Shedding light on triple negative breast cancer

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Shedding light on triple negative breast cancer

At 36, Tamera Bittinger wasn't even old enough for a mammogram. And when she found a lump in her breast last year, her doctor dismissed it.

She barely had time for her concern to abate, however, because the lump quickly grew large and painful, and she returned for another exam. After a biopsy, the mother of two was told she had stage-three "triple negative" breast cancer, an aggressive form of the disease that disproportionally strikes younger women and African-Americans, and is impervious to the newest treatments.

"Initially, even my gynecologist blew me off because I was so young," she said. "It was cancer, and it was an aggressive kind. ... I had never heard of it."

Up to about 20 percent of women diagnosed with breast cancer have the "triple negative" type, yet many people don't know about it. Researchers and doctors, meanwhile, have been somewhat stymied by it.

This cancer can spread more quickly, recur earlier and be harder to treat because no one really knows how it grows. The very characteristic that defines it — a lack of three markers that usually contribute to the growth of cancer cells — means that doctors don't have the targets used to treat other kinds of breast cancer.

That leaves fewer options for treatment.

"We're stuck with chemo," said Dr. Saranya Chumsri, Bittinger's doctor at the University of Maryland Marlene and Stewart Greenbaum Cancer Center, about the drugs in the arsenal. "Once the cancer has spread, we keep giving the patients chemo drugs, but eventually we run out of drugs for them."
Promising new therapies, however, are in development, and Baltimore is a center of that research. They attack the cancer in different ways: depriving it of blood, breaking down the cancer cell DNA or interrupting the cancer cells' effort to rebuild.

There are 14 clinical trials around the nation aimed specifically at testing triple negative breast cancer treatments, according to the National Institutes of Health's database of trials. Patients at centers at the University of Maryland, Johns Hopkins University and Franklin Square Hospital Center are participating in some of them. There also are other studies in the Baltimore area that include triple negative patients.

Developing drugs for this type of cancer means understanding it. Breast cancer is considered triple negative when three specific markers are not present: The tumor cells do not have receptors for the hormones estrogen and progesterone, or for the protein human epidermal growth factor (HER2).

These receptors and proteins typically contribute to the growth of cancers and can occur in any combination. The receptors receive signals from hormones to grow, and the proteins grow at an abnormal rate. But they also serve as targets for new drugs on the market, including Herceptin, which is boosting survival rates in women with the HER2 type of cancer.

When a patient is negative for all three, there are no special targets for treatment. That leaves only the old standbys of surgery, radiation and chemotherapy drugs for triple negative patients, and doctors say that isn't enough for some women, particularly when the cancer has spread to other organs.

A 2007 study published in the journal Cancer of women with all stages of breast cancer found that 77 percent of triple-negative patients survived at least five years, compared with 93 percent of women with other types of breast cancer.

As with all cancers, statistics are worse for those whose cancer has spread — to the lung, liver or brain. The median survival for a triple negative patient with metastasized cancer is about 13 to 14 months. Median survival for those with other types of breast cancer is two to three years, according to Dr. Katherine H. Rak Tkaczuk, professor of medicine and director of the Maryland cancer center's breast evaluation and treatment program.

The center has about 1,000 breast cancer patients, with about 200 new cases coming in a year. Up to 30 percent are triple negative breast cancer. Many are younger and African-American, though researchers do not know why.

The Maryland center is participating in two studies, one specifically aimed at triple negative patients. One more is planned.

One drug being tested at Maryland and a few other hospitals — ABT-888 — is for those with more advanced cancer. In previous trials, this family of drugs has been shown to extend life for patients with breast, prostate and ovarian cancers and has garnered enthusiasm among researchers.

The drug works by inhibiting poly (ADP-ribose) polymerase, or PARP, enzymes needed for cancer cells to repair themselves after they have been damaged by chemotherapy or genetic defect. The cells then die, Tkaczuk said.

Another nationwide study in which breast cancer patients at Maryland are participating is for Avastin, which has sparked some controversy because it has not been shown to extend life for those with advanced breast cancer and has serious side effects. The drug, which may no longer be used on those kinds of patients, works by blocking blood vessel production in cancerous tumors. Cancer cells need the oxygenated blood to survive.

This study, however, is for early-stage cancer patients such as Bittinger. For a year and a half, Bittinger, who lives in Barton in Western Maryland, came to the university center three weeks a month to participate in the trial. She had hoped she'd get both the normal standard of care and the trial drug, which she did. She finished about two months ago.

After a cocktail of chemotherapy drugs and Avastin, surgery, radiation and another course of chemo drugs and Avastin, her scans show no cancer. She once had a tumor approximately 6-9 centimeters that shrank to less than a half a millimeter before it was surgically removed.

"The tumor shrank pretty dramatically," Bittinger said. "A local doctor I had seen said if she'd not examined me beforehand herself she'd not have known there was ever anything there."

Now, the teacher's aide and mother of two boys, 12 and 14, is hopeful. Triple negative breast cancer frequently recurs in the first few years after treatment. But the longer she survives, the lower the odds that will happen.

The doctors at Maryland are optimistic, too, that new therapies will keep more women cancer-free for longer. It's not clear, however, when any of the new drugs will gain government approval. Drug trials can be lengthy, Tkaczuk said.

"There's no telling how soon some of the new drugs can make it to market," she said. "It could take a long time. But we've had favorable results here."

Researchers will soon launch a trial of a hormone therapy not thought to be effective in triple negative patients because the cancers have no hormone receptors. Researchers at Maryland have been working to "reprogram" the cancer to make the treatment more effective.

Hopkins and Franklin Square are participating in trials involving chemotherapy drugs and targeted therapies for triple negative patients. And Hopkins is also leading or participating in several trials for other types of breast cancer and is including triple negative patients.

Not everyone can and will participate in trials, however. Doctors say they often require extra tests and time in treatment for uncertain results and possible side effects. The trials also aren't always local.

Dr. Marisa Weiss, an oncologist near Philadelphia who is president and founder of an information clearinghouse, said only 5 percent of breast cancer patients participate in trials. Most, she said, just don't know trials are an option.

She said the trials are needed to develop new drugs for all kinds of cancer, but since there are no targeted drugs for triple negative breast cancer, it's especially important for women to participate.

"If anyone should be part of clinical trials it would be triple negative breast cancer patients," said Weiss, who provides trial information on her website. "But most are not treated in trials. A significant reason is they are not told and they don't ask about them. It's important to ask."

For Sharon Stewart, the treatment wasn't the problem. It was the diagnosis.

She received traditional care for her breast cancer: chemotherapy, surgery and radiation. A year after finishing the treatment, her golf-ball-sized tumor is gone, as is the cancer that had spread to a lymph node under her arm.

Stewart said she didn't even miss much work at her job scheduling appointments in a University of Maryland center that provides care for people living with viral and infectious diseases.

But she said, initially, her doctor insisted she had a cyst. When the lump she found kept growing, Stewart, then 46, decided to go early for her annual mammogram. Sure enough, it was cancer — triple negative.

"At the time, I didn't even know there were kinds of breast cancer, or stages," she said. "But in my heart I knew something was wrong."

So, her advice is to trust your instincts and seek out a second opinion.

Now she's focused on the reconstruction of her breast and on taking care of herself. She's taking medication to help repair some damage to her bones caused by chemotherapy.

"I feel good," said Stewart. "They told me the cancer could come back, but I don't believe it will."

Her example shows that triple negative breast cancer patients can have good outcomes, even without a trial drug, said Dr. Eric Winer, chief of the division of women's cancers at the Dana Farber Cancer Institute and a professor of medicine at Harvard Medical School.

Winer, a board member for the Triple Negative Breast Cancer Foundation, said traditional therapy can cure such cancer if it hasn't spread beyond the breast and lymph nodes under the arm.

For now, no breast cancer that leaves the breast and the nodes for other organs appears to be curable, Winer said. The spread can happen more quickly for triple negative patients, and that's where the trial drugs may be able to help most. He was optimistic that potential new therapies such as the PARP inhibitors could improving the quality and quantity of life for many more patients.

"But we don't assume chemotherapy can't be effective for triple negative patients," said Winer. "Many women do exceedingly well."

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Triple negative breast cancer resources

• the latest on triple negative breast cancer, including forums for survivors

• a clearing house of information on breast cancer, including trials

• information on breast cancer, including research

Source: By Meredith Cohn, The Baltimore Sun

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