MUNICHPreoperative treatment of primary breast cancer with dose-dense
sequential epirubicin (Ellence) and paclitaxel (Taxol) led to significant
increases in breast-conserving therapy and in response rates compared to
epirubicin and paclitaxel at standard doses. A prospective randomized,
controlled clinical trial conducted at multiple centers in Germany also
found comparable toxicity between the two regimens (ASCO abstract 133).
After successful prior studies in the adjuvant setting, the trial was
conducted in the neoadjuvant setting for four main reasons, stated the study’s
lead investigator Michael Untch, MD, of Klinikum Grosshadern in Munich.
- Survival equivalence was demonstrated between preoperative and
- Retrospective and prospective evidence show increased rates of breast
conserving surgery with neoadjuvant treatment.
- The pathologic complete response rate, defined by Dr. Untch as
"no evidence of invasive cancer at primary tumor site," is a very
good surrogate predictor of improved outcome.
- The preoperative setting provides a good model for investigating
Surgery After Chemotherapy
Speaking on behalf of the AGO Study Group (Arbeitsgemeinschaft
Gynaekologische Onkologie), Dr. Untch said that patients received treatment
with anthracyclines and taxanes, the two most potent classes of
chemotherapeutic agents. They were randomly assigned to receive either:
epirubicin at 150 mg/m², followed by paclitaxel at 250 mg/m², both 3 times
every 2 weeks, with G-CSF (filgrastim) support (5 µg/kg/d) on days 3 to 10;
or to receive epirubicin at 90 mg/m² and paclitaxel at 175 mg/m², 4 times
every 3 weeks, as preoperative therapy.
For both groups, surgery was performed after completion of chemotherapy.
All patients received CMF (cyclophosphamide, methotrexate, fluorouracil) 3
times every 4 weeks after surgery. Locoregional radiotherapy was also
mandatory. Also, hormone receptor positive (HR+) patients received
Included patients (n = 549, median age 50 years) had primary breast
cancer (T > 3 cm or inflammatory disease) diagnosed by core biopsy and
adequate clinical performance status (96.5% with Eastern Cooperative
Oncology Group [ECOG] status 0). About 53% were premenopausal. The median
tumor diameter was 4.2 cm (range 3.0-8.5 cm), and 16% of all patients had
inflammatory disease. "We are dealing with large tumors, here,"
Dr. Untch commented. Fourteen and one-half percent had inflammatory disease.
Mastectomy was proposed in 74.5% of cases, and 64.5% were clinical node
positive. Dr. Untch underscored that assessment was conducted not just by
clinical palpation, but by mammography, MRI, and ultrasound before
neoadjuvant therapy and before surgery.