Tamoxifen and Breast Cancer
A number of cells in the female body contain receptors for estrogen and estrogen-like substances. Examples of these organs are the breast, uterus, vagina, skin, ovaries and brain. Estrogen binds to receptors on breast cells and stimulates them to divide and replicate. This mechanism, on the other hand is turned off by Tamoxifen as it attaches to the estrogen receptors in the cell surface. With breast cancer cells that contain estrogen receptors, Tamoxifen sends these cells into a programmed cell death cycle known as apoptosis.
Tamoxifen is orally administered just like other hormones. Aside from rendering breast cancer cells into apoptosis, it also acts like estrogen on other tissues and has a positive effect on bone metabolism. Tamoxifen, in comparison to estrogen, stimulates the uterine lining more and both substances are equally effective in retaining bone calcium.
Several studies have shown that Tamoxifen increases the cure rate of women with non-invasive breast cancer, but is still controversial in its clinical use. The controversy lies on a recent clinical trial, which aimed to determine if Tamoxifen was effective in primary breast cancer prophylaxis in high risk asymptomatic women. At the end of the trial, Tamoxifen was dealt with severe scrutiny and a large amount of negative press overstating its potential adverse effects for asymptomatic women. There is, indeed, no question that Tamoxifen is an extremely potent drug in the treatment of breast cancer patients. Based on the results of another clinical trial involving the use of Tamoxifen, treatment duration plays a significant role in drug treatment outcome. This clinical trial compared five years versus ten years of using Tamoxifen after the diagnosis of breast cancer. The trial showed that five years of taking Tamoxifen significantly diminished the systemic recurrence of breast cancer. On the other hand, an additional five years added only expense and potential risk of uterus cancer with no additional benefits in cure rate. Not all breast cancers, however, respond to Tamoxifen treatment. Response rate to Tamoxifen varies upon the abundance of estrogen and progesterone receptors in the primary cancer.
Since breast cancers are very heterogeneous, they do not develop in the same cellular way. About 60 percent of breast cancers contain estrogen and progesterone receptors, while others contain less. Tamoxifen appears to be more effective in women who have more of these hormone receptors in their tumors than those who do not. On the other hand, within a given breast cancer, there may be cells that have more hormone receptors than others do. Hence, the effect of Tamoxifen on these conditions varies. It is also possible that over time, breast cancer cells that are hormone receptor positive may evolve and may not contain hormone receptors anymore. This may explain why women who receive a combination treatment of Tamoxifen and chemotherapy may have a better response to treatment than with either therapy given alone. In most cases, when chemotherapy and Tamoxifen are given in a cancer patient, they are given sequentially; initially, chemotherapy is given to destroy hormone receptor negative breast cancer cells and then followed by Tamoxifen, which can then act on hormone receptor positive cells that may be less susceptible to chemotherapeutic drugs.
In a few cases, perimenopausal women seem to have a difficulty with Tamoxifen use. Most premenopausal women in their 30s and 40s almost have no adverse effects with Tamoxifen and older women who are not in hormone replacement have little problem with Tamoxifen treatment.
The major side effect of Tamoxifen is uterine toxicity. Some women taking the drug have endometrial thickening, a stimulation of the glandular lining of the uterus, which can become cancerous if left unnoticed. The chance of developing uterine cancer as a result of Tamoxifen use is quite small, only about one percent. Nevertheless, the uterus must be monitored carefully with either an ultrasound or endometrial biopsy during the patient’s annual pelvic examination if she is taking this drug.
Tamoxifen was the first selective estrogen receptor modulator developed and has been used for over 20 years. Recently, several other drugs of this class have been released and more are presently undergoing development. The goal is to develop the “perfect” drug in this class that prevents breast cancer without stimulating the uterus, is beneficial to the skeletal system and is good for lipid metabolism with as minimal side effects as possible. The perfect selective estrogen receptor modulator should also be an excellent hormone replacement agent for women entering menopause.
Tamoxifen and Breast Cancer