NEW ORLEANSEpirubicin (Ellence) may be an effective single agent for primary treatment of operable breast cancer, according to results of a cooperative group study from the National Tumor Institute, Milan, Italy, presented at the 36th Annual Meeting of the American Society of Clinical Oncology (ASCO).
The goal of this study was to define whether by giving single-agent primary chemotherapy we could reduce tumor size and initiate breast-conserving therapy. We chose epirubicin(Drug information on epirubicin), which is active and less cardiotoxic than Adriamycin [doxorubicin], and is better tolerated by women, said Pin-uccia Valagussa, MD, study investigator for the coordinating center of the National Tumor Institute.
This prospective nonrandomized study was performed in 317 women with breast cancer measuring more than 2.5 cm, Dr. Valagussa said at a poster session. Women with tumors of more than 4 cm comprised 44% of the study group.
Usually, according to the surgical policies of each participating center, all of these patients receive mutilating surgery, which means a mastectomy. Instead, we gave three cycles of epirubicin. Then surgery was performed, and two thirds of the patients received breast-conserving therapy.
All patients were given single-agent epirubicin at a full dose schedule of 120 mg/m² every 3 weeks for three cycles. Epirubicin reduced tumor size by more than half in 68% of the patients, and only one third of the women underwent mastectomy.
After surgery, in an attempt to improve outcomes, additional chemotherapy was delivered to patients presenting with node-positive breast cancer or node-negative disease with high-risk features (histologically positive axillary nodes, estrogen-receptor-negative tumors, and/or undifferentiated tumors).
This chemotherapy consisted of CMF (cyclophosphamide, methotrexate(Drug information on methotrexate), fluorouracil(Drug information on fluorouracil)) on a 28-day standard regimen (days 1 and 8 every 4 weeks for three or six cycles) with or without tamoxifen(Drug information on tamoxifen) (Nolvadex) (20 mg/day for 5 years).
At a median follow-up of 48 months from starting epirubicin, freedom from progression in these women was 74%, and overall survival was 85%.
Low Risk of Local Recurrence
In this patient population, in whom breast irradiation after primary chemotherapy and breast-conserving surgery was intentionally delayed, the risk of local recurrence was 4%.
Delaying breast irradiation did not increase the risk of local recurrence, and the risk is not related to the size of the tumor, Dr. Valagussa said. Positive surgical margins after breast-sparing surgery, however, did negatively influence the risk of in-breast relapse.
The 4-year risk of relapse for patients with positive margins was 13.9%, compared with 2.9% for those with negative margins.
Our present conclusion is that for those women who have large tumors, this is a safe and active protocol. This multi-modal treatment can be safely administered to patients presenting with large tumors and desiring to preserve their body integrity, she said.
Dr. Valagussa and her colleagues believe that the role of primary chemotherapy is not simply to perform tumor downstaging but also to improve the prognosis. So we are pursuing an additional two-arm study with the aim of achieving good tumor downsizing, but also improving overall survival, she said.