Finasteride Not Linked to High-Grade Prostate Cancers

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Finasteride is unlikely to induce high-grade prostate cancers in men who take the drug to prevent the disease, according to two studies published online today in the Journal of the National Cancer Institute (JNCI).

In 2003, the NCI-sponsored Prostate Cancer Prevention Trial (PCPT) found that finasteride reduced the overall incidence of prostate cancer by 25 percent, but was associated with a small increase in the number of high-grade cancers, which are often aggressive. It was not known whether the drug caused more high-grade prostate cancers or merely facilitated their detection. The new studies suggest the latter.

In the first study, Dr. Yael Cohen of Gamida Cell in Jerusalem and colleagues determined that finasteride reduces the volume of the prostate and therefore increases the likelihood of finding high-grade cancer cells in a biopsy. Finasteride accelerates the detection of high-grade cancer yet may not promote its development, they conclude.

The second study analyzed prostatectomies from the PCPT and found that the relative increase in high-grade tumors in the finasteride group was less than originally believed. The findings further suggest that enhanced detection may have contributed to the increase in high-grade disease in the finasteride group, reported a team led by Dr. M. Scott Lucia of the University of Colorado Health Sciences Center.

More Americans Getting Cancer Information from the Internet

For a growing number of Americans seeking information about cancer, the Internet remains a frequent first source, even though the public's trust in online material may be on the decline, reports a government study.

The report, Cancer Communication: Health Information National Trends Survey 2003 and 2005, is based on data from the Health Information National Trends Survey (HINTS), a biennial survey sponsored by NCI's Division of Cancer Control and Population Sciences (DCCPS). First conducted in 2003, HINTS surveys the U.S. civilian adult population to assess trends in the use of health information over time and to study the links between cancer-related communication, knowledge, attitudes, and behavior.

In 2003, 44.9 percent of HINTS respondents reported looking for cancer information for themselves on the Internet; in 2005, 48.7 percent of respondents reported looking for cancer information for themselves online. In addition, in 2003, 23.9 percent of respondents reported "a lot" of trust in health information from the Internet, while this number was somewhat lower in 2005 (18.9 percent). Health care professionals were most frequently identified as a trusted source of information in both 2003 (62.4 percent) and 2005 (67.2 percent).

"The survey is not only a surveillance tool, but can be used to study relationships of how knowledge about health care is dependent on channels of communication," said NCI researcher Dr. Bradford Hesse. The researchers also looked at population estimates of cancer knowledge and beliefs, and worked with statisticians and geographic information systems specialists to create maps to portray regional geographic variation, much like weather maps.

The HINTS report is available at: http://hints.cancer.gov/hints/.

Racial Differences in Breast Tumors May Reflect Biology

A large study confirms recent reports that African American women are more likely than white women to have breast tumors that are estrogen receptor (ER)-negative, which are often aggressive and do not respond to antiestrogen therapies such as tamoxifen. A primary reason for the racial differences may be biological, researchers reported at the 2007 Breast Cancer Symposium in San Francisco.

African American women are more likely to die of breast cancer than white women, even though they are less likely to develop the disease. Lack of access to care and other factors are thought to contribute to the disparity. The new study suggests a role for biology: More aggressive tumors were found to be more common in black women than white women in all stages of disease and in each age category, even among women over age 80.

This study differs from previous reports mainly in its larger scale. Dr. M. Catherine Lee of the University of Michigan Comprehensive Cancer Center and her colleagues analyzed 170,000 cases of breast cancer in the National Cancer Data Base, a tumor registry that collects cancer data from more than 1,400 hospitals in all 50 states and Puerto Rico.

For women with invasive cancers, ER-negative tumors were significantly more common in African American women: 39 percent of black women had ER-negative tumors, compared with 22 percent of white women. Black women were also diagnosed at a younger average age (57 for black women vs. 62 for white women) and at a later stage than white women.

Hypnosis before Breast Cancer Surgery Reduces Pain, Cost

Women who received a brief hypnosis intervention before breast cancer surgery spent less time in the operating room and reported significantly less pain and discomfort after surgery than women who did not undergo hypnosis, reports a study published in the September 5 JNCI.

Investigators at Mount Sinai School of Medicine randomly assigned 200 women scheduled to undergo surgical breast biopsy or lumpectomy to either a hypnosis group or a control group. Women in the hypnosis group received a scripted 15-minute hypnosis session within 1 hour of surgery from psychologists trained in the use of hypnosis in the medical setting. Women in the control group spent an equal amount of time with the psychologists within an hour of surgery to talk and receive emotional support.

Because the women knew their group assignment, the investigators took several precautions to reduce potential bias, including blinding anesthesiologists and surgeons to the group assignments and using research assistants unaware of the group assignments to collect the women's perception of pain and discomfort.

Women in the hypnosis group required significantly less of the anesthetic propofol and the analgesic lidocaine, the doses of which are adjusted for individual patients during surgery. Although use of pain medication after surgery did not differ between groups, women in the hypnosis group reported significantly less pain intensity, pain unpleasantness, nausea, fatigue, discomfort, and emotional upset.

Women in the hypnosis group also spent about 10 and a half fewer minutes in surgery. On average, the surgical procedures cost about $770 less per patient in the hypnosis group, mostly due to reduced time in surgery.

Another Role for microRNAs: Suppressing Tumors

A number of recent studies have suggested that microRNAs are involved in suppressing tumors. These small RNA molecules, which regulate the activity of multiple genes, are increasingly recognized as important players in cell signaling.

The studies found that a family of three microRNA genes - the miR-34 family - is switched on by the tumor-suppressor gene p53 in response to DNA damage and cellular stress. The studies come to the same conclusion: microRNAs are an important component of the p53 network, and their loss may contribute to some cancers.

The most recent study, in the August 7 Current Biology, reported that the activity of two miR-34 genes was often compromised in human lung cancer. The genes were much less active than normal in 6 of 14 non-small-cell lung cancers that the researchers examined. Experiments in cells and mice showed that restoring the missing gene activity prevented some abnormal cell growth.

"These findings add one more piece to the p53 puzzle," says lead researcher Dr. Guido Bommer of the University of Michigan School of Medicine. "p53 is the major player in responding to DNA damage or other potentially harmful cellular stress, and we believe these microRNAs mediate a significant part of p53's function."

The results confirm other recent studies, including two in the June 8 Molecular Cell. One team reported that miR-34a is commonly deleted in human cancers and frequently absent in pancreatic cancer cells, while another found that in the absence of miR-34a, cells may not initiate p53-mediated cell death and thereby avoid progressing to cancer.

Finally, a report in the June 28 Nature found that miR-34 genes may play a role in causing cell death as well as inducing a state of growth arrest that normally occurs when cancer genes are activated accidentally.

Ovary Removal Linked to Cognitive Problems, Dementia

Women who had one or both ovaries removed before menopause for noncancer reasons faced an increased risk of developing cognitive problems or dementia later in life, according to a new study. But women who underwent estrogen replacement therapy until at least age 50 after having their ovaries removed were not at increased risk. The study supports the hypothesis that there may be a "critical age window for the protective effects of estrogen on the brain," the researchers write in the September 11 issue of Neurology.

The study included nearly 3,000 women, who were followed for more than 25 years. Dr. Walter Rocca of the Mayo Clinic and his colleagues studied 813 women who had 1 ovary removed, 676 women who had both ovaries removed, and a comparison group of women who did not have their ovaries removed when the study began. About half the women had their ovaries removed because of a benign condition, such as cysts or inflammation; the others had their ovaries removed prophylactically to prevent ovarian cancer. Women who had the procedure for ovarian cancer or another estrogen-related cancer (usually breast cancer) were excluded because of their high risk of death shortly after surgery.

The researchers suggest three possible mechanisms to explain the association they observed. First, ovary removal may cause an estrogen deficiency that initiates biological changes leading to the elevated risk. Second, the association may involve a deficit of progesterone or testosterone rather than estrogen secreted by the ovaries. Third, the association may be caused by susceptibility genes that independently increase both the risk of ovary removal and cognitive impairment or dementia.

The study's strengths include the long follow-up and the fact that the women were representative of the general population. Its limitations include the use of telephone interviews to assess cognitive abilities and an overall interview participation rate of 62 percent. In addition, the surgeries were done between 1950 and 1987, when surgical practices and estrogen use may have differed from today.

Nevertheless, the findings should lead to a reassessment of prophylactic removal of the ovaries in premenopausal women and of the use of estrogen treatment following ovary removal, the researchers say. "The results of this study are important for the majority of women who do not have an increased risk of ovarian cancer," says Dr. Rocca. "Women should consult with their physicians when considering the risks and benefits of prophylactic removal of the ovaries, and when considering treatment afterwards."

Genes and Environment Initiative Announces First Grants

NIH has selected the first projects to be funded as part of the Genes, Environment and Health Initiative (GEI), a unique collaboration between geneticists and environmental scientists. To identify genetic risks, researchers will use the rapidly evolving technologies used in genome-wide association studies to focus on common conditions, such as tooth decay, heart disease, cancer, and diabetes. The environmental component will begin by developing new technologies that accurately measure personal exposures with small, wearable sensors that can be used to assess environmental agents. The final component of the research strategy is to determine whether the effect of genetic variants that increase disease risk is different in the presence of environmental exposures.

In the first year, NIH will fund 8 genome-wide association studies, 2 genotyping centers, a coordinating center, and more than 30 environmental technology projects. NCI's DCCPS is the lead agency for the "Improved Measures of Diet and Physical Activity" component of the initiative.