Talk:Tamoxifen

Olof H. Pearson

Olof H.Pearson MD, an endocrinologist and oncologist, did the first research into the use of antiestrogens to treat breast cancer and was the first physician to use steroid hormones to treat lymphomas. He discovered that the hormone prolactin stimulated breast cancer growth and showed that removing the pituitary, the source of the hormone, could lengthen patients' lives. He later helped develop drugs that blocked the hormone without the need for surgery. Today, the antiestrogen tamoxifen routinely is used to treat breast cancer and prevent recurrences after surgery or radiation.

He initially experimented with using cortisone and other adrenal corticosteroid hormones to treat lymphoma and leukemia in the 1940s.

A native of Boston, Pearson earned his medical degree at Harvard Medical School in 1939. He served as flight surgeon and medical director for Pan American World Airways in North America during World War II. He taught at the Harvard and Cornell medical schools and worked at the Sloan-Kettering Institute before joining the faculty of the CWRU School of Medicine and the staff of University Hospitals of Cleveland in 1960. He retired in 1988 and passed away in 1990. 68.51.226.87 (talk · contribs)

Perhaps this should go on Olof Pearson. Is this your own work or copied from elsewhere? JFW | T@lk 12:39, 11 December 2005 (UTC)

Identified in early 1960s

Note that tamoxifen was identified in the early 1960s as an antiestrogen. The team thought that by inhibiting oestrogen in the uterus, tamoxifen might block pregnancy and act as a "morning after pill". However, later studies showed that instead of preventing pregnancy, it enhanced the chances of pregnancy in subfertile women.

Side Effects

I haven't got time at the moment as I'm revising for my finals, but this article ought to mention the side effects of Tamoxifen. My oncology lecturer mentioned that whilst the incidence of breast cancer is reduced, other cancers increase in frequency and that overall mortality of breast cancer patients is not significantly improved when using the drug. I haven't had chance to read any related journal articles in detail, but once I have time I will have look. --Shastrix 14:03, 17 March 2006 (UTC)

Excellent idea, now that Raloxifene has been shown to be just as effective, but has fewer side effects. Brian Sayrs 00:48, 18 April 2006 (UTC)

I added some clarification about the tradeoff issue (less risk of breast cancer, more risk of uterine cancer) which you could add on to if you find the citation about the average net risk reduction not being statistically significant.Youngea (talk) 06:32, 22 March 2008 (UTC)

I would like to request on behalf of the patients that may arrive here that someone please expand the section on side effects. It is my (non-medical) understanding that despite its side effects this is still an important treatment in pre-menopausal and peri-menopausal women, but the article does not make that clear if that's a correct statement; also there seems to be conflicting literature as to whether this drug does or does not cause cognitive difficulties. My understanding is that the answer is currently "maybe" but that the benefits are so clear-cut that the risk is considered worth taking. Again, I am not certain that this summary is correct and therefore do not want to edit the page. But that is the question I came here wondering about and it is currently not well addressed. 75.149.44.10 (talk) 06:59, 6 March 2011 (UTC) elinruby

The bit about how a tamoxifen user's significant other isn't told that their partner will enter early menopause seems a bit odd. I don't know how I'd go about changing it; does someone wanna take a look at it? --Younmm23 13:08, 2 September 2007 (UTC)

• I also found this newly added text odd. In addition, this statement is not backed up by a citation. I have attempted to find clinical trials that report the prevalence of libido reduction in pre-menopausal women but have been unsuccessful. Approximately 1/3 of post-menopausal women report reduction in libido, so it would not be too surprising if pre-menopausal women also experienced reduction in libido, but again, I cannot find hard data to support this. All I can do at this point is to add a "citation needed" template. Boghog2 16:42, 2 September 2007 (UTC)

• I didn't mean that it was weird it causes early menopause; the part about the mentioning to the spouse was bizarre. Listing that as a side effect (i.e. spouses not finding out about something). Not finding out something about your spouse is a communication issue, NOT a side effect of a drug. --143.200.225.126 05:11, 10 September 2007 (UTC)

• Please note that I used the phrase "in addition" to describe my concern that there was no citation. I totally agree that mentioning the spouse was bizarre. Boghog2 06:58, 10 September 2007 (UTC)

• Oops, sorry, guess thats what I get for wikipedia-ing on 4 hours of sleep.--Younmm23 12:01, 14 September 2007 (UTC)

• No problem. Cheers. Boghog2 14:47, 14 September 2007 (UTC)

I didn't want to edit the page, because I am not very knowledgeable on the topic (and I'm not quite familiar with editing articles), but I did notice that the article says Tamoxifen is only recommended for 5 years, whereas the Committee on Gynecological practice extended recommendation to 10 years (http://dx.doi.org/10.1097/01.AOG.0000450757.18294.cf). — Preceding unsigned comment added by 130.64.35.139 (talk) 01:51, 20 October 2014 (UTC)

Question

Is there a proposed mechanism of action for tamoxifen as there is for Gleevec or other targeted therapies?

• Great question that points to a weakness in this article. Tamoxifen's mechanism of action in breast cancer is as a estrogen receptor (ER) antagonist (especially through the ER-alpha isoform). In addition, breast cancers may become resistant to tamoxifen through mutations of the ER which convert tamoxifen from an antagonist into an agonist. Finally tamoxifen also binds to GPR30 and interestingly functions, like estradiol, as an agonist through this receptor. This significance of agonism through GPR30 is not clear but it may result in pro-proliferative effects that may partially counter act the antagonist effects through ER-alpha. I will add a expand the mechanism of action section when I get a chance. Boghog2 21:37, 11 September 2007 (UTC)

Ormeloxifene main article needs editors

I've tried posting in Wikiproject:Clinical medicine, and have found few who know anything about ormeloxifene. Especially needed are chemists, scientists, and doctors who are knowledgable about this SERM. Thank you! -- Joie de Vivre 14:40, 14 December 2006 (UTC)

Estrogen = Oestrogen?

Are these the same? Using a consistent spelling would make the article clearer. —The preceding unsigned comment was added by 68.190.123.114 (talk) 21:02, 17 December 2006 (UTC).

• Yes, Estrogen (American spelling) = Oestrogen (British spelling). For consistency, I have replace all occurences of "Oestrogen" with "Estrogen". Boghog2 21:43, 11 September 2007 (UTC)

Other uses of Tamoxifen

What about a short note regarding the other uses of Tamoxifen, such as in genetics experiments - ie tamoxifen-inducible Cre mediated recombination?

• Now included. Boghog2 21:47, 11 September 2007 (UTC)

Transgender men

Is tamoxifen used in treatment of FTM transsexuals? I've seen it referenced on several transgender health sites, and it seems like the sort of thing that might be useful to mention in the article, but I'm not very educated endocrinology-wise and didn't want to put it in myself. Switchercat ^talk_cont 17:14, 13 October 2007 (UTC)

If you provide references to the sites where it is mentioned, I'm sure other editors can help determine whether the information is suitable to add based on its source and its quality.Youngea (talk) 06:34, 22 March 2008 (UTC)

Figure

The figure of the Tamoxifen molecular structure is way too big but I do not know how to decrease the size of it. Anybody does? —Preceding unsigned comment added by Bteunissen (talk • contribs) 15:25, 26 March 2008 (UTC)

Something incorrect in this article

In the section of "Comparative studies"

In 2006, the large STAR clinical study concluded that raloxifene is equally effective in reducing the incidence of breast cancer, but after an average 4-year follow-up there were 36 % fewer uterine cancers and 29 % fewer blood clots than in women taking raloxifen.[4][5]

The last line: ... than in women taking "raloxifene". It should be corrected to be "tamoxifen".

The origin resource: National cancer institute "STAR trial" (http://www.cancer.gov/star) —Preceding unsigned comment added by 203.64.247.74 (talk) 04:10, 16 February 2009 (UTC)

corrected in this edit Boghog2 (talk) 20:49, 25 March 2009 (UTC)

Also, in chapter "Market": does a month of Tamoxifen tablets really cost £1.90 in UK (40-100 dollars in US)? —Preceding unsigned comment added by 194.215.240.253 (talk) 09:46, 7 July 2009 (UTC)

Tamoxifen sales

It is difficult to find definitive numbers for the number of breast cancer patients on tamoxifen vs. other therapeutics. Part of the reason is tamoxifen has gone off patent and is now available from several manufacturers making it harder to obtain the total number of prescriptions written. Also the most common source of these figures are from research firms like IMS Health and the figures are contained in pricey reports (see here for a summary, one would require the complete report to make the comparison).

The closest I could find is here where it is written:

In G6 countries, 2004

Approximately 880,000 patients currently on Tamoxifen (Estimated avg. yearly hormonal-treated population, both new and continuing)

Approximately 200,000 generally treated with aromatase inhibitors

Certainly the use aromatase inhibitors is increasing at the expense of tamoxifen and other much less used antiestrogens (i.e., toremifene and fulvestrant; please note that raloxifene is currently approved for prevention but not treatment of breast cancer). The market for aromatase inhibitors is also split (but more evenly) between several competitors (aminoglutethimide, formestane, anastrozole, fadrozole, letrozole, exemestane). So almost certainly tamoxifen would remain the single largest prescribed drug for breast cancer treatment, even if unit sales of aromatase inhibitors collectively have exceeded tamoxifen.

Therefore the statement "tamoxifen is currently the world's largest selling drug for breast cancer treatment" is almost certainly still correct, especially considering it is now generic and is significantly cheaper than aromatase inhibitors which are all still protected by patents. Unfortunately it is difficult to document this. Cheers. Boghog2 (talk) 20:49, 25 March 2009 (UTC)

OK: here is a fairly solid reference for 2004: Vose B. "AstraZenecain Cancer: Slide #15:" (PDF). AstraZeneca Annual Business Review. www.astrazeneca.se. Retrieved 2009-03-28. 2004 tamoxifen market share: 70% Source: IMS HEALTH, IMS MIDAS Monthly. July 2004. Aromatase Inhibitors + Tamoxifen {{cite web}}: Cite has empty unknown parameter: |coauthors= (help)

Requests

I would like to see a more detailed explanation of tamoxifen's side effects and how it acts on tissues in the body besides breast and bone.

I heard a researcher argue in a "research in progress" talk that estrogen affects verbal fluency. How does tamoxifen act in the brain, as a agonist or an antagonist? If it can be used to treat mania, how does it affect brains not suffering from bipolar disorder? How about in other tissues like the skin? And why does it cause a vaginal discharge--is this a result of antagonist or agonist activity?

Also, it has not been satisfactorily explained to me how tamoxifen affects ovulation and menstruation. Is it possible while taking tamoxifen to ovulate but not menstruate shortly thereafter? Or is ovulation always followed by menstruation unless pregnancy occurs? Does taking tamoxifen for breast cancer treatment change ovulation patterns, and if so, how? Does tamoxifen damage eggs that have not yet come down the pipe?Zinevra (talk) 22:29, 17 April 2009 (UTC)

Definition of competitive antagonist

The opening stub for Tamoxifin describes what a competitive antagonist with a simplified analogy regarding a broken key in a lock. For brevity's sake, it seems more appropriate to simply link to a page that explains what a competitive antagonist is. — Preceding unsigned comment added by MatthewMacd (talk • contribs) 03:21, 8 February 2011 (UTC)

Normally the use of analogies is discouraged since not all may be familiar with the analog. However I think virtually everyone is familiar with locks & keys. Furthermore the lock & key model of drug/receptor interaction is widely used. Finally the lead section of these articles need to be kept dead simple and understandable by a wide audience. In this context, I think the broken key analogy for a receptor antagonist is effective and appropriate. Boghog (talk) 20:33, 13 February 2011 (UTC)

Vitamin D serum levels

Tamoxifen lowers vitamin D serum levels (probably 25(OH)D3): http://www.youtube.com/watch?v=_uUDZ8Kx7L8&t=27m40s

Would be nice if someone looked up papers and integrated it into a paper. While Carole Baggerly is very knowledgable about breast cancer treatment and vitamin D, linking to a video might not be appropriate.. — Preceding unsigned comment added by 80.101.80.116 (talk) 14:48, 25 September 2011 (UTC)

Anabolic steroids

I think it should be mentioned that Tamoxifen is frequently taken by users of anabolic steroids in post cycle therapy. Perhaps someone more knowledgeable than me in this area could contribute. 88.88.94.217 (talk) 18:44, 24 November 2011 (UTC)

Tamoxifen vs. Raloxifene update

Hey Im not a regular contibuter or anything, but there is an update on the STAR trial showing new evidence showing raloxifene having statistically significant fewer side effects, it should be included. http://cancerpreventionresearch.aacrjournals.org/content/3/6/696.full

Pharmacogenetics and drug interactions

Pharmacogenetics and drug interactions

This part seems highly biased and seems to be supported by the DNA testing industry (link to an diagnostics site as a reference....). New studies show, that CYP2D6 genotype does not predict outcome / tamoxifen benefit.

The FDA is not recommending CYP2D6-testing anymore, CYP2D6 is not on the label anymore! Maybe someone with more wiki-experience can clean this up. 87.78.14.112 (talk) 14:47, 14 November 2013 (UTC)

External links modified

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Tamoxifen linked with depression.

The first thing that caught my eye was how TX seems to inhibit CYP2D6, an enzyme not only responsible for detoxifiation, but also synthesis of vital neurosteroids. And sure-enough, after very little digging i found a couple articles linking Tamoxifen to clinical depression:

http://jnci.oxfordjournals.org/content/93/21/1615.full http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2910997/

Please consider adding this vital and potentially life-saving information to the main body of the article. — Preceding unsigned comment added by NeferiusNexus (talk • contribs) 23:53, 10 March 2016 (UTC)

Central nervous system

• It says: "Tamoxifen-treated breast cancer patients show evidence of reduced cognition"

That's one study, with less than 800 subjects. The 'interpretation' section of the abstract says: "Our study suggests that current use of tamoxifen may adversely effect cognition. Further study of tamoxifen and cognition is needed so that healthy women considering tamoxifen for the primary prevention of breast cancer have comprehensive information about the side effects of the treatment."

So I would like to significantly weaken the claim in the article, to something like "have shown some evidence".

• It goes on to say that this effect is "a major side effect of tamoxifen".

The citation following that rather strong supplemental claim says nothing of the sort; so I am removing it as uncited. MrDemeanour (talk) 14:36, 22 November 2018 (UTC)

Collapsed table via template

User:Medgirl131, the template you added to Tamoxifen#History doesn't seem to be working correctly. It's partly off the screen for me, and I think MOS:COLLAPSE indicates that it shouldn't be collapsed. Do you know how to fix it? (Ping me if you need help – this page isn't on my watchlist.) WhatamIdoing (talk) 22:19, 20 June 2020 (UTC)