Endocrinology: U.S. Study May Explain How Estrogens Cause Cancer

Source: Cancer Weekly Plus, Feb 9, 1998 pNA(1). Subjects: Cancer - Risk factors Products: Premarin (Medication) - Adverse and side effects Electronic Collection: A20374622 RN: A20374622

U.S. chemists reported they had found a by-product of Premarin, which could explain why users have a higher risk of cancer.

Reporting in Chemical Research in Toxicology, they said it damaged DNA in a way that could cause breast cancer and all estrogen replacement drugs should be checked for the same effect.

The research team, led by Judy Bolton from the University of Illinois in Chicago, and the makers of Premarin both described the findings as preliminary.

Wyeth-Ayerst, the manufacturer of Premarin, said it doubted the findings could be extended to women.

"While we have not yet had an opportunity to read the paper ... the results of this study are very preliminary," spokeswoman Audrey Ashby said.

"It is important to point out that the entire sequence of reactions hypothesized by the author are highly unlikely and are not known to occur in women receiving estrogen replacement therapy."

Bolton and her colleagues were trying to figure out why Premarin and other forms of estrogen replacement therapy are associated with slightly higher rates of breast cancer.

They made a synthetic version of one of the components of Premarin, which is derived from the urine of pregnant mares, and studied how it breaks down in a test tube.

They found this breakdown product, or metabolite, reacted in an unusual way with DNA - the body's genetic building blocks. Damage to DNA can cause cancer.

"If this reaction were to occur with DNA in breast cells, and that damage is not repaired, mutations could result, leading to the initiation of the carcinogenic process in the breast," Bolton said in a statement.

Bolton stressed that her team used a synthetic chemical and there was no evidence that Premarin or any other estrogen broke down to make this particular metabolite in humans.

"Making the step from our study to the cell is a big step, let alone the step from the cells to the animals to the person," Bolton said in a telephone interview. "This is extremely preliminary work."

She said the effect might extend to all estrogens.

"Estrogens are carcinogenic and it's known that the longer a woman is exposed to estrogen, the higher her risk of developing cancer," Bolton said.

Cancer experts have long said a woman's higher risk of cancer that comes with hormone replacement therapy (HRT) is the same as her risk would be if she had not gone through menopause. In other words, the body's natural production of estrogen can be a cause of cancer over time.

HRT decreases a woman's overall risk of death, greatly reducing the chance she will develop osteoporosis and reducing the risk of heart disease - which kills many more women than cancer does.

Premarin is the number one prescribed drug in the United States, taken by 10 million women. Worldwide sales in 1996 were $1.39 billion.

A newly approved drug may offer many of the benefits of HRT without the risks. Eli Lilly and Co's Evista, approved in December, is the first of a new class of drugs that fight thinning bones and which might also help protect older women against heart disease.

The drug, known generically as raloxifene, works by mimicking the effects of estrogen in some parts of the body - for example its protective effects on bone - while avoiding "bad" effects such as an increased risk of cancer.

Full Text COPYRIGHT 1998 Charles W Henderson

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