Very interesting article/origins of Tamoxifen~
Comments
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"Therefore, while tamoxifen is anti-estrogenic to the breast, it also acts as an estrogen to the uterus and, to a lesser extent, the heart, blood vessels and bone. So, although it initially showed the tendency to counter breast cancer recurrence, it would soon be revealed that it also promoted particularly aggressive uterine and liver cancers, caused fatal blood clots and interfered with many other functions"
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You have to look at it from a ratio of benefit to cost and make a personal decision. For many women with ER+ cancer it improves the odds they will be around 15 years later. The incidence of fatal side effects is low compared to the lives it saves from breast cancer recurrance. Typically the uteris is monitored by ultrasound and biopsy if problems are suspected, and they can be caught very early.
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Thanks, Timothy. While not perfect and not a 100% guarantee against recurrence or se's, you have to look at the risks vs. rewards. For many, many women it has been a game changer.
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Here is a study that looked at the use of tamoxifen for the prevention of breast cancer. Thousands of healthy women were given tamoxifen for 5 years and the side effects were observed and tabulated. The article above, seems to blow the risk out of proportion, talks about rats getting cancer from it, and never states the actual rate at which women get endometrial cancer from it. It talks about liver cancer, but that doesn't seem to be prevalent at all in women. It seems like scare tactics to me.
http://www.ncbi.nlm.nih.gov/pubmed/9747868
Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study.
Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N.Source
National Surgical Adjuvant Breast and Bowel Project, Allegheny University of the Health Sciences, Pittsburgh, PA 15212-5234, USA. BFISHER1@aherf.edu
Abstract
BACKGROUND:
The finding of a decrease in contralateral breast cancer incidence following tamoxifen administration for adjuvant therapy led to the concept that the drug might play a role in breast cancer prevention. To test this hypothesis, the National Surgical Adjuvant Breast and Bowel Project initiated the Breast Cancer Prevention Trial (P-1) in 1992.
METHODS:
Women (N=13388) at increased risk for breast cancer because they 1) were 60 years of age or older, 2) were 35-59 years of age with a 5-year predicted risk for breast cancer of at least 1.66%, or 3) had a history of lobular carcinoma in situ were randomly assigned to receive placebo (n=6707) or 20 mg/day tamoxifen (n=6681) for 5 years. Gail's algorithm, based on a multivariate logistic regression model using combinations of risk factors, was used to estimate the probability (risk) of occurrence of breast cancer over time.
RESULTS:
Tamoxifen reduced the risk of invasive breast cancer by 49% (two-sided P<.00001), with cumulative incidence through 69 months of follow-up of 43.4 versus 22.0 per 1000 women in the placebo and tamoxifen groups, respectively. The decreased risk occurred in women aged 49 years or younger (44%), 50-59 years (51%), and 60 years or older (55%); risk was also reduced in women with a history of lobular carcinoma in situ (56%) or atypical hyperplasia (86%) and in those with any category of predicted 5-year risk. Tamoxifen reduced the risk of noninvasive breast cancer by 50% (two-sided P<.002). Tamoxifen reduced the occurrence of estrogen receptor-positive tumors by 69%, but no difference in the occurrence of estrogen receptor-negative tumors was seen. Tamoxifen administration did not alter the average annual rate of ischemic heart disease; however, a reduction in hip, radius (Colles'), and spine fractures was observed. The rate of endometrial cancer was increased in the tamoxifen group (risk ratio = 2.53; 95% confidence interval = 1.35-4.97); this increased risk occurred predominantly in women aged 50 years or older. All endometrial cancers in the tamoxifen group were stage I (localized disease); no endometrial cancer deaths have occurred in this group. No liver cancers or increase in colon, rectal, ovarian, or other tumors was observed in the tamoxifen group. The rates of stroke, pulmonary embolism, and deep-vein thrombosis were elevated in the tamoxifen group; these events occurred more frequently in women aged 50 years or older.
CONCLUSIONS:
Tamoxifen decreases the incidence of invasive and noninvasive breast cancer. Despite side effects resulting from administration of tamoxifen, its use as a breast cancer preventive agent is appropriate in many women at increased risk for the disease.
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http://www.cancer.gov/newscenter/qa/2006/starresultsqandA
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How many participants developed uterine cancer?
In STAR, more than half of the women entered the trial having had a hysterectomy. Women without a uterus are not at risk of uterine cancer. For those women in the trial with a uterus, the women in the raloxifene group developed 45 percent fewer uterine cancers during the trial, a statistically significant reduction: 65 of 4,739 women in the tamoxifen group developed uterine cancers compared to 37 of the 4,717 women in the raloxifene group. Tamoxifen is known to increase a woman's chance of developing uterine cancer (mostly in the lining of the uterus or endometrium) by two to three times compared to a woman not taking the drug The annual incidence rate of uterine cancer is 2.25 per 1,000 women taking tamoxifen and 1.23 per 1,000 women taking raloxifene after almost 7 years. -- -
How many participants developed blood clots?
Both tamoxifen and raloxifene are known to increase a woman's chance of developing blood clots by up to three times that of women who are not taking either drug. In STAR, women in the raloxifene group had 28 percent fewer deep-vein thromboses (blood clots in a major vein) and 20 percent fewer pulmonary embolisms (blood clots in the lung) than women on tamoxifen: 118 of 9,736 women in the tamoxifen group had a deep-vein thrombosis compared to 86 of 9,754 women in the raloxifene group. In addition, 84 of 9,736 women in the tamoxifen group had a pulmonary embolism compared to 68 of 9,754 women in the raloxifene group. The average annual rate of either kind of blood clot was 3.3 per 1,000 women taking tamoxifen and 2.5 per 1,000 women taking raloxifene after almost 7 years.
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Thank you so much, Timothy, for providing the necessary perspective. I'm on Tamoxifen myself, and feel pretty comfortable with that. For me the benefits outweigh the risks by far. Nothing in life is without risk anyway - it's the nature of the beast.
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Timothy et al,
It is easy to get blindsided when considering the pro's and the con's for any drug, since long-term usage on a wide basis is still minimal, and because reported cause of death still can be listed as due to diseases initiated by the use of a drug instead of being attributed to the drug. Because of that, I question the limited information about this drug even with its long history of use for breast cancer.
Here's why I think more questioning for the extended use of this drug is warranted:
1. The overwhelming majority of breast cancer patients are HR+, and tamoxifen is the drug of choice for any who are not completely menopausal, which includes some women into their late 50's/early 60's (whether or not they are still menstruating).
2. The overwhelming majority of breast cancers are diagnosed in women.
3. The overwhelming majority of breast cancer patients are diagnosed with bc over the age of 50.
4. Initial bc treatment often involves chemotherapy drugs that significantly impact the autoimmune system.
5. The S/S are not often attributed to the actual cause until later stages of development.
6. About 90% of those diagnosed with PBC are women.
Although PBC (primary biliary cirrhosis) is still evaluated as being a rare disease among the general population of women, the difficulty here is that this particular population is more vulnerable to it, and to having the S/S ignored until late for the best known treatment to be successful.
http://www.ojrd.com/content/3/1/1
A.A.
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AA...Thanks SO much for that info!!!
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Joellelee,
I am questioning the steadily increasing length of treatment with tamoxifen.
I may have personally benefitted from the use of it, short-term.
Imaging during a very brief initial period of use may provide a basis for who benefits from taking it, or the degree to which there is any benefit, allowing those who do benefit from it to take it for a more limited period of time, or to avoid taking it for "nothing", and allowing women to avoid many SE's on a long-term basis:
See my post of March 30th in the hormonal treatment forum thread, "Is Anyone on a Half-dose of Tamoxifen."
A.A.
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There is also an herbal alternative to Tamoxifen I am looking into called TAMWO..
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2012 Article about breast density as a way of measuring effectiveness of tamoxifen:
http://breast-cancer-research.com/content/14/4/R114
In addition, research has indicated that having a high AIB1 level is another indicator that tamoxifen may not be effective for HER2 positive patients in particular. I am not certain whether the actual testing for AIB1 is available for patient access at this point, or whether it is limited to use in clinical trials. I've seen it referred to as one form of IHC (immunohistochemistry) but it may be that additional testing of other types is required in addition to IHC, for more accuracy.
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