Free NRT Program Helps New York City Smokers Quit

A large-scale program to provide free, 6-week courses of nicotine replacement therapy (NRT) patches to 34,000 heavy smokers in New York City resulted in at least 6,000 successful smoking "quits" at a cost of $463 per quit, according to a study reported in the May 28 Lancet.

The study, conducted by the New York City and New York State health departments - in collaboration with Roswell Park Cancer Institute - addressed the many smokers who "will not be reached by cessation treatment offered in clinical settings." The free patch program received a major publicity launch in 2003, which led almost 40,000 smokers to call the New York smokers quitline.

Eligible smokers were sent 6-week courses of NRT patches. Counseling telephone calls were attempted at 3 and 14 weeks, successfully reaching more than 15,000 smokers. Recipients also were sent a follow-up survey at 6 months to assess smoking status and quit attempts.

"An estimated 5 percent of all adults in New York City who smoked 10 cigarettes or more daily received NRT" under the program, the researchers reported. "Most (64 percent) recipients were nonwhite, foreign-born, or resided in a low-income neighborhood." Among individuals contacted at 6 months, more NRT recipients successfully quit smoking than comparison group members who did not receive NRT patches - 33 percent versus 6 percent. Based on the conservative assumption that all nonresponders to the follow-up survey continued smoking, researchers estimated the quit rate among NRT recipients at 20 percent.

Improved Breast Cancer Outcomes Seen with Docetaxel Adjuvant Regimen

Substituting docetaxel (Taxotere) for fluorouracil in an adjuvant chemotherapy regimen for node-positive breast cancer improves disease survival and decreases risk of disease relapse, an international research team reported last week. At 55 months follow-up, the adjuvant regimen of docetaxel, doxorubicin, and cyclophosphamide - dubbed TAC - yielded a 28-percent improvement in disease-free survival compared with a regimen known as FAC, for fluorouracil, doxorubicin, and cyclophosphamide (75 percent vs. 68 percent).

The international study, the Breast Cancer International Research Group 001 trial, involved nearly 1,500 patients from 20 countries. After adjuvant chemotherapy, regardless of the regimen, patients received tamoxifen, radiation therapy, or both, explained study lead author Dr. Miguel Martin of the Hospital Universitario San Carlos in Madrid, Spain, in the June 2 New England Journal of Medicine (NEJM).

The superiority of TAC compared with FAC, however, came at the expense of increased toxic effects, namely febrile neutropenia: 24.7 percent in TAC patients compared with 2.5 percent of FAC patients. This occurred - wrote Dr. Edith A. Perez of the Mayo Clinic in Jacksonville, Fla., in a related editorial in NEJM - "despite the prophylactic use of antibiotics and the introduction of [granulocyte-colony stimulating factor] support after the first episode of febrile neutropenia or infection."

Dr. Perez also noted that the TAC regimen was compared with a regimen that is no longer the standard of care in this patient population. The standard of care adjuvant chemotherapy regimens in the United States today typically contain a taxane drug, such as docetaxel or paclitaxel. Whether TAC now should be used generally in the adjuvant setting, she concluded, remains "a compelling question," that may be answered by a clinical trial being conducted by the National Surgical Adjuvant Breast and Bowel Project, B-38.

Study Finds Breast Cancer Risk with NSAID Use

California researchers reported last week that daily, long-term use of ibuprofen is associated with an increased risk of breast cancer, and that long-term daily use of aspirin is associated with an increased risk of estrogen receptor/progesterone receptor (ER/PR)-negative breast cancer. The ibuprofen/breast cancer link was especially strong for nonlocalized breast cancers. The authors stressed, however, that it's unclear if use of aspirin or ibuprofen is the cause of the cancer.

The study, partly funded by NCI, was published in the June 1 Journal of the National Cancer Institute.

Dr. Sarah F. Marshall, of the University of Southern California, and colleagues looked at data on more than 114,000 women enrolled in the California Teachers Study, which included data from a self-administered questionnaire on the use of aspirin, ibuprofen, and other nonsteroidal anti-inflammatory drugs (NSAIDs). During the 6-year course of the study, 2,391 cases of breast cancer were identified.

Daily use of aspirin for 5 years or more was associated with an 81-percent increased risk of ER/PR-negative breast cancer, while similar use of ibuprofen was associated with a 51-percent increase of breast cancer and a 92-percent increased risk of nonlocalized disease.

Researchers have studied NSAID use and breast cancer because it was thought that they might protect against breast cancer by inhibiting the COX-2 enzyme, which can stimulate cancer growth. Previous case-control and cohort studies had yielded inconsistent findings on NSAID use and breast cancer risk, which led the researchers to investigate whether NSAID use influences only certain types of breast cancer types, noted Dr. Deborah Winn, chief of NCI's Clinical and Genetic Epidemiology Research Branch. Findings of an increased risk of certain types of breast cancer associated with ibuprofen and aspirin, she added, suggest that the relationship between NSAID use and breast cancer is complex and may affect certain types of breast cancer more than others.

Mouse Has p53 Tumor Suppressor Gene with On/Off Switch

Scientists have created a laboratory mouse with a modified p53 tumor suppressor gene that can be switched on and off chemically, at will. The mouse is a tool for investigating the role of the p53 protein in blocking cancer at various stages of tumor development, according to a study published online in Nature Genetics on May 29.

The p53 gene and the pathway it regulates are often inactivated in human cancers. The new mouse model could be used to see what happens when the gene is reactivated in cells with developing or mature tumors. The mouse could also be used to explore how p53 proteins "sense" and suppress emerging tumors.

"We hope the community will find the mouse useful for studying where, when, how, and why the p53 protein acts to block cancer," says Dr. Gerard Evan, who led the study at the University of California, San Francisco (UCSF). The mouse will be available through NCI's Mouse Models of Human Cancers Consortium.

Mice that produce too much or too little p53 protein already exist. To make the new model, Dr. Maria Christophorou of UCSF and colleagues replaced the p53 gene with a version that was fused to a hormone receptor. The researchers could then switch p53 on and off in nearly all mouse tissues by either administering or withdrawing a particular hormone.

In preliminary experiments, the researchers found that inactivating p53 in tissues substantially prevented the sickness and pathology induced by acute radiation or chemotherapy. The restoration of p53 about 2 days later caused no ill effects, yet prevented radiation-induced cancers from emerging.

If the same is true in people, Dr. Evan notes, this might have implications for patients undergoing radiation and chemotherapy because inactivating p53 temporarily during therapy would help prevent harmful p53-mediated side effects.

Mouse Study Suggests Optimal Cells for Immunotherapy

A new study suggests that the use of younger, less-differentiated T cells may benefit cancer patients undergoing adoptive cell transfer (ACT). This experimental immunotherapy involves harvesting a patient's T cells, stimulating them to attack tumors, and then returning them to the body.

Although the work was done in mice, "several lines of evidence suggest that the mouse findings may apply to humans," notes Dr. Nicholas Restifo of NCI's Surgery Branch, who led the study. The findings appear in the June issue of the Journal of Clinical Investigation (JCI).

Dr. Luca Gattinoni, the study's first author, found that cells stimulated for long periods outside of the body had used up their capacity to proliferate vigorously and thus were less able to successfully kill tumors. "Our goal is to enable young T cells to mature and acquire tumor-killing abilities after infusion into patients," Dr. Gattinoni explains.

ACT-based immunotherapies were developed for patients with advanced cancers that do not respond to conventional treatment. Dr. Steven Rosenberg, chief of NCI's Surgery Branch and a co-author of the study, led a recent clinical trial in which about 50 percent of melanoma patients treated with ACT achieved an "objective clinical response."

The team is now searching for ways to procure less differentiated and more "fit" cells for ACT-based immunotherapies. A JCI editorial suggests that a pragmatic strategy for ACT in humans is to keep the ex vivo stimulation phase "as short as possible."