Hope on the Horizon for Advanced Breast Cancer

New Treatments Are Prolonging Survival and Improving Quality of Life

From the WebMD Archives

The statistics are comforting and well-known: When breast cancer is detected and treated in its early stages, 86% or more of women survive at least five years.

What about women who have advanced breast cancer? What about women who are diagnosed with Stage III breast cancer, in which a number of lymph nodes may be affected, 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 49% to 56% 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

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 new 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. Herceptin is representative of a new approach to treating advanced breast cancer, and more monoclonal antibodies are in development that will target other causes of the disease. For instance, researchers are now looking at several drugs that are designed to affect another protein involved in some types of breast cancer called HER1, or more commonly, EGFR. While initial results haven't been especially positive, researchers are still hopeful that further study of EGFR-targeting drugs will be more successful.

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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 is available. Three of these drugs are currently available -- Arimidex, Femara and Aromasin -- and each is taken in pill form. These medications promise more options for women with advanced disease -- even for those whose cancer has become resistant to Tamoxifen.

In fact, 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. Arimidex has also been approved as adjuvant therapy -- drugs given after surgery or radiation -- for women with certain types of early breast cancer.

Aromatase inhibitors work differently than Tamoxifen; they actually lower the amount of estrogen the body produces. There's also evidence that they may be more effective drugs. The landmark ATAC study recently showed that Arimidex was significantly more effective than Tamoxifen in post-menopausal women with early breast cancer, and several studies have indicated that aromatase inhibitors cause less toxicity and fewer side effects than Tamoxifen.

"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.

Another anti-estrogen drug, Faslodex, is representative of a whole new class of drugs that work by destroying the estrogen receptors in cancerous breast cells. Faslodex was approved by the FDA and is now available. It's given as an injection and is approved for use in women with ER+ Tamoxifen-resistant metastatic breast cancer. At least one study shows that it may also be helpful for women who have previously received other hormonal treatments in addition to Tamoxifen, such as aromatase inhibitors.

Earlier versions of hormone therapy sometimes caused nausea, bleeding and blood clots, but those side effects 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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Chemotherapy

As with hormone therapy, cancer experts now have more chemotherapy drugs available to treat women with advanced breast cancer than ever before. Researchers are trying out both combinations of different chemotherapy drugs and approaches that use them one at a time in different sequences. While it may sound insignificant, tinkering with combinations and sequences of chemotherapy drugs has made a big difference for women with breast cancer. Dose density therapy, in which chemotherapy medications are taken more frequently than traditionally, has also been shown to be effective in women with advanced cancer, even after standard chemotherapy has failed.

Isaacs predicts that state-of-the-art care for advanced breast cancer in the future may also 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 by the U.S. Oncology Group and McGill University. Other studies have shown potential in Gemzar -- a drug currently approved to treat other types of cancer -- especially for women with metastatic cancer.

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 therapeutic vaccine to treat advanced breast cancer. This type of cancer vaccine doesn't work the way that vaccines for infections like measles do. Those are given to people to prevent disease. Therapeutic cancer vaccines are being studied to help the body's immune system "rev up" to fight the disease. Initially, at least, they would be used in women who have exhausted all other treatments.

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.

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"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. The study at the University of North Carolina is only one of several that are evaluating possible vaccines for breast cancer.

"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."

WebMD Feature Reviewed by Charlotte E. Grayson Mathis, MD

Sources

SOURCES: 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. Jonathan Serody, MD, an associate professor of medicine and researcher at the University of North Carolina's Lineberger Comprehensive Cancer Center. The American Cancer Society web site. National Institutes of Health Medline web site. The U.S. Department of Health and Human Services web site. The National Cancer Institute web site. Burstein, H. Medscape web site, "Targeted Therapies in Breast Cancer: the Champagne Has Lost Its Fizz." Hudis, C. Medscape web site, "Adjuvant Chemotherapy Overview: Old Drugs, New Tricks." Jones, S. Medscape web site, "What's New in the Hormonal Treatment of Breast Cancer?" Miller, K. Medscape web site, "Clinical Status of Antiangiogenic Therapy -- Is There Still Reason to Hope?" Perez, E. Medscape web site, "Defining Regimens with Targeted and Novel Therapies for Breast Cancer." Pritchard, A. Medscape General Medicine, June 18, 2003; vol. 5. Pritchard, K. Medscape web site, "New Prognostic and Predictive Factors: Are They Ready for Clinical Use?" Pritchard, K. "Aromatase Inhibitors: the State of the Art." Robert, N. Medscape web site, "Update on Adjuvant Endocrine Therapy." Sledge, G. Medscape web site, "Treatment of Metastatic Breast Cancer." Sparano, P. Medscape web site, "Chemotherapy Options for Breast Cancer." Sparano, J. Medscape web site. "Taxanes in Breast Cancer: From Neoadjuvant Therapy to the Treatment of Metastatic Disease." WebMD Medical News: "Millions Could Benefit from Tamoxifen." WebMD Medical News: "Condensed Chemo Improves Cancer Outcome." WebMD Medical News: "Tamoxifen Prevents Breast Cancer in Some." WebMD Medical News. "Frequent Chemo Ups Breast Cancer Survival." WebMD Medical News. "Arimidex Better than Tamoxifen Long Term." WebMD Medical News: "Breast Cancer Vaccine May Be Within Reach."

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