MEMORANDUM FOR: Science Writers and Editors on the Journal Press List

August 12, 1999 (EMBARGOED FOR RELEASE 4 P.M. EDT August 17)

Julianne Chappell, Executive Editor, Dan Eckstein, (301) 986-1891, ext. 112

Epstein-Barr Virus Found in Many Breast Cancers

In a recent study, the Epstein-Barr virus (EBV) was found in 51 of 100 breast cancer tissues studied — in tumor cells but usually not in the surrounding tissue — and was frequently associated with more aggressive tumors.

These results, suggesting that EBV may play a role in the development of some breast cancers, are presented by Mathilde Bonnet, Ph.D., and Irene Joab, Ph.D., at Institut Gustav Roussy, Paris, and colleagues, in the August 18 issue of the Journal of the National Cancer Institute.

The authors analyzed 100 consecutive biopsy specimens from patients with primary invasive breast cancer, 30 normal tissues adjacent to the breast tumors, and five lymph nodes with metastasis. DNA was extracted from the tissues, then amplified by polymerase chain reaction, with primers covering three different regions of the EBV genome. Southern blot analysis and immunohistochemistry were also used to confirm the presence and location of the virus.

EBV was detected in 51 of the 100 tissue samples from breast tumors, while only three of the 30 samples of healthy breast tissue taken from next to the tumor contained EBV. There was a statistically significant difference in the detection of EBV DNA between malignant and healthy tissue, strongly suggesting that the EBV is largely restricted to the tumor. EBV was detected in four lymph nodes for which the corresponding tumors were also EBV positive. The lymph node from the fifth patient was negative, as was the tumor in that patient. Immunohistochemistry results confirmed that EBV was restricted largely to tumor epithelial cells and that an appreciable number of these cells contain the virus.

The proportion of EBV-positive tumors was statistically significantly higher in tumors of higher histologic grade (grade III = 66%; grade II = 44%; grade I = 27%). In steroid receptor-negative tumors, which represent a poor prognosis group, EBV-positive samples were more common (79%) than in tumors having steroid receptors (45%). No association was observed between the presence of EBV and other prognostic factors, such as age, tumor size, and menopausal status.

The authors note that the point in tumor development at which EBV infection occurs remains to be determined. However, since their results show the virus to be more frequently associated with more aggressive tumors, EBV may play a role in their development.

Editorialists Ian Magrath, M.D., and Kishor Bhatia, Ph.D., of the National Cancer Institute, write that EBV infects at least 90% of the world's adult population, in most cases with no serious consequences. However, the virus does cause serious illnesses, including cancer, in a tiny fraction of the population. The results reported by Bonnet et al. support other findings of an association between EBV and breast cancer but disagree with several groups that have reported negative results, according to the editorial writers. If the EBV proves to be a causative factor in a large proportion of breast cancers, they conclude that there would be strong grounds for speeding up efforts to develop an EBV vaccine, or EBV targeted therapy, since breast cancer is the most common tumor in women worldwide.

Contact: Dr. Irene Joab, France, 33-14-249-9268; fax 33-14-249-4838. Editorial: NCI Press Office, (301) 496-6641. (Note: The media contact for the editorial is the NCI Press Office because the authors are on the NCI staff.)

Genetic Changes May Be Linked to Breast Cancer Metastasis

Genetic changes have been identified that may be related to the potential for breast cancer to spread to distant parts of the body, a finding that could have implications for better diagnosis and treatment of this disease.

Peter O'Connell, Ph.D., and colleagues at the University of Texas Health Science Center at San Antonio, present their research findings in the August 18 issue of the Journal of the National Cancer Institute.

The authors analyzed archived tissue specimens from 76 breast cancer patients, including 42 whose axillary lymph nodes were negative and 34 whose lymph nodes were positive for the spread of cancer. DNA samples were extracted from normal tissues and from primary breast tumors. DNA samples were probed with four genetic markers (D14S302, D14S265, D14S62, and D14S51) that spanned chromosome 14q31-q32. Loss of heterozygosity (LOH) was determined for paired normal and breast cancer tissues.

Contrary to expectations, more LOH events at two of the markers (D14S62 and D14S51) occurred in patients with lymph node-negative disease than those with lymph node-positive disease. Specifically, 68% of the lymph node-negative cancers showed LOH at D14S62 compared with only 24% of the lymph node-positive cancers. These results, which are statistically significant, suggest the presence of a gene that affects the metastatic potential of breast cancer. Isolation and characterization of this gene will lead to new insights regarding metastasis and may lead to new therapies for patients with metastatic disease.

The 32% of lymph node-negative patients who did not show LOH approximates the 30% recurrence rate in patients with negative lymph nodes, patients who would be expected to have a low risk for recurrence. The authors are carrying out a large prognostic study of LOH at D14S62 in primary breast cancer specimens to explore any connection between genetic state and disease progression in node-negative patients.

In an editorial, Dan Welch, Ph.D., at the Pennsylvania State University College of Medicine, and Carrie Rinker-Schaeffer, Ph.D., at the University of Chicago, note that metastasis is the most lethal attribute of cancer. Therefore, they say, it is critical that tumors be diagnosed while still local in order to achieve long-term survival and high quality of life. They also explain that markers are needed that can distinguish between weakly and highly metastatic cancers, and the complexity of the metastatic process suggests that multiple markers may be needed. Welch and Rinker-Schaeffer point out that O'Connell et al. describe a molecular marker that affords the opportunity to detect rare metastatic cells within breast tumors comprising millions of cells.

Contact (current): Dorey A. Zodrow, Baylor University, (713) 798-4712; fax (713) 798-3692. Editorial: Leilyn Perri, (717) 531-8606; fax (717) 531-6999.

Note: This memo to reporters is from the Journal staff and is not an official release of the National Cancer Institute (NCI) or Oxford University Press (OUP) nor does it reflect NCI or OUP policy. In addition, unless otherwise stated, all articles and items published in the Journal reflect the individual views of the authors and not necessarily the official points of view held by NCI, any other component of the U.S. government, OUP, or the organizations with which the authors are affiliated. Neither NCI nor any other component of the U.S. government nor OUP assumes any responsibility for the completeness of the articles or other items or the accuracy of the conclusions reached therein.



             
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