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, 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
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,
fluorouracil) on a 28-day standard regimen (days 1 and 8 every 4
weeks for three or six cycles) with or without 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
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
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.