“I hate to tell you this,” the doctor told Diane Morgan. “But you have cancer.” Morgan’s sister survived breast cancer nine years ago, as did three childhood friends. But she lost two cousins to the disease. Now, after nearly 20 years in Miami, she’s moving back to California’s wine country to be close to her loved ones. “I figure if I have health problems I’m going to want to be around family to back me up.” Morgan is one of more than 600 new breast cancer patients treated each year at the Braman Family Breast Cancer Institute at the University of Miami Sylvester Comprehensive Cancer Center. Her story is unusual—she never felt a lump, never had a suspicious mammogram—but there was nothing unusual about being diagnosed with breast cancer. She had 213,000 other people with whom to share her experience. That’s how many people were diagnosed with breast cancer in the United States in 2005 alone, including nearly 2,000 men. It would be daunting enough to try to save nearly a quarter of a million patients from this disease if it were a single entity. But breast cancer is an alphabet soup of heterogeneity, as defined by the tumor’s response to hormones, growth factors, inflammation, aggressiveness and invasiveness, and the patient’s heredity, breast density, age, and race.

Over the last quarter-century, advances in early detection and treatment have greatly improved care, with physicians from UM/Sylvester setting the pace. Fred Moffat, M.D., and a team of surgeons have played a pioneering role in the development of sentinel node biopsy to identify the spread of breast cancer. Judith Hurley, M.D., who began studying new treatments for locally advanced breast cancers more than 15 years ago, is an international leader in this area. Joyce Slingerland, M.D., Ph.D., F.R.C.P.(C), director of the Braman Family Breast Cancer Institute, is working to improve ways of blocking the growth-promoting effects of estrogen on the cancer cell by combining estrogen blockers and new molecular targeted therapies.

Three Women—Three Different Stories

Diane Morgan didn’t have breast cancer, she just had a bruise. At least that’s what she thought until that November day when the phone rang.

“All the air went out of me,” says Morgan. “I was completely in shock.” She had been clearing out water that blew into her apartment during Hurricane Katrina when she slipped on the wet floor and fell on her side, banging her right breast on a doorknob.

Her primary care doctor just asked whether she had bumped into something. But a needle biopsy confirmed the diagnosis—inflammatory breast -cancer.

JoAnn Curtright found her own lump in 2003. “I had been on a diet that changed my body shape so that’s why I was able to find it. I tell people the South Beach Diet saved my life.” Curtright’s cancer was fueled by estrogen.

At the age of 33, Karen Mock felt a suspicious lump and just knew it was breast cancer—but she couldn’t get anyone to believe her. “I tried for a year and a half. I kept telling doctor after doctor that I had breast cancer but they kept saying I was too young,” says Mock.

She’s also the mother of two.

“I finally saw Dr. Dido Franceschi, a breast surgeon at UM/Sylvester. He opened my gown, looked at me in shock and said, ‘Listen, you have breast cancer. Why did you wait so long?’” Mock’s disease was locally invasive, HER2-neu.

Three women. Three diagnoses. All breast cancer.

Treatment Strategies

There’s nothing final about a final diagnosis. A woman then has to ask her doctors and herself: Do I opt for breast-conserving surgery, mastectomy, or surgery after a period of other treatment? Will my cancer respond to hormone therapy? What about radiation—do I join a clinical trial for targeted brachytherapy or have traditional external beam? Then there’s the “C” word—chemotherapy. Chemotherapy can be challenging, but it’s often the best option available.

About two out of three diagnoses involve a hormone-responsive breast cancer—meaning they are estrogen- or progesterone-receptor positive. Hormone-responsive breast cancers account for about 130,000 new cases each year in the U.S.

Curtright’s cancer was hormone-receptor positive. In addition to the options available to most breast cancer patients—surgery, chemotherapy, radiation—Curtright’s cancer qualified her for drugs that block the growth-promoting effects of the female hormone in the body. These come in two forms: estrogen receptor blockers like tamoxifen and the newer, more potent aromatase inhibitors that block the production of estrogen.

“I’m taking exemestane, which became available at a really good time for me,” says Curtright. The drug is a new anti-estrogen being tested in young women with the goal of keeping the cancer at bay. Unfortunately, pre-menopausal women can suffer side effects. Like other drugs that block the production of estrogen, exemestane can cause hot flashes, dry skin, and a change in libido—the signs of menopause—in about one in five women.

But these drugs literally steal fuel from the cancer, cutting breast cancer recurrences by more than one-half. Finding a better way to hamper estrogen’s role in cancer has been the focus of Slingerland’s research career.

“With anti-estrogen therapy, the cancer usually responds for a period of time and then becomes resistant,” says Slingerland. “There are more than 15 million women on these drugs worldwide—and the precise number may be considerably higher. Figuring out how to keep the cancers from developing resistance to hormonal therapies presents us with a really significant opportunity.”

A Complex Disease

Different kinds of breast cancer allow different treatment approaches.

In about one-third of breast cancer cases, Human Epidermal Growth Factor Receptor 2 (HER2) is present in unusually high amounts that fuel rapid cancer growth. HER2 is a protein that is present at low levels naturally in some glandular cells like breast tissue. HER2-overexpressing tumors often develop resistance to anti-estrogens and to standard chemotherapy. Recent clinical trials have shown that Herceptin treatment after surgery and chemotherapy can reduce the recurrence of HER2-positive breast cancer by almost one-half.

As many as one in ten breast cancers occur in women with a genetic predisposition. The BRCA1 and BRCA2 gene mutations dramatically raise a carrier’s risk of breast and ovarian cancer. Mock, who lost her grandmother to breast cancer, tested negative for these mutations. “But they told me just because your cancer is negative it only means it’s negative to the genes we know about.”Inflammatory breast cancer like Morgan’s affects the skin overlying the breast tumor and shows up as red warm skin and swelling. It accounts for about 5 percent of all breast cancers. And any of these variants—HER2-neu positive, hereditary, inflammatory, ER-positive—may blend with another. The Braman Family Breast Cancer Institute Morgan, Mock, and Curtright are among the 14,000 or so women diagnosed with breast cancer in Florida each year—women whom the Braman Institute was created to serve. Norman and Irma Braman donated $5 million to UM/Sylvester to create the Braman Institute in October 2002, support that made it possible to recruit top specialists. Slingerland moved from the University of Toronto to become director of the Braman Institute because she and the Bramans share a vision that breast cancer can be eradicated. More than a dozen faculty members are now part of the Braman Institute. Curtright was one of the first patients seen by clinical director Stefan Glück, M.D., Ph.D., F.R.C.P.(C), who joined the faculty in 2003. Glück directs all areas of patient-physician interaction and coordinates the efforts of the surgeons and the medical and radiation oncologists. One of his first successes was to get all these specialists seeing their patients in the same place.

“Now we have everything in one area, so we can talk to each other if a patient has a problem that needs a multidisciplinary approach,” says Glück. The Braman Institute unites breast cancer researchers and caregivers, four surgical oncologists, six medical oncologists with another being added next year, radiation oncologists, breast pathologists, and radiologists—all dedicated exclusively to breast cancer diagnosis and care. The support staff includes nurses, nurse practitioners, clinical trials staff, and patient care coordinators.

Slingerland leads a team of faculty scientists working to unveil the molecular secrets of breast cancer. They are investigating everything from how tumor cells communicate and proliferate to how they are fueled by hormones and protein growth factors. Zafar Nawaz, Ph.D., associate research director of the Braman Institute, is at the forefront of research on genetic changes triggered by estrogen. Braman Institute colleagues are looking for novel ways to fight cancer using viruses and other targeted therapies.

Clinical Trials Offer Hope

“Since the inception of the Braman Family Breast Cancer Institute at UM/Sylvester, our clinical trials portfolio has expanded considerably,” says Glück. “Now we have 27 trials open in breast cancer, and five more will open soon.” Information about these and nearly 200 other clinical trials is available on sylvester.org.

Trials are vital for two reasons. First, they make promising experimental therapies available to patients who would otherwise have limited options. Second, they answer key questions and open new treatment options for the next generation of patients.

“I thought I might as well just do the exemestane study,” says Curtright, who planned to try hormone inhibition anyway. “Joining the clinical trial was more to benefit women who came after me, especially for my own children.”

Curtright has three daughters, all grown. She also had four aunts, each of whom died from cancer.

“The women who enroll in clinical trials hope they will benefit from it, but they know it will help someone else,” says Judith Hurley, M.D., associate professor and breast oncologist at the Braman Institute. “You never know when your opportunity to be great is going to come along. It might be saving lives or inventing something.

“Or it might be joining a clinical trial.”

Hurley was one of the first physicians in the country to test platinum-based chemotherapy to shrink large breast cancers before surgery. Hurley now combines the chemo with Herceptin, which specifically targets the HER2 protein.

Mock had neo-adjuvant chemotherapy, which means she had chemo first to attack her tumor before surgery. The results were so dramatic that Hurley could see the tumors shrink from day to day. Mock and four dozen other women in the study then had surgery, followed by more chemo.

Nationally, less than one-third of women diagnosed with HER2-positive, large, locally invasive breast cancer survive. Among the patients who were enrolled in Hurley’s recent trials at UM and Jackson, 85 percent are alive four years later, many with no sign of cancer.

A majority of Hurley’s patients come from the medically underserved population. Most are poor, uninsured, from a minority or immigrant background, and are cared for at Jackson Memorial Hospital.

“In terms of the Braman Institute, one of the most important changes we’ve instituted is that we’ve increased academic support for breast cancer care at Jackson,” says Eli Avisar, M.D., a breast cancer surgeon and associate clinical director for the Braman Institute.

Academic breast cancer specialists treat patients, but they also learn from them.

“You don’t say, ‘We want to study you,’” explains Erin Kobetz, Ph.D., M.P.H., co-leader of the Population Research Core at UM/Sylvester and a member of the Braman Institute. “You say, ‘How can we study this problem together?’”

Kobetz is doing groundbreaking research to overcome cultural barriers to breast cancer screening that can lead to earlier diagnosis. She’s working with established community organizations and three Haitian-American community health workers to identify the needs of Haitian women and to look for ways to address them.

We Treat People, Not the Disease

There is good news to report. For one thing, more than four out of five breast cancer patients in the U.S. now survive five years or more. Diagnosis and the effectiveness and comfort of treatment have all improved.

A prestigious award from the Doris Duke Foundation—only five physician-scientists in any discipline in the nation receive one—promises to help speed Slingerland’s research on estrogen-regulated breast cancer into a clinical trial. Surgeons have had great success with more targeted surgical procedures.

Lumpectomy patients can now have radiation therapy that closely targets just the tumor area and reduces the number of treatments, and medical oncologists now have more than a dozen traditional chemotherapy agents and a growing portfolio of hormone therapy tools. New anti-emetic drugs are used to fight nausea, and growth factors are used to reduce the risk of infection.

Still, one woman in eight will be diagnosed with breast cancer in her lifetime. And each year, more than 40,000 die of this disease.

It’s no wonder women list breast cancer as their top health concern in surveys. “Physicians and health care professionals involved in oncology care recognize that we don’t simply remove a tumor and send people on their merry way. We’re also concerned about women’s well-being during treatment and beyond,” says Suzanne C. Lechner, Ph.D., a clinical psychologist who does psychosocial research for the Braman Institute. “That’s one of the things I like about Dr. Slingerland’s vision and where we’re heading in the future. We incorporate a whole-person approach to cancer.”

Lechner’s latest work is studying long-term survivors, hinting at the best news of all.

There are now 2.3 million breast cancer survivors in the U.S., and survival is up dramatically from just ten years ago.

“If you have to go through this, just trust yourself, find out everything you can, and once you make a decision, just go with it,” says Curtright, whose philosophy mirrors the Braman Institute’s.

“Each person is not a statistic, they’re a human being.”

The patients chronicled here had very different cancers, but because of major progress by doctors and scientists at the Braman Family Breast Cancer Institute at UM/Sylvester and colleagues around the world, they all have something in common. They’re survivors.