What is Tamoxifen?

Oct 15, 2018

Tamoxifen is a well-known drug discovered by what is now AstraZeneca. It was originally screened in a development program centered on the introduction of new contraceptive agents. Although it proved effective in rats, it was not a useful drug for control of fertility in women; it actually induced ovulation.

While commonly referred to as an anti-estrogen, this is not entirely accurate. In actual fact, tamoxifen is more appropriately described as a selective estrogen receptor modulator. This is because it expresses both estrogenic and antiestrogenic actions, depending on the target tissue.

On mammary epithelium, its actions are strongly antiestrogenic, which is why it’s used in both the prevention and treatment of breast cancer. In contrast, on uterine epithelium its action is proestrogenic, which has fuelled the current controversy regarding its safety in cancer prevention. This is especially since an increased incidence of endometrial carcinoma has been found in women treated chronically with tamoxifen.

Tamoxifen comes as a pill to be taken once or twice daily with water and each day at a similar time. When taken, the tablets should be whole; they should not be split, chewed, or crushed. Should a person forget to take a dose of tamoxifen, they should take the missed dose as soon as they remember it, and take the next dose as is usual. However, if it is almost time for their next dose, they should ignore the missed dose and continue following the regular dosing schedule. A double dose should never be taken to compensate for a missed one.

Tamoxifen therapy is used in a number of cases:

As adjuvant therapy (treatment following successful surgery) in those with lymph node negative or positive breast cancer though cancers with positive estrogen (and progesterone) receptors in both females and males.
As treatment of both early and advanced estrogen receptor positive breast cancer in pre- and post-menopausal women.
As treatment for women categorized as high risk for the development of breast cancer to reduce the incidence of developing breast cancer.
As treatment to reduce contralateral cancer i.e. cancer in the opposite breast.
Used occasionally to induce ovulation in women who wish to become pregnant but who do not produce eggs naturally.
As preventative therapy in those women at a high risk of developing the disease. This may be predisposed due to their age, medical history (both personal and family).

For example; Women who have had treatment for DCIS (intraductal carcinoma - a less common type of breast cancer ) through surgery, chemotherapy and/or radiation are at high risk for developing invasive breast cancer in the future, and hormone therapy (with tamoxifen) prevents the development of this cancer in a great deal of women within the first five years of treatment.

The safety of tamoxifen therapy has not been established in children or in those breastfeeding due to the potential for carcinogenicity. However, the benefits of Tamoxifen therapy generally outweigh the risks in those who are able to have the therapy. With regards to these risks, the associated adverse reactions tend to be minor, well-tolerated and often easily controlled by dose reduction. The side effects include:

Depression
Hot flashes
Weight loss
Menstrual irregularities
Vaginal discharge
Pain/reddening around the site of the tumor
Dizziness and severe headache
Constipation
Muscle weakness
Vision problems (e.g. risk of cataract development)
Initial adverse reactions (such as increased bone pain) may be a positive tumor response following the onset of tamoxifen therapy.
Blood cell changes: low neutrophil counts (neutropenia), very low platelet counts (thrombocytopenia) and very low white blood cell counts (leukopenia)
Abnormalities in blood clotting due to prolonged tamoxifen therapy at usual doses: this includes deep vein thrombosis and pulmonary embolus. Patients should seek immediate help if they develop sudden shortness of breath, chest pain and/or only one swollen, red and painful calf. Fortunately, this is a rare side effect.

What is Tamoxifen?

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