Drug Prevents Mammary Tumors in Mice by Reducing Progesterone Activity

Researchers have found that inhibiting the activity of the hormone progesterone can prevent the development of mammary tumors in mice that carry mutations in a rodent version of the human breast cancer gene BRCA1. Mutant mice treated with the drug RU486, the "morning after" pill (also known as mifepristone and Mifeprex), did not develop mammary tumors by the time they were a year old, while the untreated mice developed tumors by 8 months of age.

Women who inherit BRCA1 gene mutations are at an increased risk of breast and ovarian cancers, and many reduce their risk by having their ovaries or breasts surgically removed. Though the new research was done in mice, the findings raise the possibility that inhibiting progesterone might be an additional strategy for reducing the breast cancer risk among these women.

High progesterone levels have been linked to an increased risk of breast cancer, and this study suggests a mechanism. Dr. Eva Lee of the University of California, Irvine, and her colleagues propose that the normal BRCA1 protein may help protect against breast cancer by helping to degrade the receptor protein that binds to progesterone.

If the progesterone receptor is not broken down, then the hormone's growth-promoting signal persists, and this may lead to excessive cell growth and cancer, the researchers reported in the December 1 Science. To reduce the hormone's signal, they tested mifepristone, which inhibits the progesterone receptor, and found that it prevented mammary tumors from developing.

The results suggest that the progesterone receptor function may be critical to the development of breast cancer in the presence of BRCA1 mutations. "These findings reveal a tissue-specific function for the BRCA1 protein and raise the possibility that antiprogesterone treatment may be useful for cancer prevention in individuals with BRCA1 mutations," the researchers concluded.

Previous research has suggested that the normal BRCA1 protein suppresses tumors by repairing damaged DNA before tumors develop, and the regulation of the progesterone receptor levels would be another role for the protein.

Dr. Lee noted that mifepristone has effects on other hormones in addition to progesterone and therefore might not be ideal for long-term use in cancer prevention among women with BRCA1 mutations. Other progesterone-blocking drugs are in development and may be suitable.

Bacteria, Chemo Combination Shows Potency in Mouse Model

A protein produced by a genetically modified bacterium appears to enhance the tumor-killing ability of common chemotherapy drugs that are encased in fatty capsules called liposomes. Because liposome-encapsulated drugs stay in the body longer, they can more selectively target tumors.

In a study published in the November 24 Science, researchers from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University showed that combination therapy involving the bacterium C. novyi-NT and Doxil, which is the liposome-encapsulated version of the chemotherapy drug doxorubicin, in a mouse model of colorectal cancer caused a complete disappearance of tumors in all of the mice tested; two-thirds of the mice survived for more than 3 months. Similar results were seen using a liposome-encapsulated version of the chemotherapy drug irinotecan. There was generally no evidence of toxicity from the treatment.

The same research team, from the lab of Dr. Bert Vogelstein and led by Dr. Ian Cheong, had previously shown that C. novyi-NT selectively kills tumor cells in regions of tumors that are receiving little oxygen, while sparing those in the more aerobic tumor "rim." The combination of the modified bacteria and Doxil, they found, delivered higher concentrations of the liposome's contents than could be achieved when Doxil was delivered as a single agent.

After seeing the increased efficacy of the combination therapy, the researchers sought to identify how the bacteria helped achieve this effect. They discovered a previously unidentified protein, which they dubbed liposomase, that seemed to be primarily responsible for efficiently disrupting the liposomes' fatty membrane in the tumor and ensuring that a greater amount of drug was delivered to the tumor cells.

"Because virtually any therapeutic agent can be packaged in liposomes and can thereby act as a ‘prodrug,'" they wrote, "liposomase offers a number of possibilities for the specific delivery of drugs to tumors."

Brain Scans Show Structural Effects of Chemotherapy

The cognitive impairments demonstrated by breast cancer patients who undergo chemotherapy - symptoms commonly called "chemobrain" - may be related to structural brain changes, according to Japanese researchers in a study published early online November 27 in Cancer.

The researchers used high-resolution brain magnetic resonance imaging to look at the distribution of gray and white brain matter regions in women who received chemotherapy after surgery and women who did not receive chemotherapy, with a set of healthy controls for comparison.

Fifty-one women who received chemotherapy were scanned in the first year after surgery, and 73 women were scanned 3 years after their surgery; 55 women who didn't receive chemotherapy were scanned in the first year after surgery, and 59 were scanned 3 years after surgery. The women received Wechsler Memory Scale-Revised testing for cognitive indices including attention, concentration, and visual memory.

The researchers found that in the first year of chemotherapy treatment, women had smaller right-prefrontal brain regions and smaller parahippocampal gyri - regions that are associated with memory - than women who didn't receive chemotherapy, and these changes correlated with decreased cognitive function. Other areas with similar shrinkage, also associated with memory, included the superior and middle-frontal gyri, the cingulated gyrus, and the precuneus.

Smoking Cessation Web Sites' Usage and Quality Studied

The types of smokers who are accessing the Web and the quality of Web-assisted tobacco intervention (WATI) sites were reported in two studies published in the December 1 Nicotine & Tobacco Research. Each study focused on a product developed or study funded by NCI's Tobacco Control Research Branch (TCRB) in DCCPS.

To help developers of smoking cessation programs improve the content and delivery of resources to both groups, the first study compared smokers who use the Internet with those who do not. Using data from the 2003 NCI Health Information National Trends Survey (HINTS), TCRB scientists compared characteristics of 728 Internet-using smokers with 516 non-Internet-using smokers.

"Our results showed that compared with smokers not on the Internet, those on the Internet had higher income and were more likely to be employed, despite having a younger age," noted NCI researchers Drs. Jacqueline L. Stoddard and Erik M. Augustson. "Internet-connected smokers also reported less psychological distress, fewer barriers to health care, and a greater interest in quitting smoking."

For smokers who didn't use the Web, the most common reason cited was a lack of familiarity with the Internet and a concern about the complexity of gaining access. Because this group also reported a high level of trust in information and advice from family and friends, the researchers suggested that campaigns target friends and families of smokers to increase Internet utilization for the purpose of quitting smoking.