Bone Drug May Prevent Return of Breast Cancer

Study Shows Zometa Reduces the Risk of Breast Cancer Recurrence

By Brenda Goodman
WebMD Health News

Reviewed By Laura J. Martin, MD

June 3, 2011 -- A drug that battles bone loss may have added benefits for women with estrogen-sensitive breast cancers, significantly reducing the chance that their cancer will return or spread, a new study shows.

What's more, researchers say, the lowered risk of recurrence seems to last years after the treatment, a bisphosphonate drug called Zometa, is stopped.

"I find that very reassuring. It obviously demonstrates that we can impact on the long-term outcome of our patients with an early intervention. We do not have to give these drugs forever. I'm very enthusiastic about this," says study researcher Michael Gnant, MD, professor of surgery at the Medical University of Vienna in Austria.

For the study, which is published in The Lancet, 1,803 premenopausal women with early-stage, estrogen-driven breast cancers were given a drug which suppresses estrogen production by the ovaries. They were also treated with drugs, Arimidex or tamoxifen, that help prevent cancers from using estrogen to grow.

In addition to those treatments, half were randomly assigned to receive intravenous infusions of Zometa every six months for three years.

Two years after their treatments ended, women who got the bone drug continued to have a 32% reduced risk of cancer recurrence compared to those on estrogen suppression alone.

Overall, 92% in the Zometa group were cancer-free two years after treatment compared to 88% on estrogen suppression alone.

How Bone Drugs May Stifle Cancer

Tumors can shed cells that migrate to the bone marrow, where they may hide and be protected from cancer-killing drugs.

One theory is that these wandering tumor cells appear to stimulate the activity of osteoclasts, or cells that break down bone.

The activity of osteoclasts, in turn, appears to further spur these castoff tumor cells, a synergy that can reignite the cancer and cause it to return or spread.

It's thought that bisphosphonates like Zometa put the brakes on this cycle by slowing the activity of osteoclasts, which then quiets the rogue cancer cells.

"There is kind of an expiry [expiration] date to these dormant tumor cells," Gnant says. "You don't have to use all these treatments forever. If you manage to get the right window, then basically you can eradicate them and this would eventually mean a cure for our patients, which is obviously a word we should only use very humbly."

Conflicting Findings

A large British trial presented in December at the San Antonio Breast Cancer Symposium found that Zometa treatment did not reduce the risk of recurrence in women with early-stage breast cancers.

Not all of the women in that study received estrogen-suppressing therapy, however, and experts say that may be a key difference.

A subset of women in that study, those who had been postmenopausal for at least five years and thus had naturally lower estrogen levels, did see some survival benefit after taking Zometa compared to those on conventional therapies alone.

Other studies have shown that bisphosphonates improve survival and delay disease progression in patients with lung and bladder cancers and multiple myeloma.

Rowan T. Chlebowski, MD, PhD, chief of medical oncology at the David Geffen School of Medicine at the University of California, Los Angeles, says further studies are needed to sort out which patients may get the most benefits. But he thinks the evidence for using bone drugs is positive, on the whole.

"I'm in the believer group," he says.

"So the concept is, you need a low bone turnover environment for bisphosphonates to have an anti-tumor effect that's mediated through the bone. That seems a viable concept. Maybe we'll get a little bit more data and see where we go from there," Chlebowski tells WebMD.

Other experts, however, say Zometa should be used with caution in premenopausal patients with breast cancer.

"The drug has to be used in the same clinical situation," says Stephanie Bernik, MD, chief of surgical Oncology at Lenox Hill Hospital in New York City.

"We do use ovarian suppression, but it's become less popular in the United States," Bernik says.

"The drug would have to be used in the same way or we need more clinical evidence that we can use bisphosphonates without ovarian suppression," she says.

Rarely, the use of bisphosphonates has been linked to a rare condition called osteonecrosis, or bone death.

There were no cases of osteonecrosis reported in the current study, though patients on Zometa did report bone pain, fatigue, headaches, and muscle pain.

"Drugs do not come without complications," she says. "You really have to be very careful."


Breast Cancer Awareness: Symptoms, Diagnosis, and Treatment See Slideshow

Gnant, M. The Lancet, June 4, 2011.

Michael Gnant, MD, professor of surgery, Medical University of Vienna, Austria.

Rowan T. Chlebowski, MD, PhD, chief of medical oncology, David Geffen School of Medicine, University of California, Los Angeles.

Stephanie Bernik, MD, chief of surgical oncology, Lenox Hill Hospital, New York City.

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