Stem Cells in Breast Cancer

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Stem Cells in Breast Cancer

Breast cancer stem cells were discovered in 2003 by scientists at the U-M Comprehensive Cancer Center
In the fight against breast cancer, there is good news and bad news. The good news is that, since 1990, there has been a steady decline in the death rate from breast cancer. Earlier detection and better treatments are bringing hope to women with both early and advanced disease.

The bad news is that nearly 41,000 women die of breast cancer each year in the United States alone. It is still the second-leading cause of deaths from cancer. The survival rate for women with advanced, metastatic breast cancer has not changed significantly for decades. In spite of more effective therapies, many women still experience recurrences of breast cancer after treatment.

We believe that current therapies for advanced breast cancer are limited because they may be targeting the wrong cells within a malignant tumor. These therapies were designed to shrink cancers by killing all the cells in a tumor. We believe therapies could be more effective, and cause fewer side effects, if they were aimed specifically at a small group of cells within the tumor called cancer stem cells.

Breast cancer stem cells were discovered in 2003 by scientists at the U-M Comprehensive Cancer Center, the first identified in a solid tumor. These scientists found that just a few cancer stem cells are responsible for the growth and spread of breast cancer. Unless the cancer stem cells are destroyed, the tumor is likely to come back and spread malignant cells to other parts of the body, a process called metastasis.

Because cancer stem cells are resistant to traditional chemotherapy and radiation, we need new treatments that can be targeted directly at these deadly cells. U-M Cancer Center scientists are studying breast cancer stem cells to learn more about them and to determine the type of therapy most likely to destroy the cells. We hope to begin a new clinical trial of one of these therapies sometime in 2008. It will be the world's first clinical study to target stem cells in breast cancer.

How do scientists identify breast cancer stem cells?
All cells have a unique pattern of proteins, like a fingerprint, on their surface membranes. All breast cancer stem cells have a surface protein marker called CD44, along with very low levels or no levels of two markers called CD24 and lin. Using specialized equipment and techniques, scientists can separate cells with this combination of protein markers from millions of other cells in a tumor sample. More recently U-M scientists have identified a protein called ALDH-1, which is expressed in the most aggressive cancer stem cells and can be detected in biopsies of patients' cancers.

What causes breast cancer?
Scientists know that women who inherit mutations in certain genes have a much higher risk of developing breast cancer. Mutations in genes called BRCA1 and BRCA2, are involved in many hereditary breast cancers, while HER-2 and PTEN are commonly altered in other aggressive breast cancers. Researchers have shown that these genes are involved in DNA repair and tumor suppression. U-M scientists have discovered that these genes also regulate self-renewal of breast cancer stem cells. Mutations in these genes allow stem cells to develop abnormally and increase the risk of cancer.

Non-genetic factors -- including age, radiation exposure, menstrual history and number of pregnancies -- also are associated with increased risk. But regardless of the triggering factor, we believe that all types of breast cancer originate in stem cells or cells called progenitors, which come from these stem cells in the breast.

Do breast cancer stem cells cause metastasis?
There are many factors that trigger metastasis in cancer and scientists don't yet understand how they all work. But we do know that stem cells are involved in the process. Recent research by U-M Cancer Center scientists found that cells from tumors with a higher percentage of cancer stem cells were more likely to break away and spread.

Why are women still dying of breast cancer?
Advances in mammography and magnetic resonance imaging (MRI) screening for breast cancer have made it possible for doctors to see breast tumors when they are very small. When physicians can diagnose and treat breast cancer early, they often can remove the tumor with surgery and prevent a recurrence.

Once malignant cells leave the primary breast tumor and migrate to other parts of the body, however, treatment is more difficult. Chemotherapy and radiation will kill most malignant cells and shrink the tumor, but the cancer often comes back, because these therapies don't kill the stem cells. In addition, cancer stem cells drive metastasis - the tendency of malignant cells to spread throughout the body and form new tumors. Metastatic cancer is often what causes the death of women with advanced breast cancer.

To cure metastatic breast cancer, we believe you must eliminate the cancer stem cells. Chemotherapy and radiation alone cannot do that.

Some breast tumors have more stem cells than others. Is that significant?
Recent research has shown that breast tumors with a higher percentage of cancer stem cells are more aggressive and more likely to spread. Women with these tumors have a higher risk of dying from cancer. So knowing the percentage of stem cells in a breast tumor could help us determine which patients need more aggressive treatment.

Is there a link between BRCA1 mutations and cancer stem cells? Watch the video as Dr. Wicha explains why the number of breast cancer stem cells is importantBRCA1 is a tumor suppressor gene known to be strongly linked to breast cancer. Mutations in this gene increase the risk of developing aggressive breast and ovarian cancer. Mutant forms of BRCA1 account for about 5 percent to 10 percent of cases of hereditary breast cancer. U-M Cancer Center scientists have recently discovered that BRCA1 regulates self-renewal of cancer stem cells. When the gene is mutated, cancer stem cells multiply abnormally, increasing the risk of cancer.
What type of treatment will be tested in the U-M clinical trial?
In 2008, the Cancer Center will begin the world's first clinical trial for women with advanced breast cancer that has not responded to traditional therapy. We will test a new drug combined with chemotherapy in an attempt to attack all cells in the tumor simultaneously.
Currently, the breast cancer stem cell clinical trial is still in the planning stages and is not enrolling patients. It will be a small study involving just a few patients with advanced cancer that has not responded to therapy.

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