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by Debbie “The Rat Lady” Ducommun
In several experiments, tamoxifen has been found to be effective in protecting rats against mammary cancers which have been chemically induced. Unfortunately I found only one study showing the effect of tamoxifen on spontaneous tumors. Perhaps the reason is that most spontaneous mammary tumors in rats are benign, and tamoxifen isn’t used to treat benign mammary tumors in humans; they are simply removed surgically. So what researchers are interested in is the effect of tamoxifen on breast cancer. (Tamoxifen does not seem to be effective for benign mammary tumors in rats.)
Tamoxifen seems to be a very interesting drug with different effects in different species. For instance, in chicks it has a strictly anti-estrogen effect, while in dogs it has a mainly estrogen effect. For this reason, tamoxifen does not seem to be an effective treatment for mammary tumors in dogs. In one study, about half the spayed dogs given tamoxifen had side effects caused by the estrogen effect and it has strongly negative effects on intact female dogs, causing pyometra, a serious infection of the uterus.
In humans and rats, tamoxifen has both anti-estrogen and estrogen effects on different tissues. Scientists don’t know why the effect is different in different species. The anti-estrogen effect it has in humans is the reason that it is effective in treating mammary tumors. The estrogen effect is the cause of some of the side-effects that can occur in women, including uterine bleeding, uterine tumors, and blood clots.
In rats, the major side-effect of tamoxifen is very different than that in humans. In rats, the major danger is liver cancer, which doesn’t appear to be a problem in women. This liver cancer in rats only occurs with large doses or prolonged early administration.
It seems that another possible side effect in rats, which is also seen in some women, is the reduction of the number of blood platelets which are responsible for blood clotting. For this reason, if a rat has been on tamoxifen, it is recommended that she be taken off the drug for a week or two before surgery and/or check a platelet count. Otherwise, fatal bleeding can occur during the surgery.
Mammary Tumor Prevention
The most important reference I found was a study looking at the carcinogenicity of tamoxifen in rats, and the effect of tamoxifen on spontaneous mammary tumors. (“Results of Three Life-Span Experimental Carcinogenicity and Anticarcinogenicity Studies on Tamoxifen in Rats,” C. Maltoni et al, 1997, Ann. NY Acad Sci, 837, 469-512). For the published conclusions and summary of this study, click here.
The rats in this study were divided into 3 groups. All the rats were given tamoxifen at a dose of 3.3 mg/kg (1.5 mg/lb).
Group 1 included both males and females who were given tamoxifen 6 days/week (obviously the techs had Sunday off!) starting at 8 weeks of age for their whole life. Group 2 were females started on tamoxifen at 12 weeks of age. They got it for 8 days in a row, every 8 weeks for life. Group 3 were females who started getting the tamoxifen at 56 weeks of age, 6 times/week for 40 weeks. This last group would most closely match the clinical treatment of mammary tumors.
All 3 groups showed strong, long-lasting prevention of mammary tumors, both benign and cancerous! The treatment also prevented pituitary tumors (yay!), and several other types of tumors: adrenal pheochromocytomas, islet cell pancreatic tumors, Leydig cell testicular tumors, and uterine polyps.
Here are the results of the carcinogenic effects. Group 1 had a mild increase in the number of liver cancer tumors. Groups 1 and 2 both had a borderline increase in uterine cancers. Group 3 showed no carcinogenic effect.
So here are the main conclusions of this important study. A dose of 1.5 mg/lb given once a day 6 days/week provides a protective effect against tumors. At this dose, giving tamoxifen only causes liver or uterine cancer if the rat gets it all its life. Therefore, giving tamoxifen at this dose to females with tumors, who are almost certainly going to be more than a year old, shouldn’t cause any major side-effects.
Studies on Induced Tumors
In the other studies I found where mammary cancer was induced in rats by chemicals, they would usually start giving the tamoxifen shortly after giving the tumor-inducing chemicals. In these studies there was a wide range of doses of tamoxifen given, from only 0.06 mg/rat/week to 16 mg/rat/day. In the study where the dose was only 0.06 mg/rat/week, this low dose apparently delayed the formation of the tumors, but didn't prevent them. Also, in this study, when tamoxifen was combined with 0.2 mg/rat/day of melatonin, the protective effect was boosted. In the study where the dose was 16 mg/lb, there was apparently a significant incidence of liver cancer.
It was interesting to see that in one of the studies, some of the rats were spayed before receiving the cancer-inducing chemical, and none of these rats developed cancer. In another study, they allowed the induced tumors to grow before either treating the rats with tamoxifen or spaying them or both. With both types of treatment, some of the tumors regressed.
Effect of tamoxifen on intraperitoneal N-nitroso-N-methylurea induced tumors. Martin, G. et al, Cancer Letters, 100 (1996) 227-234.
Hormone dependence of mammary tumors induced in rats by intraperitoneal NMU injection. Martin, Gabriela, et al, Cancer Investigation, 15 (1), 8-17, 1997.
Combination of melatonin and tamoxifen as a chemoprophylaxis against N-nitroso-N-methylurea-induced rat mammary tumors. Kothari, Ami, et al, Cancer Letters, 111 (1997) 59-66.
Prevention of DMBA-induced rat mammary carcinomas comparing leuprolide, oophorectomy, and tamoxifen. Hollingsworth, Alan. B. et al., Breast Cancer Research and Treatment, 47: 63-70, 1998.
For copies of the abstracts of these studies, click here.
Other Preventative Treatments
In one of the studies it was found that DHEA also protected against induced tumors. The DHEA was mixed into the food at a dose of 400 or 800 mcg/kg of diet. Some other studies showed that feeding the rats miso, a soybean product, as 10% of their diet, also had a protective effect against induced tumors. When combined with tamoxifen, the miso diet was almost 100% effective in preventing the tumors.
Another study found that flax seed comprising from 2.5 to 10% of the diet also had a protective effect against mammary tumors. This study found that the flaxseed had the effect of lengthening the rats’ estrus cycles. They also found that tamoxifen had the effect of causing irregular estrus cycles or caused the rats to stop coming into heat at all.
In a couple of the studies, the tamoxifen was administered not orally, but by implanting a small pellet of the drug underneath the skin. This would be much more convenient than having to dose them every day! Or, wouldn’t it be convenient to have a special “tumor prevention diet” containing DHEA, miso, and flax seeds!
Here are 4 success stories using tamoxifen to treat mammary tumors. These rats were given a dose of 1-2 mg/lb once a day. You could also use as much as 3.5 mg/lb. You will need to have your vet call in a prescription for the tamoxifen to a human pharmacy. You can compound the tablets yourself. The tablets I have worked with were 20 mg. If you mix one tablet with 1 ml of flavoring (such as Ensure, syrup, etc.) then 0.15 ml would contain 3 mg of the tamoxifen. You don’t have to grind up the tablet, just let it dissolve for 12 hours in the liquid. Keep the mixture in the refrigerator.
Pepper was started on tamoxifen, at a dose of 1 mg once a day. After a few
weeks, Domonique reported that the tumor had shrunk to about half its former
size. As of
Kaleigh reports that her rat Claudia was started on tamoxifen the first week in March, 2000. Claudia had two tumors diagnosed as adenocarcinoma, one under her left arm that had been removed twice and one in her groin which had been removed once. She did well on the tamoxifen initially. The tumor under her left arm shrunk slightly, then did not increase in size. The tumor in her groin went away completely while she was on the tamoxifen. On May 22 the tumor under her arm started growing again, rapidly. Kaleigh increased her tamoxifen to twice a day and that slowed it but didn’t completely stop it. Other than the cancer, Claudia was in pretty good shape despite her age so Kaleigh made the decision to try to have the tumor removed. The vet was very optimistic. Unfortunately Claudia bled quite a bit and did not survive the surgery. We now know this was probably due to the reduction of her platelets caused by the tamoxifen.
Jennifer Dedman discovered a tumor on her rat Phoebe in her right groin. The
tumor was removed, however, during the surgery, her vet Dr. Bihl found six more
tiny tumors. The tumor that was removed was sent to a lab for a biopsy and it was
adenocarcinoma, a malignant tumor. Phoebe started taking tamoxifen on
Phoebe took tamoxifen happily for three months and was very active and happy. Only the tumor in her armpit was still there, but it did not get any bigger. She did lose some of her hair and I have heard of other reports that tamoxifen has caused hair loss in rats. It seems a small price to pay to keep tumors at bay. In addition, some rats start violently refusing to take tamoxifen after a few weeks. However, the effects on the tamoxifen seem to persist, so it is worth doing it even for a relatively short period of time.
I adopted Jewel on
So, if your rat has a malignant mammary tumor I highly recommend you try treating it with tamoxifen. This drug is relatively inexpensive in the doses required for a rat. Some rats seem to have a problem with the taste, but mixing it in really tasty food will usually solve the problem. In my experience, they usually take it well for a few months, and then refuse to take it. At that point you can take a break for a couple of weeks, and then they usually take it happily again. Unfortunately, tamoxifen does not seem to be effective for benign mammary tumors, but then they can be easily removed surgically.
Tamoxifen might even be effective for mammary cancer when the rat is spayed. In 2012, I tried treating mammary cancer in my rat Pixie by spaying her, and unfortunately, it did not seem to prevent the growth of the cancer as well as tamoxifen might have. I had to euthanize her 6 months later. Although the ovaries are the primary source of estrogen in the body, in humans other organs, including the liver, adrenal glands, breasts and fat cells also produce small amounts of estrogen, so it might worth it try tamoxifen even in a spayed rat.
Because of the success we have seen with tamoxifen on mammary tumors, it might also be of benefit when a pituitary tumor is suspected in female rats. (The most common early symptoms are loss of coordination or impairment of the hind legs.) Although in a few cases where this has been tried, the symptoms advanced too quickly for the tamoxifen to be of benefit, but I know of one current case where it seems to be working well. However, a pituitary tumor should also always be treated with prednisone and an antibiotic.
Tamoxifen should not be used to treat a pituitary tumor or mammary tumor in male rats. In fact, studies show that it will increase the incidence of mammary tumors in male rats.
Cancer Other than Mammary or Pituitary
Before 2013, whenever rat owners have asked me if tamoxifen can be used to treat tumors other than mammary cancer, I have always said no, because I thought it only worked for estrogen sensitive tumors. However, in 2013 I got an email from rat owner Paul Gregor who is a scientist interested in how different drugs work. His rat had grown some tumors, so he was reading the info I have about tamoxifen on my website. He told me that there is scientific evidence that tamoxifen can help slow the growth of cancers other than mammary tumors. It appears that tamoxifen not only blocks estrogen receptor sites in tumors, but it also helps prevent the growth of new blood vessels, which a tumor must do to grow.
One study found that tamoxifen helped slow the growth of squamous cell carcinoma cells in a culture. This was an in vitro experiment, using cell cultures and not tumors growing in animals, which means that no animals were harmed for this experiment! The cancer cells used in this study were from squamous cell carcinoma tumors on the head and neck of humans, which are apparently very difficult to treat. One of the most common types of cancer in rats is squamous cell carcinoma on the head and face! Although this study showed that treatment of the cancer cells was most successful when tamoxifen was used together with a chemotherapy drug called cisplatin, just the tamoxifen by itself did help slow the grow of the cancer cells. (Cisplatin must be given intravenously, and so is not practical for rat treatment.)
Although in vitro studies are wonderful because they do not use animals, it is also good to know that tamoxifen appeared to slow the growth of malignant fibrosarcoma tumors implanted in rats, since fibrosarcoma is also a fairly common type of cancer in rats. This study found that tamoxifen helped to slow the growth of blood vessels in the tumors, which would presumably slow the growth of tumors. The rats were euthanized only ten days after the tumor cells were implanted in their legs, so this study did not look at long-term effects of the treatment.
So, if your rat has cancer, any kind of cancer, it looks like it might be worth it try treatment with tamoxifen. Here are the references for the studies to show your vet:
Tamoxifen Inhibits Angiogenesis in Estrogen Receptor-negative Animal Models. Clin Cancer Res., Blackwell, K.L. et al. November 2000 6; 4359.
Tamoxifen inhibits the growth
of head and neck cancer cells and sensitizes these cells to cisplatin
induced-apoptosis: role of TGF-β1. Tavassol, M., et al. Carcinogenesis
If any of you try tamoxifen please let me know what success you have with it. We need to gather more evidence for its benefits in rats.
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