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Profiling Breast Cancer Genes Might Tailor Treatment

Study shows it could match best therapy to each woman

WEDNESDAY, Jan. 30, 2002 (HealthDayNews) -- Screening breast cancers for their genetic signature could help doctors prescribe the best therapy for patients while sparing them the side effects of treatments that are unlikely to work, says new research.

A study by Dutch and U.S. researchers suggests the screen could help determine which patients are more likely to benefit from adjuvant therapies -- such as chemotherapy or hormone therapy -- after surgical removal of their breast cancer. The finding appears in tomorrow's issue of the journal Nature.

Currently, about 90 percent of women with breast cancer receive adjuvant therapy after surgery, based on criteria such as tumor size.

"It's known that of those selected patients, 70 to 80 percent will never develop a metastasis," says lead investigator Laura J. van 't Veer. "They are over-treated."

"If we could find a way to know beforehand which women are more likely to develop distant metastasis than others, then it would be very helpful in selecting the right therapy for them," says van 't Veer.

More than 200,000 American women will be diagnosed with breast cancer this year, and about 40,000 women will die from the disease. Death rates from the disease have declined in recent years, which researchers think is due to earlier detection and better treatments.

About 10 percent of breast cancers are linked to mutations in certain genes, such as BRCA1 or BRCA2.

The researchers examined the genetic profile of 98 breast cancer tumors, using samples of the tumors that were stored after surgical removal of the cancer. The samples came from patients who were less than 55 years old, and the cancer had not spread to their lymph nodes at the time of diagnosis.

Thirty-four of the samples came from patients whose cancer spread to other parts of the body within five years, while 44 came from patients who were disease-free for at least five years.

Of the remaining 20 samples, 18 came from patients with mutations in the BRCA1 gene and two carried the BRCA2 mutation.

Each sample was examined using a DNA microarray, a glass chip containing about 25,000 genes. The microarray revealed which genes were most active in each sample, unveiling each tumor's unique genetic signature.

"We were able, with 90 percent specificity, to find a group [of patients] where no metastasis would occur," says van 't Veer. "In a group that has a very low chance to develop metastasis, you can discuss whether to give adjuvant therapy at all or maybe only restrict yourself to adjuvant hormonal therapy, which has [fewer] side effects than chemotherapy."

"It enables you to tailor therapy for these patients," she says. "It would reduce the number of patients that are over-treated … to 30 from 40 percent."

The researchers followed up with a study of tumor samples from 19 similar women, which confirmed the predictive ability of the microarray testing.

"This provides us with the first evidence … that based on profiling the molecular changes in cancers, you can actually predict what the outcome of the cancer is going to be," says Dr. Carlos Caldas, a senior investigator at the University of Cambridge's Cancer Genomics Program in England.

But rather than suggesting that some women are receiving unnecessary treatment, he says, the most important message from these findings is this screen will better predict how an individual's cancer will progress.

At the same time, he says, it could lead to a new era in cancer therapy. Just as antibiotics are matched to fight a particular type of bacteria, says Caldas, this screening could give doctors a better idea of which drugs would most effectively fight an individual patient's cancer.

The researchers say this technique must now be adapted for clinical use, with results from a DNA microarray taking only a few days. Van 't Veer, who is now studying the tumor profiles and treatment outcomes of a larger group of patients, says that may be possible within two years.

What To Do

For more information on breast cancer, visit the National Cancer Institute or the American Cancer Society. This article from discusses genetics and breast cancer.

You can find a simple explanation of DNA microarrays on the Altruis Biomedical Network.

SOURCES: Interviews with Laura J. van 't Veer, Ph.D., associate professor, molecular biology, Center for Biomedical Genetics, The Netherlands Cancer Institute, Amsterdam; Carlos Caldas, M.D., senior investigator and medical oncologist, Cancer Genomics Program, Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, England; Jan. 31, 2002, Nature
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