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Cell Insights May Predict Breast Cancer's Spread
Date:11/16/2007

Key biomarkers could point to women at higher risk, study suggests

FRIDAY, Nov. 16 (HealthDay News) -- U.S. researchers believe they're on the way to solving a major question about breast cancer: Which women have a type of lesion in their breast duct that will progress to invasive disease?

"It's an exciting step forward -- people have been trying to get traction on this big clinical problem for about 40 years, and this is a big crack in the door," said lead researcher Thea Tlsty, a professor of pathology at the University of California, San Francisco.

Ductal carcinoma in situ (DCIS), as this type of lesion is officially known, is diagnosed in about 47,000 American women every year, according to the U.S. National Cancer Institute. To prevent its recurrence as invasive breast cancer, DCIS generally is treated by lumpectomy alone (approximately 25 percent of cases) or lumpectomy with adjunctive treatments such as radiation, chemotherapy, and/or hormones (approximately 40 percent).

In about 25 percent of cases, complete mastectomies are performed. Less than an estimated 5 percent of women choose "watchful waiting" in lieu of a surgical intervention, Tlsty said.

But doctors are still confronted with a guessing game when it comes to predicting those patients at highest risk for recurrence, Tlsty said. "Only about 12 to 15 percent of women diagnosed with DCIS are going to have a future invasive cancer, and all the others won't. Up until now, the problem was that we couldn't distinguish the 12 to 15 percent from those who were not [at risk]," explained Tlsty.

Consequently, some women unknowingly are overtreated by having a mastectomy, and others are undertreated if they chose a course of watchful waiting rather than surgical intervention, Tlsty added.

In their pilot study, published in the November issue of Cancer Cell, the UCSF team looked at how a collection of biomarkers, including molecules called p16 and ki67, interact to predict invasive tumors, she explained.

Because this initial study was done on tissue samples from 70 women, a larger retrospective study is under way at UCSF to validate the initial results, Tlsty said.

Further research, including a large prospective trial, is also needed before the findings can be ready for clinical use, she added. If that work upholds the results of the pilot study, the biomarkers could be ready for clinical use within four to five years, Tlsty said.

Dr. Joseph Geradts, a professor of pathology at Duke University in Durham, N.C., said that finding biomarkers that turn DCIS into invasive cancer is "the holy grail of breast cancer research." He said there have been a number of previous studies that have been published, but, so far, they've been "mostly a fruitless effort."

According to Geradts, the UCSF study "is valuable," because "the authors propose two new biomarkers that in the past have not been looked at." The UCSF team's findings "are intriguing preliminary data" that "merit confirmation and subsequent studies," he added.

Geradts said his own lab currently is researching whether changes in DNA may identify a tumor's capacity to metastasize or become invasive. Other researchers are looking at other DCIS biomarkers, he said.

"DCIS itself is a non-life threatening condition" with rare exceptions, noted Dr. Eric Winer, director of breast oncology at the Dana-Farber Cancer Institute in Boston, and women are usually treated to help prevent invasive cancer. If the findings of the initial UCSF study are confirmed, then with "careful investigation, we may get to the point where we don't have to treat all women with DCIS, and we may be able to tailor it so some women get less, and some women get more" depending upon their risk for invasive breast cancer, Winer said.

"It's a very complex and interesting study" added Dr. Richard Bleicher, a surgical oncologist at Fox Chase Cancer Center in Philadelphia. "We need to be cautiously optimistic."

Bleicher added that while the findings have "significant potential," women at this point shouldn't "pin all your hopes on it," because the p16 assay is not something they can ask their doctors for at this point in time.

More information

For more on breast cancer, visit the U.S. National Cancer Institute.



SOURCES: Richard Bleicher, M.D., surgical oncologist, Fox Chase Cancer Center, Philadelphia; Thea D. Tlsty, Ph.D., professor, pathology, University of California, San Francisco; Joseph Geradts, M.D., professor, pathology, Duke University, Durham, N.C.; Eric Winer, M.D., director, Breast Oncology Center, Dana-Farber Cancer Institute, Boston; November 2007 Cancer Cell


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