Gene test predicts aggressive breast cancer

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Gene test predicts aggressive breast cancer

By Mulvihill

NEW YORK, Jan 30 (Reuters Health) - An international team of researchers

have identified a " pattern of gene activity " that distinguishes very

aggressive forms of breast cancer from less dangerous forms of the

disease.

While the test is not ready to be used routinely in patients, the

investigators hope to one day use the information to identify women who

need additional anti-cancer treatment and spare those who do not.

" Nowadays, almost all women with breast cancer are treated as if they

have an aggressive form of breast cancer, " lead author J. van 't

Veer, of the Netherlands Cancer Institute in Amsterdam, said in an

interview with Reuters Health. But, she pointed out, " only 20% to 30% of

these women will develop distant metastases, " or cancer that spreads to

another part of the body.

According to van 't Veer, this means that after having a breast tumor

removed, 70% to 80% of women may be unnecessarily treated with

chemotherapy and/or hormonal therapy--both of which carry significant

side effects.

Having a test that could identify which women would benefit from the

treatment would be preferable, she explained by telephone from her

laboratory in Amsterdam.

Using gene chips, van 't Veer and colleagues collaborated with

scientists at Rosetta Inpharmatics in Kirkland, Washington, and

evaluated the activity of genes found in the DNA of breast cancer

tumors. They looked for patterns of gene expression that might signify a

more aggressive form of cancer.

The chip is approximately the size of a thumbnail, yet it can hold

hundreds of thousands of strands of DNA.

The researchers analyzed some 25,000 genes in 78 stored samples of

breast cancer tumors--34 from patients who went on to develop distant

metastases within 5 years of diagnosis and 44 patients who were

disease-free after a period of at least 5 years.

The gene chip helped the researchers identify 70 genes that were only

active in very aggressive breast cancer tumors--offering what van 't

Veer termed a " pattern of genetic activity " that may one day be used to

predict the prognosis of women with breast cancer.

" We can use the new technique to tailor treatment therapy for breast

cancer patients, " said van 't Veer. " Based on the gene activity

identified in the test, we can decide whether or not she needs

(additional treatment). "

So far, the test appears to be accurate, and was able to predict the

prognosis of 65 of the 78 patients. In a separate analysis of 19 other

samples the test identified all but two--an error rate of roughly 10%,

according to study findings published in the January 31st issue of the

journal Nature.

The next step is to use the test on a larger group of women including

those with breast cancers of varying aggressiveness, van 't Veer

explained.

Despite the promising findings, van 't Veer notes that gene chips are

still a long way off from being used in day-to-day breast cancer

diagnosis and treatment.

" It took us almost a year to obtain the results. We really need a test

that can be done in 1 or 2 days, " she told Reuters Health.

" These findings are tremendously promising, " write Drs. Caldas

and A. J. Aparicio of the University of Cambridge in the UK, in

an accompanying editorial.

" But history tells us to be cautious, and the widely accepted guidelines

for evaluating breast cancer remain essential, " they add. " Cancer

classification based solely on gene-expression profiling may well be

feasible, but this study was only a pilot and had a small sample size. "

Nonetheless, Caldas and Aparicio point out that the effects of better

selection of breast cancer patients for additional treatment by the new

method described in Nature is " potentially staggering. "

Using current predictive methods, about 70% to 91% of cancer patients

undergo additional treatment after surgical removal of a tumor,

according to Caldas and Aparicio. The new method, if developed into a

clinically useful test, would call for only 25% of these women to be

advised to undergo such treatment.

" I am very pleased to see that molecular diagnostics is taking off, "

said Dr. Dawn Willis of the American Cancer Society in Atlanta, Georgia.

" I think it is going to be the wave of the future. "

While Willis believes the current study is good news, she notes that the

gene chip test is not easy to do and more technical advances are needed

before it can be used on a regular basis.

However, Willis said that the new method, once perfected, can probably

be used on many different types of cancer to help predict which therapy

is best.

One of the study's authors, Dr. Friend, is a vice president at

Merck Research Laboratories.

SOURCE: Nature 2002;415:484-485, 530-536.