Beta-blocker Use Linked to Improved Ovarian Cancer Survival

Fran Lowry

August 24, 2015

Women with epithelial ovarian cancer who happened to be taking nonselective beta-blockers for hypertension survived longer than those who were not taking the drugs, according to a large multicenter retrospective study.

This finding was published online August 24 in Cancer.

The study involved 1425 women with ovarian cancer (median age, 63 years; range, 21 - 93 years) treated from 2000 to 2010. Of the 269 (19%) women in the cohort who had received beta-blockers, 193 (71.7%) had received beta-1-adrenergic receptor selective agents and 76 (28.3%) had received nonselective beta antagonists.

Median overall survival was longer for patients receiving any beta-blocker than for those who were not (47.8 vs 42.0 months; P = .04). But the survival benefit was greater for the women who received nonselective beta blockers than for those who received beta-1 adrenergic receptor selective agents (94.9 vs 38.0 months; P < .001).

"Over the last several years, we have been studying how chronic stress and sustained adrenergic activation can affect cancer growth and spread," said senior researcher Anil K. Sood, MD, professor of gynecologic oncology and cancer biology at the University of Texas M.D. Anderson Cancer Center in Houston.

Dr Anil Sood

"We have discovered that beta-2 and beta-3 adrenergic receptors are present on many ovarian cancer cells, and play quite important roles in promoting angiogenesis and maybe even the survival of cancer cells," he told Medscape Medical News. "They also trigger signals inside the cancer cells that are relevant for growth. These observations led us to ask whether the drugs that block those kinds of receptors could be important for cutting off the growth-stimulating effects of stress hormones."

 
This could be relevant for other cancer types as well.
 

"Even though our focus here was on ovarian cancer, this could be relevant for other cancer types as well. There are data indicating that these kinds of stress pathways can stimulate the growth of certain forms of breast cancer, colon cancer, and head and neck cancer, so there may be relevance for other cancer types, too," he said.

In this study, Dr Sood and his group builds on their previous research that showed that beta-blockers had some benefit in ovarian cancer.

This time, the researchers delved deeper to see if the subtype of beta-blocker made a difference.

"In the past, we were not able to do this; therefore, we worked with other centers to get a large enough cohort so that we could answer that question," Dr Sood explained. "We looked at both selective beta-blockers, especially beta-1 selective blockers, and the broader [nonselective] beta-blockers. We found that use of the broader beta-blockers afford the biggest benefit; the beta-1 blockers tended not to be beneficial."

He noted that the ovarian cancer patients in this study who had used beta-blockers presented with a higher disease stage than nonusers, had a higher average body mass index, and were more likely to be hypertensive, factors associated with decreased survival.

Despite the presence of these factors, overall survival was the same or better with nonselective beta-blockers than with selective beta-blockers.

Dr Sood's team is currently conducting a feasibility study to see if the role of beta-blockers in ovarian cancer can be investigated prospectively.

"Beta-blockers are not ready for prime time. The current study was retrospective, so we cannot start prescribing beta-blockers for everyone. However, now we are looking at whether we can use them safely in patients who do not have high blood pressure," Dr Sood reported. "Once the feasibility study is completed, we can start to look at beta-blockers' effects on stress hormones, how they affect progression-free survival, and other factors. The retrospective data look interesting, but we need to do things carefully and take a measured approach."

"Fascinating Clinical Article"

Dr Gary Leiserowitz

This is "a fascinating clinical article," said Gary S. Leiserowitz, MD, professor and chair of obstetrics and gynecology and chief of the division of gynecologic oncology at University of California Davis Medical Center in Sacramento.

"This work explores a longstanding interest on the part of M.D. Anderson researchers, especially Dr Sood," he told Medscape Medical News.

"He has been documenting the basic science that underlies the connection between stress hormones and the development of cancer, particularly ovarian cancer," Dr Leiserowitz explained. "In both in vitro and in vivo ovarian cancer cells implanted into immunodeficient mice, the researchers have shown that neuroendocrine hormones cause a cascade of direct cellular effects that promote enhanced growth of ovarian cancer. They have also shown that drugs that block adrenergic hormones, such as propranolol, markedly inhibit growth of ovarian cancer cells."

"Their previous studies were nonhuman, so this study shows that there may be similar strong benefits to ovarian cancer patients, although this has not been tested directly," he said.

"This could lead to clinical trials using beta-blockers during ovarian cancer treatment," Dr Leiserowitz added.

The study was sponsored by the National Institutes of Health, the Ovarian Cancer Research Fund Program project development grant, the Department of Defense, the Betty Ann Asche Murray Distinguished Professorship, the RGK Foundation, the Gilder Foundation, the Blanton-Davis Ovarian Cancer Research Program, and a Gynecologic Cancer Foundation-St. Louis Ovarian Cancer Awareness grant. Dr Sood and Dr Leiserowitz have disclosed no relevant financial relationships.

Cancer. Published online August 24, 2015. Abstract

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