Breast Cancer Relapse Risk Low after Chemotherapy or Tamoxifen
Relatively few breast cancer survivors who are disease-free for 5 years after starting a systemic adjuvant therapy such as chemotherapy or tamoxifen experience a recurrence, but preventive treatments are needed to reduce the relapse rate further, according to a study published online August 11 in the Journal of the National Cancer Institute.
Dr. Abenaa Brewster of the University of Texas M.D. Anderson Cancer Center and her colleagues tracked breast cancer recurrence in 2,838 women treated with chemotherapy, tamoxifen, or both, between 1985 and 2001. The disease recurred in 7 percent of survivors diagnosed with stage I breast cancer, 11 percent of women treated for stage II disease, and 13 percent of women with stage III disease.
Along with stage of cancer, tumor grade, hormone-receptor status, and endocrine therapy were associated with risk of recurrence. Overall, however, 89 percent of the study population did not experience a recurrence at 5 years (approximately 10 years after a woman's initial diagnosis), and 80 percent did not experience a recurrence at 10 years (approximately 15 years after diagnosis).
While the overall results should be encouraging for patients, the study also highlighted the need to develop risk-reduction strategies for premenopausal breast cancer survivors, the researchers note. Extended adjuvant therapy with letrozole (Femara) is available for postmenopausal women with hormone receptor-positive tumors who have completed 5 years of tamoxifen therapy. But nothing similar is available for premenopausal women.
A limitation of the study is that it did not include women who received adjuvant therapy with trastuzumab (Herceptin) or 5 years of an aromatase inhibitor. Data were not available on HER2/neu status, and few women in the group received an aromatase inhibitor.
Novel Monoclonal Antibody Effective in Some Relapsed NHL Patients
Treatment with a novel type of monoclonal antibody that attracts powerful immune-system cells to cancer cells has caused tumor shrinkage and disease remission in some patients with non-Hodgkin lymphoma (NHL) who had relapsed after previous treatments, according to the results of a phase I clinical trial.
Published August 15 in Science, the results from these 38 patients show that small doses of the bispecific T-cell engager (BiTE) antibody, called blinatumomab, not only induced partial and complete responses in some patients, but could eliminate cancer cells in the bone marrow, thought to be an important source of NHL relapse. Overall, the seven patients treated with the highest dose used in the trial had tumor regression, wrote the study's lead author, Dr. Ralf Bargou from the University of Wurzburg in Germany, and colleagues. Disease regression in one patient has lasted longer than 13 months, and three others have had regressions that lasted 6 months or longer. "No relapse has thus far been observed in responding patients treated with blinatumomab at dose levels of 0.03 and 0.06 mg/m² per day," the study authors wrote.
The antibody works by attaching to target cells - in this case, lymphoma cells - and then attracting T cells that then become activated and destroy cancer cells via a process known as lysis. Blinatumomab was developed by Bethesda, MD-based Micromet Inc., and is being taken through clinical testing in conjunction with another Maryland-based biotechnology company, MedImmune.
The doses used in the trial, explained study co-author and Micromet Chief Scientific Officer Dr. Patrick Baeuerle, "are approximately five orders of magnitude lower than serum levels needed by conventional monoclonal antibodies for achieving tumor regression in this disease. This may relate to the high anti-tumor activity of cytotoxic T cells recruited by blinatumomab."
Several other BiTE antibodies are in early clinical testing for other cancer types.Cord-Blood Transplant into Bone Restores Blood Counts
In a preliminary clinical trial, most patients with acute leukemia who received a cord-blood stem cell transplant through an injection directly into the iliac crest of the pelvic bone, experienced complete hematologic recovery - a restoration of normal white blood cell and platelet counts, produced by the donor stem cells - within an average of 36 days.
Previous clinical trials testing cord-blood stem cells delivered intravenously have shown that intravenous transplants fail in about 20 percent of patients. The current trial, published online August 9 in Lancet Oncology, tested whether cord-blood transplantation (which provides a lower number of stem cells than bone-marrow transplantation) would be safe and more successful if delivered directly into the bone marrow, where blood cells form.
The investigators, led by Dr. Francesco Frassoni of San Martino Hospital in Genoa, Italy, enrolled 32 patients who were eligible for bone-marrow transplantation but could not find an HLA-matched donor. After conditioning chemotherapy with or without radiation, all patients received a cord-blood transplant into the left iliac crest, the right iliac crest, or both sites. All patients received immunosuppressive drugs to prevent graft-versus-host disease (GvHD).
Four patients died within 12 days of the transplant, and one patient died 30 days after the procedure, before platelet restoration. The remaining 27 patients regained normal blood counts, regardless of whether they received the injection in one or both sites, and 45 percent survived at least 1 year after transplantation. Other studies using intravenous transplantation have shown platelet recovery rates of only 40 percent to 70 percent at 100 days after transplantation.
None of the participants developed high-grade acute GvHD. Other studies have shown the incidence of GvHD with intravenous cord-blood transplant to be between 35 percent and 45 percent.
The authors caution that their findings will need to be confirmed in larger studies that follow patients for a longer period of time.
Esophageal Adenocarcinoma Rates Rise in Men and Women
A new study confirms that the incidence of esophageal adenocarcinoma has risen over the last 3 decades in white men in the United States, and it indicates a similar increase in incidence among white women. Esophageal cancer is still fairly rare, however, with projections of fewer than 16,500 new cases in 2008.
The study - conducted by NCI researchers using information in the Surveillance, Epidemiology, and End Results (SEER) database from nearly 23,000 white patients diagnosed with esophageal cancer between 1975 and 2004 - showed that incidence of esophageal adenocarcinoma has increased by more than 460 percent in white men and 335 percent in white women. The number of esophageal adenocarcinoma diagnoses among African Americans and those of other races in the registry was too low to conduct a meaningful analysis, noted Dr. Linda Morris Brown and colleagues from NCI's Division of Cancer Epidemiology and Genetics online August 11 in the Journal of the National Cancer Institute.
The increased incidence spanned all ages and stages of disease, they found. "However, the rate of increase may be slowing, especially for localized disease," they continued, "indicating that the overall increase in adenocarcinoma incidence is unlikely to reflect heightened surveillance and earlier diagnosis."
Findings from previous studies, they noted, "indicate that increases in obesity, particularly abdominal obesity, may account for part of the upward trend in the incidence of adenocarcinoma." Obese individuals are more prone to developing gastroesophageal reflux disease, a well-established risk factor for esophageal adenocarcinoma, which is also on the rise in the United States. The decreasing frequency of infections with the bacterium Helicobacter pylori, which may provide some protection against a precursor condition for esophageal adenocarcinoma known as Barrett esophagus, may also play a role, they wrote.
Suicide Risk Higher in Cancer Patients than the General Population
The incidence of suicide among U.S. cancer patients is nearly twice that of the general population, and suicide rates vary among patients with cancers of different anatomic sites, according to a study published online August 11 in the Journal of Clinical Oncology (JCO). The risk remained elevated for as long as 15 years after diagnosis.
Researchers from the University of Washington analyzed Surveillance, Epidemiology, and End Results (SEER) data from nearly 3.6 million patients diagnosed with cancer from 1973 to 2002. They compared those data, which included 5,838 suicides, with data from the U.S. general population collected by the National Center for Health Statistics. The cancer patients had an adjusted rate of 31.4 suicides per 100,000 person-years, compared with 16.7 suicides in the general population. Suicide rates were particularly high for cancers of the lung/bronchus (81.7), stomach (71.7), oral cavity/pharynx (53.1), and larynx (46.8).
Two other studies that examined the association between cancer and suicide appear in the same issue of JCO. The second study, using data from Medicare patients in New Jersey, found that the "risk of suicide in older adults is higher among patients with cancer than among patients with other medical illnesses, even after psychiatric illness and the risk of dying within a year were accounted for." A third study of cancer center patients in Edinburgh, United Kingdom, found, "A substantial number of cancer outpatients report thoughts that they would be better off dead or had thoughts of hurting themselves."
In an editorial, Dr. Timothy Quill of the University of Rochester Medical Center, noted, "What is interesting and potentially important about the studies is that these thoughts about suicide and the associated risk factors that are relatively well known for terminally ill patients may be just as important for those patients with cancer who are survivors or are living with the disease."
Vitamin C Injections Slow Tumor Growth in Mice
Injecting high doses of vitamin C into mice with aggressive cancers slowed the growth of their tumors significantly without affecting normal tissues, researchers are reporting. While the potential anticancer effects of vitamin C (also known as ascorbate or ascorbic acid) have been studied for decades, the new findings provide "a firm basis" for advancing vitamin C as a pharmacologic agent for treating human cancer, they write in the August 5 Proceedings of the National Academy of Sciences.
To test vitamin C injections, Dr. Mark Levine of the National Institute of Diabetes and Digestive and Kidney Diseases and his colleagues delivered high doses of ascorbate into the veins or abdominal cavities of mice with aggressive forms of brain, ovarian, and pancreatic tumors. The injections reduced tumor growth by approximately half compared with xenografts in untreated mice.
The delivery method appears to be critical for efficacy. When vitamin C is taken orally, the body prevents blood levels of ascorbate from exceeding a narrow range. This may explain why two previous NCI-sponsored clinical trials found no survival benefit from vitamin C given orally. Although scientific interest in vitamin C for cancer diminished after the second study appeared in 1985, some complementary and alternative medicine practitioners have continued to administer high doses of ascorbate to cancer patients.
The new findings suggest that hydrogen peroxide formation, a result of the ascorbate treatment, is responsible for the anticancer activity. Thus, the study provides a much-needed biological rationale for testing the strategy in patients, notes an accompanying editorial.
The vitamin C treatments did not cure the mice, so the study authors suggested that high doses of intravenous ascorbate should be studied in combination with other cancer therapies in humans.