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SERMs ward off common breast cancer over long term

Selective oestrogen receptor modulators good for women at high/average risk

Caroline White

Tuesday, 30 April 2013

The group of drugs known as SERMs (selective oestrogen receptor modulators) significantly cut the risk of developing the most common type of breast cancer in women at both high and average risk of the disease, shows the first comprehensive analysis of all SERM prevention trials, published in The Lancet.

Tamoxifen, raloxifene, arzoxifene, and lasofoxifene work well both during treatment, and for at least 5 years after stopping it, the findings show.

“Despite their effectiveness, many women have opted not to take SERMs because of concerns about toxic effects”, explains Jack Cuzick from Queen Mary, University of London who led the research funded by Cancer Research UK.

“But our longer-term findings clearly show that the benefit-harm balance is now more favourable than previously calculated for short-term follow up. The benefits of these drugs continue well after treatment has stopped, whilst most of the side effects do not,” he adds.

SERMs protect against oestrogen receptor positive disease, which make up about 70% of all breast cancers by binding to the oestrogen receptor and blocking the breast cells’ ability to grow and multiply.

In this new analysis, which included 83, 399 women who were tracked for an average of 65 months, those taking SERMs were 38% less likely to develop breast cancer than those given placebo. This was more noticeable in the first 5 years (42% in first 5 years vs 25% in years 5–10). No effect was noted for oetrogen receptor-negative breast cancers.

The authors calculated that 42 women would need to be treated to prevent one breast cancer event in the first 10 years.

All SERMs significantly increased the risk of blood clots, including  deep vein thrombosis. Only tamoxifen was associated with significantly higher rates of endometrial cancer, although this difference disappeared after tamoxifen was stopped.

No overall reduction in heart attacks, strokes, or transient ischemic attacks was noted in patients taking SERMs compared with those taking placebo, despite a 10–20% reduction in LDL cholesterol.

According to Cuzick, lasofoxifene is likely to be a very promising candidate for prevention and should be a priority for prevention research:

“It not only had a large effect on breast cancer incidence [reduction of 81%] but also showed benefit for stroke [reduction of 36%], cardiac events [32%], and vertebral fractures [42%], with no increase in endometrial cancer.”

But he adds: “Unfortunately, at the present time, none of these drugs is being actively marketed for breast cancer prevention, and approval by the US Food and Drug Administration or any other regulatory authority for this indication will probably not be sought for lasofoxifene or arzoxifene.”

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