By Karen Feldscher
Illustrations by Vivienne Flesher

I know someone who has breast cancer.

It’s a statement that’s true for most of us. In my life, two good friends were diagnosed within the past twelve months. So was an office colleague who works down the hall. Another woman I know has, in her mid-forties, lost her two best friends to the disease.

Occurrence statistics are grim, so grim that breast cancer is often called an epidemic. It’s the second most common cancer among women. The leading cause of cancer death for women age forty to fifty-five. If you’re a woman and you live long enough, you have nearly a one-in-eight chance of developing it.

“When you’re in a room full of women, you look around and wonder how many of them are going to face breast cancer,” says Virginia Minichiello, a School of Nursing clinical specialist. “There’s no avoiding it, because the numbers are against us.”

And breast cancer doesn’t strike just women; a small percentage of men get it, too.

That’s the bad news.

The better news? With early detection, breast-cancer survival rates are pretty high. Many effective treatments exist, and they’re getting more effective all the time. Diagnostic techniques are improving. A number of studies are seeking the causes of breast cancer, with an eye toward prevention.

Not surprisingly, Northeastern has bands of researchers fighting breast cancer on each of these fronts, with a dedication that speaks to the university’s commitment to critical scientific and scholarly exploration. They work in disciplines ranging from chemistry, to engineering, to pharmaceutical sciences, to nursing, often partnering with faculty at other high-profile institutions.

Some search out novel ways to deliver anticancer drugs directly to tumors. Others, intensely aware of the importance of early diagnosis, experiment with sophisticated imaging techniques, or attempt to determine the relationship of gene behavior to the progression of the disease. Still others focus on ways of stopping breast cancer before it begins.

They speak eloquently, often passionately, of their efforts. Their careful explanations are peppered with cancer-study terminology — “proteins,” “polymers,” “spectrometry,” “tomography,” “receptors.” They talk about the disease’s complex and wily nature. They explain there are no easy answers, no simple cures; years will pass before clinical trials prove potential treatments safe and effective.

And yet no one appears deterred by the enormity of the challenges they face. Nor by the fact that the holy grail they seek isn’t at the top of the health-care industry’s to-do list.

As chemist Robert Hanson puts it, “Finding new breast cancer treatments doesn’t have the kind of financial rewards that other treatments—like a cure for obesity—have.” But it doesn’t matter, he says; when you’re fighting breast cancer, every research result is “such a worthwhile end.”

To spare the patient

Hanson is one of a handful of Northeastern researchers looking for breast cancer treatments that are effective, yet humane. Such methods are sorely needed.

The toxic nature of current chemotherapy and radiation treatments make many patients feel very sick, long before they’ve noticed any effects from the disease. “The side effects of cancer drugs are horrendous,” says pharmaceutical sciences associate professor Mansoor Amiji. “It’s absolutely crazy.” And so the scientists working on treatments pursue essentially the same goal—figure out how to attack the tumor without attacking the patient.

Hanson, for instance, in collaboration with fellow chemistry professor Graham Jones, is searching for ways to block estrogen from going to tumors, but not to healthy cells. This could help the 60 percent of women breast-cancer patients who have hormone-responsive cancer, the kind fed by the body’s own estrogen or by estrogen supplements.

Drugs such as Tamoxifen that reduce estrogen levels throughout the entire body are a far-from-ideal approach, because estrogen supports normal tissue function in the heart, brain, and bones. That’s why women who take Tamoxifen or its pharmaceutical cousins often suffer side effects that vary from the troublesome (hot flashes, nausea, weight gain, mood swings) to the life-threatening (blood clots, endometrial cancer).

“You talk to women who’ve had antihormone therapy, and while it had a very dramatic effect on the tumor, they’ll say it caused some really horrible symptoms,” Hanson says.

To lessen the ravages, Hanson and Jones—working with colleagues in Germany and at the University of Chicago; the University of Massachusetts Medical Center, in Worcester; and Yale University—are trying to develop new chemical compounds that bind solely to estrogen receptors in breast tissue.

Their work has been fueled by research over the past decade that has shown clearly how hormones bind to estrogen receptor proteins. “I wish we could have had half this information twenty years ago,” Hanson says with a tinge of regret. “At least now, progress will happen more swiftly.” He says that though he’s chastened by the fact he’s only after a treatment—not a cure, or a means of prevention—he relishes the chance “to improve quality of life, and prolong life.”

In addition to his collaboration with Hanson, Jones is pursuing a second method of delivering drugs directly to tumors. The focus of this study is enediynes, naturally occurring but rare and difficult-to-derive bacterial products that are highly toxic to cells. In 1996, while working at Clemson University, Jones and his research group won a patent to create synthetic enediynes, which, when coupled with estrogens, killed breast cancer cells in vitro.

Now, to target the treatment more precisely, Jones and his Northeastern group have created light-activated versions of the same toxins. The new compounds, Jones explains, release their anticancer poisons only after they’ve been subjected to ultraviolet or infrared light through photodynamic therapy. “The initial experiments got us very excited,” Jones says. “We know this works in the lab.”

The next step is animal studies. If light-activated enediyne therapy wins approval for human use, which Jones says could be a decade away, breast cancer patients may be able to sidestep the nausea, hair loss, and gastrointestinal-tract irritation many now face during treatment.

Mansoor Amiji, in yet another quest to target drug delivery, is using a water-soluble polymer to devise nanoparticles with armlike chains, which may one day be used to carry such treatments as Taxol, Tamoxifen, or cancer-fighting genes directly to tumors.

Under a microscope, the particles look like little octopuses. Though they pass easily through normal blood vessels, their arms get caught in the spongelike holes of tumor-fed blood vessels. The goal, Amiji says, is to keep the particles stable until they reach the tumor site, where they catch, slowly disintegrate, and release their contents.

He has reason to be optimistic; preliminary results from mice studies have shown the particles do become enmeshed just outside the nuclei of tumor cells. In these initial tests, the particles have carried only “reporter” genes, which indicate the particles’ location. Future tests will involve an actual anticancer therapy. Human trials, Amiji estimates, could be five years away.

This research began four years ago, spurred by a twelve-month sabbatical Amiji spent working with world-renowned chemical and biomedical engineering professor Robert Langer at the Massachusetts Institute of Technology. Their collaboration continues: Today, Langer’s bioengineering lab makes the polymer; Amiji’s lab fashions the particles.

It’s a lengthy trial-and-error process, Amiji says. “We check each and every variable as we’re making these things,” he says. “That is really what is required in science—a lot of perseverance. Digging, and digging, and digging.”

To see what can’t be seen

In breast cancer detection, the gold standard is still mammography, which spots 80 percent of all breast cancers.

Eric Miller is after the other 20 percent.

For the past six years, the electrical engineering associate professor has been studying diffuse optical tomography, a technique that examines the way infrared light disperses through tissue. Miller describes it as “kind of like a CAT scan on steroids.”

He explains: “A CAT scan shoots x-rays and collects a shadow of whatever is inside. In diffuse optical tomography, the laser light looks sharp going in but diffuses away” within the body’s tissue. Once researchers examine how the light is dispersing, they have a clearer idea of what an internal structure looks like. “Because we know the physics of the way light diffuses through tissue,” Miller says, “hopefully we can get reliable reconstructions of what’s going on internally.”

Though diffuse optical tomography can, like mammograms, produce images, researchers are actually more interested in interpreting the numbers collected by measuring the laser light’s dispersal. Says Miller, “We do the algorithms and the modeling, and try to either build an image of the internal structure of the breast or, more directly, ascertain whether there are anomalous regions, like tumors.”

In this work, Miller is collaborating with Electrical and Computer Engineering department colleague Dana Brooks; professors at Harvard and Tufts universities; and a Montreal company that builds tomographic systems for research trials. He estimates diffuse optical tomography could become a standard practice in breast cancer screening within five to ten years.

Across campus, three analytical chemists are also searching for new ways to detect and characterize breast cancer, as well as predict who’s at high risk for the disease.

Barry Karger, director of the Barnett Institute of Chemical and Biological Analysis; William Hancock, the institute’s Bradstreet chair; and staff scientist Jo Tsai are working on two projects involving proteomics, the analysis of proteins. For both, the researchers are developing state-of-the-art techniques that couple liquid chromatography, which separates and quantifies chemical components, with mass spectrometry, which identifies the components.

In one effort, Karger, Hancock, and Tsai are working with Massachusetts General Hospital pathologists to examine protein levels in breast tumors, seeing if they can find biomarkers—elevated levels of particular proteins—that help indicate the stage of the disease. Such an analysis could help doctors choose the most appropriate level of treatment for a patient.

“You can throw an atom bomb at a tumor, but sometimes that’s not necessary,” Karger says. “If you could determine the disease’s stage through analysis, that would be wonderful.”

The size of a typical cell sample makes such analysis challenging. “When you’re dealing with tissues, you often have a limited amount of sample,” says Karger. That means his group has had to develop new technologies that will eventually result in analysis “a hundred- to a thousandfold more sensitive than we have today,” he says, “which is pretty exciting.”

In the other proteomics project, a joint effort with a Boxborough-based cell analysis company called Cytyc, the researchers are isolating biomarkers in breast fluid. By comparing protein levels in healthy and diseased samples, they’re looking to pinpoint the biomarkers that indicate a high risk for breast cancer. “We hope to work with Cytyc on a large national study that looks at women with a family history of breast cancer to try to predict whether these women need to be concerned or not,” says Karger.

A more profound goal of the study: Simply gaining a better knowledge of how breast cancer works. “If we see elevation in certain proteins,” Karger says, “we want to understand why they’re elevated.”

To keep breast cancer at bay

Barnett Institute fellow and chemistry professor Roger Giese wants to stop the disease before it strikes. Toward that end, he’s working on developing a test that uses mass spectrometry to measure potential cancer-causing substances in the blood.

“We know there are substances that cause cancer, called carcinogens, and we know sixty to ninety percent of cancer comes from the ‘environment’ in the broadest sense,” says Giese. “Not just from pollution, but from one’s personal environment—diet, lifestyle, occupation, medications.”

These harmful chemicals can attach to genes to form “DNA adducts,” creating mutations that can cause cancer. “These mutations are permanent,” Giese explains, “and they can get passed on to future generations.”

Now Giese and his colleagues are trying to develop a simple blood test that locates DNA adducts and identifies which harmful chemicals a person has been exposed to, giving that individual a better idea of what to do or what to avoid to lessen the likelihood of developing cancer. Because such technology will have to first be evaluated by cancer epidemiologists, Giese says it could be a while before it’s available.

“People have wanted this kind of test for twenty years,” he says. “But what you’re measuring is about a billion times less [detectable] in the blood than cholesterol. This is not a high school science project. Sometimes there’s an idea that’s ahead of its time, and it takes a while before technology finally catches up.”

Along with looking at blood, Giese is studying breast milk to learn more about cancer’s environmental causes. This investigation involves combining extracts from breast milk with a culture of human breast cells, assessing any resulting damage, and trying to identify the culprit chemicals. “We know gene-damaging chemicals show up in breast milk, also in the breast tissue,” he says. “There’s great interest in identifying them. We have a freezer full of breast milk.”

At the School of Nursing, Virginia Minichiello has her own interest in the causes of breast cancer. Spurred by the death of a forty-one-year-old cousin more than two decades ago, Minichiello first became active in the American Cancer Society’s effort to train doctors and nurses to use breast exams and mammography for early detection.

But she wasn’t satisfied. “It became obvious that just telling women to do breast exams and mammography wasn’t getting to prevention,” Minichiello says. Or giving her answers to heart-wrenching questions. “I needed to respond to women asking, ‘Why do I have breast cancer?’” she says. “I wanted to be able to articulate something about the reasons.”

But, without advanced scientific training, Minichiello found it hard to understand the findings in the latest research papers. So in 1998 she took the radical step of leaving family and friends behind in Boston to spend two and a half years earning a doctorate in nursing at the University of North Carolina in Chapel Hill.

Even though Minichiello’s husband initially questioned why she had to go so far away, in her mind it was a golden opportunity she couldn’t pass up. Through a fellowship from the National Institutes of Environmental Health Sciences, she would be studying in the lab that first located BRCA-1, also known as the “breast cancer gene.”

“I worked with the people who discovered the gene,” Minichiello says. “I did bench research, used a mouse model to look at BRCA-1. They had people from all over the world coming in every day to give lectures. I don’t think I missed one session.”

She became an ace at reading research reports. “Now I can understand exactly what the researchers have done, why they did it, and what the outcomes are,” she says. “It’s phenomenal. It’s like knowing a different language.

Her current goal—in addition to finishing her dissertation—is to write articles on breast cancer for the broader public, describing the latest information on genetics, diet, and environment in plain terms. “We have all this wonderful information, but it’s so hard for women to understand,” Minichiello says. “When women want medical information, they turn to the women’s magazines, they go to the web, they look at articles in the lay press.”

Minichiello is also helping a nonprofit research organization called the Silent Spring Institute, which explores the links between the environment and women’s health, write a grant proposal aimed at educating nurses about breast-cancer risk factors. And she’s planning to seek funding for an effort that encourages minority women to study their family histories, to help them assess their breast cancer risk.

A steady pace

Clearly, the campaign against breast cancer is a multilateral assault, a war of attrition. The Northeastern researchers expect it to be a complicated and lengthy fight, with no guarantees. Most pause when asked to predict how it will play out over the next decade; everyone is understandably cautious.

Still, they cannot contain their underlying optimism. They believe their work, as well as the research of others, is exciting and will aid the offensive. They’re proud of how Northeastern’s institution-wide involvement is adding powerful muscle to the effort. “Even though we don’t have a medical school here,” Giese says, “we’re really plugged into the medical community.”

And occasionally, they have the pleasure of looking forward to victories that are closer on the horizon, successes that may not require five or ten years to flower. Like Minichiello, who even as she acknowledges the difficulty of getting women to make preventive lifestyle changes, dreams about doing it anyway.

“I swear,” she says, “we could go out there and say to young women, ‘You can’t smoke because that’s going to increase your risk, and you really have to avoid fats. And if you keep a vegetable and fruit diet, free from pesticides, and your family history doesn’t have a lot of cancers, you probably could get through life without breast cancer.’

“It’s the kind of scene I envision and think, Wow, wouldn’t that be fabulous?”

Karen Feldscher is a senior writer.

Getting in Touch

“I get these frantic calls from radiation oncology nurses,” says physical therapist Nancy Roberge. “And I just had a woman who finished radiation therapy and said, ‘Nancy, it was worse than I imagine medieval torture would be.’ It killed her. There’s no reason for that.”

So Roberge, BB’74, MEd’84, is on a crusade, trying to educate women and their health-care providers about the importance of making physical therapy a part of breast cancer treatment. “We need to get women exercising before surgery, and get them exercising as soon after surgery as possible,” she says.

Physical therapy after—even before—breast cancer surgery sound like a novel approach? Though it currently may not be a routine aspect of care, Roberge says it should be. In her Wellesley, Massachusetts, practice, she sees breast cancer patients almost exclusively. She says she could use some backup.

“There are so few of us doing this work,” Roberge laments during a recent visit to Northeastern to talk to physical therapy students. “That’s why I’m here today—to try to excite and motivate, get physical therapy students to think about a patient population not normally thought about in our profession.”

Roberge also does a lot of talking to nurses and doctors, and other physical therapists, because she’s seen what can happen to women after breast cancer surgery. An arm’s range of motion may decrease. A shoulder may freeze. Some women can’t get their arm into the proper position for radiation treatments.

Or a lifelong condition called lymphedema may strike, when lymph node removal—common in breast cancer surgery—leads to an accumulation of lymphatic fluid, causing painful swelling.

“My patients who have lymphedema tell me nobody ever told them this could happen,” says Roberge. “Do you believe women aren’t told about this? That’s why I’m up on my soapbox.”

Before surgery, says Roberge, soft-tissue massage and exercise can help prevent range-of-motion problems by loosening tight muscles and healing existing shoulder injuries that surgery could aggravate. After surgery, the same techniques can be used to clear radiation-induced scar tissue and increase range of motion.

To prevent or treat lymphedema, physical therapists can manually drain lymphatic fluid to decrease the swelling. And they can advise patients on other ways to avoid the condition—by wearing a compression sleeve during certain activities, for instance, and taking meticulous care of cuts and burns.

Though physical therapists who work with breast cancer patients need specialized training, “this is not rocket science,” Roberge says. “It’s just another application of physical therapy that has been overlooked and underutilized.”

Roberge’s first exposure to post­ breast surgery problems came in 1974 when she was a Bouvé student doing a senior clinical affiliation. “A woman, six months after breast cancer treatment, had a frozen shoulder,” she recalls. “And when you’re a student, you’re not afraid to ask questions. So I said to my supervisor, ‘Why wasn’t that woman just sent to physical therapy, right after surgery?’ My supervisor said, ‘Good question.’”

But her question’s relevance didn’t hit Roberge with full force until twenty years later, when a good friend, also a physical therapist, had her own bout with breast cancer.

After surgery, the friend “did instinctively what physical therapists do with soft tissue mobilization,” says Roberge. “She worked on her range of motion, and she healed herself. The doctor was absolutely surprised at how well she’d done. As she’s relating this story to me, the light bulb went off. I thought, ‘Omigod, look at all these women who need us!’

“I literally started knocking on radiation oncology department doors,” she continues, “introducing myself: ‘I’m a manual physical therapist, I know about the problems associated with soft tissue after surgery or radiation, and I think I can do a lot for your patients. Try me.’”

Now, nearly twelve years later, she says the doctors and nurses she works with believe she can “make their patients feel better and more functional.” Still, physical therapy has yet to become integrated into what Roberge calls the “critical pathway” of breast cancer treatment.

To ensure that end, Roberge is pursuing a doctoral degree in physical therapy at Simmons College, hoping the credential will strengthen her case. “A doctorate,” she says, “opens doors for you. People are willing to talk to you, willing to read your articles.”

Beyond helping patients avoid frozen shoulders or lymphedema, Roberge also wants to improve their overall quality of life.

“Their bodies have just been brutalized by chemo and radiation therapy,” says Roberge. “When I get patients exercising—some who have never been much for exercise—and they feel better than they ever did before breast cancer, then I feel like I’ve really done something good for these women.”

— Karen Feldscher