Elusive cure

In a darkened slice of a convention center ballroom, Dr. Leisha Emens takes her place in front of hundreds gathered to hear about her latest research.

The Johns Hopkins oncologist doesn't look particularly comfortable in the spotlight. This is no way to really talk to people. She's used to the nonjudgmental ways of a microscope or the one-on-one with a patient. But this is how the game is played.

By speaking at major conferences like this one in late May, the American Society of Clinical Oncology in Chicago, scientists create a buzz around their work, networking with others who may someday help move their research forward.

Emens' hand absently pushes her light-brown hair out of her eyes, her voice with its hint of the South quavering a bit as she begins. Her red pointer jerks across a towering video screen displaying a series of slides. One shows the mouse models that her experimental breast cancer vaccine was tested in. Another shows how it was administered to the first 28 women in her small clinical trial. A third goes over a formula she used to determine which doses of chemotherapy seem to have yielded the best immune responses.

Much of what she is saying would have flown high above the heads of her patients. It flies over many in the room - all that talk of "one-sided Fisher's Exact tests" and "HER-2/neu transgenic mice." But to those in cancer vaccine research, to those who understand what a breakthrough it would be to train the body to attack its own cancer, she is clearly saying, "There's hope here."

Hope is what has drawn 42 women so far to enroll in two small clinical trials being run by Emens, to donate their cancer-stricken bodies to her unproven science. Despite being told it is unlikely, they hope for a cure. She can't even promise she can extend their lives beyond the one to two years that are typical once cancer has spread beyond the breast.

In science, entire careers are spent working toward cures that don't come. Scientific progress comes slowly, if at all. That is the nature of experiments. Every step must be taken deliberately, each one building upon the last. There can be no short cuts. This is how Emens has been trained. This is how Emens operates.

10 years of uncertainty
It was nearly five years from when Emens first began manipulating breast cancer cells to when the first patient was injected. It has been almost five more years since then, and still Emens has few concrete details on whether the vaccine works, no information on whether it will extend lives. She is right on schedule, scientifically speaking.

The women enroll certain that the vaccine will make them better. It may be their last chance at survival. They cannot look to a future 10 or more years away. They have Stage IV cancer. For them, there is no time for protocols of science.

Many put her on a pedestal. One patient calls her a "rock star." They revere her and depend on her. They need assurance that the experiment to which they have devoted so much of their remaining time will amount to something.

One day a week, Emens, 46, sees patients, oftentimes the women who are part of her studies. She opens their charts, sits straight up in her chair and goes over the basics. Beyond that, she volunteers little. There is so much the women feel they need to know, and so little Emens can share.

"These trials are so small," she explains, "you can't say anything with any level of certainty."

Most days, Emens' job is focused on what is being done in the laboratory now and in the future. The blood of the women in her studies is combed for evidence of immune response and for clues about how to better attack cancer down the road. She and her technicians study how mice react to new combinations of chemotherapy or other cancer drugs given to better prepare the immune system to beat back the disease.

But mice don't ask tough questions. They don't hope for miracles. They aren't depending on her for a cure.

Well prepared
Emens arrived at Hopkins in 1998 as an oncology fellow holding a medical degree and a doctorate in cell biology from Baylor College of Medicine in Houston. One of the first doctors she met was Dr. Elizabeth Jaffee, a pancreatic cancer vaccine researcher considered a pioneer in her field.

They had lunch and talked science. Emens soaked up what she could about the prospects for cancer vaccines, the direction in which Hopkins was headed and where it had been.

In 1993, doctors from Hopkins and MIT - including Jaffee - had published a groundbreaking paper describing how they used a protein called granulocyte-macrophage-colony stimulating factor, or GM-CSF, to stimulate an immune response in mice. Not a single mouse got cancer when it was exposed to the protein.

This protein is still central to many of the vaccines in development around the country.

Jaffee - who is just a couple of years older than Emens - became a mentor to Emens. In one of their conversations, Emens told Jaffee why she wanted to focus her life's work on breast cancer.

When Emens was in the fifth grade, her mother, Rita, was diagnosed with breast cancer. Rita Emens was in her early 30s.

It was a time when people didn't talk about breast cancer. And despite the career path she chose, Emens has never asked for the particulars of just what her mother went through. She thinks her mom had a mastectomy soon after the lump was found. She knows her mom didn't want chemotherapy. She didn't want her hair to fall out.

She remembers the time the family of five, headed back home to Los Angeles from a vacation in Canada, had to stop at a hospital because of her mother's intense back pain. There, doctors told her mother the cancer had returned.

"She lived until I was 16," she says. In the Emens family, "we don't talk about it still."

Though Emens didn't know it at the time, something was cemented in her as she watched her mother die: a need to find a way to do something about the disease that took her down in the prime of her life.

Start of her research
With the backing of Jaffee and other vaccine researchers at Hopkins, Emens got to work in July 1999 on a breast cancer vaccine. She painstakingly grew cancer cell lines in the lab, finding the just the right ones to genetically modify with GM-CSF. She wrote protocols and grants to pay for her research.

Nine years later, Emens is overseeing her own clinical trials, paid for mostly with money from the National Institutes of Health with help from charitable organizations such as the Avon Foundation. The two trials cost more than $2 million each.

At the oncology conference, Emens reported that between nine and 14 of the women who received the vaccine had immune responses. Administering a very low dose of one chemotherapy agent, she told the doctors in the room, elicited a better response than giving more.

This is where Emens is most original, others say, in not just mixing together drugs to see if they make tumors disappear but in methodically testing which drug combinations may work and why. She is determining just where the balance is tipped.

"She's got the most innovative stuff," said Dr. Bernard Fox, president-elect of the International Society for Biological Therapy of Cancer. "She's got a lot more work to do, but it's encouraging."

For now, Emens says she doesn't know how well the vaccine is working. She won't say how many of the women in the first trial - the last woman just received her final shot - are still alive. She says she can't share those kinds of details until her scientific paper is complete a year or so from now and the results have been reviewed and legitimized by her peers.

What she can say is that some women are responding. What she can't say is whether that equates to longer survival, to the extension of life her patients desperately want.

Her short-term goal is to see if the immune system reacts to the vaccine by arming itself with cancer-fighting antibodies and T-cells. In the medium term, Emens hopes to give a vaccine to women with early-stage breast cancer, alongside standard chemotherapy and radiation, to help keep the disease from coming come back. In the long term, Emens and others dream of creating a vaccine in every sense of the word, for healthy women at high risk of developing breast cancer. Many groups of researchers are working to get there.

Trials like hers can be, by their nature, difficult to draw conclusions from. How much can be learned about whether the vaccine could work on the healthy when the test subjects enroll as long shots for survival?

There is so much talk about all that can be done for breast cancer patients now, but that's the story of early-stage disease. When the cancer returns elsewhere in the body - as it will in up to 40 percent of cases - it can no longer be cured. Each year, 40,000 American women still die of breast cancer. They are the ones Emens yearns to help. They are the ones who remind her how difficult that will be.

"If I took every failure to heart, I couldn't come to work every day. Is it a failure? We're not curing them," Emens says. "But we're helping them to live their lives. You do the best you can with what you have and you focus on making better tools."

She stops and takes a breath before continuing. "It affects me more than you think."

Climbing for funds
Emens arrives on a swampy evening in early June at a Timonium fitness center. She exchanges her white lab coat and stethoscope for gym clothes and weights, priming her middle-aged body to scale one of the highest peaks in the world.

In five days, she and 21 others leave for Tanzania, where they will tackle Mount Kilimanjaro. It's not all for pleasure. The climbers will raise roughly $200,000 toward Emens' research.

A sprite of a trainer marches the doctor through a grueling workout: doing push-ups on a giant exercise ball, hoisting a 30-pound pack over her head as she walks backward at a 15-degree incline, lifting dumbbells as she balances on a moving platform.

The first of these charity climbs - to Mount Cotopaxi in Ecuador - was planned two years earlier by Baltimore Jewish Times publisher Andrew Buerger, whose sister has advanced breast cancer. Emens told him she wanted to come along. There's no room for spectators, he told her. Oh no, she replied, she planned to reach the 19,000-foot summit.

She had never before climbed a mountain.

Now, she can't seem to stop.

more on the series
Coming tomorrow in The Baltimore Sun: Some women see the vaccine trial as one last chance for a breast cancer cure. How one woman comes to terms with the fact that, despite the vaccine, her disease keeps spreading.

Online at Watch a video of Dr. Leisha Emens discussing the breast cancer vaccine and find more photos and yesterday's installment of the series

Tonight on WJZ: Watch one woman's personal story as she battles breast cancer. Can this study save her life? The emotional interview, Monday at 11 on WJZ Maryland's News Station