels and a lowering of the risk of osteoporosis.
Known side effects of Tamoxifen include endometrial cancer
(cancer of the lining of the uterus), pulmonary embolism (blood
clots in the lung) and deep vein thrombosis (blood clots in major
veins). The side effects can be quite serious, so doctors are urged
to discuss the use of Tamoxifen very carefully with their patients
before deciding to begin therapy. For the most part, only women at
high risk for developing breast cancer are receiving the drug as a
A cancer preventative?!?
n October of 1998, the Food and Drug Administration approved
Tamoxifen for use in breast cancer prevention. Their decision
came after the FDA studied the results of research done by the
National Cancer Institute, as part of NCI's national clinical trials
networks called the National Surgical Adjuvant Breast and Bowel
Project (NSABP). This study found that Tamoxifen dramatically
decreases the incidence of breast cancer (but at a price of
increased risk of endometrial cancer and blood clots). After the
preliminary results were analyzed, the trial was stopped 14 months
early so the FDA could approve the drug for general use.
The NSABP's website tells women everywhere to talk to their own
physicians about using Tamoxifen to prevent breast cancer. While
not officially approved as a preventive drug for breast cancer,
because it is already approved for breast cancer treatment, any
physician can prescribe it for any purpose if, in the doctor's
judgement, there is scientific support. Typically, this is done when
there are several studies published in peer-reviewed (looked at by
a panel of doctors) journals supporting the new use for the drug.
But, in this case all the evidence rests solely on one study and its
unreviewed results, not to mention a lot of media coverage.
The Results We Know So Far
Overall disease rates were comparable between the groups. The study took more than 13,000 women who were classified as being at high risk for breast cancer and at low risk for pulmonary embolisms. The women were divided into two groups. One group got Tamoxifen and the other group took placebos (a sugar pill with no drug in it). At the time the trial was stopped, 175 women not taking the drug were diagnosed with breast cancer, and only 89 of those taking Tamoxifen were diagnosed with breast cancer. This is how researchers reached the conclusion that Tamoxifen will reduce a woman's risk of breast cancer by nearly one half. What is usually glossed over are the higher rates of endometrial cancer, pulmonary embolism, and deep vein thrombosis. If you take these into account, the rate of disease reduction is only about 15%.
Death rates between the two groups were the same. Of those not taking Tamoxifen, five died of breast cancer. Of those taking it, five also died (three from breast cancer and two from pulmonary embolism). Keep in mind that to be in this study a woman had to be high risk for breast cancer and low risk for blood clots.
What This Means for the General Population
It is reasonable to speculate that if Tamoxifen were more widely used by all women that a lower percentage would be saved from breast cancer. This is because there are less high-risk women in the general population than were used in this study. The percentage of women dying from pulmonary embolism would be the same, assuming that those with clotting risk will still not be prescribed the drug. This would all depend on the criteria for breast cancer risk to warrant the drug. One of the criticisms of the study was that we do not yet have enough information to accurately assess breast cancer risk, so it is difficult to accurately and consistently identify high-risk women. It is also known that minority women were not well represented in this study, in spite of efforts to do so. So whatever the final results may be, they may not apply to all women.
What the Results Don't Tell Us
Because the information about Tamoxifen being used to prevent breast cancer came in the form of a press release, instead of a scientific study, there are many unanswered questions. Once some of these questions are answered, the claim of a 40% reduction in breast cancer may be lowered.
We don't know who dropped out of the study. The researchers only stated the absolute number of women in each group that had each type of problem. It is well known that the group taking the drug may drop out at a higher rate than the placebos because of the side effects of the medication. The lower numbers of breast cancer cases may be in part due to a lower number of women in the Tamoxifen group who actually completed the study.
Most importantly, we don't know what the long-term effects of taking Tamoxifen are in healthy women. Is there an overall decrease in disease in women who take it? Is there an overall increase in life span? Right now, it looks like a few women traded dying from breast cancer for dying from pulmonary embolism. Given that the latter kills faster, the Tamoxifen group could be worse off.
The goal of breast cancer prevention is to have a longer, healthier life; not to trade a natural disease for a drug induced one. We need more information than a press release to know if we have this with Tamoxifen.