Scientists probe breast drug danger

Doctors believe they are uncovering why a drug which could help thousands of UK breast cancer patients may trigger heart failure in a few.

They think that Herceptin - which will soon be made available to many more British women with advanced cancer following a government decision - suppresses a protein which is vital to heart function.

Approximately one in five women taking Herceptin in combination with another type of chemotherapy drug, suffers some kind of "toxicity" of this kind.

Wariness about combining the two types of drug mean that women recently treated with a particular drug class called anthracyclines may be ruled out for Herceptin treatment.

Identifying how this damage occurs means the scientists can begin to work on new versions of the drug which lessen or remove this risk.

Stunted development

Herceptin works by targeting a protein called Her2, which appears to be over-abundant in some breast cancer cells.

However, the latest results suggest that Her2 may have an additional role in keeping the heart healthy.

"A great many more women are likely to be candidates for Herceptin in the future - any progress in this area would be most welcome"

Kefah Mokbel, St George's Hospital, London

Dr Kuo-Fen Lee from Salk Institute in California created laboratory mouse embryos lacking the protein - and their heart and brain development was so stunted that they could not even be born.

His new experiments also knocked out the gene which create the protein, but only after birth and in the heart itself.

This allowed him to mimic the effects of treating a more developed animal with the drug.

Hearts taken from the mice at between one and six months of age showed clear signs of heart problems, including a thickening and weakening of the heart muscle.

Heart muscle cells from the mice appeared to be more vulnerable from damage from other chemotherapies used in concert with Herceptin.

Drug help

Dr Lee said that it was possible that the heart could be protected during Herceptin treatment.

He said: "If we could develop agents that stimulate the heart...then those might allow you to use Herceptin aggressively while protecting the heart."

However, he said that he hoped that a Herceptin-like drug could be engineered to interfere with breast cancer cell growth without impacting on the heart.

Mr Kefah Mokbel, a breast cancer surgeon and Herceptin researcher from St George's Hospital in south London, said that most doctors now avoided giving Herceptin in combination with anthracyclines.