Talk:Trastuzumab

Too technical ? - Need less technical version as well ?

Boy, I do agree the article is a tad too technical. I grasped a bit what he or she is saying, but had my moments of scratching my head. But wouldn't making it easier to read be downgrading the quality of the article for the more knowledgable? In my opinion, I would recommend writing a less technical link and putting a pointer to the more accessable article somewhere on the top of this article. Wk muriithi (talk · contribs).

If you want this, I would recommend starting a new version on Trastuzumab/Temp, putting everything there that you know, and discuss this version here. JFW | T@lk 10:28, 23 October 2005 (UTC)

What specifically were you having the most problems with in your understanding? Courtland 03:01, 19 December 2005 (UTC)

Use for other cancers

This article says that Herceptin is only used to treat certain breast cancers. That is inaccurate, and should be updated. All the disputes I read here about technical language vs simple language for the average reader.....how about ACCURACY in what the drug is used for??? My husband is receiving Herceptin for liver mets from esophageal junction cancer. The liver mets was discovered in July of 2011; at that time Herceptin had recently been approved for use in some HER2+ GI cancers. This article was updated in January of 2013, yet doesn't even mention that Herceptin is now used for other types of cancer besides breast cancer. I think that's an important fact & should be included in this article. Some dates, such as when it was first approved for breast cancer, and then updates on what types of cancer it is being used for, & what types of cancer have ongoing research concerning treatment with Herceptin, would be very helpful to cancer patients & their families when they are trying to research treatments. I have talked to many esophageal cancer patients & their families in on-line support groups that are looking for info on Herceptin, & can't find anything about it being used for esophageal cancer.....these are updates that should be included in this article if you are truly trying to help the average person looking for information on cancer treatment.Redcct (talk) 16:47, 25 January 2013 (UTC)redcct

I agree the application of Herceptin needs to be updated in the article. 15 to 20% of gastric cancers are HER2 positive. Herceptin is FDA approved for Stage III and IV gastric cancer. I am currently getting adjuvant therapy for gastric cancer using Herceptin. — Preceding unsigned comment added by 72.47.86.68 (talk) 03:33, 11 March 2015 (UTC)

Side Effects

although this drug claims to have only one side effect, that being on the heart, my mother-in-law sufferred from severe anxiety while taking this drug. given, she was going through major crisis with her diagnosis and treatment. even when her chemo ended and she was still taking herceptin however, she experienced anxiety that prevented her from sleeping and making day-to-day decisions. just wondering if anyone else has experienced similiar side effects and/or knows someone who may have sufferred as she did.

It has far more than 1 side effect. It's just that the heart effect is the most important common effect. Anyway, this isn't really the place for discussion about anaecdotal evidence. Besides, it's pretty likely that somebody suffering with cancer develop anxiety irrespective of any medication they're on.128.250.5.246 (talk) 13:36, 26 April 2009 (UTC)

Costs

It says in Australia it will cost the PBS (Pharmaceutical Benefits Scheme) $1 million a year. that does not sound right. In a press release on the health.gov.au website it said herceptin would cost $470 million over around 4 years.

I agree: http://www.medicare.gov.au/provider/patients/late-breast-cancer.jsp talks about patients for Herceptin in the thousands - it can't possibly be costing $1m. Perhaps it's a typo for $100m? —Preceding unsigned comment added by 124.181.12.197 (talk) 01:51, 14 August 2008 (UTC)

Should jsut remove the whole section on Australia. The 1 million thing is clearly incorrect, and there just doesn't seem to be enough to warrant Australia by itself.128.250.5.246 (talk) 13:40, 26 April 2009 (UTC)

I thought the article is very well written as is, but the Australian bit seems very out of place, with no reference, a questionable figure, and a quick anecdote. I think it should be either fixed, or removed.216.123.198.2 16:42, 11 June 2007 (UTC)

24 Sept 2009: This has now been corrected with the appropriate figure (A$470,000,000) and a reference.

Absurdity ! (info not explicit)

It is a big absurdity to write an article about a medicine like this and say nothing about: A. Where it comes from B. How it is made: is it a natural product from some plant or animal, or is it a totally synthetic chemical product? C. How it is purified, or what kind of chemical processing does it need? For example, there is natural penicillin that comes from a kind of a mold, there is an elaborate purification process, and the kinds of penicillin that are used now have to be chemically modified in factories to make a useful product. D. As far as I can tell, the article doesn't even say what company processes and distributes it. E. For another example, it is widely-known that the anti-cancer drug Taxol is made by the Pacific Yew Tree, and then processed into a usable form. F. There is no information about it molecular form, not even its molecular weight, and nothing about what solvents it is soluble in - and especially not the solvent that is used to dissolve it for injection or intravenous injection.

Someone is so involved in the esoterics and controversies of this drug that they have completely omitted to put in anything about the basic information about it. The history section is also extremely sketchy.74.163.36.44 (talk) 01:19, 19 October 2008 (UTC)

Since "Wikipedia is an encyclopedia that anyone can edit", most omissions in articles occur because, well, no one has gotten around to adding it to the article. If you have information based on reliable sources, please add it. As for your specific comments:

A, B, & C. The article notes that "Trastuzumab is a humanized monoclonal antibody". Following the monoclonal antibody link explains the process of generating them in a lab.

D. "The biotech company Genentech gained FDA approval for trastuzumab in September 1998. The drug was jointly developed by that company, where the antibody was first discovered..."

E & F. As an antibody, the concepts of molecular weight and solubility don't really apply in any meaningful way.

-- MarcoTolo (talk) 02:16, 19 October 2008 (UTC)

Less technical

I rewrote this a bit to make it less technical, particularly in the introduction.

Molecular biologists will be relieved to see that I didn't take anything out (although I did rewrite some of it into simple English).

I like to leave in the technical terms, so people will recognize them when they come upon them again, but only after I've explained it in language that the reader can understand. Nbauman (talk) 18:34, 8 March 2009 (UTC)

it would be simpler, and IMO much better, to just hyperlink the technical terms so that a reader can click thru to learn about the terms they are not familiar with. Anyone disagree ? - Rod57 (talk) 22:50, 6 October 2012 (UTC)

I am a molecular biologist and I think the intro is still too technical. What for example is hazard ratio? I am more used to seeing log-odds ratios or p-values based on the magnitude of the effect. Marchino61 (talk) 05:39, 2 September 2015 (UTC)

Other side effects of Trastuzumab known as Herceptin (eg weight gain, heart effects)

May 13, 2009, I have found that I gained wieght in the abominal area, I wondered why because I don't eat much food. I can't because my stomach feels full on just a glass of water. So I asked on my breast cancer site if any other women were gaining wieght. More that 60 women replied that they all gained weight especially, in the stomach area. I tried dieting, which I have never ever had to do and exercise and nothing helped the weight gain. But so many women were very happy that I posted this complaint about herceptin (Trastuzumab) many of the women were told by there onocologists, that it was age, previous chemotherepy etc. I was completely off of any chemotherepy for 11 months before I started Trastuzumab and the wieght gain started on the third treatment. One of the ladies that finished herceptin said it took her three months of dieting and steady excerise to finally get rid of the spare tire. I am wondering if any women (not) on my bc site have had the same side effect. Also I in the side effects section if you look up traztuzumab it can cause agitation. Having Cancer can cause nerves to fray, but the agitation I feel is a different feeling like a panic attack right out of the blue and it can happen at anytime. I for one can't wait to finish my year of herceptin I have 7 treatments left and with each treatment it feels like playing russian roulette with my heart. I really dislike the thought that it can cause heart problems. and is a side effect of this monoclonal antibody. And the reason Austrailia was mentioned was because Austrailia and Finland did there own studies on Trastuzumab and found it was effective if given for nine weeks and did not cause cardio side effects. I found the Finnish Study and it has led me to wonder why Trastuzumab is given for 53 or for some women 104 week of therepy. It's usually infused every three weeks. Somehow the above drug was fast tracked into the systme and I can't find any long term studies on Cardiac effects and this drug was given in trials in 1990. When I looked for this information I googled Finland and Trastuzumab Clinical Trials, and Austrailia and Clinical Trials, for Cardio side effects I looked up Trastuzumab and Heart Side effects. I also googled Herceptin and Hype and found many articles about how it was fast tracked. I hope this helps if anyone else is looking up this medication for Her2 Positive Breast Cancer. I still haven't found an answer on why the drug is used for such a long time when it can cause some nasty side effects.—Preceding unsigned comment added by Emmiegirl (talk • contribs) 16:27, 13 May 2009 (UTC)

The authorities generally don't require long-term trials to approve a drug - if they did, the drug would be off-patent before going on sale! Most trials are two years at most. The authorities then rely oh doctors reporting any dangers or side-effects. Each country has its own system for doing this. To the best of my knowledge, no drug has ever had a true long-term, double-blind trial. Such a trial could also be unethical because you would need to deprive the patients in the control group of a medication that has been shown to be superior to a placebo.

The reason is is prescribed despite the risk of heart disease is because the benefits are reckoned to outweigh the risk. As I understand it, Herceptin is a used to combat cancers that are resistant to other medications. Marchino61 (talk) 05:47, 2 September 2015 (UTC)

Overexpression, not mutation, of HER2 is a mechanism of human breast cancer

The last line in the 2nd paragraph, alleges that defects in HER2 cause cancer, and cites a reference:

...the HER2 receptor is defective and stuck in the "on" position, and causes breast cells to reproduce uncontrollably, causing breast cancer.

However, neither that reference nor other 2007 references claim that defects in HER2 receptors contribute to the uncontrolled cell growth that is malignancy. Instead they state that overexpression of HER2 can dysregulate cell growth. One possible mechanism admittedly is that overexpression can lead to cleavage of the extracellular domain while leaving the cytoplasmic domain (P95) free to stimulate cell growth. The refs emphasize the likelihood that two well-formed HER receptors form a dimer which activates cell-growth pathways. Furthermore, trastuzumab can only affect the receptor before cleavage, since it binds to the extracellular domain, so any claim in an article about trastuzumab, to the effect that defective HER2 is a mechanism of cancer, should note that limitation.

I therefore propose rewriting that sentence, replacing "defective" with "overexpressed", and possibly adding the ref:

G. Valabrega, F. Montemurro, M. Aglietta. Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer Annals of Oncology 18: 977–984, 2007 doi:10.1093/annonc/mdl475

A similar problem exists with a later sentence under Mechanism of Action, and its citation, "However, in cancer, HER2 sends signals without being stimulated by mitogens first (that is, they are constitutively transmitted). these signals promote invasion, survival and growth of blood vessels (angiogenesis) of cells.[6] ... [6] Ménard S, Pupa SM, Campiglio M, Tagliabue E. Biologic and therapeutic role of HER2 in cancer Oncogene. 2003 Sep 29;22(42):6570-8.

HER2 is unusual in that no ligand is known to stimulate it; instead it typically transduces signal due to dimerization with other HER receptors, often other HER2 receptors. This characteristic may have been mistaken for "stuck in the "on" position."

There is discussion in the literature about "Truncated Neu" genes, but that seems to refer to genes experimentally produced for the purpose of creating epitopes for prophylactic or therapeutic vaccination. I found a reference to mutations in mice whose tumors were experimentally caused with known carcinogens, rather than as a description of typical human tumor etiology. In fact the only reference I found describing tests to descern whether mutation or overexpression is to blame, described genetic analyses that only found human tumors had a "neutral" mutation in the trans-membrane motif, which would not be oncogenic: DJ Slamon, W Godolphin, LA Jones, JA Holt, SG Wong, DE Keith, WJ Levin, SG Stuart, J Udove, A Ullrich, and others. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science, Vol 244, Issue 4905, 707-712. DOI: 10.1126/science.2470152. http://www.sciencemag.org/cgi/content/abstract/244/4905/707?ijkey=ab36e26b3fab326b6b46b1378656bf77e1d9d4ae&keytype2=tf_ipsecsha

C4dn (talk) 05:16, 2 December 2009 (UTC)

Note that the distinction between overexpression and mutation, is important to mAb therapy; overexpressed receptors make ideal targets for mAb therapy. However, receptors which have defects rendering them "always on," might not be switched off by binding by a mAb. Mutated receptors might even escape binding by the mAb, depending on where the mutation occurs, how extensive the protein deformation is as a result. Furthermore, if there is no dominant mutation in the patient population that could be targetted by a single mAb, mAb therapy might require customization for each patient, rendering it extraordinarily expensive. As it is, since signal transduction by HER2 is activated by dimerization, binding by a similar receptor's extracellular domain, mAbs can block signal transduction by blocking the binding site normally bound by dimerization.

C4dn (talk) 05:24, 2 December 2009 (UTC)

I can't find a citation right now, but I've seen it described as being stuck in the "on" position in many places by top scientists, including Nobel laureates. My main sources are the New England Journal of Medicine, and occasionally Science. Scientists commonly refer to oncogenes and suppressors as being automobile accelerator pedals or brakes, stuck in the on or off position.

I would recommend that you follow the advice of Nobel Laureate Francois Jacob:

I heard one of the prize winners, Professor [Francois] Jacob, forewarn an audience of specialists more or less as follows: "In describing genetic mechanisms, there is a choice between being inexact and incomprehensible." In making this presentation, I shall try to be as inexact as conscience permits. [1]

We have an strong requirement that Wikipedia is understandable to the ordinary reader. We get comments in the talk page all the time from people who can't understand medical articles because they're too technical.

The introduction is a special case. If a reader can't understand the introduction, they'll stop reading. If a reader can't understand your writing -- why are you writing it?

In the introduction, I try to limit myself to a normal, everyday vocabulary as much as possible, and avoid using terms that are specific to medicine or biology. (There's a scientific literature on how people understand medical writing, some of which was commissioned by the editors of JAMA for their patient page, and I'm trying to follow their advice.)

"Overexpression" has a precise meaning. It helps me understand what they're talking about when I read it in NEJM or Science. But it's a term of biology. It's not a term that an ordinary reader knows. The ordinary reader to me is a high school student studying biology for the first time, or a patient who has just been diagnosed with cancer, or an IT manager who wants to know what the scientists he works for are talking about, etc. And remember that most people in the world who use English are not native speakers of English.

I'd have to read those NEJM articles again carefully, but in my understanding they said that in at least some cases, there was a defect in the receptor, and sometimes the extracellular part was missing and the receptor was constitutively expressed. Here's the first Google hit on "constitutive expression her2" http://www.ncbi.nlm.nih.gov/pubmed/14696118

I'm particularly concerned about the introduction. That's the place where the reader absolutely must understand you, even if you have to sacrifice precision.

You can be more precise further down in the article. Some Wikipedia articles get very technical, and clearly are not understandable by the average reader. I'm willing to ignore that violation of the rule, because lay readers can skip it and it doesn't do any harm. And it helps me understand the research. But we should follow the rules in the introduction. --Nbauman (talk) 21:07, 5 December 2009 (UTC)

Thanks, those comments are very helpful. I will try to follow that approach; now I just hope i get around to actually making the edits I proposed.  :) Perhaps we should say something down in the technical part of the article that "the promotion of HER2 gene expression can get stuck in the on position. Resulting overexpression of normal HER2 protein, can promote MMPs which cleave the extracellular domain of HER2, possibly leaving the remnant fragment of the HER2 protein stuck in the on position, also." That nicely implies a runaway, positive feedback loop involving MMPs (the metallomatrix proteins which can cleave HER2), but I doubt I will explicitly mention that. C4dn (talk) 22:42, 5 December 2009 (UTC)

I have just modified the wordings that referred to defective HER2 receptor, or mitogens binding to that receptor. I think I actually simplified those sentences for the most part. I left the explicit description of cleaved extracellular domain causing constitutive signaling. C4dn (talk) 04:41, 19 December 2009 (UTC)

What is mechanism of cardiac damage

Are there any theories on this that we can report ? Rod57 (talk) 04:31, 1 January 2010 (UTC)

Damned if you do - or don't [ use technical terms ]

My wife has been diagnosed with breast cancer. Her cancer is agressive and multifocal, and she has had surgery. Fortunately, the tumor(s) were small, and there was no node involvement. She will have a 'preventive round of chemotherapy' using a combination of drugs, and then her medical oncologist has recommended a course of Herceptin. So, I am here to learn more about the drug from a supposedly impartial source.

I am concerned about the drug's usage, dosage and side effects. Some of that is here - but not all of it. And it's cloaked in technical terms. But before I call the article 'too technical', I have to point out that the medical profession uses these terms - and if you're a retired businessman like me, you are overwhelmed by them all the time. You do learn what they mean - maybe from another Wikipedia article - and eventually you begin to understand how they relate to your situation. So, when I come here, I understand at least the same terms that the doctor uses when they are used in this article. You have to do that because that's the lingua franca of medicine - although I wager I'd be much happier if I didn't HAVE to know what the terms mean.

My wife's tumors overexpress HER-2 at the 3+level, so she is a candidate for this therapy. The article does have information related to how this number is determined and what the treatment is intended to do. And the article has to explain that treatment in technical terms - up to a point. But I would expect a bit more (in plainer language) so that I can feel more comfortable discussing the treatment plan with my wife and her doctor.

My wife has some health problems (who at 65+ doesn't?), and breast cancer is typically an older person's disease. I came here to find out what side effects to look for, and how they relate to the administration of the drug. Some information is in here somewhere, but two general paragraphs aren't enough. The person who wrote this article is very knowledgable about the drug - but it appears that (s)he isn't very good at side effects. Where are the references to studies? Perhaps this shortcoming is due to the age of the article? Whatever the reason, it's important to note that we're now in 2011, not 2006, and we have five years of 'catch up' to do.

I understand that I can go to the drug maker's website and look at the 'fact sheet' they publish. An article here has to cover the same bases - and I expect it to go a bit farther so that I can determine what propaganda is in the fact sheet and what information I can use. Is that too much to ask from an article here?

Factsneeded (talk) 13:34, 13 May 2011 (UTC)

Reading all that it seems you are asking for more on side-effects. - Rod57 (talk) 22:42, 6 October 2012 (UTC)

QALY or cost effectiveness

Given the choice of a 52 or 9 week course and the costs in different countries - what can we say about the QALY which is important in the UK and probably elsewhere ? - Rod57 (talk) 22:45, 6 October 2012 (UTC)

Article needs updating with respect to efficacy and safety

The drug is under serious re-consideration at the moment because of its high risk benefit ratio. About 33 more women have their lives prolonged while 21 more end up having serious cardiac toxicity, when Trastuzumab is compared with standard therapy. . There are a lot of commentaries and primary studies cited. Would it be best that these are replaced with the reference of the Systematic Review?. Manu Mathew (talk) 05:23, 2 February 2013 (UTC)

Results for more biosimilars

[2] mentions results for CT-P6 and SB3, and says MYL-1401O has a recommendation for approval from an FDA advisory committee. - Rod57 (talk) 12:21, 21 August 2017 (UTC)

Duration of treatment

Needs updated as of 2018 in light of various large duration comparison trials such as PHARE, PERSEPHONE, ShortHER.