News Release

Long-term survival results favor chemotherapy before surgery for locally advanced breast cancer

Peer-Reviewed Publication

University of North Carolina Health Care

CHAPEL HILL - Long-term survival results from a breast cancer treatment study begun in 1992 at the University of North Carolina at Chapel Hill's Lineberger Comprehensive Cancer Center strongly favor chemotherapy followed by surgery for women with large, locally advanced tumors.

Traditionally, women with breast cancer receive surgery followed by chemotherapy. However, the new findings also show that chemotherapy followed by surgery - neoadjuvant therapy - often allows less drastic and breast-sparing surgery, lumpectomy versus mastectomy.

Despite efforts at early detection, locally advanced breast cancer remains prevalent and is a challenge to control. In the past, many of these patients were considered inoperable because of the sheer volume of their tumors and the belief that they would soon die from spread of the disease well beyond the breast, or distant metastatic disease.

Over the last decade, studies of neoadjuvant therapy for patients with large primary tumors had demonstrated that successful tumor downstaging, or improvement, could result in increased rates of breast-conserving therapy. Moreover, a few reports indicated that tumors larger than three centimeters that were successfully downstaged with neoadjuvant chemotherapy could be controlled.

Still, the overall effect on long-term survival has remained unclear; the new findings help clarify this issue.

At a median follow up of 70 months, 76 percent of patients in the UNC study who received neoadjuvant therapy survived for at least of five years. Post-treatment follow up ranged from 35 to 117 months.

In addition, neoadjuvant therapy may make surgery a viable option for women whose tumors were considered inoperable due to their seriously advanced stage, said Dr. William G. Cance, professor of surgery, chief of surgical oncology and a member of the cancer center.

"I think this study now provides a surgical advantage for women with locally advanced breast cancer who undergo neoadjuvant therapy," he said.

Cance presented the follow-up results April 25 at the 122nd Annual Meeting of the American Surgical Association in Hot Springs, Va. Cance, along with UNC colleagues Drs. Mark Graham II and Julian Rosenman, wrote the original protocol for the study, which ended in 1998. Drs. Lisa A. Carey, Benjamin F. Calvo and David W. Ollila also joined the study.

"This is among the longest follow ups in neoadjuvant therapy nationally," Cance said, adding that the treatment regimen used was aggressive, dose-intense and time-intense.

It was also one of the briefest treatments used, he added. "Our neoadjuvant treatment protocol emphasized timely completion of all modalities of therapy - chemotherapy, surgery, post-operative chemotherapy and radiation therapy - within 32 weeks, with minimal interval between modalities," he said.

The 62 women studied all had locally advanced primary breast tumors greater than five centimeters, with skin or chest wall involvement, or with extensive involvement of the axillary (armpit) lymph nodes. The median age was 44 years, and roughly two-thirds were white and one-third were black. At diagnosis, 51 (82 percent) of the patients had tumors at clinical stage III, with 34 at stage IIIA and 17 at stage IIIB. Three patients were considered at stage IV. In addition, 13 patients (21 percent) had inflammatory breast cancer, which traditionally has been thought to have a poor prognosis.

Overall, 84 percent of patients showed a significant clinical response to chemotherapy. No patient's tumor worsened while taking dose-intense neoadjuvant treatment with doxorubicin. A total of 28 patients (45 percent) had sufficient downstaging of their tumor to permit an attempt at breast conserving therapy, or lumpectomy (segmental mastectomy). Of these, 22 (79 percent) had successful breast preservation, while six required complete mastectomy due to laboratory determination of cancer in the margins of surgery after lumpectomy.

Patients with inflammatory breast disease were not considered candidates for breast-conserving therapy, regardless of clinical response to chemotherapy. When this group was discounted statistically, of the 49 remaining patients, 22 (45 percent) had successful breast conservation, Cance said.

"Our results demonstrate that patients with locally advanced breast cancer can achieve outstanding control of disease and long-term survival by undergoing a dose- and time-intensive regimen of neoadjuvant chemotherapy," he said.

"These data provide evidence that breast conservation can reasonably be accomplished in up to 45 percent of patients with non-inflammatory locally advanced breast cancer," Cance said. "Furthermore, the tumor response to chemotherapy can help identify the subgroup of patients with a more favorable long-term prognosis. Those patients who have clinical downstaging of their tumors and are candidates for breast conserving therapy have the best long-term outcome."

He added that patients who had mastectomy - while at higher risk of relapse as well as development of new tumors in the other breast - still have five-year survival rates of more than 50 percent.

"Thus, dose-intense and time-intense neoadjuvant therapy should be standard care for patients with locally advanced breast cancer," he said.

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By LESLIE H. LANG

Note: Contact Cance at (919) 966-5221or cance@med.unc.edu
School of Medicine contact: Les Lang at (919) 843-9687 or llang@med.unc.edu


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