Correction In the article on esophageal cancer in the May 16 NCI Cancer Bulletin, there was an error in the HTML and PDF versions. Regarding research being conducted by Dr. Brian Reid and colleagues at Fred Hutchinson Cancer Research Center, the article stated that the researchers were trying to determine whether cell cycle abnormalities were predictive of progression to esophageal adenocarcinoma in people with Barrett's esophagus. It should have stated "abnormalities in the amount of DNA in a cell," not the "cell cycle." It was corrected on May 17.

Use of Recombinant Human Erythropoietins May Pose Risks

Administration of the drugs epoetin or darbepoetin - recombinant human erythropoietins that stimulate the bone marrow to make red blood cells - can reduce the need for blood transfusions during cytotoxic chemotherapy. However, recent hearings before the Food and Drug Administration questioned whether there is an association between the use of erythropoietins and increased risk of thrombo-embolic events such as stroke. In addition, several papers have presented conflicting evidence on the association between erythropoietins and survival. An updated systematic Cochrane Review published in the May 17 Journal of the National Cancer Institute (JNCI) analyzed data from 57 trials comprising 9,353 patients to better clarify possible risks posed by the use of erythropoietins.

The relative risk of a thrombo-embolic event was found to be significantly increased in patients receiving either epoetin or darbepoetin. In addition, the updated analysis "found no association between treatment and survival and possibly even that decreased survival might be associated with treatment." This result differed from the authors' original review published in 2005, which showed a possible association of erythropoietins with increased survival.

The investigators propose that this difference might be due to newer trials that enrolled nonanemic patients or that aimed to increase hemoglobin to levels higher that those recommended by the product labels, but they did not have the individual patient data needed to clarify these possible associations. Therefore, they advise caution when using either erythropoietin "in combination with chemotherapeutic agents that are known to be thrombogenic or for cancer patients who are at high risk for thrombo-embolic events."

Most Statin Use Not Associated with Breast Cancer Risk

The use of the statins class of cholesterol-lowering drugs was not found to increase the risk of breast cancer, according to results of the Women's Health Initiative (WHI) study reported in the May 17 JNCI.

Previous clinical studies yielded "mixed results" on the association of statins with breast cancer risk. The WHI study of more than 156,000 postmenopausal women collected data on use of statins and other lipid-lowering drugs. Statins were used by 11,710 (7.5 percent) of the women. After an average follow-up of 6.7 years, 4,383 invasive breast cancers were found. Breast cancer incidence was 4.09 per 1,000 person-years among statin users, compared with 4.28 per 1,000 person-years for non-users, the researchers report. The lower incidence among statin users was not statistically significant.

"Overall statin use was not associated with invasive cancer incidence," the researchers note. However, the use of "hydrophobic" statins such as simvastatin, lovastatin, and fluvastatin among 8,106 women was "associated with an 18 percent lower breast cancer incidence," they add. "Our finding that use of hydrophobic statins may be associated with lower breast cancer incidence suggests possible within-class differences that warrant further evaluation."

This observation "is consistent with a cell culture study in which only hydrophobic statins (lovastatin, simvastatin, and fluvastatin) but not a hydrophilic statin (pravastatin) had anticancer activity," the researchers explain. "Our results, taken together with the existing literature, indicate that breast cancer risk is at least not increased in statin users. Whether or not statin use is associated with reduced breast cancer risk is less certain."

Combination of Antibody-Based Therapies Kills Tumors in Mice

Researchers have used a combination of antibody-based therapies to eradicate established tumors in mice. The combination included three monoclonal antibodies that together caused the death of tumor cells and the activation of tumor-specific immune cells.

A team from the Juntendo University School of Medicine in Tokyo induced tumor cell death, or apoptosis, using a monoclonal antibody that acts through a receptor called DR5; they activated tumor-specific CD8-positive T cells using monoclonal antibodies against the molecules CD40 and CD137. The combination, which the researchers call trimAb, "potently" induced the rejection of established tumors in most mice tested.

TrimAb therapy eradicated mammary tumors in 80 percent of mice tested, whereas other combined or single monoclonal antibody treatments did so in less than 30 percent of mice tested. When the researchers treated larger tumors, trimAb therapy eradicated tumors in 70 percent of mice, whereas the rate was less than 20 percent for all other combinations, according to findings published online in Nature Medicine. The researchers also tested tumors of the colon and the lung.

No side effects of trimAb therapy were observed in the mice, and the researchers say it would be important to minimize autoimmune reactions in adapting the therapy for humans. More research is needed, but the current results suggest that a combination therapy that both causes tumor-cell apoptosis through DR5 and activates T cells "may be an effective strategy for cancer immunotherapy in humans," the researchers conclude.