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The latest human studies show a sixfold increase in liver cancer among women taking tamoxifen for more than two years." Liver failure and tamoxifen-induced hepatitis, although rare, have been reported. Even Zeneca admits that tamoxifen is a liver carcino- gen—while nevertheless aggressively promoting its use. at the M. D. Anderson Cancer Center at Houston and at Yale University School of Medicine discovered that breast cancer patients who develop uterine cancer while using tamoxifen are likely to have a fast-moving, lethal form of the disease. It should be noted that tamoxifen has also been associated with gastrointestinal cancers. OE ate wetter ee Uterine (Endometrial) Cancer As early as 1967, ICI scientists noted that "tamoxifen persists Breast Cancer for some days in the uterus". In rats, a tamoxifen metabolite (a The premise for taking tamoxifen is its supposed role in pro- breakdown compound almost similar in structure to the original) tecting breast cancer patients from recurrence of the cancer. It was found to influence the uterus to be more receptive to oestro- was further postulated that it prevented breast cancer from occur- gen. (The more oestrogen, the greater the chance of unnatural ring in the opposite breast (contralateral). cell-division leading to cancer.) ICI also reported liver carcino- However, disturbing findings continue to surface, challenging genicity of tamoxifen as well as both ovarian and testicular tamoxifen's effectiveness. In 1992 the New England Journal of tumours in mice in its description of the drug in the standard Medicine showed that tamoxifen may reduce the incidence of Physicians Desk Reference. contralateral cancer, but this was demonstrat- Uterine growths such as polyps, tumours, ed only in premenopausal women and only in endometrial thickenings and cancers occur three out of eight trials. In another 1992 in a significant number of women taking study, reported in Octa Oncologica, it was tamoxifen. One study detected abnormal shown that tamoxifen not only failed to endometrial cells in subjects the day after Uterine growths such as reduce contralateral cancers in pre- the first tablet was taken.'? Precancerous menopausal women, but it actually increased uterine and endometrial changes were seen polyps, tumours, their incidence.* in 10 per cent of the women taking tamox- | andometrial thickenings The irony of tamoxifen is that, while wide- ifen in a recent study. The higher the dose . ly publicised as the leading treatment against of tamoxifen and the longer it is taken, the and cancers occur ina the recurrence of breast cancer, it is a known greater the risk of changes. Women taking significant number of and listed carcinogenic substance. the standard dose of 20 mg for two years run . . a risk of uterine cancer that is 2 to 3 times | WOMEN taking tamoxifen. Heart Disease and Osteoporosis greater than normal. After five years, the Another promise of tamoxifen was its sup- risk is 6 to 8 times greater.” posed protective benefits for the heart In February 1996 a review by the One study detected and bones. It was theorised that its abnormal endometrial International Agency for Research on oestrogenic properties would help Cancer, composed of scientists from . . reduce heart disease and osteoporosis in cells in subjects the day after the first tablet various countries, definitively conclud- women, but once again the theory was taken. ed that "there is sufficient evidence to crumbled under the weight of hard regard tamoxifen as a human carcino- facts. gen that increases a woman's risk of Several trials with tamoxifen failed to developing cancer of the endometrium, show that it has any effect on bone den- the inner lining of the uterus".”! sity and thus on prevention of osteo- A large Swedish study linking porosis. In three other trials, bone den- tamoxifen to uterine cancer forced sity increased slightly in lower spinal Zeneca to send letters in April 1994 to vertebrae but not in longer bones or hip 380,000 physicians across the USA, in bones which are particularly susceptible defence of the drug. The Swedish to fractures and potentially fatal com- researchers had studied 1,371 breast cancer patients who took 40 _ plications. mg per day for two to five years and found that there was a six- Initial data seemed to indicate that it decreased the incidence of fold increase in uterine cancer among those patients who took heart attacks, but they have been disproved by more recent stud- tamoxifen when compared to 1,327 who did not. A second study ies. According to Dr Susan Love: "It doesn't seem to have a bad involving patients who took 20 mg per day (the recommended effect on lipids, but that's a far cry from preventing heart attacks." dose) also showed a marked increase in uterine cancers compared A detailed review of the drug's alleged protective cardiovascu- with the control group.” lar effects prompted the British National Heart, Lung and Blood When the news came out that breast cancer patients who took _ Institute, a once strong proponent of tamoxifen, to withdraw its tamoxifen for five years or longer (the same regimen that seems support because the evidence of benefit proved so inadequate.** to prevent recurrence) might have tripled their risk of uterine can- According to the January 1996 issue of The Network News, it cer, British cancer researcher Richard Peto, head of the cancer was reported at a closed-door meeting of the National Cancer research unit at Oxford University, sought to dismiss it. If caught Institute that tamoxifen failed to prevent heart disease in breast early, he said, endometrial cancer seldom kills, so "it's no big cancer patients. deal". That statement infuriated critics who noted that the treat- ment for uterine cancer is hysterectomy. Dr Adriane Fugh- | THE BREAST CANCER PREVENTION TRIAL Berman, a leading women's health activist, angrily responded: Based far more on wishful thinking than on science, the US "To some of us, it is a big deal to lose your uterus." National Cancer Institute (NCI) leaped to the conclusion that Shortly after Peto's flip dismissal of uterine cancers, researchers — tamoxifen's anti-oestrogenic effects in relation to breast cancer One study detected abnormal endometrial cells in subjects the day after the first tablet was taken. rc v plications. Initial data seemed to indicate that it decreased the incidence of heart attacks, but they have been disproved by more recent stud- ies. According to Dr Susan Love: "It doesn't seem to have a bad effect on lipids, but that's a far cry from preventing heart attacks." A detailed review of the drug's alleged protective cardiovascu- lar effects prompted the British National Heart, Lung and Blood Institute, a once strong proponent of tamoxifen, to withdraw its support because the evidence of benefit proved so inadequate.** According to the January 1996 issue of The Network News, it was reported at a closed-door meeting of the National Cancer Institute that tamoxifen failed to prevent heart disease in breast cancer patients. THE BREAST CANCER PREVENTION TRIAL Based far more on wishful thinking than on science, the US National Cancer Institute (NCI) leaped to the conclusion that tamoxifen's anti-oestrogenic effects in relation to breast cancer 46 - NEXUS JUNE - JULY 1998 significant number of