Effectiveness of Antibiotics, Supplements Against Precancerous Gastric Lesions Varies

A team led by NCI's Division of Cancer Epidemiology and Genetics (DCEG) has found that one-time treatment of Helicobacter pylori (H. pylori) with amoxicillin and omeprazole reduces the prevalence of precancerous gastric lesions, whereas 7 years of supplementation with a garlic preparation or with a mixture of vitamins C, E, and selenium did not, as reported in the July 19 Journal of the National Cancer Institute.

Chronic infection with the H. pylori bacteria causes inflammation and ulcers in the stomach or small intestine. People infected with H. pylori have an increased risk of gastric cancer, the second leading cause of cancer mortality worldwide.

The researchers conducted a randomized double-blind factorial trial of three treatments: a 2-week H. pylori treatment with amoxicillin and omeprazole; daily garlic supplement for 7 years; or daily combined vitamin C, E, and selenium supplement for 7 years. The study included 3,365 adults aged 35 to 64 from 13 randomly selected villages in Shandong Province, China, where the prevalence of precancerous gastric lesions is high, and gastric cancer accounts for 42 percent of cancer deaths.

"Amoxicillin and omeprazole eradicated 73 percent of infections initially, and decreased the severity and development of precancerous gastric lesions 7 years later," said Dr. Mitchell Gail, study leader and chief of DCEG's Biostatistics Branch. "Favorable trends in the data suggested, but did not prove, that treating H. pylori with antibiotics might reduce gastric cancer incidence. Long-term vitamin and garlic supplements had no significant effect on the development of precancerous gastric lesions or on gastric cancer incidence." Dr. Gail added that the results should encourage larger studies to prove that treatment for H. pylori reduces gastric cancer incidence.

Combined Estrogen and Testosterone Use Increases Risk of Breast Cancer

Based on studies suggesting that testosterone can improve mood, sexual functioning, and bone-mineral density in postmenopausal women, the hormone is currently included in some postmenopausal hormone therapies (PMH). However, no prospective clinical studies had examined the breast cancer risk of exogenous testosterone before its incorporation into these treatments. A prospective cohort study published in the July 24 Archives of Internal Medicine demonstrates that the use of combined estrogen and testosterone (E&T) therapy significantly increases the risk of invasive breast cancer.

Women participating in the Nurses' Health Study from 1978 to 2002 returned an initial questionnaire that recorded the type of PMH they had used during the preceding 2 years. Follow-up data was collected using questionnaires mailed to participants every 2 years. Incidences of invasive breast cancer were identified by self reporting on returned questionnaires and verified by a review of patients' medical records.

Over 24 years, 4,610 incidences of invasive breast cancer occurred in postmenopausal participants. Women who used E&T therapy at diagnosis had a 77-percent greater risk of developing breast cancer than women who never used any type of PMH. Women who used estrogen alone had a 15-percent greater risk, and women who used estrogen and progesterone (E&P) therapy had a 58-percent greater risk than women who never used any type of PMH.

The authors recommend caution when considering the use of hormone therapy: "Given the substantial evidence implicating combined E&P therapy in breast cancer and the results of the present study regarding E&T therapies, women and their physicians should reconsider use and, more specifically, long-term use of these therapies."

Scientists Develop New Model for Estimating Melanoma Risk

Melanoma develops slowly and can often be cured when detected as a thin lesion in the outer layer of skin. Invasive melanoma can be deadly, however. A calculator, based on results of a study in the August 1 Journal of Clinical Oncology, can be used by health professionals to identify individuals at increased risk of melanoma and help them plan for potential interventions.

The model used to construct the tool was developed by a team of researchers led by Dr. Thomas R. Fears of NCI's DCEG. The model's attributable risk is 86 percent for men and 89 percent for women. Attributable risks did not vary by age, ultraviolet-B exposure history, or hours spent outdoors, and the observed individual risks varied widely, depending on age, other host characteristics, and geographic area.

To develop the model, the researchers employed a clinic-based case-control study of 718 non-Hispanic white patients with invasive cutaneous melanoma, as well as 945 outpatient controls. The gender-specific model uses information that health care providers can easily obtain during a routine office visit (e.g., complexion, sun exposure, and a physical examination of the back and shoulders). The back and shoulders were chosen as indicators of melanoma risk because the evaluation of moles, freckling, or sun damage to these areas is more telling than on chronically exposed areas (e.g., the face); and the number of nevi, or benign moles, on the back are highly correlated with the number of nevi on the whole body.

"Routine screening of the general population for melanoma isn't feasible," said Dr. Fears, "because of cost and the high proportion of negative examinations. Using the melanoma tool would help health professionals identify the appropriate high-risk people for interventions."

The tool is now available at http://www.cancer.gov/melanomarisktool.

Imatinib Linked to Cardiotoxicity

Researchers have identified a link between the use of imatinib (Gleevec) for patients with chronic myelogenous leukemia and cardiotoxic effects, including severe congestive heart failure, according to a study published early online July 23 in Nature Medicine.

Dr. Thomas Force of Jefferson Medical College in Philadelphia and colleagues reported on 10 individuals with normal heart function prior to receiving imatinib who, after treatment ranging from 1 to 14 months, developed left ventricular dysfunction and congestive heart failure. Myocardial biopsies from two of the patients, they reported, revealed abnormalities that are "characteristic of toxin-induced myopathies."

To further evaluate whether imatinib may have cardiotoxic effects, the research team treated healthy mice with the drug for 3 or 6 weeks using a range of doses. In addition to detecting mitochondrial abnormalities that are indicative of cardiotoxic effects, they found that mice treated for 3 to 4 weeks with a 200 mg dose also developed left ventricular contractile dysfunction and dilation. Imatinib could also induce cell death in cultured cardiomyocytes, the researchers found, and appears to do so as a result of its inhibition of the tyrosine kinase c-Abl, which they argued "has a previously unknown survival function in cardiomyocytes.

The study "raises concerns" about other "agents currently in development that target Abl and other nonreceptor tyrosine kinases," the authors concluded. In a news release, Dr. Force said clinicians need to be aware that imatinib could have cardiotoxic effects, but given the success seen with the drug, he added, "patients need to be on it."

Annual Cancer Prevention Lecture Delivered

In 1994, when the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study showed that beta-carotene was associated with lung cancer, many questioned earlier dietary epidemiology studies demonstrating its protective effects. Dr. Frank L. Meyskens, Jr., director of the Chao Family Comprehensive Cancer Center at the University of California, Irvine recently spoke about this conundrum at the 2006 Annual Advances in Cancer Prevention Lecture, sponsored by NCI's Division of Cancer Prevention and held on the NIH campus last week.

Dr. Meyskens argued that showing the efficacy of a dietary compound in a large nutritional epidemiology study should not necessarily warrant the sort of phase III study that is normally conducted. While clearly something is preventing cancer, he reasons, the "black box" of a large observational trial does not control for enough factors to identify the causative agent. The dietary epidemiologists, he said, falsely identify the micronutrient they are focused on as the active agent primarily responsible for the observed preventive effect. In a disease process as complex as cancer, he noted that a "biological action package" of multiple interacting regulatory molecules is much more likely to be involved, as well as the biochemical microenvironment at the organ site; neither of these factors is controlled for adequately in observational or randomized studies of nutrition.

Looking forward, however, Dr. Meyskens expressed excitement about the development of safer agents and more integrated multimodality strategies. He expects futuristic technologies such as noninvasive imaging, but is less optimistic about validating biomarkers. The scourge of lung cancer is not medicine's problem to solve, he stated, and will only yield to behavior change in the young.

To view the lecture, visit http://videocast.nih.gov/PastEvents.asp?c=4.