Gene Mutation May Predict Lung Cancer Patients Response to Iressa
Patients with non-small cell lung cancer (NSCLC) whose tumor cells have a mutation in the gene that produces a protein called epidermal growth factor receptor (EGFR) are more likely to respond to the drug gefitinib (Iressa) than patients without the mutation, according to two new studies.
Iressa was approved by the U.S. Food and Drug Administration 1 year ago for the treatment of lung cancer.
In clinical trials, however, Iressa caused tumor regression in only a small subset of patients. The drug was more likely to work in patients from Japan, in women, in nonsmokers, and in patients with adenocarcinoma. The molecular mechanisms that might explain why only these patients responded to the drug were unknown.
In a study published April 29 in Sciencexpress, the early release section of Science, J. Guillermo Paez, Ph.D., of the Dana-Farber Cancer Institute in Boston, and colleagues searched for gene mutations in nonsmall-cell lung tumors from 58 Japanese patients and 61 American patients. One of the American patients and 15 Japanese patients had a mutation in the gene. When the researchers analyzed tumor samples from patients who had been treated with Iressa, the five patients who had responded to the drug had the mutated gene, whereas the four whose tumors did not respond did not have the mutation.
In a second study, published online April 29 in the Early Release section of the New England Journal of Medicine, Thomas J. Lynch, M.D., of Massachusetts General Hospital in Boston, and colleagues discovered similar mutations in the EGFR gene in eight of nine NSCLC patients who responded to treatment with Iressa, but they found no mutations in seven patients who did not respond to the drug. To determine the function of the mutations, the researchers developed cultures of cells that expressed two of the mutated receptor proteins. These proteins responded at a higher level to epidermal growth factor. When the cells were treated with Iressa, the mutated receptor proteins were 10 times more sensitive to inhibition by the drug than normal proteins.
The researchers at Massachusetts General Hospital are developing a test to identify lung cancer patients with the newly discovered mutation. The Dana-Farber team plans to conduct clinical trials to determine if patients who do not benefit from Iressa may instead benefit from a combination of the drug with other targeted treatments.
Pap Smears and Mammograms Should Be Directed at Healthy Elderly Women
Many healthy women older than age 70 are not getting needed Pap smears and mammograms, and some older women in poor health are getting tests they do not need, according to a new study.
The risks of cancer screeningssuch as unnecessary tests resulting from false-positive results and psychological distressare thought to outweigh the benefits for elderly women with a life expectancy of less than 5 years. Because health status is often a better predictor of life expectancy than age, many cancer guidelines recommend basing screening decisions on an elderly persons health status. It has not been known, however, if physicians are using these guidelines in recommending cancer screening.
In the May issue of the Annals of Internal Medicine, Louise C. Walter, M.D., of the University of California, San Francisco, and colleagues reviewed data from 4,792 women age 70 and older who took part in the 2001 California Health Interview Survey.
Of those who responded to the survey, 78% reported having a routine mammogram within the previous 2 years and 77% reported a Pap smear within the previous 3 years. Screening rates decreased with age but not with health status. The least healthy women were just as likely to have reported having a Pap smear or mammogram as the healthiest. In addition, 39% of women who had had a hysterectomymost of whom would therefore not have a cervixreported having a recent Pap smear.
The authors recommended that Pap smears and mammograms may be better targeted to healthy older women who are more likely to benefit from the tests and should be avoided by older women in poor health. They also recommended developing better tools for identifying those women who may benefit the most from these tests.
Highly Processed Soy May Increase Breast Cancer Growth
A new study showed that highly processed soy, the kind more commonly marketed to and consumed by American women, may stimulate the growth of estrogen-dependent breast tumors in mice.
Soybeans contain numerous biologically active compounds that may be important in cancer prevention, including three isoflavones: genistein, daidzein, and glycitein. Although the association between soy consumption and decreased cancer risk has been well documented in Asian populations, the soy foods consumed in Asia are usually made from lightly processed soybeans or soy flour. In the United States, soy products, in the form of highly processed soy isoflavones, have been marketed to postmenopausal women as a natural alternative to hormone replacement therapy. These soy products may pose a risk, however, because of their ability to mimic estrogen and stimulate growth in estrogen-dependent tumors.
To evaluate the effects of increasing degrees of soy processing on tumor growth, Clinton D. Allred, Ph.D., of the University of Illinois at Urbana-Champaign, and colleagues fed diets containing various soy products (soy flour, extracts of soy, a mixture of isoflavones, and pure genistein) to mice injected with tumor cells that mimic estrogen-dependent breast cancer. The soy-containing diets were controlled so that they all had the same amount of genistein. While tumors in the control mice shrank over time and tumors in mice that were fed the soy flour stayed the same size, tumors in the mice fed more processed forms of soy (soy extracts, isoflavones, and genistein) grew and also had increased cellular proliferation.
The researchers suggested that genistein may have a negative effect on the growth of estrogen-dependent breast tumors and that other biologically active compounds in less processed soy products, such as soy flour, may offset these effects. The study was published online in May in Carcinogenesis.
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