Highlights of the 2005 Symposium
Download the Symposium Proceedings as a PDF file (3.89MB)
Table of Contents
A Message from the Director
Plenary Session: The Unequal Burden of Breast Cancer
21st Century Methods for Detecting and Curing Breast Cancer
Psycho-oncology and Psychoneuroimmunology
Clinical Trial Fundamentals: Getting Started in Translational Research
Plenary Poster Presentations
Communities Conducting Research
Exploring Cause and Prevention
New Treatment and Detection Strategies
Emerging Topics in Breast Cancer Biology
A Scientific Meeting Like No Other
We are pleased to provide this summary of the presentations made at the California Breast Cancer Research Program's fifth symposium, "From Research to Action: Seeking Solutions," held in Sacramento, September 9-11, 2005. During those three days, more than 500 people came together to focus California's attention on one of the biggest threats to the lives of young and middle-aged women in our state—breast cancer.
Our symposium brought together the power of scientists, health care professionals, and women whose lives have been affected by the disease. Together, we discussed controversial and promising areas of research into a cancer that strikes two American women every minute of every hour of every day.
Breast cancer robs Californians of our sisters, our wives, our daughters, our partners, and our friends. The California Breast Cancer Research Program is committed to funding the research that will move us most quickly to the future we all long for—a future without breast cancer.
In the U.S. today, it is not easy to find out the results of scientific research. Scientific journals are not widely available and subscriptions are expensive. Yet for research to have an impact on breast cancer, scientists, health care professionals, women who have the disease, and women at risk all need to know the results.
That's why the California Breast Cancer Research Program (CBCRP) is committed to getting the results of the research we fund out to as wide a public as possible. One way we do this is by holding, every two years, a statewide conference, free to the public, where researchers funded by the CBCRP present their results.
Roughly half of our attendees are researchers and half are general public and healthcare providers, which allows for the spirited exchange of ideas between researchers and the people most affected by breast cancer, as well as increased networking opportunities between the diverse attendees.
The CBCRP has set a national standard for holding scientific meetings that involve and inform non-scientists. At "From Research to Action: Seeking Solutions," research scientists presented their findings to a concerned public. Equally important, women whose lives have been affected by the disease shared their priorities and hopes with researchers.
We make a special effort to bring women who have, had, or are at risk of breast cancer to these conferences. Seventy-two women received scholarships that covered their travel and accommodations.
To get the word out even more widely, we are providing this report, free to the public, with summaries of the presentations made at "From Research to Action: Seeking Solutions." It gives a capsule look at a conference that expressed our urgency to put research into practice—and our commitment to ending the suffering caused by breast cancer.
Plenary Session – The Unequal Burden of Breast Cancer
Unequal exposure to cancer-causing substances in the environment may explain a lot about the unequal burden of breast cancer. For example, cosmetics for African American women contain problematic levels of chemicals that act like estrogen, a hormone that plays a role in breast cancer.
- African American women get mammograms as often as white women, but on average the tumors found in African American women are larger, and therefore more dangerous.
- White women are the group most likely to get breast cancer, but African American women are most likely to die of the disease.
- High-income Latina and Pacific Islander women have far higher rates of breast cancer than low-income women from these groups.
- Older women with breast cancer get less timely treatment than younger women.
These are some of the ways the burden of breast cancer falls unequally on various groups of women, presented by William Wright, Ph.D., of the California Department of Health Services. Uncovering the reasons for disparities like these could shed light on breast cancer and be key to prevention, treatment, and cure. That's why the CBCRP has made the unequal burden of breast cancer one of three critical issues to be investigated in our five-year Program Initiative. "Many of the answers to the problem of disparities in breast cancer are probably already out there, and it may be a matter of making the right connections between people and ideas," said Debra Oto-Kent, M.P.H., of the nonprofit Health Education Council. This plenary session outlined previous research about the unequal burden of breast cancer and suggested future directions.
Inequalities in breast cancer require action at the societal level. The U.S. government has set a national goal of eliminating health disparities by 2010, and made 14 specific recommendations for reaching this goal for cancer in a report called, "Making Cancer Health Disparities History." However, not enough progress is being made.
Moderator Robert Hiatt, M.D., Ph.D., of the University of California, San Francisco Comprehensive Cancer Center, pointed out that California has a large, diverse population that allows researchers to study inequities in health. The state also has the largest breast cancer registry in the world—with information on every individual case—plus top-rated universities. All these resources make California an ideal laboratory for research on breast cancer's unequal burden.
Can the unequal burden be explained by genetic differences? When looked at from the viewpoint of biology, the categories used to study this question may not be useful, according to Lovell Jones, Ph.D., of the University of Texas MD Anderson. For example, most African Americans are descendents of slaves who came from many different African countries. People in these various countries today differ in their genetic makeup and have widely varying breast cancer rates. Another example: Latina women living near the Mexican border have low breast cancer rates. But, Lovell said, the incidence of breast cancer rises the farther they live from the border, until "in Chicago, Hispanic women have the same breast cancer rate as whites." National data for population groups may mask wide disparities within the groups.
- A recommendation for action on this question is for future research to investigate breast cancer disparities within the subgroups usually studied.
Can the unequal burden of breast cancer be explained by inequalities in access to health care and information? Sandra Millon-Underwood, Ph.D, FAAN, of the University of Milwaukee, said this is a critical part of the explanation. She interacts with low-income, minority communities where "women are not receiving the evidence-based care they need." While Millon-Underwood has seen progress in these communities in screening and follow-up care, there is still little access to palliative and end-of-life care. Relatives of women with breast cancer have nowhere to turn if they are concerned about their own risk. "Physicians are not graduating from medical school able to provide care across cultures," she said. However, Dr. Lovell pointed out that unequal access is not the entire cause of breast cancer's unequal burden. For example, black women having less access to quality health care does not explain why they get the disease at younger ages than women from other groups.
Recommendations for reducing inequalities in access to breast cancer health care and information include:
- Increase science education for all ethnic and minority groups, to involve a broader segment of society in health care issues.
- Raise awareness among health care professionals about the biases of their own cultures, so they can more effectively care for people from the many diverse subcultures in the U.S.
Can unequal exposure to cancer-causing substances in the environment explain the unequal burden of breast cancer? Rachel Morello-Frosch, Ph.D., of Brown University, said that if more research is done, toxic exposures may explain a lot. These exposures can come in a variety of ways. One is consumer products. Cosmetics for African American women contain problematic levels of chemicals that act like the hormone estrogen. This hormone plays a role in breast cancer. Exposure can come through work, like the cancer-causing chemicals used in the semi-conductor industry. Exposure can come through pollution. Residential segregation leads to high pollution levels in low-income communities. Less segregated areas have less pollution overall.
Preventing breast cancer may depend on ending the marketing of toxic products, ending on-the-job exposure to toxic chemicals, and reducing discrimination in housing. Recommendations to spur progress include:
- Make scientific research relevant to diverse communities by involving those communities in collaborative research.
- Get the research translated into policy changes.
Presenters on this panel also made additional recommendations for future research and action on the unequal burden of breast cancer, including:
- Identify gaps in research evidence about specific populations.
- Get what is already known through research about breast cancer's unequal burden translated into effective local prevention and treatment programs.
21st Century Methods for Detecting and Curing Breast Cancer
Within three decades, it will be possible to have a device at home that will analyze a drop of blood, e-mail the results to a lab, and the lab will tell you if you have early stages of breast cancer or 20 other diseases.
What breast cancer researchers have been doing isn't working, and a revolution in thinking is needed. Systems biology shows promise for rapid progress against breast cancer and many other diseases. That's the consensus of presenters in this workshop, moderated by Kim Pierce, of the Los Angeles Breast Cancer Alliance. James Heath, Ph.D., of the California Institute of Technology, said that the current approach—research into individual genes and proteins involved in a breast cancer cell—is like taking out one part of a radio at a time and studying it. "Instead we need to develop the equivalent of the engineer's radio circuit diagram for the cell," he said. This diagram will show how all the genes and proteins interact together.
The hypothesis of systems biology is that disease arises from perturbed networks of the proteins and genes that make up the systems of life. Leroy Hood, M.D., Ph.D., of the Institute for Systems Biology, and the developer of the automatic gene sequencer, said that curing cancer may not be possible. But with early diagnosis, cancer could be eliminated.
The need for earlier breast cancer diagnosis was underscored by Michelle Rakoff, from the Breast Friends peer support mentoring program at Long Beach Memorial Medical Center and a 17-year breast cancer survivor. "Mammography is not good enough. Young women have a 'normal' mammogram and then two months later, find a one-inch lump," she said.
Some research has been done on the kind of measurements necessary for a systems biology approach to early cancer diagnosis. Research on progression from early to late stage prostate cancer has found that 2,000 out of 18,000 genes differed from normal, 40 networks of interactions between genes and proteins were turned up or down, and 60 proteins were secreted into the blood. It took 100 million measurements to get this information. There are also 60-80 proteins associated with breast cancer that are secreted into the blood. What researchers don't know is how many of these "blood fingerprints" will need to be detected in order to make a very early stage diagnosis of breast cancer. Dr. Hood believes the number will be 10-20, and that with 1,000-2,000, all diseases could be detected. To make these measurements, breakthroughs in nanotechnology—devices to measure the presence of molecules—will be needed. Prototype technology that has already been invented points to these breakthroughs being feasible.
Dr. Hood predicted that within three decades, it will be possible to have a device at home that will analyze a drop of blood. "The device will e-mail the results to a lab, and the lab will tell, from molecular fingerprints in the blood, if you have early stages of breast cancer or 20 other diseases," he said. The lab will also specify the treatment to stop the disease. To get to this point will require a massive cross-disciplinary systems biology effort involving chemists, physicists, mathematicians, computational experts, and new technology.
A technology that's already available—positron emission technology (PET) scanning—will be used in the future within hours of a patient being given the first dose of a breast cancer drug, to check on a molecular level if the drug is working. That's the prediction of the PET scan's inventor, Michael Phelps, Ph.D., of the University of California, Los Angeles. PET scans, he said, "take pictures of molecules as they go about the work of maintaining the body." These scans provide information about metabolism, proteins, and DNA. PET scans can now be used to detect if cancer has spread to another part of the body. Mammograms are not effective at detecting cancer in dense breasts, which younger women often have. PET scans do much better. However, Medicare and Medicaid currently will not reimburse the use of PET scans for breast cancer.
All presenters cautioned that rapid progress against breast cancer using a systems biology approach is technologically feasible, but politically challenging because it will take a huge financial investment. Yet if the investment is made, the payoff at the end could be low-cost technology. "It took $180 million to sequence the first gene. Today, sequencing a gene costs $6," said Dr. Phelps.
Psycho-oncology and Psychoneuroimmunology: Problems, Possiblities, and Pragmatics
The stress of having a close relative die of the disease may itself raise a woman's risk for breast cancer.
Emotional recovery from chemotherapy is significantly better if the therapy is given every three weeks, instead of every two. Women with a fighting spirit survive longer after breast cancer, compared to women who feel hopeless, but the effect disappears after 10 years. The most common diagnostic test for suspected breast cancer—the core needle biopsy—produces an anxiety level higher than that found in general surgery patients. These are some of the findings of recent research into the psycho-oncology of breast cancer, the intersection of psychology and breast cancer treatment, presented in an overview by David Wellisch, Ph.D., of University of California, Los Angeles. He said most of this research has been done with upper-middle class white women, and called for more research with minority women.
Psychoneuroimmunology, a related field, is the study of interactions between social factors and the immune system. Research in the past 20 years has focused on the effect of stress on the immune system, but scientists don't yet understand the immune system's role in breast cancer.
A pioneer in psychoneuroimmunology, Dana H. Bovbjerg, Ph.D., of Mount Sinai School of Medicine, is investigating women with a family history of breast cancer. These women have a higher risk for the disease, and only some of this risk is caused by inherited genes. Dr. Bovbjerg's hypothesis is that the stress of having a close relative die of the disease may itself raise a woman's risk for breast cancer. Another possibility is that a family history of breast cancer may make a woman more sensitive to the effect of stress in daily life. His research provides some physiological support for both of these theories.
While Dr. Bovbjerg's research studies an aspect of the brain possibly influencing the immune system, Julie Bower, Ph.D., at the University of California, Los Angeles, is investigating a way the immune system may influence the brain. Her research focuses on the biological mechanisms of fatigue. Fatigue is the most common side effect of breast cancer and its treatment. Breast cancer patients rate the fatigue involved in the disease as more distressing than the pain. The immune system communicates with the brain via chemicals called pro-inflammatory cytokines. When animals are given excess cytokines, it leads to fatigue, decreased food and water intake, changes in social and sexual behavior, alterations in sleep and brain function, and mood disturbance. This list is similar to what many women experience during breast cancer treatment. Dr. Bower has found that the more elevated a breast cancer survivor's cytokine activity, the more fatigue she reported. Breast cancer and its treatment may have disturbed these women's immune functioning. Dr. Bower is currently running an experiment where breast cancer survivors experiencing fatigue are receiving a medication to block cytokines, or doing yoga designed to improve the immune system.
Linda Luecken, Ph.D., of Arizona State University, suggested future areas for research that included:
- Taking a multi-systems approach that can evaluate the many complex biochemical interactions involved in the stress response, well-being and cancer.
- Investigating the independent impact of both risk and protective factors. For example, a low measure of depression doesn't necessarily mean a high sense of well-being.
- Finding out which biological and social interventions promote well-being and protect against disability in the face of breast cancer. Individual traits that promote resilience, such as a sense of mastery, have been studied, but community resources that promote resilience have received little attention.
- Using daily journal studies to research the dynamics of the coping process.
Most chemicals stay in the body only a few days or weeks, do their damage, and they're gone. To get around this problem, scientists are looking for changes in the body that reveal traces of past chemical exposure.
Biomonitoring, the testing of people to find out what chemicals and other toxic substances from the environment are in their bodies, is a tool that will be needed to find the environmental causes of breast cancer. Three presenters joined moderator Joyce Lashof, M.D., of University of California, Berkeley, at this workshop to discuss the history and present state of biomonitoring.
Richard Jackson, M.D., M.P.H., of the University of California, Berkeley, presented an American biomonitoring success story. In 1969, children were dying from lead poisoning. Over time, as lead was removed from gasoline and other lead removal measures were taken, the average level of lead in the blood of American children and adults dropped. The level in children dropped enough to raise the average American child's IQ by 5 or 6 points. Biomonitoring of lead in Americans' blood by the federal Centers for Disease Control later kept the government from allowing lead to be re-introduced into gas. The moral, Dr. Jackson stressed, is that, "regulation does work. And altering the environment works."
In addition to leading to protective government regulations, biomonitoring can be a tool that empowers communities to win change, said Sharyle Patton, of the Commmonweal Biomonitoring Resource Center. She gave several examples.
Annie Alowa, a native American elder of the Yu'pik people on St. Lawrence Island, Alaska, noticed that local people, fish, and seals had cancer. She got her neighbors biomonitored and fish samples tested. Annie Alowa died of breast cancer, but now her community is using the study to pressure the U.S. military to clean up hazardous chemicals it dumped on the island. The community has also used the biomonitoring data to keep their island from being used as the location of another hazardous waste site.
A funeral parlor worker in Anniston, Alabama noticed abnormalities in bodies he was working on. The community got biomonitoring, which showed blood levels of the chemical PCB that were 200 times higher than the general population. They sued Monsanto, the corporation that had dumped PCBs in Anniston, and won a multi-million dollar settlement plus 20 years of free health care.
As useful as biomonitoring can be, it is also expensive—$5,000 to $10,000 per person to test for hundreds of chemicals.
Biomonitoring research in breast cancer has clustered around PCBs, chemicals that were banned in the 1980s but persist in the body fat, "probably of everyone in this room," Gina Solomon, M.D., M.P.H., told the audience. Solomon, a senior scientist at the nonprofit Natural Resources Defense Council said research on breast cancer and PCB exposure has had mixed results, with some studies showing a relationship and others not. One study did show that higher PCB levels raised the breast cancer risk for women with certain genes. Scandinavian studies show that women who have both high levels of the pesticide dialdrin and breast tumors that don't depend on the hormone estrogen have a worse prognosis.
Going beyond these chemicals, Solomon said, things get difficult. Most chemicals stay in the body only a few days or weeks, do their damage, and they're gone. If women with breast cancer were exposed to many toxic chemicals in the past, the best current biomonitoring can't tell if there's a connection. To get around this problem, scientists are looking for changes in the body that reveal traces of past chemical exposure.
How should biomonitoring be used and who should be monitored? Gina Solomon said her breast cancer patients sometimes ask to be biomonitored, but that it is seldom useful for individuals. She cited an example of a breast cancer patient who had worked for many years as an agricultural inspector, with heavy exposure to many pesticides. Most pesticides don't accumulate in the body, and today's biomonitoring technology couldn't tell if the woman's pesticide exposure was related to her breast cancer. Another reason for being cautious about biomonitoring individuals is that they may try to detoxify themselves with unproven, possibly dangerous and expensive treatments marketed by alternative medicine sources.
However, the more people know about the chemicals in their bodies, the more likely they are to take action to reduce everyone's toxic exposures. That's why Sharyle Patton encourages biomonitoring for individuals. "Some say, you don't have a right to know what's in your body. You might become hysterical," she said. "Try me."
All speakers agreed that biomonitoring is an important public health tool, if used to measure communities of people with toxic exposures that are causing harm, and then to get the toxins removed from the environment. When biomonitoring revealed that high lead levels in children's blood were damaging them, the solution was not to treat individuals to remove lead, although some children did need and get this treatment. The solution was to get lead out of the environment.
Suggestions for future uses of biomonitoring in breast cancer research included:
- Instead of investigating single chemicals, figure out how to measure the combined effects of the mixtures of chemicals to which women are exposed.
- Investigate groups of chemicals that all interact in the body in a similar way. For example, many chemicals mimic the action of the hormone estrogen. Biomonitoring could reveal if a high body burden of this group of chemicals is related to breast cancer.
- Start biomonitoring women, checking for the list of chemicals in widespread use that cause tumors similar to human breast cancer in lab animals. If the chemicals are present in women's bodies, check to see if they affect human cells the same way they affect animal cells. If so, conduct studies to see if having a higher body burden of these chemicals is linked to breast cancer.
Clinical Trials Fundamentals: Getting Started in Translational Research
"We need more people involved in translational clinical research, and you can do it."
One goal of the California Breast Cancer Research Program is to get scientific discoveries translated as quickly as possible into better treatments for breast cancer.
Mark Pegram, M.D., and David Reese, M.D., of the University of California, Los Angeles, provided an overview on how to conduct research studies, using humans, on new breast cancer treatments. These studies are known as clinical trials. There are four types.
A Phase 1 trial tests a new drug or other treatment on humans for the first time to discover the appropriate dose, side effects, and what the body does to the drug as it metabolizes it and eliminates it. Often, at this stage, researchers investigate what the drug does to the body on the level of chemical interactions. Phase 2 trials test whether the drug is effective, safe, and whether there are rare but serious side effects. Drugs that look promising after the first two phases may enter a Phase 3 trial. In a Phase 3, patients are selected randomly to receive either the experimental treatment or the standard treatment. Phase 4 trials may be required by the U.S. government's Food and Drug Administration (FDA) after a drug is approved, to monitor such concerns as long-term effectiveness, safety, and quality of life for people under treatment.
A good clinical trial has the best possible science behind it, can be completed as quickly as possible, and will yield reliable data that has a clear meaning.
A clinical trial will usually start with the researcher's idea. The first step is to write a research protocol, which is a user's manual for the study and a binding legal document.
The research protocol has a very structured format that includes:
- Background: Builds the case for the trial, describes the problem being addressed and presents supporting lab data.
- Objectives: States in a very defined way what the study will accomplish. In a Phase 3 trial, for example, the objective is FDA approval of a new drug.
- Study Design: Tells the research team what to do, when to do it, and how.
- Participants: Describes who will be eligible to take the drug or other treatment being investigated. Setting the criteria too broadly will make the data less useful. Setting the criteria too narrowly makes it hard to enroll patients in the trial.
- The Treatment Being Studied: Describes how the drug or other treatment is administered, anticipated side effects, and how to handle those side effects.
- Statistical Design: Makes clear how the statistical design will lead to meaningful interpretation of the data.
Once the protocol is written, it needs approval from an Institutional Review Board or Ethics Committee. The research must also be formally monitored by the institution or institutions where it is being conducted. Monitoring is required to assure that researchers are adhering to the protocol, that the data is accurate, and that all regulations are met. The researchers must also set up a formal, secure mechanism to capture the data in a way that assures the confidentiality of the people being studied.
Before any trial can start, in most cases, it needs to be approved by the FDA. "The FDA is actually very friendly. You can call them up for advice and they will give it to you," Dr. Pegram said. Some types of research, such as investigations of gene therapy, also need regulatory approval from special committees.
If a drug that has not yet been approved by the FDA is being studied, the research team must file an Investigative New Drug (IND) Package with the FDA, along with a Form 1571.
The IND package includes any pharmacology or toxicology studies on the new drug, and any previous human studies. Sometimes, a drug's manufacturer already has this information on file with the FDA and the researchers can just refer to it. The IND Package also includes the research protocol and manufacturing information on the drug. The Form 1571 identifies the sponsor of the trial, the disease being studied, and has check boxes to make sure all required IND Package information is included. Researchers also need to submit a Form 1572 for each principal investigator in the study, listing the name and the locations of all facilities being used in the research. Regulatory documents also need to be filed for each of these facilities.
After the IND Package has been submitted, researchers must wait 30 days. If the FDA doesn't contact them within 30 days, the research can proceed. More often, the FDA sends a letter or phones to discuss issues with the study. The result is often that the researchers agree to change the research design and submit a new IND Package.
The FDA has a useful website that can help with research on investigative drugs (http://www.fda.gov/cder/regulatory/applications/ind_page_1.htm). The U.S. government's Code of Federal Regulations, Part 21, can also be downloaded from the Internet (http://www.fda.gov/oc/gcp/default.htm). It describes everything necessary to know about federal regulations governing clinical trials. "It's painful, but worth it, to read through it all once," said Dr. Pegram. "And there are sections of it I refer back to all the time."
Once the FDA has signed off on the research, the investigators meet and go over the plan in detail. They also train the monitors for the study. They go to each site, review the protocol with the people who will be administering the drug or other treatment, and make sure the site complies with all regulations. Once the research begins, data starts coming in. The researchers need to continually monitor the trial, documenting and dealing with any mistakes, and filing a formal report with the FDA on the mistakes. Mistakes are made in all clinical trials, but they only become serious problems if they are covered up or not dealt with.
Real-life examples of some issues that arose in a recent Phase 1 clinical trial of a possible new cancer drug called NB1011 included the recruiting of patients. In this study, patients had to have advanced colon cancer. However, they had to be healthy in other respects, such as having normal liver and kidney function. It can be a challenge to find patients who are ill enough to need treatment with an experimental drug, but well enough to study the effects of that drug. In this era of targeted therapy, it is also important to have diagnostic tests to find the patients whose tumors actually have the target of the therapy.
In Phase 3 trials, another problem arises if a new treatment is tested against a placebo, a treatment that actually has no effect. Patients are less likely to sign up for a clinical trial if they know they may not actually get the treatment being tested.
Although designing and conducting a good clinical trial is complicated, Dr. Reese encouraged physicians and scientists to consider going into this work, saying, "We need more people involved in translational clinical research, and you can do it."
CBCRP Funded Research
Plenary Poster Presentations
Colorful posters illustrating the results of 80 research projects funded by the California Breast Cancer Research Program (CBCRP) were on display throughout the symposium. Breast cancer advocate volunteers and researchers were on hand at posted times to speak directly with the public, interpret the results, and answer questions. Six projects represented the high quality of CBCRP-funded research.
A New Theory About How Breast Cancer Cells Get a Blood Supply
In order to grow and spread, breast cancer cells need a blood supply. The traditional theory has been that tumor cells begin the process of getting a blood supply by breaking down a layer of cells surrounding them called the extracellular matrix, then breaking into blood vessels and taking them over for the tumor's use. Sanford Barsky, M.D., of the University of California, Los Angeles, presented evidence that a breast tumor begins to get a blood supply by attracting bone marrow stem cells that circulate in the blood. Stem cells have the ability to turn into a wide variety of cells, and the breast tumor secretes proteins that turn the stem cells it attracts into blood vessel cells. Previously, it has been thought that breast cancer starts in the breast and can eventually spread to the bone marrow. This research provides evidence that bone marrow stem cells may cause breast cancer to spread and even possibly to form.
An Alternative to Preventive Breast Removal
Most breast cancer is not due to inherited risk. However, between 9,000 and 18,000 U.S. women per year get breast cancer due to inherited genes. These women tend to get breast cancer at younger ages, and have many relatives with the disease. From 60-70 percent of women with inherited breast cancer have a cancer-prone version of genes known as BRCA1 or BRCA2. Frequent mammograms don't help this group of women survive. One drastic preventive treatment is surgery to remove both breasts and ovaries. Allison Kurian, M.D., of Stanford University, presented evidence that magnetic resonance imaging (MRI) of the breast can detect small tumors in this group of women that mammograms miss, and that women experienced frequent MRI testing as a good alternative to preventive breast removal. However, MRI's high rate of false positives keeps it from being a good detection method for the general population of women.
Is "Chemo Brain" Real?
Does chemotherapy cause women with breast cancer to think more slowly and forget things? Many women who've had the treatment say so. Rebecca Rausch, Ph.D., at the University of California, Los Angeles, tested the cognitive function of women before chemotherapy, 11 months after, and 3 years after. She compared these women to breast cancer patients not receiving chemotherapy and to healthy women. Women who had chemotherapy scored lower on verbal learning after 11 months, but their scores went back up after 3 years. However, their self-reported memory problems still persisted after three years. Brain scans of women who had chemotherapy showed signs of early aging in the areas of the brain that deal with memory.
A "Crazy" Way to Prevent Breast Cancer
The hormone estrogen stimulates the growth of many breast tumors. So Satyabrata Nandi, Ph.D., thanked the CBCRP for funding his controversial hypothesis that others might dismiss as "crazy"—estrogen to prevent breast cancer. Working at the University of California, Berkeley, Nandi built on the well-established finding that a full-term pregnancy before age 20 reduces a woman's risk for breast cancer by 50 percent. During pregnancy, a woman's body has much higher levels of estrogen and another hormone, progesterone. Dr. Nandi found that young rats who received 1-3 weeks of pregnancy levels of estrogen or estrogen along with progesterone had 80 percent fewer tumors than untreated rats. The treatment protected the rats by lowering the levels of hormones that allow breast cancer to grow, and had no effect on the rats' later weight or ability to reproduce. This research could lead to an inexpensive treatment that would mimic what the body does naturally during a pregnancy before age 20. This treatment could protect women from breast cancer with no loss of their ability to have children later.
Do Buddies Help?
Each year, 65,000 U.S. women with breast cancer receive services from some kind of program that matches them with a buddy, a woman who has had the disease. But little research has been done into what makes a buddy program helpful. Janine Giese-Davis, Ph.D., of Stanford University, collaborated with women from WomanCARE, a Santa Cruz agency providing support services for women with cancer. The researchers matched newly-diagnosed women with trained volunteer counselors who had been diagnosed with breast cancer a year or more. The counselors saw, phoned, or e-mailed the newly-diagnosed women 1-4 times per week. Compared to women who didn't get peer counseling, women who got it experienced improved quality of life, and less anxiety, distress, and trauma symptoms. A finding from this study that can help in the design of other buddy programs is that counselors needed to initiate contact, because newly-diagnosed women often felt overwhelmed and unable to reach out.
Finding Meaning When Breast Cancer Has Spread
When breast cancer spreads to other parts of the body, it becomes more life-threatening. Jill Mitchell, M.A., of the University of California, Los Angeles, used face-to-face open-ended interviews, psychological tests, and chemical tests for stress hormones to investigate what meaning women make of their experience of breast cancer that has spread. Women find some positive meanings, such as a new perspective on life and an enhanced appreciation of everyday experience. Finding such positive meanings may lead to beneficial changes in the immune system. However, women can also feel that a duty to find positive meaning is being imposed by those around them.
Poster Award Winners
Congratulations to the Cornelius L. Hopper Poster Award winners. These awards acknowledge investigators whose presentations excelled in three areas that are highly valued by the CBCRP: potential impact on breast cancer, research innovation, and best presentation for a lay audience. The advisory Breast Cancer Research Council, whose backgrounds reflected the diverse makeup of the symposium audience, selected the poster award winners.
Best Presentation to a Lay Audience
African American Women Using the Every Woman Counts Program: Who Are They?
Priscilla Banks, Carol Somkin, and Joan Bloom
African American Advisory Committee on Cancer (AAAC), Kaiser Permanente, and University of California, Berkeley
High Resolution imaging of Human Tumor Formation and Angiogenesis in a novel Zebrafish model
The Scripps Research Institute
Highest Potential Impact
Breast Cancer Prevention with Estrogen
University of California, Berkeley
Communities Conducting Research
Community groups and academically-trained scientists team up to investigate questions about breast cancer that are important to California's diverse communities.
In 1997, the CBCRP pioneered the Community Research Collaboration Awards. These grants go to community groups and academically-trained scientists, who team up to investigate questions about breast cancer that are important to California's diverse communities. This session, moderated by Shiraz Mishra, M.D., Ph.D., of the University of Maryland and Barbara Balaban, of the West Islip Breast Cancer Coalition, showcased three Community Research Collaboration studies. All teams mentioned that the CBCRP funding for this type of research collaboration was crucial to starting their project.
Kathleen Brown, M.D., of the Association of Black Women Physicians, and Patricia Ganz, M.D., of the University of California, Los Angeles, formed a partnership to study how to get more minority women involved in testing new preventive strategies for breast cancer. When they began their research, a large study was testing whether chemotherapy could be used to prevent breast cancer in high-risk women; 96 percent of the women being studied were white. Yet if research is going to be applied to minority women, they need to be included as research subjects. Ganz and Brown found that most people who take part in research studies get steered into them by their physicians. The researchers developed educational materials to encourage black women physicians to refer their patients. They also developed materials for use by the Association of Black Women Physicians' ongoing breast health education at local African American churches. Seventy-two percent of women receiving this education said they would consider taking part in a future research study.
A second research project grew directly from the experience of the team's community-based investigator. Years before the project began, when Caroline Bliss-Isberg, Ph.D., first learned she had breast cancer, she wasn't ready for a support group, but found it helpful to talk to women who had been through the experience of diagnosis and treatment. She wanted to investigate whether this would also be helpful to other women. She worked with the Santa-Cruz-based cancer support organization WomanCARE and the CBCRP matched her with academic researcher Janine Giese-Davis, Ph.D., at Stanford University. The team found that assigning a trained volunteer peer counselor improved quality of life for newly-diagnosed women, compared to women who didn't get this counseling. (This research was also discussed in the Plenary Poster Presentation, see page #.) However, the research team also found that without monthly supervision, the peer counselors experience stress because they relive their own traumas. This suggests that support for peer counselors needs to be built into these programs.
A third team studied how to support women who are making crucial decisions about breast cancer treatment. Sara O'Donnell, of the Mendocino Cancer Research Center; Jeff Belkara, Ph.D., of the University of California, San Francisco; and Julia Ohnemus, M.D., of the Humboldt Community Breast Health Project, studied a technique they developed called Consultation Planning. A trained Consultation Planner—who is either a volunteer or an agency staff member, and possibly also a breast cancer survivor—goes over important questions the breast cancer patient will face in a visit to a medical cancer specialist. The planner writes down the patient's responses, and prepares a written agenda for the patient to take to her medical appointment. The research team found that telephone Consultation Planning was feasible for rural, isolated women. Latina and Native American women wanted face-to-face sessions, preferably with a planner from their own culture. Working with Latinas, it was important for the planner to realize that other family members might be involved in making breast cancer treatment decisions, and to include all family decision makers in planning. For Native American breast cancer patients, silence was an important part of the session, because it gave them time to gather their thoughts. The team has allowed us to post their presentation.
Essiac tea either did not stop, or actually promoted, breast cancer.
"It's not a hardship to make small lifestyle and dietary changes. We need research on the breast cancer-environment connection now. In fact, it's past time," said session moderator Ann Fonfa. She's a breast cancer survivor who founded The Annie Appleseed Project, an organization that provides Internet-based information from a patient perspective about alternative and complementary cancer treatments. Presenters in this session explored some types of exposures and behaviors that can lead to breast tumors.
Ana Soto, Ph.D., of Tufts University pointed out that since the 1940's the risk of breast cancer in the U.S. has gone from 1 woman in 23 to 1 in 7. During these same years, many chemicals that act within the human body, like the hormone estrogen (which is involved in breast cancer), have been released into the environment.
One chemical that acts like estrogen is DDT, a pesticide banned in this country during the 1970s, but still in use in other nations. DDT accumulates in the environment and is stored in human fat. Some studies have shown that high exposure to DDT leads to a higher risk of breast cancer, but other studies have not. Vicki Davis, Ph.D., who conducted her CBCRP-funded research when she worked at Cedars-Sinai Medical Center, explained that when the body stores DDT, it converts it into several different compounds. Different people have different ratios of these various compounds. One of these compounds acts like estrogen in the human body. Another blocks the action of male sex hormones, which circulate in women's bodies at low levels. In Dr. Davis's studies on mice, high levels of the DDT compound that blocks male sex hormones led to mice getting the equivalent of breast tumors at earlier ages. Her study suggests the risk for breast cancer in women exposed to DDT may be related to the ratio of the compounds that results from the body processing DDT. This could explain the mixed results of studies into the DDT-breast cancer link.
Essiac tea is an herbal preparation available over the counter and widely taken, either along with or instead of conventional therapy, to treat cancer and prevent recurrence. Although it has been in use for 50 years, no research had ever been done on whether it was effective before the CBCRP funded Kristin Kulp, Ph.D., at the Lawrence Livermore National Laboratory to study the question. She found that commercially available Essiac tea products do not protect cells grown in lab cultures from the DNA damage that initiates cancer. She also found that breast cancer cell lines grew when exposed to Essiac tea. In a study of rats exposed to a strong cancer-causing substance, giving the rats Essiac tea before, during, or after exposure did not stop tumor formation. In summary, Essiac tea either did not stop, or actually promoted, breast cancer. Dr. Kulp graciously allowed us to post her presentation.
Alcohol's role in breast cancer is a good subject for study, because women can control their alcohol intake, said Shelley Enger, Ph.D., of Kaiser Permanente. Higher alcohol consumption raises a woman's risk for breast cancer. The type of beverage doesn't matter, suggesting that alcohol, and not some other part of the drinks, is the culprit. Dr. Enger's research showed that drinking more than two drinks a day after menopause raised a woman's risk for breast cancer by as much as 80 percent. This was true, however, only for the type of breast cancer that depends on the hormone estrogen to grow (ER-positive). The results were different for ER-negative breast cancer. This provides evidence that alcohol's mechanism for causing breast cancer is related to hormones. It also provides evidence for the theory that the two types of cancer may be different diseases with different causes. Dr. Enger graciously allowed us to post her presentation.
Women who had surgery between days 1-14 of their menstrual cycle had greater than twice the risk of recurrence and death.
In the U.S., the death rate from breast cancer has gone downward over the past 15 years. Session co-moderator Douglas Yee, M.D., of the University of Minnesota, credited this decline to improved detection and treatment. However, detection and treatment need much more improvement, and three CBCRP-funded investigators described their research toward this goal. The session was also moderated by Sandra Stanford of the Alamo Breast Cancer Foundation.
Thomas Nelson, Ph.D., of the University of California, San Diego, has built two breast CT (computer assisted tomography) scanners. Ordinary CT scanners deliver radiation to all tissues, the breast CT scanner delivers radiation only to the breast, at about the same level as a mammogram. During the scan, the woman lies down, and her breast hangs into the scanner. This eliminates the uncomfortable compression of the breast necessary to take mammograms. The breast CT scanner produces 300 images in 15 seconds. Multiple computers analyze the results, providing much smaller details than does a mammogram image. Breast tumors can be detected almost a year earlier than with mammograms.
Another promising detection strategy that can also be used in treatment is a blood test. David Hoon, Ph.D., of the John Wayne Cancer Institute, is developing tests based on DNA floating in the blood. Both normal cells and cancer cells release DNA into the blood, but the cancer DNA seems to stay in the blood longer. Dr. Hoon is using the same techniques the FBI uses on criminals, plus other technology, to test DNA for abnormalities associated with cancer. The markers include DNA with missing chunks, which, when detected in the bone marrow, can show how advanced a tumor is. Testing for another marker, a turned-off gene, can predict whether a tumor will spread to the lymph nodes. In the future, this type of marker could be used to detect breast cancer in the earliest stages. A third type of marker, a high number of repeats of a certain gene sequence, can be used to discriminate between stages of breast cancer and reveal if the cancer has spread to the lymph nodes. In the future, this type of marker could be used to find out if treatment is working or if disease is present after surgery.
The third new strategy presented was timing of breast surgery to a woman's menstrual cycle. Hillary Klonoff-Cohen, Ph.D., of the University of California, San Diego, said the 42 studies on this question have had contradictory results. She is conducting a five-year study of 300-400 white, African American, Latina, Asian and Pacific Islander women. Prior studies were not ethnically diverse. Prior studies also used women's self-reports about their menstrual cycles. Dr. Klonoff-Cohen's team is using daily urine tests to accurately determine the menstrual phase. Among the first 200 women studied, those who had surgery between days 1-14 of their menstrual cycle had a worse outcome, with greater than twice the risk of recurrence and death. Timing of breast surgery to the menstrual cycle is a minor, easy-to-implement treatment modification, with no side effects, and it may save lives.
Normal-appearing breast cells more than an inch away from a breast tumor have a pattern in the DNA that is typical of cancer cells.
Tumor cells do not exist in isolation. An emerging trend in breast cancer biology research is the study of interactions between tumor cells and their environment. That was the context for this session, set by co-moderators Danny R. Welch, M.D., of the University of Alabama, Birmingham, and Karin Noss of the Y-ME National Capital Area.
Normal-appearing breast cells as far as 32mm (1¼ inch) away from a breast tumor have a pattern in the DNA that is typical of cancer cells. Shanaz Dairkee, Ph.D., of the California Pacific Medical Center, said this DNA pattern may be an early sign that these normal-appearing cells are susceptible to becoming cancer. Testing for this DNA pattern, called LOH, could in the future be used to monitor high risk women for precancerous changes in their breasts.
Interactions between different types of cells in the breast play a role in breast cancer. Mary Helen Barcellos-Hoff, Ph.D., of Lawrence Berkeley National Laboratory is studying a protein made by all cells called TGF-β. This protein exists in both latent and active form. The hormones estrogen and progesterone regulate the action of TGF-β causing it to suppress proliferation of cells, and to suppress tumors. When regulation of this protein goes awry, cells that contain the estrogen receptor protein proliferate. These cells, in turn, stimulate other breast cells to grow. Cells with the estrogen receptor increase in pre-cancerous breast tissue. This change could be due to deactivation of TGF-β, and deactivation of this protein could also be the reason why estrogen-receptor-positive cells increase with age.
Stem cells may play a role in breast cancer, both as cause and cure. Brunie Felding-Habermann, Ph.D., of the Scripps Research Institute, described her research into the hypothesis that breast cancer spreads to other parts of the body by sending out mutated stem-like cells capable of multiplying and forming different cell types. She has found cells in breast tumors that have some of the characteristics of stem cells, coexisting with cells in the same tumor that don't have stem cell characteristics. In related research, she is attempting to harness normal stem cells to heal tumors. She injected human tumor cells on one side of a mouse brain, and normal human neural stem cells on the other side. By day 38, the normal stem cells had migrated across the brain and started to repair the tumor.
A Scientific Meeting Like No Other
This meeting keeps the human face of breast cancer in the forefront.
Our symposium involves more than scientific reports on the latest research and forecasts of future research trends. Our attendees bring their passion, not only for the research work they’re sharing, but also for sharing their experiences, for sharing the ways that people can help each other against the disease, and for sharing their thoughts on improving what we do. In written evaluations, many attendees said that they liked the conference because it exposed them to groups they normally didn’t interact with.
All of our funded researchers were invited to display posters of their work, and they were asked to attend poster viewing sessions to answer questions and share their work with the public. Trained advocates were on hand to help non-scientist attendees.
At a Meet the Experts breakfast, the public discussed breast cancer topics in small groups with research scientists and other experts. Topics ranged from alternative medicine to academic careers in breast cancer research to support groups. Attendees new to breast cancer research attended the workshop, Breast Cancer 101, led by M. Ellen Mahoney, M.D., F.A.C.S., of the Community Breast Health Project, where they learned the basic concepts of breast cancer, the jargon, and how to understand the findings they’d hear at the meeting.
The symposium included an extra day of training for members of community organizations and experienced researchers interested in teaming up to conduct research with funding from the CBCRP's Community Research Collaboration awards.
The CBCRP designed our statewide symposium to be healthy and environmentally friendly. We took measures that included offering free yoga classes each morning, serving organic produce when available, providing opportunities for recycling, and reducing the use of plastic in our food service.
Representatives from California community organizations provided information about what women could do for themselves and for their communities to reduce the impact of breast cancer, including reducing their risk of getting the disease, finding support groups, and joining advocacy efforts to advance policy changes that improve access to care.
This scientific meeting was intertwined with personal stories of women affected by breast cancer. At a Friday evening reception, author and actress Marcia Wallace shared her story of twenty years as a breast cancer survivor. It began when she met Mr. Right, she said, "and he asked me to marry him. Three days later, I was diagnosed with breast cancer." Her inspiring keynote speech encouraged women to take control when facing a cancer diagnosis.
The meeting also showcased the arts. A curated art exhibition, on display throughout the symposium, used paintings, sculpture, photography, and other media to reflect the far-reaching impact of the disease. Some of the artists were seasoned professionals; others were new to art's healing power. The exhibiting artists included women with breast cancer, their family members, and their friends. Also on view was Expressions: the Art of Science and Healing, the CBCRP's unique collection of wearable breast art, which has been exhibited in California art galleries. At Saturday's luncheon, the Sacramento-based DIVA Chorus performed three selections from Sing for the Cure, a collaborative collection of breast cancer-themed music and readings.
CBCRP Listens, a town-hall meeting, invited feedback on the research we fund, the symposium, and our other activities. We take this feedback from the public seriously. At previous CBCRP Listens sessions, participants asked, "Why don't you do more research on cancer and the environment?" This feedback is one factor that led us to set aside 30 percent of our research funds for a five-year initiative that will investigate the influence of lifestyle and the environment on breast cancer and to uncover the reasons for the unequal burden of breast cancer.
We also use feedback from both CBCRP Listens and the symposium evaluation forms to set the symposium agenda. One result this year was the Saturday keynote address by an expert with three decades experience in environmental health research, Kenneth Olden, Ph.D., Sc.D., L.H.D. "The environment is moving to the center of the national research agenda," he said. "It's going to make all the difference for the prevention of diseases like breast cancer."
Our symposia encourage attendees to commit to action, to apply the shared ideas and information to their research, their activism, and their lives. In 2007, “From Research to Action” will return to further the explorations towards understanding and eliminating breast cancer. In the interim, we invite you to continue the discussion by sending your feedback through the CBCRP Listens form on our website (www.cbcrp.org/contact/cbcrp_listens.php), by contacting us directly, or by any other means of participation.