Tamoxifen Citrate

Tamoxifen Citrate
Introduction
Tamoxifen citrate is an estrogen receptor antagonist and partial agonist which has been shown
to induce apoptosis in human malignant glioma cells and to block VEGF production in breast
cancer cells. The structure of tamoxifen citrate is showed in figure 1.
Fig. 1 Structure of tamoxifen citrate
Function of tamoxifen citrate in the treatment of breast cancer
Introduction of breast cancer
About one-fifth of cancer patients suffer from breast cancer worldwide. Breast cancer is cancer
that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a
change in breast shape, dimpling of the skin, fluid coming from the nipple, a newly inverted
nipple, or a red or scaly patch of skin. In those with distant spread of the disease, there may be
bone pain, swollen lymph nodes, shortness of breath, or yellow skin. Figure 2 shows the types of
breast cancer.

Fig. 2 Types of breast cancer
Various chemotherapeutic agents are used to treat the breast cancer, such as letrozole,
anastrozole, exemestane, goserelin, leuprorelin, etc. Among the plenty of APIs, tamoxifen citrate
is a nonsteroidal weak estrogen that has found successful applications for each stage of breast
cancer in the treatment of selected patients.
Mechanism of action
In 1973, tamoxifen citrate was approved by the UK Committee on the Safety of Medicines for the
treatment of breast cancer. Tamoxifen citrate subsequently became available in more than 110
countries as first-line endocrine therapy for the treatment of breast cancer.
Tamoxifen is a type of hormonal therapy known as a selective estrogen receptor modulator
(SERM). The drug attaches to hormone receptors (specific proteins) in breast cancer cells. Once
the medication is inside the cells, it stops the cancer from accessing the hormones they need to
multiply and grow.
Although tamoxifen exhibits direct anti-estrogenic activity, it is best thought of as a pro-drug.
Metabolism generates several metabolites of tamoxifen. Two of these metabolites,
4-hydroxy-tamoxifen and 4-hydroxy-N-desmethyltamoxifen, exhibit much greater anti-estrogenic
effects compared with tamoxifen. The minor metabolites – metabolite-Y, metabolite-Z, and
4-hydroxy-N-desmethyltamoxifen – all contribute to the antitumor actions of tamoxifen because
they are all antiestrogens that inhibit the binding of estradiol to the estrogen receptor.

Fig. 3 The metabolism of tamoxifen is humans
The results from the in vivo DMBA studies demonstrated that a 1-month course of tamoxifen
therapy in rats given 1 month after the carcinogenic insult only delayed the appearance of
mammary tumors; continuous therapy for 6 months, on the other hand, resulted in 90% of the
animals remaining tumor free. Indeed, tumors appeared whenever tamoxifen therapy was
stopped. Thus, tamoxifen was shown to have a tumoristatic component to its mode of action and
the laboratory results indicated that long-term (up to 5 years) or indefinite therapy might be the
best clinical strategy for adjuvant tamoxifen treatment.
Side effects of tamoxifen citrate
Serious side effects:
o
o
o
o
o
vision changes
easy bruising or bleeding
swelling of the ankles or feet
eye pain
mood changes

o
unusual tiredness
Common side effects:
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
hot flashes
changes in menstrual periods
leg cramps
bone pain
cough
fatigue
headache
loss of sexual ability/interest (in men)
flushing
nausea
abdominal cramps
muscle pain
swelling
hair thinning
depression
References
1. V.C.Jordan. Tamoxifen. Comprehensive Medicinal Chemistry II, 2007,8: 83-102.
2. Michael C. Milone. Therapeutic Drug Monitoring of Selected Anticancer
Drugs. Therapeutic Drug Monitoring, 2012: 291-321.
3. Tamoxifen Citrate - API / Alfa Chemistry (alfa-api.com)