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Frequently Asked Questions about Tamoxifen
Sharon Mitchell, PharmD, UCSF & Robert Ignoffo, PharmD, Clinical Professor UCSF

How does Tamoxifen work in the management of breast cancer?
What is the significance of estrogen-receptor-positive (ER+)
and estrogen-receptor-negative (ER-) breast cancer and response to treatment?
Will I benefit from Tamoxifen?
Are there other benefits from Tamoxifen?
What are the risks of Tamoxifen therapy?


How does Tamoxifen work in the management of breast cancer?
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The hormone, estrogen, enters many normal cells including mammary (breast) cells and signals growth and multiplication. In breast cancer, this growth is accelerated. Tamoxifen is an anti-estrogen, a compound shaped like natural estrogen, that binds to estrogens receptors in the nucleus of breast cancer cells and prevents the cell from growing. By binding in the place of estrogen, Tamoxifen slows or stops individual breast cell (tumor) growth.


What is the significance of estrogen-receptor-positive (ER+)
      and estrogen-receptor-negative (ER-) breast cancer and response to treatment?

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Cancer growth may be stimulated by various physiological mechanisms, including the binding of estrogen. The measurement of hormone binding to sites on breast cancer cells helps health professionals identify those women who will most likely benefit from Tamoxifen therapy. If breast cancer cells are ER+, Tamoxifen exerts a maximal effect.by inhibiting further tumor growth. If breast tissue tests ER-, clinical response to Tamoxifen is less likely to occur. However, Tamoxifen is sometimes still recommended in ER- breast cancer since it has some benefit.


Will I benefit from Tamoxifen?
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Tamoxifen is recommended in the treatment of both early and advanced breast cancer and in the prevention of breast cancer in high-risk patients.

Treatment Of Early Stage (stages 1-3)
Tamoxifen is prescribed as an adjunct to primary surgery for both pre- and postmenopausal women with early stage breast cancer. Early stage cancer means that malignant cells cannot be detected in any tissue (eg. Liver, lung, bones) outside of the initial mass or regional lymph node. In early stage breast cancer, there is the risk that cancer cells have spread in the blood and potentially traveled to other parts of the body. Tamoxifen treatment has been shown to do the following in early stage breast cancer:
* Reduce the recurrence of breast cancer
* Reduce the chances of cancer spread or metastasis
* Reduce the development of cancer in the opposite breast by 39%
* Prolong overall survival

Treatment Of Advanced Stage (stage 4)
Tamoxifen is also useful in the treatment of breast cancer that has spread from the primary growth site in both pre- and post-menopausal women. Studies demonstrate that tamoxifen slows down tumor growth and induces cancer remission. Although tamoxifen does not cure advanced breast cancer, the medication decreases tumor progression and improves the quality of life

Prevention Of Breast Cancer
Women who have a first-degree relative (ie. Mother or sister) with breast cancer are at increased risk for developing breast cancer. Tamoxifen is being studied in a large cooperative national study group to determine if it can prevent breast cancer in women at high risk.


Are there other benefits from Tamoxifen?
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In addition to blocking the effects of estrogen and cellular growth, tamoxifen also exerts some other estrogen-like effects on the body. Some of these are positive while others may be bothersome. Estrogen helps protect the cardiovascular system prior to menopause. After menopause, as estrogen levels decrease, the incidence of hot flashes, etc. in women significantly increases. Due to its estrogen-like activity and cholesterol-lowering effects, tamoxifen may decrease cardiovascular events, especially after menopause. In addition, tamoxifen can increase bone density and may, therefore, reduce the incidence of osteoporosis and bone fractures.


What are the risks of Tamoxifen therapy?
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Due to its estrogen-like effects, tamoxifen can enhance endometrial cell growth in some women. In several studies performed by large cooperative cancer study group, the incidence of uterine cancer was increased from 1.7 to 7-fold. Between 70 and 80% of the uterine cancer cases have been low grade, stage I pathology. However, several other studies have reported no association with uterine cancer. So, this question is very controversial. Thus, to date a causal relationship of endometrial cancer has not been proven. Current ongoing prophylactic studies will be very helpful in determining what, if any, relationship may exist between endometrial cancer and use of tamoxifen. In the meantime, routine monitoring with annual PAP smears is recommended.

Tamoxifen may also thicken the blood and increase the chances of developing a blood clot. The risk of stroke, lung clotting, and leg clotting is increased slightly. Patients with a h/o these disorders should not be on tamoxifen and should be taking anticoagulants. to prevent these risks. Birth control pills also have this effect due to their estrogen content.




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