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Tamoxifen Can Prevent and Treat Tumors

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 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 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). 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 were 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 .06 mg/rat/week to 16 mg/rat/day. In the study where the dose was only .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 .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, the tumors regressed.

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 tamoxifen, DHEA, miso, and flax seeds! Perhaps I'll have to work on this!

Successes

Here are 3 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.

On Oct. 10 I examined Domonique Vaughn's rat Pepper, and found what appeared to be a cancerous mammary tumor. It appeared identical to the type of tumor that was diagnosed as adenocarcinoma, or in other words, breast cancer, in one of my rats. I have seen several of these types of tumors before in Domonique's and my rats, and it has proved impossible to remove them surgically. Each of these tumors was down near the rat's vagina, tightly embedded in the underlying muscle tissue, and contained a dark red fluid, and in this way they can be distinguished from the more common benign mammary tumors.

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 January 10, 2000 the tumor had totally disappeared! I could not feel even a vestige of it left. In April, Pepper developed 5 more mammary tumors and this time tamoxifen treatment was not successful. Surgery was attempted in May but Pepper died 2 hours after the surgery. She was 3 years old and the tamoxifen had given her 6 extra months!

Kaleigh reports that her rat Claudia was started on tamoxifen the first week in March, 2000. She 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.

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 September 25, 2000. When she had been on it for 17 days, 4 of her tumors, which had been on her left shoulder, were gone. Another one of her tumors, in her left armpit, had been about as big as a marble before they started the tamoxifen. After 17 days it was about half that size. The sixth tumor, right below the marble-sized one, was about the size of a pea and has stayed that size.

Phoebe has been taking tamoxifen for three months now and she is very active and happy. Only the tumor in her armpit is still there, but it has not gotten any bigger. The only thing that has changed is that she is losing some of her hair. 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.

So, if your rat has a mammary tumor, especially a malignant tumor, and you either can't or don't want to have it surgically removed, 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 tasty food will usually solve the problem.

Pituitary Tumors

Because of the success we have seen with tamoxifen on mammary tumors, I am starting to also recommend it 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 the few cases where this has been tried, the symptoms advanced too quickly for the tamoxifen to be of benefit, I believe it is worth a try. Especially since otherwise a pituitary tumor is always fatal. 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.

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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