Sandy Hutchens Cancer Prevention

UK scientists say they have discovered why some women fail respond to breast cancer treatment, and it is a gene error they believe they can fix.

Tamoxifen is given to most women diagnosed with breast cancer to prevent the cancer returning.

But not all women respond to the drug – experts estimate a third get no benefit.

The work in the journal Cancer Research suggests the problem is too much of a gene called FGFR1.

This discovery could lead to new treatments for these women as scientists “switch off” the action of FGFR1, enabling Tamoxifen to work.

The team of scientists in the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research have already shown this is possible in the lab.

They introduced a drug which “switched off” the action of FGFR1.

Once FGFR1 was stopped, hormone-based treatments like Tamoxifen could get back to work in destroying cancer cells, they found.

The researchers believe this could ultimately help thousands of women each year.

They say one in 10 breast cancer patients has too much of the FGFR1 gene.

Dr Nick Turner, who led the research, said: “Understanding how this gene can cause Tamoxifen resistance reveals a new drug target for treating breast cancers in patients who would otherwise have a poor outcome.

“There are a number of drugs in development that stop FGFR1 working, and clinical studies are investigating whether these drugs work against cancers with too many copies of this gene.

“The next step is to set up a clinical trial to see whether a drug that blocks the action of this gene can counteract hormone therapy resistance in breast cancer patients.

“If these trials confirm our lab work we could be on the verge of a potentially exciting new treatment for breast cancer.”

Dr Lesley Walker of Cancer Research UK, the charity which helped fund the work, said: “Cracking the problem of resistance to treatments such as Tamoxifen would be a major advance in treating breast cancer.”

Breast cancer is the most common cancer in the UK affecting more than 45,500 women each year.

Tamoxifen blocks the female sex hormone oestrogen that fuels the growth of some breast tumours.

Researchers from the University of Michigan have reported that women at high-risk of breast cancer understand the risks and benefits of tamoxifen [Nolvadex®] prevention, but only 6% choose to take it. The details of this study were published in an early online publication in Breast Cancer Research on November 12, 2009.

Several large clinical trials have shown that tamoxifen can decrease the risk of breast cancer in high-risk women. There are, however, two issues that have prevented widespread use of tamoxifen for breast cancer prevention:

* Who is at risk? The definition of who is high risk is problematic and differs from trial to trial. Generally, high risk includes women with a family history of breast cancer, early menarche, later or no childbirth, or previous breast biopsy, even if negative.

* What are the side effects? In one study, it was found that less than one in five women at high risk would take tamoxifen due to their fears of side effects and the fact that they assumed they were at relatively low risk for developing breast cancer.

Two reports in the February 21, 2007 issue of the Journal of the National Cancer Institute document that tamoxifen can prevent hormone-positive breast cancer in women at high risk.

Researchers affiliated with the Royal Marsden Randomized, Double-Blinded Tamoxifen Breast Cancer Prevention Trial reported 20-year follow-up data. This trial randomly allocated 2,494 women at high risk of developing breast cancer to receive tamoxifen or placebo for eight years. A total of 82 women in the tamoxifen group and 104 in the placebo group developed invasive breast cancer. Researchers affiliated with the first International Breast Cancer Intervention Study (IBIS-I) reported that the breast cancer preventative effects of tamoxifen persist for at least 10 years after a five-year treatment period. This trial randomly allocated 7,145 women at increased risk for developing breast cancer to receive five years of tamoxifen or placebo. With a 96-month follow-up, there were 142 breast cancers in the tamoxifen group and 195 in the placebo group. They observed a preventive effect during the entire period of observation. The main side effects were an increased risk of deep-vein thrombosis and pulmonary embolism during but not after tamoxifen treatment. The estimated risk for developing estrogen receptor-positive breast cancer was 34% lower in the tamoxifen group.

The authors of the present trial sought to determine why few women with increased risk of breast cancer use tamoxifen for chemoprevention. They evaluated 632 women with an average 2.56% risk of developing breast cancer within five years. These women were presented with a tailored decision aid concerning the effectiveness of chemoprevention with tamoxifen and the known side effects. After reviewing the decision aid, 29% of women said they would seek more information from their own physician, and 6% said they would agree to take tamoxifen. These researchers thought that these women had adequate knowledge to make a decision. The stated: “Participants were concerned about the risks of tamoxifen, and many believed that the benefits of tamoxifen did not outweigh the risks.”

Discovering Key to Tamoxifen’s Effectiveness in Treating Breast Cancer may Mean New Treatments

Sandy Hutchens Cancer Prevention, August 26, 2009 – Tamoxifen is an estrogen-blocking drug. This class of medication is specifically designed to block the estrogen receptor to prevent the growth of breast cancer cells. But, unfortunately, not all breast cancers have the estrogen receptor. Those that don’t are usually more aggressive and metastasize more rapidly.

Researchers from Fred Hutchinson Cancer Research Center in Seattle looked at 728 women diagnosed with breast cancer. Those women were compared to 367 others diagnosed with both a first and second breast cancer.

The main finding from the study, published online Tuesday in the journal Cancer Research, was that tamoxifen lowered the risk of any second breast cancer overall by about half, said lead author Dr. Christopher Li.

“For the estrogen receptor-positive cancer, we have targeted therapy that again has been proven to again reduce mortality,” said Li. “That’s one of the reasons why ER-negative cancers are more worrisome because we don’t have a targeted treatment for them.”

Li said it’s important to remember that any treatment has risks and benefits associated with it, and tamoxifen is no exception.

Tamoxifen lowers breast cancer patients’ risk of dying of the disease, and has also been shown to lower a woman’s risk of developing a recurrent breast cancer and a second breast cancer, he noted. But use of tamoxifen also comes with risk of stroke, as well as the risk of endometrial cancer, he added.

“So here we’re finding that we’re adding potentially another risk to the risk-benefit equation,” Li said. “We’re finding that there is this increased risk in this more aggressive subtype of second breast cancer. However, we also overall found using tamoxifen did lower the risk of any type of second breast cancer overall.”

“For that reason, we don’t really think that this study changes the overall risk-benefit equation because the benefits for most women who are eligible to use this treatment are going to still outweigh the risks.”

Every tumour is a mix of receptor-positive and receptor-negative cells, she said. If the types of cells that predominate are receptor-negative, it gets read as an increased risk of receptor-negative breast cancer if tamoxifen is taken for five or more years.

Dr. Jay Harness,Tamoxifen And The Side Effects put up by Sandy Hutchens.

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