Beta-blockers reduce breast cancer metastasis

LOS ANGELES High blood pressure is one of the most common medical conditions plaguing Americans. Pearl Lozano, 53, has been trying to keep hers under control for 20 years.

"Off medication it has been 180 over 90, which is not good at all," said Lozano.

Now, a new study presented at the European Breast Cancer Conference finds a common inexpensive blood pressure drug may help women survive breast cancer.

"It certainly is a promising new area of research," said White Memorial Medical Center oncologist Dr. Duvivier.

Dr. Duvivier says this is the first to study to show such a connection between breast cancer and a class of drugs called beta-blockers.

These drugs appear to suppress stress hormones in the body which helps cancer cells proliferate and spread. This is called metastasis.

"So the whole goal would be to prevent a metastasis from occurring," said Dr. Duvivier.

Of the 466 breast cancer patients on beta-blockers, researchers say not only was the cancer less likely to spread, the medication also reduced the chances of it coming back.

"They did a calculation which showed that there was about a 70 percent reduction in their risk of dying from disease," said Dr. Duvivier.

But Dr. Duvivier says many questions remain. Were these women taking beta-blockers before they were diagnosed with cancer? Could these drugs actually prevent cancer in women without high blood pressure?

"In women who do not have high blood pressure, the real question is, 'Would introduction of a beta-blocker give them the same benefit?'" said Dr. Duvivier.

Beta-blockers have a lot of side effects including: slowing down your heart rate, fatigue and causing sexual dysfunction. And doctors say it's too early to make any recommendations to women.

Yet patients with high blood pressure think the news is promising.

"That's absolutely wonderful news," said Lozano. "That's one less thing I have to worry about."

Authors of the study say it would be reasonable to believe women without hypertension would respond favorably to beta-blockers. But the dosage and how women would react to side effects still need to be studied.

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Treatment with beta-blockers can help reduce the spread of cancer in patients with breast tumors, a researcher will tell the seventh European Breast Cancer Conference (EBCC7) in Barcelona today (Friday). In a controlled study, Dr. Des Powe, a senior healthcare research scientist at Queen's Medical Centre, Nottingham University Hospital NHS Trust, Nottingham, UK, and his team found that the group of patients treated with beta-blockers showed a significant reduction in metastasis and better survival. The scientists believe that they are the first in the world to have investigated the effect of beta-blockers in breast cancer patients.

In collaboration with Professor Frank Entschladen's group at Witten University, Germany, Dr. Powe looked at three groups of breast cancer patients: those who were already being treated for hypertension by beta-blockers, those whose hypertension was treated by other medications, and those who did not suffer from hypertension and were therefore not taking any treatment for it. Forty-three of the 466 patients were already taking beta-blockers and, in this group, there were significant reductions in both distant metastasis and local recurrence. They also had a 71% reduced risk of dying from breast cancer compared with the other groups.

"We were also able to study the presence of one receptor for beta-blockers, as a potential biomarker for predicting clinical response to beta-blocker treatment," says Dr. Powe. "But we did not find that this correlated directly to the outcome of treatment. We are currently looking at other target receptors as predictors of clinical outcome."

Previous cell line laboratory studies have shown that beta-blockers work against various types of cancer because high levels of stress hormones in the tumor increase cell proliferation and migration (the movement of cells to other locations). "These effects are induced by the stress hormones norepinephrine and epinephrine acting on specific target receptors in a kind of lock and key fashion," says Dr. Powe. "We sought to translate these laboratory findings into clinical research."

Beta-blocker drugs bind to a specific kind of receptor to prevent the stress hormones from reaching their target; in cancer cells this prevents the hormones from stimulating and activating them. The researchers say that they are sure that their results are due to the effect of beta-blockers rather than a protective effect of hypertension.

"If that had been the case, we would have seen similar survival benefits in patients receiving other forms of treatment for hypertension," says Dr. Powe, "But we did not. It is reasonable to speculate, therefore, that some non-hypertensive women with breast cancer will respond favourably to beta-blocker treatment, though doses and side effects would need to be investigated in clinical trials. We also need to look at whether beta-blockers could be given as a supplementary therapy with existing breast cancer treatment."

This finding may assist treatment in two ways, say the researchers: it appears to slow down tumor growth and could also be used to target those patients who have an increased risk of developing secondary cancers.

"Our first study is relatively small, and we now intend to validate it in a larger group," says Dr. Powe. "We will be looking for funding and collaborators to test the effectiveness of beta-blocker treatment on patients diagnosed with breast cancer. We are very encouraged by these first results which have already shown that by using a well-established, safe, and cost-effective drug, we can take another step on the road to targeted therapy in breast cancer."

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