IU Research and Creative Activity Magazine
Indiana University Research & Creative Activity

On the Human Condition

Volume XXVIII Number 2
Spring 2006

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Susan Clare
Susan Clare
Photo Rocky Rothrock, IU School of Medicine Visual Media

Susan Clare and Julia Carson
Susan Clare shows a mammorgram to U.S. Rep. Julia Carson during the taping of a public service announcement regarding mammograms.
Photo Rocky Rothrock, IU School of Medicine Visual Media

Breast Cancer, Outside the Box

by Elizabeth Rosdeitcher

Through narrow, mazelike hallways down to the basement of the Indiana University Cancer Center and into a small, cluttered office, Susan Clare retreats after a morning of surgery. It's late October 2005, still breast cancer awareness month, and a small pink ribbon on her lapel stands in contrast to the sheer whiteness of her lab coat.

Clare herself is a bit of a study in contrasts--with an M.D. and a Ph.D., she has forged a career as both a breast cancer surgeon and a cancer research scientist at the IU School of Medicine, using each discipline to the advantage of the other.

In the morning's surgery, Clare performed a mastectomy on a woman with inflammatory breast cancer, a relatively rare but aggressive form of the disease. This is somewhat unusual because Clare's bias as a surgeon, she explains, is toward breast conservation.

If the patient wishes to have reconstructive surgery, Clare prefers to perform it at the time of the mastectomy. "My experience is that a woman who wakes up with a breast--whether it's her breast because she has had a lumpectomy or one through reconstruction--does a lot better psychologically than if she wakes up to see that gash on the chest wall."

This time Clare could not perform reconstructive surgery at the time of the mastectomy. Treatment for inflammatory breast cancer makes the combined operation difficult because of the radiation therapy that follows the surgery. Skin changes that occur during radiation therapy make the cosmetic outcome of reconstruction less desirable.

As Clare talks, a distinction between breast cancer and other forms of cancer comes into focus. First there is its visibility--the breast is an external organ. And secondly, "there are huge psychological and sexual manifestations," says Clare. She explains, for example, that when she first conveys the news of a breast cancer diagnosis to her patients, she spends much time not only discussing the diagnosis and various treatments but also helping her patients "deal with the realization of how this affects the way they view themselves. If you're counseling someone about a colon operation, I don't think all of that fits into the mix."

It is not hard to imagine Clare engaged in the detective work of both diagnosing disease in her patients and researching its causes in the laboratory. Her affinity for the unexpected and unorthodox is clear. She describes a study of mastectomies, for example, conducted by her mentor, Monica Morrow, at Northwestern University. Morrow's study revealed that the frequency with which mastectomies are performed has more to do with the difference between rural and urban lives than physician or patient bias, as conventional wisdom suggests. For people who live a long way from a community hospital, traveling to radiation therapy in the weeks after a lumpectomy is not a practical option, making it more likely that they will get mastectomies.

In the world of breast cancer, as in larger life, Clare suggests that things are often not as they appear. For instance, "inflammatory breast cancer" is a misnomer, she says. "It looks like the breast is inflamed, but it is not. It is really that there is a tumor in the lymphatics of the skin."

When it comes to treatment for breast cancer, she says, we sometimes "lose sight of the smaller picture." A study of why some women do not get treatment may fail to take out-of-pocket costs into consideration, or a woman may have health insurance but be unable to pay for the bus rides to the hospital for chemotherapy.

We can also ignore what is right in front of us. "Forgive me for being blunt," Clare says, "but American culture is a boob culture. We use sex to sell just about anything. For many women [the breast] is already an important part of their sexuality, but our culture puts on more above and beyond that. To be in jeopardy of losing all that is traumatic. Not for all women, but for many."

As Clare makes plain, breast cancer defies neat categories. It raises questions about culture and psychology, sexuality and aesthetics, not to mention economics, history, and politics--of which the pink ribbon is a subtle reminder. To think inside the box, any box, would be to ignore the scope of the illness.

Data That Doesn't Fit

In shaping her career, Clare says she has taken her cues from those "outside the group orthodoxy." She traces the initial idea for her current research back to a 2002 lecture given at an international conference by University College of London Professor Michael Baum. Baum, she says, "prompts people to think. He sometimes says things that are really way out and sometimes things that are only slightly outside the norm. But he always thinks outside the box."

In his lecture, Baum presented what he called "data that does not fit." He compared two sets of historical data: one from a breast center in Milan from 1964 to 1980 and another from Middlesex Hospital in England from 1835 to 1933. In the Milan patients, cancer most often recurred at 18 months after the first diagnosis, whereas in the older set of data, recurrence took place most typically after five years.

How to account for the difference? The women in 20th-century Milan had an operation, while the women in 19th-century Middlesex were admitted to the hospital. Something about the intervention, Baum proposed, caused the earlier recurrence in the first group. At the end of the lecture, Clare recalls, "he kind of threw down the gauntlet, saying, ‘I wish someone would come up with an experiment proving whether I'm right or wrong.' I filed that at the back of my head."

Some researchers believe that by taking away the primary tumor, secondary metastatic deposits elsewhere in the body can then recruit the blood supply needed to grow. Clare attributes renewed growth after surgery to something slightly different--to the wounding itself that takes place with surgery and spurs the body to produce "growth factors" (proteins and other substances) that close the wound and seal the skin.

To test her theory, Clare designed an experiment, funded by the U.S. Department of Defense Breast Cancer Research Program, in which mice were given a tumor in the area where the breast would be. If the mice were left without intervention, she found, they died as a result of the primary tumor, without metastases to the lungs or elsewhere. When the original tumor was surgically removed, the mice got metastatic disease in 10 weeks.

Clare then drew blood before the operation and at intervals afterward to determine which proteins went up and which went down as a function of the operation. Having a state-of-the-art proteomics institute at IU enabled Clare to organize her research around the analysis of proteins.

Now, she explains, "we're in a position of having hundreds of likely proteins as candidates for instigating the reproduction of cancerous cells. Some look to be important because we know they are involved in proliferation or recruiting a vascular supply. Once we have our candidates, the next step is to reproduce this data in humans."

Clare's explanation is so lucid, it's easy to forget that her research actually challenges a core professional orthodoxy of breast cancer treatment: that surgery is part of the cure. And for most women, Clare repeatedly asserts, it is. But when she appeared on the IUSM's public radio show Sound Medicine, the show's host felt compelled to ask if her colleagues looked upon her as a traitor. Clare replied that while her IU colleagues are supportive, "the first time I present my work at a national conference, I better get the tomato shield up."

The Future of Breast Cancer

Nonetheless, Clare remains optimistic about her work and about the treatment of breast cancer more generally. Despite the fact that the statistics say this year in America, more than 211,000 women will be diagnosed with the disease and 43,300 will die from it, Clare points out that "we can now cure the vast majority of those with early breast cancer. If you have a small tumor and you are node-negative, your risk of recurrence is very low." Also, she reports, in the last five years, breast cancer mortality rates have gone down for the first time in the United States and the United Kingdom. "Not the nose dive we'd love to see," she admits, "but we're going in the right direction."

In fact, Clare believes that 2005 marked a milestone in the history of breast cancer. "When we look back at 2005 or thereabout, we'll say there was a time before and a time after. In 2005, a clinical trial testing the use of the breast cancer drug Herceptin in combination with chemotherapy reported a 50 percent reduction in recurrence, the best ever for a clinical trial."

She explains further: "Forty percent of women with breast cancer have HER-2 positive breast cancer, named for a certain protein on their breast cancer cells called HER-2/NU. Herceptin is an antibody that targets HER-2 and assists in its killing. So while HER-2 positive breast cancer used to be a bad thing to get, we can now treat it, which in some ways makes it a better thing to get."

And yet, while praising the work of cancer researcher colleagues, she concludes that "if anybody wants to make an impact on this disease, it would be by preventing it in the first place. If you look at any kind of medical history, you see that preventing a disease is always better than treating it. And as a public health measure, it's cheaper."

Clues to breast cancer causes are available, Clare continues. "Many types of breast cancer are responsive to estrogen. In Western industrialized countries, exposure to estrogen over a lifetime has increased. Young girls have started menstruating earlier, due to better diets. Menopause is later. The pregnancy rate is lower, and first pregnancies are later. All of these factors increase the cumulative exposure to estrogen over a lifetime."

She relates one line of reasoning that sees the possible root cause of breast cancer in the lifestyle of young women. "Physical activity may be especially important since it can delay the onset of menstruation." When it comes to diet, however, for women of all ages, there is no good evidence that corrections in eating habits can prevent breast cancer. "Everything has a confounding variable," says Clare. "It's very hard to do conclusive long-term studies of diet."

New technology, such as DNA chip technology, will have a major impact on breast cancer research, but the most crucial key to solving the mysteries of breast cancer is always seeking out fresh angles on the problem, says Clare.

"I think our future hope lies in being unorthodox and trying to involve other disciplines."

Sounds familiar. In fact, Clare has positioned herself to do just that, leaving the rest of us that much more hopeful.

Elizabeth Rosdeitcher is a freelance writer in Bloomington, Ind.