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OneThousandOne represents the amount of time, verbally, that it takes to count to one second. In this one second of time, a great thing happened at Nebraska Medicine. In fact, several great things probably happened. A patient was cured, a researcher found the missing link, a nurse treated an injury, a doctor comforted a family or maybe a child just smiled.
MOMENTS IN MEDICINE
Summer | Fall 2007

A New Era in Breast Cancer Treatment

On this particular day, she has a full schedule of patients in her clinic. As oncologist Beth Reed, MD, one of the region’s leading experts on breast cancer, scans the schedule, she notes that she’ll see women at a variety of stages in their cancer journey:  four newly diagnosed patients, four who are a year or more out from treatment and the remaining eight patients who are breast cancer survivors of five years or more – a milestone Dr. Reed is sharing with an increasing number of her patients all of the time.

“Breast cancer today is a very curable disease.”
Beth Reed, MD

As Dr. Reed enters the room of Theresa Fitzgerald, a three-year breast cancer survivor, she is greeted with a warm smile and hug. “Dr. Reed has become as much a friend as my doctor,” says Fitzgerald. “Dr. Reed helped make one of the most difficult times in my life, more tolerable. She really listens.” During the lowest points in her treatment, Fitzgerald says Dr. Reed lightened her pain by “listening, talking through her concerns, commiserating about middle age, laughing and connecting.”  “When you are with her, you feel like she really cares about you,” says Fitzgerald. “She focuses all of her attention on you.”

The breast cancer Dr. Reed and her patients are fighting is that of the new millennium – a new era of how we treat and think about breast cancer. While the road of a cancer patient is still a long and arduous one, it is encouraging to know that one of the fastest growing populations among cancer patients is that of the survivor – a trend mirrored in Dr. Reed’s earlier clinic schedule.

Half of all men and one-third of women in the United States will develop cancer in their lifetimes. Thanks to advances in early detection and treatment, the number who survive has more than tripled over the past three decades. Today, there are more than 10 million cancer survivors in the United States, up from a mere 3 million in 1971. And one of the most promising areas for cancer survival is that among breast cancer patients.

The Nebraska Medical Center has established a formidable reputation in the Midwest for its commitment to breast cancer diagnosis, treatment and research. Along each step of the process, The Nebraska Medical Center offers a team of medical specialists, from radiologists, to oncologists, surgeons and researchers, each of whom is dedicated to eradicating breast cancer through his or her special area of expertise.

Dr. Reed has been treating breast cancer and conducting research to provide new hope and cures for more than 20 years. “I was attracted to the cancer field because this field provides so much hope for new treatments and cures and I wanted to be a part of that,” she says.

The numbers tell the story: for the first time in recent history, mortality for breast cancer has declined. Between 1990 and 2000, the rate decreased by 2.3 percent annually. That is combined with the stark statistics that as baby boomers age, we will continue to see a gradual increase in the number of women diagnosed with breast cancer. Last year, there were 200,000 new cases of breast cancer diagnosed. That number is expected to climb dramatically to as many as 450,000 new diagnoses by 2018.

Last year, there were 200,000 new cases of breast cancer diagnosed. That number is expected to climb dramatically to as many as 450,000 new diagnoses by 2018.

Theresa Fitzgerald has come for her six-month evaluation – a schedule she’ll maintain until she reaches the celebrated five-year mark. Then her visits will decrease to once annually. Fitzgerald looks forward to her six-month check-ups. Each visit, she says, is a celebration of another milestone in the cancer survivor’s checklist. It’s also confirmation that all is well and her fears can be tucked away until the next visit.

As the president, CEO and founder of the Children’s Respite Care Center, a program that provides services to special needs children with medical or developmental problems, Fitzgerald understands the meaning of empathy. When faced with the stark reality that she had breast cancer, she looked for the same type of personal and compassionate care she provides her own clients at the Respite Care Center. She found that care in Dr. Reed and her staff.

“Dr. Reed and her entire staff have all been so wonderful,” says Fitzgerald. “And that is a reflection of Dr. Reed. She is someone I am never going to forget.”

Over the past 20 years, Dr. Reed has been a part of the evolution that has seen breast cancer transform from less a death threat than a chronic condition. During this evolution, Dr. Reed also has witnessed her share of advancements. “More women are living with breast cancer today than ever before in our history,” says Dr. Reed, a trend she attributes to better screening and detection methods, improved chemotherapy and surgical techniques and the advent of targeted therapies. “It’s no longer the frightening, fatal disease that it used to be in the past. Today, I think of it more as an event that needs a solution and it’s my job to provide that solution.”

That solution can be found in an array of treatment options now available to women which can be customized to meet their individual needs and cancer type. Treating cancer, however, is more than chemotherapy, radiation treatments, nausea drugs and surgery. “It’s about listening, comforting, determining priorities and helping patients make good choices,” says Dr. Reed.  “This is what makes a good oncologist – understanding what is important in a patient’s life, helping them prioritize things in their lives and helping them understand the ramifications of the disease and their choices.”

Dr. Reed’s gift of connecting with her patients is what keeps a steady flow of patients coming through her doors five days a week. “Dr. Reed develops a very warm relationship with her patients,” says Ann Privetera, RN, BSN, OCN, case manager in the Peggy D. Cowdery Patient Care Center, who has worked with Dr. Reed for the past 13 years. “She has a knack for understanding people and being able to explain difficult things to them in a way they can understand. She is also an excellent clinician and a huge patient advocate. If she has a problem she needs some answers to, she will get on the phone with other physicians and get help and won’t give up until she knows her patient is taken care of.”

Dr. Reed, who is mother to an 11-year old daughter, says having a child of her own has had a significant impact on her ability to empathize with her patients. “It deepened my empathy for these women,” says Dr. Reed. “Having a child of your own changes your whole perspective on life. It made me understand what it means to be afraid to die.”

Research provides new hope

In a large, seven-floor building, adjacent to The Nebraska Medical Center is the UNMC Eppley Cancer Center’s Eppley Institute for Research where internationally recognized cancer researchers are fighting the battle against  cancer with an entirely different arsenal – that of test tubes, Petri dishes, microscopes and high-tech machines that sort cells, identify DNA and separate gene molecules.

As one of only 60 National Cancer Institute- (NCI) designated cancer centers in the United States, the Eppley Cancer Center is nationally and internationally recognized for its groundbreaking work in cancer research, treatment and patient care and has recently seen a tripling of its funding from the National Institutes of Health and other government sources.

“The overall survival rate is in the 80 percent range, depending on when you are diagnosed and what kind of cancer you have.”

Oncologist Kenneth Cowan, MD, director of the Eppley Institute for Research and director of UNMC Eppley Cancer Center, leads hundreds of basic research studies and clinical trials to help researchers find the answers to such questions as to what turns certain genes on and off, the molecular mechanism that leads cells to become resistant to anti-cancer therapy, how DNA is damaged, what causes cells to mutate and how. The answers to these types of questions are key to bringing novel therapies developed in the lab to patients in clinical trials, providing our patients access to the newest treatments and improved patient outcomes.

Ying Yan, PhD, Dr. Cowan’s research assistant the past eight years, talks enthusiastically about their progress in understanding the function of the BRCA-1 gene, a gene that increases a woman’s risk of developing breast cancer by 95 percent. Of course, we are still a long way from seeing this translate into a cancer prevention drug, but the research is promising and Dr. Yan is hopeful that their research may someday help prevent cancer in thousands of women in the future. “This is what makes this job so rewarding,” she says. “My father died of cancer and knowing that I may be able to have an impact on helping others survive the disease in the future – that’s gratifying.”

Much of Dr. Cowan’s breast cancer research focuses on the development of new forms of treatment called targeted therapies that are being used in combination with traditional treatments to improve outcomes for breast cancer patients.

Targeted therapies refer to drug treatments that attack tumors without harming healthy tissue. They are categorized into three major types based on the method in which they attack the tumor: aromatose inhibitors, HER-2 therapy and anti-angiogenesis drugs.

Doctors use these therapies by first developing a customized care plan based on the biology of a patient’s cancer – what it is, how big it is and how it acts. Depending on how the cancer has been classified, doctors then treat the cancer with traditional chemotherapy and surgical techniques, and then add targeted therapies to the mix.

Researchers like Dr. Cowan, and his colleagues, including Dr. Reed and Dr. James Talmadge, are involved in one of the most promising and cutting edge forms of cancer research called gene therapy, which is being funded by a grant from the National Cancer Institute. Researchers have pinpointed a specific protein – P53 – that is found in all cancers. This protein, says Dr. Cowan, is responsible for altering genes, causing them to become genetically unstable. This causes other mutations and can eventually lead to cancer. Gene therapy involves pinpointing specific genes, that when injected into cells through a carrier molecule called a vector, will then unload their genetic material and attack cancer cells – with the hopes of killing them. Dr. Cowan says researchers in Florida currently are seeing promising results with the use of the P53 vaccine in treating lung cancer patients.

Dr. Cowan also talks enthusiastically about another area of groundbreaking research that involves using a person’s own white blood immune cells to generate an immune response against cancer cells. The process involves manufacturing dendritic cells – immune cells, which when activated, identify proteins that are foreign and help form an immune response to destroy them. The hope is that when these cells are injected into the tumor, they will help the immune system form an immune response against the tumor and eliminate the cancer tumor.

“The future of breast cancer lies within research,” says Dr. Reed, who has been involved in conducting studies since her early days of practice. “If it weren’t for trials and research, we wouldn’t have on-going improvements in treatments. If you can get large numbers of people enrolled in clinical trials, then you can make big advances.” Dr. Reed says she offers an investigational choice to all of her patients. “Providing patients with investigational choices is an opportunity to get tomorrow’s best therapy today,” she says. “We wouldn’t be where we are today if it weren’t for people being involved in research studies.”

Treatment Advances improve outcomes

In the surgical suite where oncologist James Edney, MD, performs the majority of his surgeries, Dr. Edney slips on some sterile gloves, pulls up his mask and prepares for his eighth breast cancer surgery of the day. Today, more than 70 percent of his patients are candidates for breast conservation which involves preserving the majority of the breast by removing the tumor only. The procedure, called a lumpectomy, is an outpatient surgery that takes about an hour. That is a far cry from 20 years ago when a breast cancer diagnosis was synonomous with more radical operations such as radical mastectomy or even double mastectomy. Not only is a lumpectomy a much less radical operation, but it also provides improved results, says Dr. Edney.

Dr. Edney, a surgical oncologist who specializes in breast cancer, dedicates 90 percent of his time to breast cancer patients. He estimates that he has treated thousands of women with breast cancer since he began practicing at The Nebraska Medical Center in 1981.

“I decided to specialize in breast cancer because I knew that if I wanted to have an impact on this disease, to make a greater contribution, my efforts had to become more focused,” says Dr. Edney. “Thirty years ago, women diagnosed with breast cancer not only had to deal with their own mortality, but they also feared that they would die surgically mutilated and feeling unwanted and unloved. That is no longer the case today. There is so much more hope and women have so many more surgical options.”

The introduction of sentinel node biopsy in the latter part of the 1990s has been another advancement that has greatly improved the treatment process for women. Dr. Edney was the first surgeon in the region to begin performing this procedure. Approximately one in four women with breast cancer will have tumors that have spread to their lymph nodes. In the past, most of the lymph nodes under the armpit were removed during breast surgery to eliminate the threat that cancer may have spread.  Sentinel node biopsy is a minimally invasive procedure that is performed by injecting a safe, radioactive tracer near the tumor which migrates from the cancer to the lymph nodes. Those nodes which pick up the dyes are the first to possibly harbor any cancer cells and are examined for signs of cancer. If they are cancer-free, this indicates the absence of cancer in the other lymph glands and eliminates the need to remove them, sparing many women more extensive surgery than is necessary and the complications that result from removal of the lymph nodes.

The Nebraska Medical Center also is one of a handful of centers in the country embarking upon a promising clinical trial involving the use of Intrabeam low-energy radiation therapy. The therapy involves delivering a single dose of radiation to the cancer site at the time of surgery compared to the typical six-week regimen of daily radiation therapy that is delivered to the entire breast.

“We’re delivering an equivalent dose of radiation but we are doing it in 25 minutes rather than stretched over six weeks,” says Dr. Edney. “And instead of radiating the entire breast, we are delivering the radiation to the exact site of the tumor, eliminating radiation to other tissue. This procedure has the potential to make breast conservation available to even more women by eliminating the geographic and time barriers posed by the six-week regimen of radiation therapy that accompanies lumpectomy.”

Prevention is still the key

In the Olson Women’s Center at The Nebraska Medical Center, where women can go to meet all of their healthcare needs, radiologist Cheryl Williams, MD, sits in a reading room lined with banks of large computer screens. This is where she and her colleagues read thousands of mammograms, breast ultrasounds and MRIs each year to diagnose cancer or screen images with the hope of detecting breast cancer in its very earliest stages. Digital mammography, which captures images in computer code, has recently replaced view boxes and mammogram films, providing physicians with crisper, brighter images of breast tissue. A study published in the “New England Journal of Medicine” in 2005 found that digital mammography was more accurate than film mammography as a screening tool for women with dense breasts, those younger than 50 and those who are premenopausal or perimenopausal.

With a click of her finger, Dr. Williams, the lead interpreting radiologist, can zoom in on a suspicious calcification or adjust the brightness and contrast of the image to get a clearer view. She zooms in on the tiniest of white spots – about the size of a needle point –  that could very easily be missed by an untrained eye, and looks more closely for irregular edges – an indication that it could be a tumor. This one checks out okay. She also looks for clustered calcifications or masses that appear whiter or denser than nearby tissue.

With more than 18 years of experience under her belt, her colleagues often consult with Dr. Williams when they need a second opinion.  “Statistically, experience is incredibly important when it comes to reading mammograms,” she notes. “Studies have shown that radiologists who read a lot of films and have been doing it for a long time, find more cancers than less experienced physicians.”

Statistics show mammograms reduce cancer deaths by 20 to 35 percent in women between the age of 50 and 69 and by about 20 percent in women in their 40s. Other sophisticated techniques, such as ultrasound and MRI, which can be used in combination with mammography for special cases, are helping physicians narrow the gap in detecting tumors that might be missed by mammography.

“These screening methods are the best tools we have to help us detect breast cancer early,” says Dr. Williams. “For women, this means a greater chance of survival and more treatment options.”

Cancer support

Today, cancer programs that provide support to patients during treatment and well after recovery are becoming more commonplace among many communities. They are fulfilling a need that cancer patients have known about all along –  cancer doesn’t end after treatment – instead, it marks the beginning of a new phase of life – that of a cancer survivor. When active treatment ends, these people’s special needs may be just the beginning. This includes challenges like job discrimination, financial struggles, insurance issues, as well as other social, emotional and physical challenges caused by aggressive treatment therapies.

In the words of one cancer patient, “You fall off a cliff when your treatment ends. The doctor says you're done with cancer treatment, but you're just beginning a whole new phase of your healthcare. Nobody's got the roadmap for that."

To help provide a transition for these patients, The Nebraska Medical Center offers a cancer survivorship program. Deb Darrington, MD, internal medicine specialist, is director of the program and oversees a primary care clinic to provide medical care to meet the special needs of cancer survivors.

Depending on the length and type of treatment, many patients must deal with the lingering health effects that some cancer treatments can cause, notes Dr. Darrington. These include problems with mobility or memory, nerve damage, sexual dysfunction or infertility, early menopause, osteoporosis, myledysplastic syndrome (pre-leukemia), impaired organ function or recurring cancer. There may also be long lasting side effects like pain, lymphedema, scarring, disfigurement, depression, heart damage and stresses related to cosmetic changes.

Of the 1,020 cancer survivors polled by the Lance Armstrong Foundation in October 2004, 57 percent said that although cancer may leave their bodies, it will always be a part of their lives. In addition, 70 percent have struggled with depression; 54 percent with chronic pain; and 53 percent with secondary health problems. The majority said the practical and emotional consequences of the disease were more painful than the medical issues. Being denied life or health insurance, losing a job or a promotion, and going into debt are not uncommon sequels to a cancer diagnosis. Forty-nine percent of survivors said their non-medical needs were not being met by the healthcare system.

“Our goal is to aid in the transition after treatment – to provide support and serve as a point of care before the patient returns to their primary care doctor," says Dr. Darrington. "Many patients express that they feel abandoned or on their own after completing cancer treatment and they want to see someone experienced in caring for cancer survivors. We are there to listen, to develop a plan to meet their unique needs and communicate these needs to their primary care doctor or provide primary care needs for patients who don't have a physician."

Another component of the program involves a multi-disciplinary clinic that is offered twice monthly at Clarkson West Medical Center. The Breast Cancer Survivorship Clinic is available to breast cancer survivors who are cancer-free, who have completed therapy and are generally two years out from diagnosis. The patient is seen by a multi-disciplinary group of clinicians that includes Dr. Darrington, Dr. Reed, a social worker, physical therapist, RN case manager and nutritionist who perform an assessment and develop a "survivorship care plan" based on the patient's special medical, physical and nutritional needs. This plan serves as the patient's long-term care plan to share with their primary care physician and addresses long-term medical issues like diabetes, heart disease, blood cholesterol and bone mass.

“We’re delivering an equivalent dose of radiation but we are doing it in 25 minutes rather than stretched over 12 weeks.”
James Edney, MD

"Because we specialize in seeing cancer patients, we are in better tune to their unique needs and long-term medical problems and these patients really appreciate that," says Dr. Darrington. "We are the bridge that will ensure their needs are met long after treatment has ended.”

It’s compassionate programs like this and the dedicated individuals that make them happen that make The Nebraska Medical Center one of the most progressive medical facilities to practice medicine, receive care and provide hope for today’s patients and tomorrow’s survivors. They represent the new era of how we treat and think about breast cancer.

Targeted therapies hold promising hope for the future of breast cancer

A woman diagnosed with breast cancer has more treatment options than ever before. Evidence is mounting that newer forms of treatment called targeted therapies, used in combination with traditional treatments, are improving outcomes for breast cancer patients. Targeted therapies refer to treatments that attack tumors with minimal harm to healthy tissue. They are categorized into three major types based on the method in which they attack the tumor: aromatase inhibitors, HER-2 therapy and anti-angiogenesis drugs.

For the past 10 years, women whose tumors are hormone-receptor positive – meaning they are fueled by the hormones estrogen and progesterone – have been treated with a hormonal drug called tamoxifen for approximately five years after breast cancer surgery. The drug works by reducing estrogen’s ability to fuel cancer growth. Treatment of patients with hormone- sensitive breast cancer using tamoxifen reduced their risk of recurrence by 25 percent. More recently, a new class of drugs called aromatase inhibitors have been found to be significantly more effective than tamoxifen in reducing the ability of these cancers to grow. Aromatase inhibitors in post-menopausal patients with estrogen-receptor positive breast cancer are now considered first line of adjuvant therapy.

New hope has also arrived for women who develop an aggressive class of cancer tumors that produce too much of a gene called HER-2. These women tend to be younger and until recently, had little or no options after completing chemotherapy. That was the standard of care until the monoclonal antibody drug Herceptin was introduced to the market. The drug works by slowing or halting the growth of cancer cells with large amounts of HER-2. With 52 weeks of infusion with this antibody, more of these women are likely to be cured of their cancer.

Another class of drugs not limited to a specific type of tumor are anti-angiogenesis drugs. These drugs work by inhibiting the formation of new blood vessels that feed tumors. “They do not make the tumor go away, but they have been very effective in preventing their growth,” says James Talmadge, PhD, research specialist. One of these drugs, called Avastin, has been effective in treating colorectal cancer, and has recently shown success in prolonging survival rates in breast cancer as well.

“These new drug therapies are having a significant impact on our ability to fight breast cancer and hold much promise for the future of breast cancer treatment.”, James Talmadge, PhD

The development of vaccines is another area of drug research that is showing potential for fighting breast cancer. “We know they work and they have the advantage of being non-toxic,” says Dr. Talmadge. “The problem is that chemotherapy inhibits the activity of vaccines.” Even so, there are several vaccines in clinical trials that are showing promise.  “I think we will begin seeing success with more vaccines in the future,” says Dr. Talmadge. “Currently, there is tremendous excitement about a vaccine that has been shown to prevent the development of cervical cancer in 97 percent of women. We anticipate seeing additional success in the development of vaccines to prevent and treat cancer in the future.  These new drug therapies are having a significant impact on our ability to fight breast cancer and hold much promise for the future of breast cancer treatment.”

Next article in the Summer | Fall 2007 issue of One Thousand And One:
Making Healthcare Work