News Release

UCSF study finds genetic link between initial early stage breast cancer cells and disease recurrences

Peer-Reviewed Publication

University of California - San Francisco

UC San Francisco researchers have found a strong genetic link between early stage, non-invasive breast cancer cells and recurrences of the disease after the initial tumors have been removed. The finding provides evidence that second tumors are caused by residual cells left over from the primary lesion and are not new, separate lesions, the researchers said.

The study underscores the importance of surgeons making wide surgical margins to completely remove all of the tumor cells and reinforces other clinical studies that have shown the effectiveness of lumpectomy followed by radiation, said Frederic Waldman, MD, PhD, UCSF professor in laboratory medicine and lead author of the study. The study results will be published in the February 16 issue of the Journal of the National Cancer Institute.

Researchers examined the tissues of ductal carcinoma in situ (DCIS) tumors in 18 women. DCIS is a neoplasm, or growth, of non- invasive tumor cells in the milk ducts that have not broken through to invade the rest of the breast. The disorder is considered to be a precursor to invasive breast cancer. Before the 1980s, treatment of DCIS was primarily by mastectomy. More recently, lumpectomy--often accompanied by radiation--has been the recommended treatment for such tumors and is effective in up to 95 percent or more of all cases.

But breast-conserving surgery raises the possibility DCIS may show up again in the remaining breast tissue, according to the new study. The incidence of local recurrences following lumpectomy, in which only the tumors are removed and not the entire breast, ranges from five percent to 25 percent, depending on postoperative treatment. The recurrence of DCIS following mastectomy is only one to two percent.

"The question was, 'Are the tumors really coming back or are the women who have pre-invasive cancer more likely to have a different tumor in the same breast or in the opposite breast?' ", Waldman said.

Using technology called comparative genomic hybridization, (CGH) researchers isolated DNA from tissue samples to analyze the genetic changes in the 18 tumors and to compare those changes to the recurrent lesions. CGH is a powerful molecular tool that yields a genetic profile for each tumor.

"Now we have a tool to test whether these recurrences are related to the primary tumor or not," Waldman said. "We used genetic technology to define a genetic signature of each lesion and compared that to the genetic signature of each patient's own recurrence." In 17 patients, the chromosomal changes in the initial lesion agreed strongly with those of the second incident, showing that the recurrent tumor was most likely a result of persistent residual cells left over from the first tumor. Only one patient's second tumor was a new growth. The period between the primary tumor and the second was between 16 months and nine years, with an average of 4.2 years for patients in the study. "This is an important confirmation that these recurrences are the same tumors, sitting there quiescent and coming back at a much later time," Waldman said. "It gives us more of an understanding of what is going on when there are recurrences and it shows us that most of the time it's the same DCIS tumor coming back when we get local recurrences, even if they are many years later."

Other authors of the study are Sandy DeVries, MA, research associate for the UCSF Comprehensive Cancer Center; Karen Chew, specialist in the UCSF Comprehensive Cancer Center; Dan Moore II, PhD, UCSF associate professor of epidemiology and biostatistics; Karla Kerlikowske, MD, MS, assistant professor of medicine, epidemiology and biostatistics; and Britt-Marie Ljung, MD, professor of clinical pathology.

The study was funded by the National Cancer Institute, the National Institutes of Health, U.S. Department of Health and Human Services and by the California Breast Cancer Research Program.

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