New Metastatic Breast Cancer Treatments Improved Survival Over Time

A Canadian population-based study, published online July 23 in Cancer, found that survival among women diagnosed with metastatic breast cancer (MBC) in British Columbia has improved over the past decade, and that this appeared to be related to the introduction of several new therapeutic agents for MBC during the 1990s.

Researchers from the British Columbia Cancer Agency (BCCA) analyzed data from 2,150 women in the Canadian province who were diagnosed and treated in 1 of 4 "time cohorts" spanning the 1990s. The earliest cohort (1991-1992) was the baseline, while subsequent cohorts were matched against the introduction of new agents for MBC: (1994-1995) paclitaxel and vinorelbine; (1997- 998) aromatase inhibitors and docetaxel; and (1999-2001) trastuzumab and capecitabine.

"There was a significant improvement in survival for women with MBC over time," the scientists reported. "Although there was no difference between the first two cohorts, the later two cohorts had significant improvements in overall survival." The median survival for patients in cohorts 1 through 4 was 436 days, 450 days, 564 days, and 661 days, respectively. "Survival of women who were diagnosed with MBC in [British Columbia] in the later part of the 1990s improved by approximately 30 percent compared with a similar cohort of women who were diagnosed in the early and middle parts of the 1990s," they added.

"Although MBC still is an incurable disease, this study provides optimism for those women who are diagnosed with MBC today and should provide enthusiasm and evidence that continued research to discover better therapies may translate into further improvements in outcome in the future," they concluded.

"Tumor Paint" May Improve Excision of Multiple Tumor Types

Researchers from Fred Hutchinson Cancer Research Center and collaborators in Seattle have developed a fluorescent bioconjugate that targets numerous tumor types with high resolution. The details of their study appeared July 15 in Cancer Research.

The researchers called their molecule "tumor paint," building it from chlorotoxin, a scorpion venom protein that is nontoxic in mammals and has been shown to target glioma cells, and Cy5.5, a molecule that emits fluorescent light without requiring enzymatic cleavage within the cell and with minimal light absorption by water or hemoglobin.

After administering an early version of tumor paint to mice, the researchers found that adding Cy5.5 to chlorotoxin improved its tumor-targeting ability. "The resolution of cancer foci from normal tissue under simulated operating conditions was exquisite," down to the level of a few hundred cells, they wrote.

The researchers suspect the specific target of the chlorotoxin on the cell membrane may be matrix metalloproteinase-2 (MMP-2). They transfected cells that failed to bind to tumor paint with plasmids containing MMP-2 and found that this facilitated attraction. Microscopy showed that the tumor paint and the MMP-2 clustered within the transfected cells. However, pull-down assays were unable to show a direct bond between MMP-2 and tumor paint, and other experiments were unable to show an enzymatic relationship between them.

Algorithm Predicts Response to Anticancer Drugs

A team led by researchers from the University of Virginia at Charlottesville has developed an algorithm that uses comparative microarray data and responses of a panel of 60 human cancer cell lines maintained by NCI (NCI-60 panel) to anticancer drugs to predict responses in other cell lines and in human tumors. The study, published in the July 24 Proceedings of the National Academy of Sciences, then used the algorithm to identify experimental compounds with potential activity against bladder cancer.

The algorithm, called COXEN, consists of several steps: determining a drug's molecular activity in a first set of cells (in this case, the NCI-60 panel); measuring the normal molecular characteristics of those cells; identifying which molecular characteristics most accurately predict the drug's activity; measuring those characteristics in a second set of cells; identifying a subset of molecular characteristics that shows a pattern of coexpression between the two cell sets; then predicting the drug's activity in the second set based on its activity in the first set and the molecular characteristics shared between the two.

When tested using a panel of 40 human bladder cancer cell lines (BLA-40) as the second set of cells, COXEN significantly predicted response of BLA-40 to the drugs cisplatin and paclitaxel. The researchers then modified the algorithm to test whether it could predict in vivo response in human tumors from the NCI-60 in vitro data. When comparing NCI-60 molecular characteristics with microarray data from two breast cancer clinical trials, one of docetaxel and one of tamoxifen, COXEN significantly predicted clinical response to both drugs.

Finally, the investigators used COXEN to predict chemosensitivity patterns of BLA-40 cells to 45,545 experimental compounds screened using the NCI-60 panel. They identified eight compounds to which more than 50 percent of BLA-40 cells were predicted to be sensitive, thereby finding possible candidates for early clinical trials.

The investigators, which include John N. Weinstein of NCI's Center for Cancer Research, caution that "our COXEN approach needs to be further validated before it is applied in clinical practice." They will make the algorithm available to the scientific community at http://www.coxen.org in September, 2007. The NCI-60 microarray data are at http://discover.nci.nih.gov.

SPORE Investigators' Meeting Highlights Upcoming Program Changes

On July 7-10, NCI hosted the 15th Annual Investigators' Workshop for the Specialized Programs of Research Excellence (SPOREs) translational research grants which are designed to help participating cancer centers move basic research findings from the laboratory to clinical settings as rapidly as possible. NCI currently funds 57 SPORE grants covering 14 cancer types.

The 2007 investigators' workshop gave SPORE researchers working on the same cancer type a chance to share results and pursue opportunities for collaboration. A special session on Saturday focused on the challenges found in using biomarker evidence in translational research, including tissue acquisition and sample size requirements for clinical trials, methods for quality assurance, and validation of the clinical utility of a potential biomarker.

The theme of collaboration grew in importance this year, as the SPORE program readies itself for a major programmatic shift. Instead of keeping the focus of the SPOREs on the 14 current cancer types, explained Dr. Jorge Gomez, chief of NCI's Organ Systems Branch, beginning in 2008 competition for the grants will be open to any type of cancer.

"The program has been and remains very popular," said Dr. Gomez. "Many groups want to compete and participate." He hopes that the increased competition will encourage collaborators from different institutions to apply together for a single SPORE grant, instead of the majority of applications coming from single institutions as they do now.

Breast Cancer Survivors Test Diet High in Fruits, Veggies

Women who adopted a low-fat diet that was very rich in vegetables, fruit, and fiber after treatment for breast cancer did not reduce their risk of recurrence compared with similar women who consumed 5 or more servings of fruits and vegetables a day. After 7 years, both groups of women had essentially the same risk of recurrence, incidence of new primary breast cancers, and risk of overall mortality.

Even women whose diets at baseline were low in fruits, vegetables, or fiber or high in fat did not appear to benefit from the intervention, according to findings in the July 18 Journal of the American Medical Association (JAMA). The results are from the Women's Healthy Eating and Living (WHEL) study, a randomized controlled trial that included 3,088 women who were treated for early-stage breast cancer.

The researchers caution against applying their findings to populations beyond those in the study, which included women who had completed their initial therapy and excluded women diagnosed after age 70. The findings appear to be at odds with interim results from the Women's Intervention Nutrition Study (WINS), which suggest that a low-fat diet may help prevent breast cancer recurrence in some women.

Different patterns of weight gain and loss between the trials may account for some of the varying results, according to an editorial in JAMA. Women in both arms of the WHEL trial on average gained weight, whereas women in the intervention arm of WINS lost weight. New studies that assess interventions based on physical activity and energy intake for breast cancer survivors are warranted, the editorial concludes.