Hope on the Horizon for Advanced Breast Cancer

Last Editorial Review: 1/31/2005

New Treatments Are Prolonging Survival and Improving Quality of Life

By Gina Shaw
WebMD Feature

Reviewed By Charlotte Grayson

The statistics are comforting and well-known: When breast cancer is detected and treated in its early stages, nearly 85% of women survive at least five years.

What about women who have advanced breast cancer? What about women who are diagnosed with cancerous lymph nodes (Stage III) or metastatic breast cancer (Stage IV) that has spread to other parts of the body?

Without doubt, they face a tougher battle. Yet medical research is making strides in their care. Indeed, women with Stage III breast cancers currently have a 50% to 60% chance of surviving five years, while women diagnosed with metastatic breast cancer -- once considered hopeless -- now have a 16% chance of surviving five years. Moreover, new treatments being tested offer great hope that these women may soon live longer and better lives.

To understand the gains in treating later-stage breast cancer WebMD turned to three prominent oncologists: Claudine Isaacs, MD, co-director of the breast cancer program at Georgetown University Medical Center; Edith Perez, MD, professor of medicine at the Mayo Medical School in Jacksonville, Florida; and, Jonathan Serody, MD, an associate professor of medicine and researcher at the University of North Carolina's Lineberger Comprehensive Cancer Center.

Here's their summary of drugs offering hope on the horizon:

Immunotherapy  |  Hormone Therapy  |  Chemotherapy  |  Vaccines


The biggest news today for women with advanced breast cancer is a drug called Herceptin. No other treatment in recent years has done as much to prolong the lives of women with later-stage disease: In a study published in the New England Journal of Medicine, Herceptin improved the average survival time for women with Stage IV HER2-positive disease from 20 months to 25 months. That's the most significant improvement in survival for these women that's been seen in a long time.

Herceptin is one of a class of drugs called monoclonal antibodies -- lab-engineered antibodies designed to mimic the body's own immune system response. Herceptin targets the HER2 protein, which, when it's overproduced in breast cells, leads to the proliferation of abnormal cells or cancer. When the drug finds HER2 proteins on the surface of the tumor cell, it binds to them and either kills the cancerous cells outright or stops their proliferation.

Herceptin is only effective in the 20%-30% of women whose cancers involve overproduction of the HER2 protein. Still, for these women, "Herceptin has improved survival rates more than anything else," says Claudine Isaacs, MD, associate professor of medicine and oncology at Georgetown University Medical Center and co-director of the breast cancer program.

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Hormone Therapy

The female hormone estrogen stimulates the growth of breast cells, including cancerous cells. So drugs that block estrogen in various ways can combat cancers that are estrogen receptor positive (ER+). In essence, the drugs "starve" the abnormal cells of the estrogen they need to proliferate. Tamoxifen (brand name Nolvadex) is the best known hormone therapy. It was the first anti-estrogen drug available for use for treating advanced breast cancer, and it works by selectively blocking estrogen's effects on breast cancer cells. (These types of drugs are called SERMs.) Another drug, Fareston, works similarly to tamoxifen, and is available to treat advanced breast cancer. Unfortunately, not all breast cancers respond to SERMs, and others become resistant to this treatment over time.

But now, a new type of anti-estrogen drug called an aromatase inhibitor is available. These drugs promise more options for women with advanced disease -- even for those whose cancer has become resistant to tamoxifen.

In fact, two aromatase inhibitors, Arimidex and Femara, are now approved for initial use in postmenopausal women with advanced breast cancer, rather than as a second-line of defense after tamoxifen has failed.

Aromatase inhibitors work differently than tamoxifen; they actually lower the amount of estrogen the body produces. Three brands are in current use: Arimidex, Femara and Aromasin. Each is taken in pill form.

"In terms of hormonal therapies, we now have a significant number of agents available, with new ones appearing all the time, and we can sequence them," says Isaacs. Several studies are underway comparing these drugs to tamoxifen or testing their use before and after tamoxifen.

Another new anti-estrogen drug, Faslodex, which works by destroying the estrogen receptors in cancerous breast cells, was approved by the FDA earlier this year and went on the market in May. It's given as an injection and is approved for use in women with ER+ tamoxifen-resistant metastatic breast cancer.

Earlier versions of hormone therapy sometimes caused nausea, bleeding and blood clots, but those have been reduced significantly with the newer drugs. "Quality of life with these drugs is much better and the side effects are much more tolerable," Isaacs says.

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As with hormone therapy, cancer experts now have more chemotherapy drugs available to treat women with advanced breast cancer than ever before. Isaacs predicts that state-of-the-art care for advanced breast cancer in the future may combine chemotherapy with newer types of drugs: immunotherapy, hormone therapy, and even vaccines.

"The big move is to look at novel agents given in conjunction with standard chemotherapy. That may be a way to really make a dent on prolonging survival," Isaacs says. Genentech, the company that developed Herceptin, is now testing an antibody that blocks a growth factor that's important to the formation of new blood vessels. Such an antibody could work in combination with chemotherapy to choke off the growth of cancerous cells.

In a one-two punch, Herceptin is also being combined with the chemotherapy drugs, Taxol and carboplatin (brand name Paraplatin), in a large clinical trial now underway at Mayo Medical School in Jacksonville, Florida. "We've seen a high response rate and good tolerability so far," says Edith Perez, M.D., a professor of medicine and the study's lead investigator. "The duration of the responses, in my opinion, will have a very significant impact on the lives of patients with breast cancer." It's too soon for numbers, she says, but in a study reported in late 2000, just the Taxol-carboplatin combination alone yielded tumor shrinkage in 62% of the women, and a projected one-year survival rate of 72%.

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The Promise of Vaccines

At the University of North Carolina's Lineberger Cancer Center, scientists are about to complete a early human study of a vaccine to treat advanced breast cancer. Cancer vaccines don't work the way that vaccines for infections like measles do. Those are given to people to prevent disease. Cancer vaccines are being studied to help the body's immune system "rev up" to fight the disease.

In this case, the vaccine is customized for each individual woman. Doctors take a woman's dendritic cells -- a type of white blood cell that alerts the immune system to the presence of abnormal proteins present in breast cancer cells -- and engineer them to boost their response against a particular type of abnormal protein.

"We're looking for ¼ regression of established tumors. By definition, this means at least a 25% shrinkage of established tumors," said researcher Jonathan Serody, MD, when the trials began. He can't say yet whether they got the expected response, but he notes that the vaccine was well tolerated by the dozen or so women in the trial. Serody expects the vaccine to be most effective in combination with other treatments, such as hormone therapy or chemotherapy.

"With things like vaccines, combination therapies, and other fascinating possibilities, we're starting to look beyond standard chemotherapy and into novel agents to attack advanced breast cancer," says Isaacs. "We're developing an array of treatments that work by different mechanisms of action, that give women with advanced breast cancer more options than they've ever had before."

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Originally published July 2002.

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