Test+3+Tamox

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What is Tamoxifen?
Tamoxifen is a competitive inhibitor of the estrogen receptor. It is part of a class of drugs called selective estrogen-receptor modulators (SERM). These drugs can act as an inhibitor or analogue of estrogen depending on the type of tissue it is in. In breast cancer, it is anti-estrogenic. It's two metabolites, N-desmethyltamoxifen and trans-4-hydroxytamoxifen, are what causes it's drug activity. The trans conformation and dimethylation are crucial for tamoxifen activity and account for the metabolites' affinity to the estrogen receptor. Tamoxifen was first used in the prevention of breast cancer recurrence, but in 1998 was approved by the FDA to be used for breast cancer chemoprevention after the Breast Cancer Prevention Trial started in 1992. Tamoxifen is taken orally daily at a dose of 20 mg per day for five years.



**What are the side effects?**
General side effects of Nolvadex include endometrial cancer, deep vein thrombosis, pulmonary embolism, stroke, and cataract formation. The mechanism of endometrial cancer is unknown, but it has an estrogen-like effect. However among metastatic breast cancer patients [|hypercalcemia], increased bone/tumor pain, distaste for food, depression, vaginal dryness, and peripheral edema have been reported within weeks of treatment. Pregnant women are discouraged from taking Nolvadex since treatment may cause fetal death or birth defects. Some common side effects premenopausal women experience are menopause-like symptoms: hot flashes, vaginal discharge, and irregular menses.




 * 1) Major symptoms include :
 * Blood clots
 * Endometrial cancer
 * Uterine sarcomas
 * Strokes
 * Cataracts
 * 1) Minor symptoms include :
 * Menopausal symptoms
 * hot flashes
 * vaginal discharge
 * Fatigue
 * Nausea
 * Vomitting

**What are Tamoxifen's Uses?**
 Tamoxifen is used as an [|adjuvant drug] in postmenopausal women and a preventative drug in cancer treatment for estrogen receptor positive breast cancers in pre- and post-menopausal women. Nolvadex, tamoxifen brand drug, reduces contralateral breast cancer in patients receiving adjuvant therapy as well as reduce the incidence of breast cancer in women with high risk. It is also a hormone therapy for men with breast cancer. More obscure uses include treatment of bipolar disorder infertility.

    **What is breast cancer?**      Simply, breast cancer is an accumulation of malignant tumors in the breast. In women the breast is made up of lobules, ducts, and stroma. Lobules are the milk-producing glands, ducts are the tubes that carry the milk from the lobules to the nipple, and the stroma consists of the fatty and connective tissue.   <span class="wiki_link_ext"> <span class="wiki_link_ext">

<span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> Most breast cancers start in epithelial cells lining the ducts; these are called ductal cancers. Cancers in the cells that line the lobules are called lobule cancers. cancers can spread through the body due to the breast's proximity to the [|lymphatic system]. <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> // What types of breast cancer are there? //


 * //Is Tamoxifen a preventative drug for all breast cancer types?//
 * No, only for hormone receptor breast cancer//s//
 * //What does it mean to be at risk for breast cancer?//
 * //Who is at risk and how does that weigh into decision making about preventative medicine?//
 * //Are there other drug options available for those who want to prevent breast cancer?//

What are the FDA regulations concerning Tamoxifen?
The Food and Drug Administration (FDA) regulates and standardizes, local and foreign, products sold or prescribed to US inhabitants. The approval processes varies depending on the product. However, in accordance with our research question we shall focus on drug approval.

<span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> The following statements dictate what must be conducted for a drug to be a approved:

<span class="wiki_link_ext"> For a drug to be tested on humans the following must be conducted:
 * Comply with FDA's good laboratory practice rules (covers record-keeping, personnel training, animal handling, and equipment requirements)
 * Extensive preclinical testing in the lab on animals, including nonclinical tests
 * nonclinical tests provide information about how the drug functions
 * More than one clinical study on human beings (exception are drugs that treat biological, chemical or radiological toxicity ie. anthrax)


 * Submit appropriate application for an investigational new drug or investigational new animal drug
 * Specify how sponsoring institution and researcher plan to determine safety of the investigational new drug in humans
 * Investigational new drugs intended to treat serious illnesses are allowed to make the drug available to patients who are not part of the clinical trial

<span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext">Tamoxifen has multiple uses for breast cancer patients. These uses were discovered from the multiple trials that were conducted to test Nolvadex, a tamoxifen citrate, under FDA regulations.

<span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> __<span class="wiki_link_ext">Dosage and treatment length: __ <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> The proper dosage of Nolvadex was found in the first phase of the clinical trial conducted on rats.<span class="wiki_link_ext"> A carcinogenesis study in rats of all doses of Nolvadex found that tumors were most prevalent among rats treated with 20 or 35mg/day than those given 5mg/day. The incidence of carcinogenesis was greater among rats treated with 5mg/day of tamoxifen than those given a placebo. Therefore, from this stage scientists determined that 20mg/day or lower was a safe amount of tamoxifen that can be prescribed to a patient.

<span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext">Once the dose was set the amount of time a patient should be treated had to be identified. The Early Breast Cancer Trialists' Collaborative Group found a study that focused on women who were estrogen receptor positive. These women were treated with Nolvadex in varying lengths of time: 1 year<span class="wiki_link_ext">s, 2 year<span class="wiki_link_ext">s and 5 year<span class="wiki_link_ext">s. They found that women involved in the study had a reduced rate in breast cancer of 21%, 29% and 47% respectively. These results were independent of age and estrogen receptor status of the primary tumor. To confirm the length of time tamoxifen should be prescribed, the NSABP trial randomized treatment of Nolvadex (20mg/day) and placebo pills for 5 year<span class="wiki_link_ext">s and re-randomized treatment for an additional 5 year<span class="wiki_link_ext">s. They found that continuing hormone therapy beyond the 5 year period did not provide any additional benefit to the patient. Therefore, Nolvadex at this stage should not be taken longer than 5 years.

<span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> __<span class="wiki_link_ext"> Tamoxifen a s a breast cancer prevention drug<span class="wiki_link_ext">: __ <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext">Tamoxifen was initially reconigzed as a hormone therapy drug for early breast cancer patients. The Early Breast Cancer Trialists‚Äô Collaborative Group<span class="wiki_link_ext"> conducted an overview of systemic adjuvant therapy for these patients and found that tamoxifen-treated women who were estrogen receptor positive and had positive nodes had a slightly higher survival rate than placebo-treated women in the control group.This discovery provided an alternative form of treatment for breast cancer patients and was soon to be identified as a chemoprevention drug. T<span class="wiki_link_ext">he trial initiated by the National Cancer Institute<span class="wiki_link_ext"> revolutionized the pharmaceutical industry by supporting the prevention quality of tamoxifen.

<span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext">The Breast Cancer Prevention Trial (BCPT) was a double-blind randomized trial that analyzed the role of Nolvadex in the reduced incidence of invasive breast cancer in high risk women. The study also sought to evaluate the incidence of ischemic heart disease and observe the incidence of bone fractures. The Gail Model was used to calculate the predicted risk for breast cancer of the women participants. Risk factors include but are not limited to: age, number of 1st degree female relatives with breast cancer, previous breast biopsies, presence/absence of atypical hyperplasia, and age at menarche. Based on the Gail Model, all trial participants must have a predicted risk of greater than or equal to 1.67% of contracting breast cancer within 5 years. The BCPT found that 44% of the women assigned to Nolvadex had a reduced incidence of invasive breast cancer, among all ages and women with or without lobular carcinoma in situ. There was no significant difference of ischemic heart disease related events, breast cancer-related mortality or hip fractures between the two treatment groups. However, Nolvadex decreased the incidence of small estrogen receptor positive tumors and not estrogen receptor negative tumors. Based on these findings Nolvadex is proven to be an adjuvant drug and a chemoprevention drug for women at risk.

<span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext">Now that we know Nolvadex is safe for the general population of women, how does it affect pregnant women? <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext">A clinical phase 1 study conducted on pregnant rabbits found a lower incidence of embryo implantation and higher incidence of fetal death or utero growth and low learning behavior among those treated with Nolvadex. In fact, treating rabbits 0.125mg/kg during day 6-18 of pregnancy resulted in an abortion or a premature delivery. An additional study on rats found a decreased fertility after 0.04mg/kg for two weeks prior to mating through day 7 of pregnancy. All fetuses were found dead and there was a significant decrease in the number of implantations. Based on the detrimental effects of fetal death/ reduced fertility found in animals, no clinical trial of pregnant women was conducted. Therefore, tamoxifen must not be taken if women are pregnant or believe they may be pregnant. Whether tamoxifen is safe to treat women who are breast feeding is questionable since more studies need to be done to determine if tamoxifen can be excreted in human milk.

<span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext"> <span class="wiki_link_ext">It is unknown if Nolvadex delays the appearance of cancer or actually decreases the number of tumors that will develop since long-term studies have not been completed. The FDA approved and recommended dose for breast cancer patients, whether at risk or fighting the disease, is 20mg for 5yrs.