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SECTION II: Neoadjuvant Therapy

Abstract 140
Accuracy of Sentinel Node Biopsy After Neoadjuvant Chemotherapy in Breast Cancer: Updated Results from NSABP B-27
Eleftherios P. Mamounas, MD, Associate Professor of Surgery, Northeastern Ohio University College of Medicine, Aultman Cancer Center, Canton, Ohio

The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-27 trial demonstrated that the addition of sequential Taxotere (docetaxel) to neoadjuvant therapy with doxorubicin (Adriamycin, Adiblastine, Adriablatina, Doxil, and others)-cyclophosphamide [Cytoxan, Cytokan, Endoxon, Neosar, Neosar For Injection] (AC) significantly increased overall clinical response and almost doubled pathological complete response (pCR) rates in patients with large operable breast cancer. A separate analysis of B-27 also evaluated sentinel node biopsy (SNB) in patients treated with neoadjuvant therapy. In women in whom SNB was attempted, the overall success rate was 85%, suggesting that SNB may be an acceptable alternative to axillary node dissection in the neoadjuvant setting, reported Dr. Eleftherios P. Mamounas during a presentation at the 38^th annual ASCO meeting.

NSABP B-18 was the largest trial designed to compare anthracycline chemotherapy in the neoadjuvant versus the adjuvant setting in patients with operable breast cancer (Fisher B et al. J Clin Oncol 1998;16(8):2672-2685). The trial demonstrated equivalent survival for neoadjuvant therapy with AC compared to adjuvant AC. In the B-18 trial, the main predictive factor for survival was pCR. Patients who achieved a pCR following neoadjuvant AC had a 50% relative risk reduction in mortality. Neoadjuvant AC also contributed to an increase in the rate of breast-conserving surgery.

Review of NSABP B-27 Findings
The B-27 trial was undertaken to evaluate the value of neoadjuvant Taxotere following AC as well as adjuvant Taxotere following neoadjuvant AC. The study completed accrual in the year 2000, with more than 2,400 patients enrolled. At baseline, 44% of patients had tumors >4 cm, and 41% had tumors ranging from 2.1 to 4 cm.

Patients were randomized to one of three chemotherapy regimens:

Neoadjuvant AC (doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m²) every three weeks for four cycles, followed by surgery;
Neoadjuvant AC followed by Taxotere. AC (doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m²) every three weeks for four cycles, followed by Taxotere 100 mg/m² every three weeks for four cycles, and then surgery;
Neoadjuvant AC plus adjuvant Taxotere. AC (doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m²) every three weeks for four cycles, followed by surgery, followed by Taxotere 100 mg/m² every three weeks for four cycles.

All patients who underwent lumpectomy received radiotherapy, and all patients in the trial received tamoxifen (Nolvadex, Dignotamoxi, Istubol, Kessar, and others) for five years starting with chemotherapy.

Efficacy
The overall response rate was significantly higher with the addition of neoadjuvant Taxotere than with AC alone — 91% vs. 85% (p<0.001). The pCR rate was almost doubled in patients receiving neoadjuvant AC-Taxotere compared with those receiving neoadjuvant AC alone — 25.6% in the Taxotere-treated patients vs. 13.7% in those receiving AC (p<0.001). The pCR with neoadjuvant AC alone (13.7%) was virtually identical to the rate achieved with neoadjuvant AC in the B-18 trial (Table 3). There was a reduction in the number of patients that were node positive with the addition of neoadjuvant Taxotere (40.5%) compared to AC alone (48.5%, p<0.01).

Table 3. NSABP B-27 Trial Tumor Response

Table 3. NSABP B-27 Trial Tumor Response

Source: Adapted from Eleftherios Mamounas, MD, as presented at the 38^th Annual Meeting of the American Society of Clinical Oncology (ASCO), May 18-21, 2002, Orlando, Florida. Abstract 140.

Results of Sentinal Node Biopsy Analysis
A subset of 428 women enrolled in the B-27 trial underwent SNB. The sentinel node was identified and successfully removed in 363 of these patients, 94% of these patients also had axillary node dissection. The false-negative rate was found to be 11%. The success rate in identifying the sentinel node increased with use of a radioisotope versus blue dye, Dr. Mamounas noted. The success rate was not affected by patient age, clinical nodal status, tumor size or calendar year.

No significant association was found between sentinel node false-negative rate and clinical characteristics or tumor response to neoadjuvant therapy, Dr. Mamounas said, and no significant trends were observed toward lower false-negative rates with smaller tumors and with use of isotope versus blue dye alone.

"Sentinel node biopsy is a promising alternative to axillary node dissection. We need to develop neoadjuvant protocols that account for SNB and we need to use radioisotope with blue dye to improve the accuracy rate," stated Lisa Newman, MD, Associate Professor of Surgery, Karmanos Cancer Center, in Detroit, Michigan, who discussed Dr. Mamounas' paper at the ASCO meeting.

Key Points In Focus:

In the NSABP B-27 trial, the clinical complete response rate was significantly higher with neoadjuvant AC followed by Taxotere compared with AC alone — 91% vs. 85% (p<0.001).
pCR was almost doubled with the addition of neoadjuvant Taxotere compared to AC alone — 25.6% in the Taxotere-treated patients vs. 13.7% in those receiving AC (p<0.001).
Analysis of a subset of patients in the NSABP B-27 trial suggests that SNB is applicable and feasible in breast cancer patients following neoadjuvant therapy.
The success rate for identification and removal of the sentinel node was 85% and the false-negative rate was 11%, which are comparable to rates reported in pub-lished studies of SNB following breast cancer diagnosis.

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