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A new peril for breast cancer survivors

Drugs seen ineffective in fighting brain tumors

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Amy Cohen Soscia and her husband sat across from Dr. Eric Winer in a ninth-floor consultation room at Dana-Farber Cancer Institute, awaiting the results of an MRI scan of her brain. Winer pulled his chair close to hers.

This can't be good, she thought.

More than four years earlier, in September 1998, Soscia had been diagnosed with an aggressive type of breast cancer. Then 43, she underwent a grueling year of treatment that included a mastectomy and reconstructive surgery on her right breast, three chemotherapy drugs, and radiation.

Still, the cancer spread to her liver and spine. So doctors prescribed a promising new drug called Herceptin. Miraculously, her cancer began to shrink, and Soscia began to let herself think that she would conquer the disease.

But now, on this afternoon in January 2003, Winer gently told her about two small brain tumors that appeared on her MRI.

''I hate this disease," Soscia shouted, bolting from her chair. ''I was so discouraged that I was on treatment for five years and I still got brain lesions," she said in a recent interview. ''I had that same feeling again, the knot in my stomach, not being able to breathe, just feeling sick."

Doctors across the United States say they are treating a growing number of breast cancer survivors who have brain tumors, where drugs have halted the spread of cancer in their bodies, but not in their brains. ''We're seeing something we have not seen before; women whose cancer from the neck down appears to be gone on the scans," said Dr. Nancy Lin, also at Dana-Farber. ''Yet they have cancer in their brain."

In the past, many of these women would have developed brain tumors very close to the end of their lives, while they were dying of cancer elsewhere in their bodies. Now, a new generation of drugs is controlling the cancer in women's bodies far better. Many are not effective in the brain, however, so many women feel vital and healthy when brain cancer comes out of the blue.

Doctors say the phenomenon is particularly striking with women who have the aggressive type of breast cancer like Soscia's and who take Herceptin. Studies show Herceptin extends the lives of women with advanced breast cancer that has spread by 6 to 12 months on average. But Herceptin is a large molecule that does not easily cross the blood-brain barrier, a network of blood vessels that are so tightly constructed that certain substances cannot pass from the bloodstream into the brain. Winer and several other doctors said they do not believe Herceptin is causing the cancer to spread to the brain, just that it's not working there.

About 150,000 Americans a year are diagnosed with ''metastatic" brain tumors, meaning the cancer has spread from another location, usually their lungs or breasts. The chances that a woman with metastatic breast cancer will develop brain tumors is 10 to 15 percent. But these odds appear to be worse for a woman such as Soscia, whose breast cancer has a genetic mutation known as HER2-positive that makes it very aggressive. Twenty-five to 35 percent of women with metastatic HER2-positive cancer end up with brain cancer, Winer said.

''Having cancer spread to your brain is pretty devastating," he said. ''To feel this added threat, that cancer is going to take away your ability to think, is horrible."

In the past, average survival after HER2-positive cancer spread to the brain was less than a year, but Winer believes women are now living longer for reasons that are unclear.

Hospitals and doctors had not focused on metastatic brain tumors in the past, largely because patients' situations seemed hopeless, but some are now launching research initiatives and clinical programs.

Dana-Farber is preparing educational pamphlets for women with breast cancer that has spread to the brain, and is starting a clinical trial testing whether a compound called lapatinib, which researchers believe may inhibit HER2-positive cancer, shrinks brain tumors. Soscia was one of 39 women who participated in an initial trial of the drug. (Both Winer and Lin have been paid consultants for GlaxoSmithKline, the company that makes lapatinib.)

The Cleveland Clinic is planning to test whether eight common breast cancer drugs, including Herceptin, are ever able to cross the blood-brain barrier. In the trial, patients with brain metastasis will get one of the medications the day before surgery to remove their tumors. Doctors then will test tissue from the tumor to see whether the drug was able to penetrate the barrier and reach the tumor.

''The reason we care about brain metastasis now is because we can; women with breast cancer are living so much longer," said Dr. Hope Rugo, director of breast cancer clinical trials at the University of California San Francisco, where researchers are trying to figure out which types of breast cancer are most likely to spread to the brain.

When cancer does spread to the brain, some women have clear symptoms. Judi Broderick collapsed one day in October 2001 at her Framingham home. Her husband, Patrick, took her to the emergency room. At the hospital, doctors diagnosed a fractured hip, caused by a previously unrecognized breast cancer that had spread to her bones. Broderick, who was 35, began a regimen of Herceptin and chemotherapy.

Despite the late stage at which doctors caught her cancer, she responded to the drugs. But a year later, Broderick began to get headaches and blurry vision. An MRI revealed tumors in her brain, and she underwent whole brain radiation. When more tumors appeared, doctors tried another type of radiation. Still, more tumors grew.

In the end, Patrick Broderick said, his wife suffered seizures and eventually lost her sight and hearing. She died at home last August. ''We really hoped with how well she did on Herceptin that they had cured the cancer," said Broderick, who is raising the couple's three children while managing a hotel.

For Soscia, the brain cancer diagnosis came without warning, when she felt good and was optimistic. Her cancer had been controlled for three years when routine blood tests indicated it might be growing again. Scans of her body showed no changes, so Winer ordered the brain MRI.

In the consultation room, Winer told Soscia that the tumors were ''small and treatable," and offered to show her the picture of her brain. She refused to look. ''I said 'Eric, there are no right words. Except two. You're cured,' " she recalled. ''I've seen people who've lost their minds from brain cancer. I thought that was going to be me."

Winer and his nurse practitioner Janet Kunsman scheduled an appointment that afternoon with a radiation oncologist, who recommended that Soscia have whole brain radiation for 20 consecutive weekdays. The treatment was exhausting, making it impossible for her to go to work as a preschool disability coordinator for the Rhode Island Department of Education. Her hair fell out.

The radiation appeared to wipe out one tumor, and shrink another, but that one grew back, and last July Soscia enrolled in the clinical trial for lapatinib.

It is at such times that Soscia thinks about death. Driving alone in the car, she'll hear a song on the radio and write it down, in case she needs to plan her funeral.

She knows her illness has been hard on her husband, Ken, and especially her two daughters, Abby, 10, and Ariel, 16. Both girls worry about their mom. Ariel, who is a high school junior, wants to stick nearby and attend college at the University of Rhode Island in Narragansett, where the family lives. Almost every night, Abby crawls into her parents' bed. She has told her mother that she worries she won't be there in the morning.

But there are good times. Last June, for her 50th birthday, her husband planned a dinner party at a nearby restaurant and flew in one of her best childhood camp friends from Chicago as a surprise.

Last month Soscia had a small setback. The tumor in her brain grew slightly and she had to stop taking lapatinib because it wasn't effective. Two weeks ago, she had a different kind of radiation, a high-intensity beam focused just on the tumor. She will return to Dana-Farber in eight weeks for a follow-up test. Dr. Naren Ramakrishna, the radiation oncologist, said more than 90 percent of tumors respond to the therapy.

Soscia remains hopeful, comforting herself with the idea that if the tumor remains small, it won't affect her daily life. But she also has learned that even though Herceptin continues to keep the cancer at bay in her body, she cannot let down her guard.

''There is no cure for metastatic breast cancer," Soscia said. ''It never goes away. You just move from treatment to treatment."

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