National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
May 4, 2010 • Volume 7 / Number 9

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Cancer Research Highlights

Breast Tissues May Express Biomarkers Linked to DCIS Recurrence

Biomarkers found in the breast tissue of women with ductal carcinoma in situ (DCIS) may predict subsequent risk of DCIS recurrence and invasive breast cancer, according to a report online April 28 in the Journal of the National Cancer Institute. “Interestingly, the combinations that predicted subsequent [invasive breast cancer] were different from those that predicted DCIS,” wrote Dr. D. Craig Allred from the Washington University School of Medicine in St. Louis in an accompanying editorial.

Using SEER data, researchers from the University of California, San Francisco, and the San Francisco Veterans Affairs Medical Center identified 1,162 women who had originally been treated by lumpectomy alone for DCIS between 1983 and 1994 at 63 hospitals in the Bay area. After an average of 7.5 years, 838 had no recurrence, while 170 had developed invasive breast cancer and 154 had their DCIS recur. Tissue samples preserved from their original lumpectomies were tested for a number of histopathologic characteristics and molecular markers that have since been associated with breast cancer.

The researchers found that 28 percent of the women expressed three key markers: p16, Ki67, and COX-2. The 8-year risk for invasive breast cancer in these women was 19.6 percent, compared with 4.1 percent when those markers were negative.

The factors associated with greater risk of DCIS recurrence were positive or uncertain surgical margins and two different sets of markers: 1) p16 positive, Ki67 positive, and COX-2 negative, or 2) estrogen receptor negative, Ki67 positive, and human epidermal growth factor receptor-2 positive. In addition to these marker combinations, consistent with other studies, the 15–20 percent of women whose DCIS lesions were detected by palpation had a higher risk of invasive breast cancer than did those whose lesions were detected by mammography.

“The mode of detection and the biomarkers p16, COX-2, and Ki67 may be used to help stratify a woman’s risk of subsequent invasive cancer and to help her decide whether she should undergo adjuvant therapies,” wrote lead author Dr. Karla Kerlikowske and colleagues.

A number of limitations to this study, however, were noted by the authors and Dr. Allred, including the fact that the treatment regimen received by women who were included in the study—lumpectomy alone—would be uncommon in current medical practice.

Circulating Tumor Cells Detected in Patients with Localized Cancers

Researchers from Massachusetts General Hospital (MGH) have isolated tumor cells circulating in the blood of patients with localized prostate cancer as well as from patients with advanced disease. The researchers were then able to characterize genetic changes in these circulating tumor cells (CTCs), which they stressed was an important step toward potentially using CTCs to guide the selection of therapies and improve patient care. The findings appeared in the March 31 Science Translational Medicine.

The discovery of CTCs in men with localized disease was unexpected, but this may simply have been because until now the technology had not been sensitive enough to capture the cells in patients with early-stage disease, noted one of the lead authors, Dr. Sunitha Nagrath of MGH and Harvard Medical School.

She presented the study’s findings at the recent American Association for Cancer Research annual meeting in Washington, DC. At the same meeting, researchers from Ohio State University presented a poster about a new way to detect CTCs in patients with breast cancer. They also found the cells in women with localized disease.
 
“We develop our notions about the nature of CTCs based on the existing technologies, but advances in technology can change these assumptions,” said Dr. Nagrath. “What we have found until now is only the tip of the iceberg. We believe these cells have tremendous potential not only for diagnostic purposes and early detection, but also to noninvasively monitor patients and the effectiveness of treatments over time, enabling targeted therapeutic treatments in the new era of personalized medicine.”

Although the MGH technology, a microfluidic device called a CTC chip, is not ready for clinical use, the researchers are enrolling 200 patients with various stages of prostate cancer in a clinical trial. The trial will evaluate the prognostic and predictive value of monitoring these rare cells as a kind of “liquid biopsy” in patients.

Of particular interest will be whether CTCs can help solve one of the major problems in managing prostate cancer—the inability to distinguish patients with early-stage disease who need aggressive treatments from those who do not.

Costs and Use of Diagnostic Imaging Rise among Medicare Patients

The use of diagnostic imaging in older cancer patients has increased rapidly, and the expense of these procedures has grown at a rate faster than the overall rate of increase in cancer care costs, according to researchers at the Duke Clinical Research Institute. Their report appeared in the April 28 Journal of the American Medical Association.

Most patients with cancer are enrolled in Medicare. The study used claims from a 5 percent sample of Medicare beneficiaries to identify 100,954 cancer patients between 1999 and 2006 and measured imaging use for a period of up to 2 years after diagnosis. The researchers selected a sample of patients with major cancers for which diagnostic imaging is commonly used––breast, lung, colon, prostate, leukemia, and lymphoma. Together these cancers account for about 57 percent of all cancer costs paid by Medicare.

They found that the number of positron emission tomography (PET) scans per Medicare beneficiary increased each year of the study by 35.9 to 53.6 percent. Meanwhile, the costs of PET and five other imaging technologies increased by 5.1 to 10.3 percent annually, compared with increases in overall cancer care costs of 1.8 to 4.6 percent each year.

The researchers pointed out that growth in the use of PET during the study period coincided with expanding FDA approvals of its use for multiple cancer types. To a lesser extent, use of the other advanced imaging modalities for cancer care also increased each year: bone mineral density scans (6.3–20.0 percent), echocardiograms (5.0–7.8 percent), magnetic resonance imaging (4.4–11.5 percent), computerized tomography scans (4.5–7.6 percent), and ultrasound (0.7–7.4 percent). Conventional x-rays are still the most commonly used imaging modality, but their use during the study period either stayed the same or decreased in each group of cancer patients.

Lead author Michaela A. Dinan and colleagues wrote, “It is unclear whether the rapid increase in the use of advanced imaging is a result of the novelty of the technologies, better outcomes, or a shift to new revenue sources.” They noted that the health reform legislation passed by Congress in March 2010 aims to reduce reimbursement for imaging tests, and that the consequences of this effort will likely become an area of increasing study in the years ahead.

Also in the Journals: Updated Guidelines on Hormone-receptor Testing for Breast Cancer

Up to 20 percent of the results from hormone-receptor tests of breast tumors could be inaccurate due to differences in the way the tests are conducted and how the results are interpreted. New guidelines developed jointly by the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) aim to mitigate the rate of false-negative and false-positive results by outlining specific algorithms for conducting and criteria for interpreting these tests.

The guidelines—an update from those last released in 2007—were published early online April 19 in the Journal of Clinical Oncology. ASCO and CAP will promote their use with educational opportunities in print, online, and at society meetings for the benefit of clinicians, patients, third-party payers, and regulatory agencies; through partnerships with other clinical organizations; and with a certificate program that CAP is developing for pathologists and laboratories to encourage quality control.

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