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Genetic Study Finds Clue to Gastrointestinal Stromal Tumors

Posted Oct 04 2010 9:00pm

Less-invasive Lymph Node Surgery Safe for Women with Breast Cancer

In the largest randomized surgical trial in breast cancer patients to date, women with biopsies that detected no cancer cells in their sentinel lymph nodes (SLN) who forwent axillary lymph node dissection (ALND) had the same overall survival 8 years after treatment as women who had ALND. The trial results were reported online September 20 in Lancet Oncology.

Researchers led by Dr. David Krag of the University of Vermont enrolled 5,611 women between 1999 and 2004 in the NSABP B-32 trial , which was designed to test whether women with negative SLN biopsies would have the same survival as women who had negative SLNs followed by ALND, a more invasive procedure that carries a greater risk of side effects including lymphedema and nerve damage. The women studied were randomly assigned to undergo SLN surgery plus ALND (group 1), or SLN surgery followed by ALND only if cancer cells were detected in the sentinel nodes (group 2).

A total of 3,986 patients had no apparent cancer cells in their sentinel lymph nodes. After 8 years of follow-up, 54 women in group 1 had a local recurrence of their cancer, compared with 49 women in group 2. Eight women in group 1 had cancer recur in the lymph nodes closest to the site of surgery (the regional lymph nodes), compared with 14 women in group 2. The estimated 8-year overall survival was 91.8 percent in group 1 and 90.3 percent in group 2. These differences were not statistically significant .

In an accompanying editorial , Dr. John Benson of the University of Cambridge in the United Kingdom explained that more than 80 percent of the women in the trial had small tumors (2 centimeters or less in diameter), which tend to have a lower risk of recurrence. Therefore, “the conclusions of this trial in terms of the appropriateness, safety, and effectiveness of SLN biopsy are justified for this population but might not necessarily apply to patients with larger…or multifocal tumors who commonly undergo SLN biopsy,” he cautioned.

HPV Screen-and-Treat Methods Prevent Cervical Cancer Precursors in Low-resource Settings

Women who were treated with cryotherapy immediately after testing positive for high-risk human papillomavirus (HPV) DNA or who had precancerous lesions detected by visual inspection of the cervix had large and statistically significant reductions in high-grade cervical cancer precursors compared with women who did not have immediate treatment, researchers from Columbia University recently reported. The long-term results of the randomized screening trial were reported online September 30 in the Journal of the National Cancer Institute.

A research team led by Dr. Thomas Wright, Jr., followed 6,637 South African women between the ages of 36 and 65. Cervical samples from all women were tested for the presence of high-risk HPV DNA; all women also underwent visual inspection of the cervix. The women were then randomly assigned to one of three study groups: DNA test-and-treat, in which women with an HPV-positive DNA test were treated with immediate cryotherapy; visual inspection-and-treat, in which women with precancerous lesions were treated with immediate cryotherapy; or control, in which further evaluation and treatment were delayed for 6 months. All women had colposcopy with biopsy at 6 months, and a subset of women, including all of those who were HPV positive or visual-inspection positive at study entry, were followed for 36 months.

After 36 months, the cumulative risk for advanced cervical lesions ( CIN 2+) was 73 percent lower among women in the DNA test-and-treat arm than in women in the control arm. By comparison, the risk of advanced lesions was reduced by 32 percent in the visual inspection arm compared with the control arm.

“These results suggest that cryotherapy may have long-term implications for low-resource settings where it is difficult and costly to re-screen women at regular intervals,” the researchers wrote.

The researchers also observed an increase in HIV infection in women in both screen-and-treat groups compared with women in the control group. However, this increase was not statistically significant. The authors recommended that this association be carefully evaluated in screen-and-treat programs conducted in settings where the incidence of HIV infection is high.

In an accompanying editorial , Drs. Julia Gage and Philip Castle of NCI’s Division of Cancer Epidemiology and Genetics noted that although there is an HPV vaccine , it will be decades before the vaccine will have an impact on cervical cancer rates globally, making screen-and-treat approaches a valuable tool for preventing cervical cancer in some areas of the world.

“Screening women with simpler, more robust technologies and immediately treating those who screen positive can reduce the incidence of cervical cancer in the population,” said Dr. Castle. “That’s the kind of approach we need in a developing country where resources for prevention programs are limited.”

Black Patients with Advanced Cancer Are More Likely to Receive Unwanted Care at End of Life

Compared with black patients who have advanced cancer, “white patients appear to have undefined advantages when it comes to receiving end-of-life care that reflects their values,” concluded the authors of a prospective longitudinal cohort study. Findings from the study, which was carried out at a number of hospitals and major cancer centers in the Northeast and in Texas, were published September 27 in the Archives of Internal Medicine.

The researchers found that, although black patients discussed end-of-life issues with their doctors as often as white patients, black patients were more likely to prefer life-prolonging care and less likely to have do-not-resuscitate (DNR) orders after the discussions. Moreover, black patients with DNR orders were just as likely as black patients without DNR orders to receive life-prolonging end-of-life care.

Between 2002 and 2007, Dr. Jennifer W. Mack of the Dana-Farber Cancer Institute and her colleagues interviewed 71 black and 261 white patients who were enrolled in the Coping with Cancer Study . All of the patients had metastatic cancer and were no longer responding to chemotherapy, and all of the patients died during the course of the study.

Through interviews, the researchers established the extent to which patients had discussed end-of-life issues with their doctors, their awareness of terminal illness, whether they had DNR orders, and whether they preferred life-prolonging care at the end of life, even if it would cause more pain and discomfort, or symptom-directed care (relief of pain and discomfort only). What actually happened at the end of life was gleaned from medical records and caregiver interviews.

The researchers noted that issues beyond patient–physician communication, such as continuity of care or preconceived notions among health care providers about patient preferences, could explain the racial disparity in the translation of preferences into the actual care received at the end of life. “These issues should remain a topic of ongoing research and a priority for physicians who care for patients at the [end of life],” they concluded.

Genetic Study Finds Clue to Gastrointestinal Stromal Tumors

Researchers have identified a gene called ETV1 that may contribute to the development of some types of gastrointestinal stromal tumors (GISTs). Although preliminary, the findings suggest that ETV1 could be a marker for diagnosing the disease and may also be a potential therapeutic target. Drs. Charles Sawyers of Memorial Sloan-Kettering Cancer Center (MSKCC) and C. David Allis of Rockefeller University and their colleagues reported their findings online in Nature on October 3.

The researchers discovered the gene while searching gene expression data sets for GIST-specific genes. Among 11 such genes that appeared in three data sets was ETV1, which is a member of the ETS family of transcription factors—genes that regulate the activity of other genes. This gene was of immediate interest because overexpression of other ETS transcription factors has been associated with prostate and other cancers. ETV1 was highly active in all the GIST tumor samples and cell lines they examined and in the cells where these tumors may originate. Further experiments then showed that ETV1 was essential for the growth and development of GISTs.

In addition, the researchers found that the transcription factor may cooperate with the product of the KIT gene in the development of GIST. Most GISTs harbor mutations that activate KIT, but these mutations alone are not sufficient to cause GIST. The reason could be that KIT mutations promote the development of cancer only in the presence of high levels of ETV1 expression, according to co-author Dr. Yu Chen of MSKCC.

“These findings establish an oncogenic role for ETV1 in GIST,” the authors concluded. Although transcription factors have been considered “undruggable,” recent studies have begun to challenge this idea, they noted.

See: New Drug Blocks “Undruggable” Target in Cancer Cells


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