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

By Leslie Harris

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.