Laura Esserman
With one in every eight US women diagnosed with breast cancer in her lifetime, this disease has affected the population on a grand scale.
Each year, roughly 200,000 women are diagnosed with breast cancer and more than 40,000 die. With exceptionally high rates in the Bay Area - Marin County's is among the highest in the country - UCSF scientists have joined the fight with full force, and are continually making advancements in risk assessment, diagnosis and clinical care.
Laura Esserman, breast cancer surgeon and clinical leader of the UCSF Comprehensive Cancer Center's
Breast Oncology Program at the UCSF Mount Zion campus, says there are many factors that influence the risk of breast cancer. Only about 5 percent of cases are attributed to hereditary cancer syndromes, mostly based on a rare mutation in two genes: breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2).
Most scientists agree that increased risk is more strongly associated with environmental and lifestyle factors. Such factors include being overweight after menopause, minimal exercise and having an unhealthy diet with high alcohol consumption. There are also "reproductive" factors, such as having children later in life, not bearing children, not breastfeeding, early age at onset of menstruation and late menopause - all of which increase estrogen levels and increase risk.
Esserman also suggests that hormone replacement therapy increases breast cancer risk. "In Marin County, there was a decline in hormone therapy a few years ago, and last year, we saw the first-ever decrease in reported breast cancer in this area," she says. "I don't think that is a coincidence."
There is also epidemiologic research suggesting that exposure to environmental toxins during a specific window of time in adolescence (during breast development) increases the risk of developing breast cancer later in life. This was seen in women who received radiation therapy during childhood, in Japanese women exposed to radiation from an atomic bomb blast as girls and in laboratory mice exposed to chemical carcinogens prior to sexual maturation.
UCSF and the Bay Area Breast Cancer and the Environment Research Center are currently part of a research consortium with three other research institutions nationwide seeking to identify additional environmental exposures that may increase breast cancer risk. Robert Hiatt, the director of population sciences for the UCSF Comprehensive Cancer Center, is the principal investigator for the study. In this study, 400 Bay Area 7-year-old girls will receive regular checkups and be surveyed about diet, exercise and other potential risk factors.
Early detection of breast cancer increases the survival rate up to 90 percent. Mammograms are the most cost-effective diagnostic tool for screening the population. On a national scale, mammograms detect cancer in one to two per 1,000 women in their 40s and in five to seven per 1,000 women in their 50s. Esserman recommends that every woman over the age of 40 be tested annually, and at an earlier age if the woman has risk factors.
Although mammograms are less expensive than magnetic resonance images (MRIs), mammograms do not detect all cancers. So Esserman recommends alternating MRIs with mammograms every six months for women over 40 with several risk factors. She also recommends blood tests for all women to assess risk.
New Drug Therapy
A recent advancement in drug therapy for women with breast cancer is Herceptin, manufactured by Genentech. Herceptin is an antibody that attaches to receptors - protein called human epidermal growth factor receptor 2 (HER2) - surrounding breast cells. Blocked by the drug, the HER2 protein, which causes cells to grow and divide, cannot enter the cell.
HER2 genes, which produce HER2 protein, regulate normal growth of breast cells, but too much HER2 protein can turn a normal cell into a cancer cell. In conjunction with chemotherapy, Herceptin also aids in the destruction of HER2-positive cancer cells.
"Herceptin is a huge advancement," says Esserman. "This shows that understanding the biology behind tumors, and tailoring treatments accordingly, will make a tremendous difference. But all drugs don't work for everyone, so the trick is to figure out what works for whom."
To this end, Esserman recently led the first of a series of trials - the I SPY TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis) - which has a goal of creating a model for practitioners to identify the best therapy plan for individual patients. The trial is funded by the National Cancer Institute, and includes nine cancer centers nationwide. The MRI technique used by the researchers was developed by UCSF physicist Nola Hylton.
In this first trial, 237 women with localized advanced breast cancer (having tumors at least 3 centimeters in size) were tested to identify unresponsiveness to standard treatment regimens. Researchers analyzed tissue samples to better understand the molecular makeup of the tumors and conducted MRIs to observe how tumors responded to therapy.
With this information, researchers are identifying biomarkers - changes in breast images or in the tumor's molecular makeup. Early in the course of the treatment process (during presurgical chemotherapy), practitioners can track these biomarkers and determine whether or not a patient is responding to therapy.
Recently, 114 patients were added to the study to analyze more tissue and assemble novel imaging techniques. A second trial, I SPY 2, is currently in the planning stages. In I SPY 2, researchers will take the information from the initial trial, which identified patients unresponsive to standard treatment, and begin to modify treatment and introduce alternative therapies, thus tailoring treatment to each individual patient.
"The goal is to be able to tailor everyone's therapy by 2008," says Esserman. "With so many factors involved, there isn't going to be one pill or one treatment to defeat breast cancer. But I think we are winning the war and I feel, in 20 to 30 years, we may get there."
Related Links:
Carol Franc Buck Breast Care Center
Breast Cancer and Environment Research Center (BCERC)
UCSF 101 Related Features
