Technique helps put freeze on need for repeat breast surgeries

Women with breast cancer who undergo lumpectomy could avoid a return trip to the operating room, thanks to a laboratory test that quickly confirms whether surgeons have removed the entire tumor — before their patients head home, University of Florida physicians report.

A UF study, published this month in the Journal of the American College of Surgeons, revealed that women whose tumors are studied using a method known as frozen section analysis are less likely to need a second or third operation to remove cancerous cells missed during the first surgery.

“We were the first institution, to my knowledge, to extensively evaluate lumpectomy margins using frozen section,” said Edward Copeland III, M.D., the UF surgeon credited with helping to develop the technology. “One of the beauties of this technique is that we can take out the minimum amount of breast tissue possible and get safe results.”

More than 200,000 women in the United States will be diagnosed with breast cancer this year, according to the National Cancer Institute.

Patients diagnosed with noninvasive or early stage invasive breast cancer often undergo breast-conserving lumpectomy, an alternative to total mastectomy, to excise the tumor while preserving as much healthy breast tissue as possible.

Surgeons at most institutions rely on a labor-intensive method called “permanent section analysis” to check whether any cancerous cells remain along the margins of an excision. But the technique is cumbersome: Once doctors obtain tissue samples from the margins, a pathologist spends several hours treating the samples and embedding the tissue in paraffin wax. When the “permanent sections” are finally ready for analysis two to three days later, the surgery has already ended and the patient has been sent home.

If any cancerous cells are detected, the patient must return for a second procedure. Copeland, who was the first director of the UF Shands Cancer Center, began using frozen section analysis 20 years ago when he tired of waiting for results from the traditional method. The technique is efficient: Tissue samples are frozen in an embedding compound and sent to a pathologist for immediate analysis. In the typical case, where five margins are evaluated, frozen section adds only 15 minutes to the operative time, Copeland estimated.

As a result, surgeons have a better chance of removing all affected tissue during the initial operation, significantly reducing the need for further procedures. After the surgery, doctors consult the permanent sections to confirm that the margins are clean.

“There is no question that frozen section saves about 50 percent of women with positive margins a second operation,” Copeland said.

In the recent study, Copeland and UF surgeon Juan Cendán, M.D., used frozen section analysis to evaluate the lumpectomy margins of 97 patients who underwent lumpectomy between 2001 and 2004. The women, mostly between 48 and 71 years of age, were diagnosed with a noninvasive form of breast cancer called ductal carcinoma in situ or with stage I or II invasive carcinoma.

The researchers compared the accuracy of frozen section analysis with traditional permanent section analysis. Study results clearly indicated that frozen section analysis is a safe and effective way to evaluate breast tumor margins, Copeland said. More than half of the 97 patients in the study were spared additional trips to the operating room because cancerous tissue was successfully detected during the surgery. However, the procedure failed to detect cancerous margins in 19 patients, indicating that frozen section analysis should continue to be used in conjunction with permanent section, Cendan said.

Frozen section analysis adds approximately $851 to the cost of each surgery. Still, the procedure is relatively inexpensive, considering the cost of returning to the operating room for a second surgery, which Cendán estimated would be well into the thousands of dollars.

Despite the apparent advantages, analysis of the frozen sections is tricky. Adipose, or fat-storing, tissue is poorly preserved during the freezing process. As a result, frozen sections are of lower quality than permanent sections and are sometimes difficult to evaluate, emphasizing the importance of experienced and capable pathology technicians. False positive results could result in unnecessary mastectomy, say opponents of the technique, a situation that Copeland points out has never occurred at UF. Many surgeons prefer to wait for permanent section results before removing additional breast tissue on the spot.

Nonetheless, during the UF study, there were no false positives, said Dominique Coco, M.D., a UF pathology resident who performed the data analysis, “which means that the surgeons did not remove additional breast tissue unnecessarily, based on the results of frozen section analyses.”

Other institutions have reported similar results, including the Moffitt Cancer Center in Tampa and the University of Wisconsin School of Medicine. Yet despite its promise, the technique is not widely used. Shands at UF is the only hospital in North Florida and one of a handful in the country that performs frozen section analysis on a regular basis.

“Frozen section analysis is used in many institutions for other diseases,” Cendán said. “For example, during gastric cancer resection or during a sarcoma resection, the pathologist will look at sections while the patient is on the table. It has not become commonplace [for analysis of lumpectomy margins] because breast tissue is difficult to interpret on frozen section.”

Said Paul G. Curcillo II, vice chairman of the department of surgery at the Drexel University College of Medicine in Philadelphia, “Frozen section is not widely accepted, but I would definitely not classify it as a risky procedure. In a year or so, if things pan out and we see that it works well, then I would consider using it.”

Cendán said he hopes that Curcillo is not alone.

“I hope that our report will make people re-evaluate whether they should be [performing frozen section analysis] as well,” Cendán said. “We showed no damage to the patient. We were able to save quite a few patients from going back to the operating room for a second procedure.”