NCI Cancer Bulletin: A Trusted Source for Cancer Research NewsNCI Cancer Bulletin: A Trusted Source for Cancer Research News
September 14, 2004 • Volume 1 / Number 35 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Cancer Research HighlightsCancer Research Highlights

Differences in Long-Term Outcomes after Prostate Cancer Treatments

Five years after treatment with radical prostatectomy or external beam radiotherapy (EBRT) for localized prostate cancer, men continue to live with the treatment's effects on their quality of life, according to NCI scientists. In the September 15 Journal of the National Cancer Institute, Dr. Arnold L. Potosky and colleagues from NCI's SEER Program published a study on quality of life outcomes after prostate cancer treatment.

Using survey data collected from more than 1,100 men enrolled in the Prostate Cancer Outcomes Study (PCOS), begun in 1994, researchers analyzed long-term side effects for men treated either with radical prostatectomy or EBRT. They found that at 5 years after baseline diagnosis, overall sexual function, including libido, frequency, and potency, declined to a similar level in both treatment groups. Erectile dysfunction and incontinence were reported more frequently in the radical prostatectomy group at 5 years, while bowel urgency and hemorrhoids were cited more often in the EBRT group.

The authors note that "because there is continuing uncertainty about the superiority of any single treatment strategy for clinically localized prostate cancers...patient preferences for outcomes among competing treatment strategies may be an important factor that drives treatment decisions." Although this study compared surgery with EBRT, the authors identified the need for additional prospective research using population-based samples comparing complications from all available treatments, including radioactive seed implants and hormonal therapy.

Chromosome Regions Linked to Prostate Cancer

An international team of researchers has identified chromosome regions that may be related to prostate cancer susceptibility, according to a paper in the August 18 Journal of the National Cancer Institute. Using genome-wide scanning techniques, the NCI-funded study analyzed blood samples from families with a high incidence of prostate cancer.

Previous studies have shown that some genes may increase susceptibility for prostate cancer, but were unable to pinpoint the exact genes or chromosome regions responsible due to small sample sizes, heterogeneity, environment-induced cases, and other factors.

To address these issues, Dr. Jeffrey Trent of the Translational Genomics Research Institute and colleagues conducted a genetic mapping study of 426 families from 4 existing hereditary prostate cancer studies. Dr. Trent's team primarily used nonparametric multipoint linkage analysis, grouping families with similar clinical and demographic backgrounds to limit heterogeneity. They found one chromosome region, 17q22, that was strongly linked to prostate cancer. Through stratified analysis, other regions were shown to possibly be linked.

"The large number of...families in our study will make it possible to test for gene-gene interactions in future linkage analyses," the authors wrote. They added that "results of this large genome-wide scan for prostate cancer susceptibility genes provide a basis for renewed interest, excitement, and confidence in genetic linkage studies of prostate cancer."

CDKN2A Mutation May Increase Risk of Pancreatic Cancer

CDKN2A is the major known melanoma susceptibility gene, but a recent study that looked at prospective risk of cancers other than melanoma found that CDKN2A mutations could also increase the risk of pancreatic cancer. The study, which appeared in the June 2004 Journal of Medical Genetics, was conducted by Dr. Alisa Goldstein and colleagues in the Division of Cancer Epidemiology and Genetics at NCI. While most previous studies used family mutation status, this study used individual mutation data in estimating risk.

The authors determined the status of the CDKN2A gene in 253 individual family members from 15 families known to carry hereditary CDKN2A mutations; 117 individuals tested positive for the mutation (carriers) and 136 tested negative for the mutation (noncarriers). The researchers then compared the cancer incidence between the two groups, using the expected incidence rates for the general population as a baseline.

Twelve mutation carriers developed a cancer other than melanoma during the study period, compared with only two cancers among the noncarriers. Pancreatic cancer (four cases among carriers) was the most predominant, and since the expected number within the general population is only 0.1 cases, these data suggest that the risk of developing pancreatic cancer is significantly increased in individuals who carry the CDKN2A mutation. "However," said the authors, "we cannot yet identify any specific genotypes that predispose individuals to pancreatic cancer."

The authors cautioned that the sample size was limited, so studies with more individuals and a broader spectrum of CDKN2A mutations are required. Also, while nonmelanoma cancers were the focus of this study, there were 49 cases of melanoma and 14 melanoma deaths among the carriers during the study period. "Melanoma remains the major contributor to morbidity and mortality in these subjects," noted the authors.

New Therapy Tested for Metastatic Breast Cancer Tumors

Scientists from NCI's Center for Cancer Research have investigated an alternative treatment for metastatic breast cancer patients. This therapy - allogeneic hematopoietic stem-cell transplantation (HSCT) - has been used to treat other blood cancers such as leukemia, but has been viewed with caution because of significant morbidity and mortality rates. However, recent advances in reduced intensity transplant conditioning regimens have been associated with decreased toxicity and raise the possibility of using allogeneic HSCT as a treatment option. In a study reported in the August 16 online Journal of Clinical Oncology, researchers investigated whether allogeneic HSCT could serve as a treatment for patients with metastatic breast cancer.

Between May 2000 and April 2003, 16 metastatic breast cancer patients were enrolled in the study. The patients underwent a reduced-intensity transplant conditioning regimen before the allogeneic HSCT treatment. Overall, six partial responses and four minor responses were observed after donor lymphocytes were given after the transplant. For all 16 participants, the median overall survival time was 10.3 months.

While these results suggest that metastatic breast cancer may be treated using allogeneic HSCT, it is not an ideal treatment option in its current form. The authors caution that, "The observations of late tumor regressions in this trial suggest that immune-mediated responses against breast cancer are possible. The clinical question that remains is how to optimally and safely exploit the responses seen with allogeneic cellular therapy for metastatic breast cancer in the context of currently available treatments."

Two Studies Implicate Rho and TrkB Genes in Metastasis

One of the most insidious traits of cancer cells is their ability to metastasize, or break away from, a primary tumor and spread through the entire body. A pair of recent studies now shows some of the mechanisms underlying metastasis - demonstrating how cancer cells can detach from their moorings and then survive when removed from the host tissue.

Most attached cells die when they become dislodged from their matrix, a process known as anoikis. Many cancer cells can survive, however, which allows them to invade foreign tissues. As reported in the August 26 Nature, Dr. Daniel S. Peeper and colleagues at the Netherlands Cancer Institute found a gene - TrkB - that renders cells anoikis-resistant. The main role of this gene is to promote the growth and survival of neural cells. When expressed, TrkB can activate a series of enzymes, including the PI3 kinases that prevent a cell from destroying itself through apoptosis.

While Dr. Peeper's findings help explain how detached cancer cells can survive, a study in the August 24 Proceedings of the National Academy of Sciences explains how some cancer cells can break off from their host tumors in the first place. Dr. Edward Bonder and colleagues at Rutgers University found that overexpression of the Rho gene can lead to improper orientation of the mitotic spindle during cell division. As a result, some of the newly formed daughter cells may not properly adhere to the cell matrix when cell division is complete, enabling them to subsequently detach.

Taken together, these two studies provide a possible scenario of metastatic initiation. Joint expression of Rho and TrkB could cause some of the rapidly dividing cells in a tumor to slough off and survive long enough to find a new home.