Other highlights in the May 2 JNCI

Study Confirms Tamoxifen Prevents Breast Cancer in High-Risk Women

Women at high risk for breast cancer who have undergone a hysterectomy appear to benefit from taking tamoxifen to prevent breast cancer, according to an extended follow-up of the Italian Randomized Tamoxifen Trial.

The initial findings from the Italian trial showed no significant reduction in breast cancer risk with tamoxifen use. However, the National Surgical Adjuvant Breast and Bowel Project’s Breast Cancer Prevention Trial found that tamoxifen reduced the risk of estrogen receptor-positive breast cancer.

Umberto Veronesi, M.D., of the European Institute of Oncology in Milan, and colleagues randomly assigned 5,408 healthy women who had a hysterectomy to receive tamoxifen or a placebo for five years.

After 11 years of follow-up, 136 women developed breast cancer—74 in the placebo group and 62 in the tamoxifen group. Among low-risk women, rates of breast cancer were similar in the tamoxifen and placebo groups. But for women at high risk, breast cancer rates were lower for those taking tamoxifen. Women taking tamoxifen experienced more side effects, including hot flashes and heart problems, than women in the placebo group.

"A complete assessment of the baseline cardiovascular risk should become an important component of counseling women on the use of tamoxifen, particularly in the prevention setting," the authors write.

Contact: Donata Francese, European Institute of Oncology, dfrancese@consulenti-associati.it, +39 02 89 075034

Drug Combination Halts Tumor Growth Better Than Single Agent

Treatment with three drugs that inhibit the human epidermal growth factor receptor (HER) stops HER2-positive breast cancer tumor growth in mice better than treatment with just one or two of the drugs.

Grazia Arpino, M.D., Ph.D., of Baylor College of Medicine in Houston, and colleagues measured tumor growth in mice with human breast cancer tumors that overexpress HER2. Some mice received one of three HER inhibitors—pertuzumab, trastuzumab, or gefitinib—or a combination of two or three of the drugs. The mice also received different combinations of hormonal therapy, including estrogen supplements, estrogen withdrawl, and tamoxifen.

A combination of all three HER inhibitors was more effective at slowing tumor growth than a single drug or combination of two drugs. The tumors grew after 49 days in mice that received all three drugs, compared with 21 days for mice in the estrogen-only group and 28 days for mice that got estrogen and pertuzumab. The addition of tamoxifen to any of the three drugs also inhibited tumors growth in the mice, but after two months the tumors grew resistant to the treatment. In mice treated with all three HER inhibitors plus tamoxifen or estrogen withdrawal, most tumors completely disappeared and did not progress for more than 189 days after treatment.

"These results support the hypothesis that acquired resistance to the individual agents is the result of [an] incomplete blockade of this complex network at the receptor level and not activation of a different survival pathway," the authors write.

Contact: Kimberlee Barbour, kbarbour@bcm,tmc.edu, (713) 798-7971

Chemotherapy with Rituximab Is Better for Indolent Lymphoma Patients

Patients with indolent or mantle cell lymphoma have higher overall survival rates when given the antibody rituximab in addition to their standard chemotherapy, a combination called R-chemo.

The R-chemo regimen has previously been shown to improve progression-free survival in patients with indolent or mantle cell lymphoma, but its impact on overall survival had not been demonstrated. Holger Schulz, M.D., of the University of Cologne in Germany, and colleagues conducted a meta-analysis of randomized controlled trials that examined overall survival of patients with advanced indolent or mantle cell lymphoma treated with R-chemo or chemotherapy alone.

Looking at data from seven trials, the researchers found that patients treated with R-chemo had better overall survival than chemotherapy-only patients, but they were more likely to have fever and lower white blood cell counts.

"Concomitant treatment with rituximab and standard chemotherapy regimens should be considered the standard of care for patients with indolent and mantle cell lymphomas who require therapy and for patients with follicular lymphoma," the authors write.

Contact: Holger Schulz, holger.schulz@uni-koeln.de, +49 221 71077019

New Lung Cancer Models Predict Risk with Modest Accuracy

Researchers have developed three lung cancer risk prediction models for current, former, and never smokers.

Reliable risk prediction models would be of great value for determining an individual’s likelihood of developing lung cancer and his or her potential benefit from preventive treatment or clinical trials. However, existing models focus primarily on long-term smokers.

Margaret Spitz, M.D., of the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues developed and validated separate risk prediction models for current, former, and never smokers. The models were based on data from a case–control study of lung cancer that included 1,851 lung cancer patients and 2,001 matched control subjects. The models predicted lung cancer development with modest accuracy, similar to that of other cancer prediction models. Risk factors in the models include exposure to second-hand smoke, family history of cancer, dust exposure, prior respiratory disease, and smoking history.

"The purpose of this analysis was to create a parsimonious model for assessing lung cancer risk with a minimal number of risk predictors that is realistic to use in clinical practice and to validate the model in an independent sample from the same population. In our experience, patients are agreeable to completing health questionnaires, either self-administered or administered by personal interview," the authors write.

Contact: Laura Sussman, lsussman@mdanderson.org, (713) 745-2457

EMBARGOED FOR RELEASE: 1 MAY 16:00 EST

Also in the May 2 JNCI:

• http://www.eurekalert.org/emb_releases/2007-05/jotn-tc042607.php
• http://www.eurekalert.org/emb_releases/2007-05/jotn-ls042607.php

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jnci.oxfordjournals.org/.