National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
May 19, 2009 • Volume 6 / Number 10

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Cancer Research Highlights

Ginger Helps Reduce Nausea from Chemotherapy

Ginger helped prevent or reduce chemotherapy-induced nausea when taken with traditional anti-nausea drugs by patients with cancer, researchers have found. The results are from a randomized, double-blind, placebo-controlled clinical trial, the largest study to examine the potential effects of ginger on chemotherapy-related nausea. The study will be presented May 30 at the ASCO annual meeting in Orlando, FL.

“We have found that ginger supplementation is an effective tool against chemotherapy-related nausea,” said lead investigator Dr. Julie Ryan of the University of Rochester Medical Center, who discussed the findings at a press briefing last week. All doses of ginger evaluated in the study significantly reduced nausea compared with placebo, she noted.

The trial, funded by NCI’s Community Clinical Oncology Program, included 644 patients, most of them women, who were receiving chemotherapy for breast, digestive, lung, or other cancers. These patients received a placebo or one of three doses of ginger (0.5 g, 1.0 g, or 1.5 g) for 6 days, including 3 days leading up to the first day of chemotherapy and 2 days after chemotherapy began. They also received traditional anti-nausea medications during the study. Patients rated their nausea four times per day on a scale of 1 to 7.

Each dose of ginger was more effective than the placebo at mitigating nausea. The most effective doses were either 0.5 g or 1.0 g, taken during the first day of chemotherapy. Effectiveness decreased linearly over a 24-hour period. The highest dose may not be as effective, the researchers speculated, because it is more than the maximum absorption dose for biological activity.

Sentinel Lymph Node Biopsy Suitable for Staging Penile Carcinoma

A new study led by the Netherlands Cancer Institute (NKI) and published online May 4 in the Journal of Clinical Oncology confirms that sentinel lymph node biopsy (SLNB) is a valid staging option for men with early stage penile cancer.

Removal of the lymph nodes in the groin (called inguinal lymph node dissection) is often performed in patients who have early stage penile carcinoma and no obvious lymph node metastases to prevent the possible growth of undiscovered metastases. However, this procedure can cause significant long-term side effects and may be unnecessary in 75 to 80 percent of these patients.

Researchers from two institutions performed SLNB on 323 patients using a modified procedure involving ultrasound imaging and other improvements to reduce the rate of false-negative results seen in earlier studies. Lymphatic mapping after surgery to remove the primary tumor was performed 596 times (including both sides of the body in most patients). Seventy-nine groins contained a sentinel lymph node positive for tumor cells; these patients underwent immediate inguinal lymph node dissection. Patients with a negative SLNB did not have further surgery.

After a median follow-up period of 17.9 months, the overall false-negative rate was 7 percent: 6 patients with negative SLNB had an inguinal recurrence of their cancer. The researchers pointed out that no learning curve was seen when the modified procedure was introduced from the first institution to the second; the earlier procedures performed at the second institution were not more likely to produce false-negative results.

Although the authors caution that a longer follow-up time may reveal more false-negative results, they conclude that “with the use of an up-to-date protocol, sentinel node biopsy for penile carcinoma is a suitable procedure to identify patients with clinically node-negative disease who have occult metastasis…The risk of a false-negative procedure should be weighed against the morbidity of an elective inguinal lymph node dissection.”

Three Genes Help Breast Cancer Invade the Brain

Breast cancer can appear in the brain years after a tumor in the breast has been removed. This, researchers say, suggests that breast cancer cells must acquire special abilities in order to metastasize to the brain, possibly through the activation of certain genes. Three genes involved in this process in mice have now been identified by Dr. Joan Massagué of Memorial Sloan-Kettering Cancer Center (MSKCC) and his colleagues, according to a study published online in Nature on May 6.

While the research is in its early stages, the hope is that it could eventually lead to new strategies for preventing and treating brain metastases. These are needed because many women are living longer with breast cancer and, as a result, the incidence of brain metastases in breast cancer is rising.

Two of the genes, COX2 and HBEGF, were found to help breast cancer cells enter into the brain. These genes were previously found to help breast cancer cells invade the lungs. A shared mechanism underlying breast cancer’s spread to the brain and lungs may help explain why some patients develop the disease in both organs, the researchers said.

But additional mediators seem to be required to help cancer cells get across the blood-brain barrier, which prevents harmful substances from reaching the brain. A third gene, ST6GALNAC5, may offer assistance. Though the gene is normally active only in brain tissue, it appears to help breast cancer cells acquire a “coating” that allows them to cross into the brain, the researchers reported.

“The next step is to develop a better understanding of how these three genes allow the tumor cells to get into the brain,” said Dr. Paula D. Bos of MSKCC, the study’s first author. “Other genes are almost certainly involved, and we will use our model to find and evaluate them,” she added.

DEAR1 Gene May Help Drive Early-onset Breast Cancer

In a new study led by researchers at the University of Texas M.D. Anderson Cancer Center, a gene has been identified that regulates the development of the cells that form milk-secreting glands in the breast. The gene, called DEAR1, is mutated or not expressed in many cases of early-onset breast cancer, and it may also serve as a biomarker for identifying patients at high risk of local recurrence.

After using a technique called suppression subtractive hybridization to identify DEAR1 as a gene of interest, the researchers tested cell lines and tissue samples to determine its role in breast cancer. Expression of DEAR1 was absent or reduced in six out of eight breast cancer cell lines examined; in addition, 13 percent of 55 primary breast tumor samples tested contained DEAR1 mutations.

The researchers used gene-transfer techniques to restore DEAR1 expression in a breast cancer cell line. Without DEAR1, over 60 percent of the cultured cells formed large, disorganized structures. With the introduction of DEAR1, more than 80 percent of cells produced small, normal-shaped structures. When the gene was silenced in normal breast cells, they failed to form normal structures and instead showed morphology similar to breast cancer cells.

The researchers screened tissue samples from 158 premenopausal women with breast cancer and found that 56 percent of the tumor samples had completely lost DEAR1 expression, noting that this “correlated with a strong family history of breast cancer in this young cohort.” Loss of DEAR1 expression also correlated significantly with triple-negative breast cancer, which is the most difficult type to treat successfully.

Because DEAR1 expression was also a significant prognostic marker for local recurrence in early-onset tumors, the authors suggested that measurement of DEAR1 expression “could be an important marker to stratify early-onset breast cancer patients for increased vigilance in follow-up and adjuvant therapy.”

Formaldehyde May Cause Some Blood Cancers, but Risk Drops over Time

Follow-up data from an ongoing study of U.S. industrial plant workers exposed to formaldehyde support previous findings of a possible link between formaldehyde exposure and risk of death from cancers of the blood and lymphatic system. The latest report by NCI researchers, which appeared online May 12 in the Journal of the National Cancer Institute, includes data through 2004, extending the previous observation period by 10 years.

Since the 1980s, researchers from NCI’s Division of Cancer Epidemiology and Genetics have studied a cohort of 25,619 people who worked in 10 formaldehyde-using or -producing plants before 1966. The researchers estimated formaldehyde exposure among the workers by a number of methods, including the use of monitoring data and information about individual jobs. Death certificates and the National Death Index were used to record mortality and the cause of death.

Their analysis showed that, overall, those who were exposed to formaldehyde had a risk of death from all causes that was similar to that of the general U.S. population. However, workers with highest peak exposure to formaldehyde had a statistically significant relative risk (RR) of 1.37 for death from blood or lymph cancer compared with those at the lowest level of peak exposure. This represents an excess risk of death from several specific cancers, including Hodgkin lymphoma, multiple myeloma, and myeloid leukemia—the type most often associated with chemical exposure. The observed increase in risk of death from myeloid leukemia was 1.78, and 1.42 for all leukemias. The highest level of increased risk of death from myeloid leukemia in this study occurred early on and has been declining steadily over time. This pattern could be due to chance, but the investigators note that similar risk patterns over time have been seen for agents that are known to cause leukemia relatively soon after exposure.

The relationship was observed only for those who had been exposed to formaldehyde at the highest level of peak exposure relative to members of the cohort who had minimal exposure. There were no significant relationships observed when exposure was classified using average-intensity or cumulative exposure.

ALSO IN THE NEWS

Canary Foundation and NCI Team up to Fund Lung Cancer Research

The nonprofit Canary Foundation and NCI’s Early Detection Research Network (EDRN) recently announced a new funding partnership to find biomarkers to detect early stage lung cancer in people who have never smoked. Researchers at five institutions in the United States will use this new funding initiative to study cell lines, tissue, and blood samples from such people who developed the disease. The EDRN and Canary Foundation are each providing initial funding of $1 million for the initiative. More information, including a list of the funded projects, is available online.

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