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Breast Cancer Breakthrough

by Robin Roenker

Photo of pink ribbon with UK pinEdward Romond stepped to the podium last May at the Orlando, Florida, convention center to address an army of doctors united by a common enemy: cancer.

Five thousand of the nation’s premier clinical oncologists at this hastily called symposium at the annual American Society of Clinical Oncology meeting sat waiting for what they had heard was extremely good news. What Romond, a professor of medicine in the UK College of Medicine, didn’t know at the time was that 3,000 more people watched eagerly on video screens in overflow rooms nearby.

Romond was there to talk about the results of a massive, five-year clinical trial focused on a drug called Herceptin, research sponsored by the National Cancer Institute (NCI) that was published last October in The New England Journal of Medicine. At issue was the drug’s effectiveness in reducing the spread of cancer in patients with a particularly aggressive form of breast cancer.

Romond began his presentation not with talk of trial methodology, molecular makeup of receptor proteins, or statistical P-values of the data obtained, but with a focus on the patients themselves.

“On behalf of the 3,351 women who participated in this clinical trial,” Romond began, “I have the privilege of presenting these results to you.” Recalling that opening months later, Romond pauses and glances out of his office window. His soft-spoken voice cracks and gets even softer. “It’s very important to emphasize the courage of these women,” he says. “It was ...,” he pauses again, “pretty emotional.”

Photo of Edward RomondEdward Romond has been involved in clinical trials in cancer research since he came to the University of Kentucky 22 years ago. He says that because of molecular biology and targeted therapies, the progress in breast cancer treatment in the next 10 years will be even much greater than in recent years.

When Romond had finished his 15-minute presentation of what he calls “the single biggest advance in the treatment of breast cancer in decades,” the response was amazing, he says. Applause rang out for minutes. Colleagues told him later that members of breast cancer advocacy groups in the audience were in tears.

Tears and applause, to greet the news that in Herceptin may lie the power to—in Romond’s words—“change one of the deadliest types of breast cancer into something we can treat successfully.” In short, Herceptin can save lives.

The Herceptin Story

The extremely aggressive form of cancer on trial is called HER-2 positive breast cancer. Compared to other types of breast cancer, HER-2 is more likely to spread to other organs—even in spite of chemotherapy—and to recur more often after treatment.

Of the more than 211,000 women who will be diagnosed with breast cancer this year, around 20 to 25 percent will get the bad news that they have HER-2 positive breast cancer, according to estimates by the National Institutes of Health. Their risk of dying from cancer has been significantly higher than women with other types of breast cancer. But because of Herceptin, that possible death sentence may soon be lifted.

Developed in the 1990s as an antibody to block the HER-2 protein, Herceptin—the prescription name for trastuzumab—has been FDA approved since 1998 for treatment of patients with advanced HER-2 positive breast cancer that has spread to outlying organs such as the bones, lungs or liver.

So while physicians knew of Herceptin’s potential to prolong life and shrink tumors for patients whose cancer had spread, researchers wanted to test whether administering the drug just after diagnosis might prevent the spread of the disease in its early stages to other organs.

Answering that question through the clinical trial, which featured over 500 testing sites throughout the United States and Canada, was the objective of Romond and the other cancer researchers involved. Early last January, his study merged with a similar NCI-sponsored national clinical trial that sought to answer essentially the same question. The merger of the two trials provided researchers with a much larger dataset for analysis—3,351 women—which allowed for statistically significant results much sooner than either study would have yielded separately.

Both trials enrolled women whose HER-2 cancer had not yet spread to other organs, but whose cancer did show a tendency to spread, as evidenced by its presence in at least one lymph node. Half of the patients received chemotherapy only, while half received Herceptin along with chemotherapy. Those who got Herceptin were given the drug intravenously once a week during a three-month chemo regimen, and then weekly for nine months after chemo.

Photo of woman wearing pink ribbonThe results were straightforward and incredibly encouraging: The trials showed that the number of cases of recurrent breast cancer was 52 percent less in the women who received Herceptin along with their chemotherapy, compared to those who received chemotherapy alone. “It was absolutely incontrovertible that this benefit is real,” Romond says, his tone an exclamation point.

Citing the 52 percent reduced risk of cancer recurrence and a 33 percent improvement in survival rate, Gabriel Hortobagyi, president-elect of the American Society of Clinical Oncology and chair of the breast medical oncology department at the University of Texas M.D. Anderson Cancer Center, says, “In oncology, we get excited about improvements of 2 percent to 4 percent. We haven’t seen anything of this magnitude in breast cancer research in 30 years.”

“One of the striking things in the data is when you get three or four years out from when the cancer is diagnosed, 90 percent of the women who received Herceptin have no detectable cancer anywhere else in their body,” Romond says. “And these are women whose prognosis of having cancer spread with chemotherapy alone was worse than a 50-50 chance.”

The health of the 3,351 women in the study will be monitored for the rest of their lives, but neither study is accepting new patients. Here’s why: When presented with the initial study data in mid-April of 2005, monitoring committees told Romond and his colleagues to immediately stop both trials. “They said unequivocally—and I’m happy to echo their words—‘The question is answered. Herceptin is overwhelmingly beneficial,’” says Romond.

Since the results of the trials were released, Herceptin has also been offered to members of the control group who were within one year of their cancer diagnosis.

To make the drug available to recently diagnosed HER-2 positive breast cancer patients everywhere in America, all that’s left is FDA approval. It’s a status Romond believes might be granted even before the end of this year, given the compelling results of the clinical trials—and the potential of the drug to save lives.

A Death Sentence No More

Romond has seen the drug’s success stories firsthand, and the numbers aren’t mere statistics to him. When he talks about this trial, it’s clear he’s thinking of the names and faces of his own patients—patients who are alive today because they received Herceptin.

He tells of a young woman from near London, Kentucky, who was in her early 30s with two young children at the time of her breast cancer diagnosis three years ago.

“When I talked to her about it, I said, ‘This is really bad breast cancer, I have to be honest with you,’” Romond recalls. He recommended that she enter the clinical trial in hope of receiving Herceptin. But the woman said she doubted whether she could join the study, since the car she owned wasn’t reliable enough to get her back and forth to Lexington, a 150-mile round trip, for weekly treatments.

The next day, though, the woman called Romond to tell him her father, who lived in Texas, had bought her a car so she could participate in the trial. “She got randomized to receive Herceptin, and she finished it two years ago. I saw her yesterday, and she’s fine,” Romond says. “Perfectly fine. Cancer-free.” One life saved.

It’s easy to see when you talk with him that as wonderful as the statistics are, for Romond the lingering impact of the study is in Herceptin’s potential to save the lives of his patients. “It’s rewarding to me because of my patients,” he says. “They’re right there in front of me. And I know the difference it’s made in their lives.”

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