Annals of Surgical Oncology Cite Track
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
10.1245/ASO.2006.03.592
Annals of Surgical Oncology 13:483-490 (2006)
© 2006 Society of Surgical Oncology
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cox, C. E.
Right arrow Articles by Minton, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cox, C. E.
Right arrow Articles by Minton, S.

Original Article

Sentinel Node Biopsy Before Neoadjuvant Chemotherapy for Determining Axillary Status and Treatment Prognosis in Locally Advanced Breast Cancer

Charles E. Cox, MD, John M. Cox, MD, Laura B. White, BS, Nicholas G. Stowell, BS, John D. Clark, BS, Nathon Allred, Michael Meyers, Elisabeth Dupont, MD, Ben Furman, MD and Susan Minton, DO

Department of Surgery, Comprehensive Breast Cancer Program, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, 12902 Magnolia Drive, Tampa, Florida 33612

Correspondence: Address correspondence and reprint requests to: Charles E. Cox, MD; E-mail: coxce{at}moffitt.usf.edu.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Background: Treatment of locally advanced breast cancer with neoadjuvant chemotherapy assesses an in vivo tumor response while increasing breast conservation. Axillary clearance of nodal disease after treatment defines prognostic stratification. Our study objective was to show that sentinel node staging before treatment can optimize posttreatment prognostic stratification in clinically N0 patients.

Methods: Eighty-nine patients with locally advanced breast cancer were treated with neo-adjuvant chemotherapy. Of these, 42 (47%) clinically palpable or image-detected nodes (cN+) were histologically confirmed before treatment (group 1), and 47 (53%) patients without palpable lymph nodes (cN0) had a sentinel lymph node (SLN) biopsy before treatment (group 2). Survival analysis was conducted with the Kaplan-Meier method.

Results: In groups 1 and 2, 82 (92%) of 89 patients had node-positive disease before treatment. Seven (8%) of 89 had negative SLNs and no completion axillary lymph node dissection, 24 (27%) patients had a complete pathologic axillary response (pCRAX; 11 [26%] of 42 in group 1 and 13 [33%] of 40 in group 2), and 58 (65%) of 89 had residual disease in the axilla. Breast-conserving therapy was applied to 27 (30%) of 89 patients. The seven SLN-negative patients had no axillary recurrence at 25 months, and pCRAX patients had a significantly higher overall survival than patients with residual disease.

Conclusions: This study validates the prognostic stratification of patients with a complete pathologic axillary response to neoadjuvant chemotherapy. The addition of SLN biopsy to cN0 patients before treatment increased accurate nodal staging by 53%, eliminated completion axillary lymph node dissection in 15%, and demonstrated an improved prognosis in 28% of pCRAX patients. SLN biopsy before treatment provides accurate staging of cN0 patients; allows acquisition of standard treatment markers, prognostic biomarkers, and microarray analysis; and affords prognostic stratification after treatment.

Key Words: Sentinel lymph node mapping • Axillary staging • Neoadjuvant chemotherapy • Locally advanced breast cancer


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Sentinel lymph node (SLN) biopsy has been shown to be very effective in determining the axillary status in early-stage breast cancer.1–4 Patients with locally advanced breast cancer (LABC) have been given surgical treatment with modified radical mastectomy to control local disease. Recent studies have shown that patients with LABC and positive axillae can be treated with neoadjuvant chemotherapy before definitive surgery and can demonstrate a pathologic tumor and axillary response.5–8 Furthermore, the cytoreductive effect of neoadjuvant chemotherapy provides the surgical option of breast-conserving therapy to many patients.5,9

The presence of LABC or large primary breast tumors has been a relative contraindication for SLN biopsy. However, studies demonstrate that SLN biopsy can be performed in patients with large breast tumors before neoadjuvant chemotherapy with almost the same success rate as in those with smaller breast cancers.10,11 Many patients with LABC have clinically palpable nodes that can be detected by the clinician; however, a subset of patients have large primary breast tumors with corresponding clinically negative axillae. Kuerer et al.5 demonstrated that patients with LABC plus confirmed positive nodes were prognostically stratified to an 80% 5-year overall survival and disease-free survival when the nodal basin was pathologically cleared by neoadjuvant chemotherapy. Patients with LABC were entered onto this study on the basis of the confirmation of positive axillary nodes by fine-needle aspiration (FNA), incisional biopsy, or core biopsy. Therefore, according to these entry criteria, any patient with LABC and clinically negative nodes was not entered onto that trial.

Furthermore, results of the study by Kuerer et al.5 required pretreatment axillary staging of patients with LABC who were candidates for neoadjuvant chemotherapy to determine the pathologic axillary response to treatment. Bedrosian et al.11 showed that SLN biopsy is accurate in patients with large tumors, and their study concluded that SLN biopsy should be considered for the staging of clinically negative axilla in patients scheduled to receive neoadjuvant chemotherapy.

This study presupposes that SLN biopsy can be used to evaluate axillary status in patients with LABC with clinically negative axillae (cN0) before treatment with neoadjuvant chemotherapy and proposes the abandonment of posttreatment SLN mapping for LABC and the application of pretreatment SLN mapping only. Our results validate the M. D. Anderson study5 and suggest pretreatment lymphatic SLN mapping of patients with nonpalpable (cN0) disease while eliminating completion axillary lymph node dissection (CALND) for patients with negative SLNs according to the results of Schrenk et al.12

This study documents pretreatment nodal staging in LABC (Tc ≥ 4.5 cm) patients who have clinically positive or nodal disease by performance of a noninvasive biopsy of palpable or clinically evident disease. These patients are then compared with patients with nonpalpable disease (cN0) by SLN mapping and biopsy of non–clinically detected disease. All patients are then treated with neoadjuvant chemotherapy and receive a CALND upon definitive operation. The patients with no axillary involvement before treatment, as determined by a pathologically negative SLN, are spared a CALND after treatment, and their response to therapy is measured by tumor response only.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Patients
Institutional review board approval and appropriate local guidelines were met by all patients entered onto the study. Eighty-nine patients with stage II or III tumors ≥4.5 cm (mean tumor size, 8 ± 3.5 cm) with breast cancer (inflammatory types excluded) were treated with neoadjuvant chemotherapy at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, FL, between March 1999 and March 2004.

The patients were divided into two groups. Group 1 was a validation study of the method of Kuerer et al.5 for patients with palpable axillary disease. Forty-two clinically palpable or enlarged nodes noted on imaging studies were histologically confirmed by FNA or core biopsy of the palpable node before treatment with neoadjuvant chemotherapy (group 1). These patients were then assessed for pathologic tumor and axillary response after surgery. Patients received a mastectomy or breast-conserving therapy. The true axillary response was determined with a CALND.

Group 2 patients were those with nonpalpable axillary disease staged before treatment with SLN biopsy. Forty-seven patients with LABC had clinically negative nodes (cN0; group 2). The axillary status before treatment was determined by an SLN biopsy. Patients with a pathologically positive lymph node were treated with neoadjuvant chemotherapy and upon definitive surgery underwent CALND. The patients with clinically negative nodes who had pathologically negative nodes on SLN biopsy were spared a CALND after neoadjuvant chemotherapy.

For patients with histopathologically positive nodes by FNA, core biopsy, or SLN biopsy before treatment, patient response was determined by comparing the pretreatment tumor and axillary findings with the findings after definitive surgery and CAL-ND. For the patients with negative nodes on SLN biopsy, the tumor response was the only factor assessed.

Neoadjuvant Chemotherapy Treatment
Forty-five patients were treated on a single-institution trial conducted at the H. Lee Moffitt Cancer Center and Research Institute (institutional review board No. 5292; Moffitt Cancer Center No. 11971). In this trial, patients with T3 breast tumors received dose-dense neoadjuvant chemotherapy with doxorubicin 80 mg/m2 for three cycles every 2 weeks and docetaxel 100 mg/m2 for three cycles every 2 weeks. The other 44 patients were treated with either an anthracycline-based chemotherapy regimen or a sequential anthracycline-/taxanebased chemotherapy regimen as a part of their standard care. Chemotherapy regimens did not differ according to the nodal biopsy technique. Positive-SLN patients were treated with the same regimen as FNA-positive patients. It was not the objective of this study to compare chemotherapeutic regimens with tumor response. Furthermore, the results of chemotherapeutic regimens used as a part of this trial and novel markers for the chemotherapeutic response were reported separately for a subset of these patients.13

Histological Evaluation of Lymph Nodes
SLNs were submitted separately by the surgeon for routine analysis. The lymph nodes were then sectioned and stained with hematoxylin and eosin (H&E). The nodes that were questionable or negative on H&E were serially sectioned and stained by using immunohistochemical cytokeratin staining techniques. The remaining nodes from a CALND after positive SLNs were found were embedded in paraffin and processed for routine H&E staining. Positive nodes were nodes that indicated metastases on H&E or immunohistochemical cytokeratin staining; also, nodes with small malignant cell clusters upon staining with immunohistochemical cytokeratin were considered positive for tumor.

The pathologic axillary response was determined by comparing the pretreatment axillary status with the results found on final histological analysis of the axillary nodes removed upon CALND. Patients with no positive nodes on final analysis were considered to have a complete pathologic response in the axilla (pCRAX). Patients were also assessed clinically after treatment and clinical response rates were assessed. For patients with pathologically and clinically negative nodes before treatment, the clinical response with respect to the axilla was not applicable.

Histological Evaluation of Tumor
Tumor histological characteristics were assessed with a biopsy before treatment. Excisional, core, and incisional biopsies were performed on patients with LABC. Where possible, central incisional biopsy through the long axis of the tumor was accomplished to ascertain a true cross-sectional size of the tumor. Tumor size was also clinically and radiographically assessed before treatment to compare tumor size upon definitive surgery. Upon final surgery, intraoperative assessments of tumor margins were obtained using by touch imprint cytology, and the results were relayed to the surgeon. The surgeon then re-excised the margins if the intraoperative assessment was positive or terminated excision of the tumor upon a report of clear margins.

The final pathologic work-up and staging were completed after definitive surgery. Final pathology reports were reviewed to see whether residual tumor remained after treatment. Patients were labeled as having residual or no residual tumor. Patients with no residual tumor after treatment with neoadjuvant chemotherapy were considered to have a complete pathologic tumor response to treatment.

Statistical Analysis
Comparison between patients with a pCRAX after neoadjuvant chemotherapy and those with residual axillary disease after neoadjuvant chemotherapy was conducted by using the standard Kaplan-Meier method. Overall survival was calculated from the date of surgery to the date of last follow-up or date of death for deceased patients. Disease-free survival was calculated from the date of operation to the date of recurrence or death. Any P value ≤.05 was considered statistically significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Group 1: Patients With Clinically Positive Lymph Nodes
Forty-two clinically positive nodes determined by palpable masses in the axilla were histologically confirmed by FNA or core biopsy of the palpable node (group 1). Most patients in group 1 had stage III disease (Table 1Go). All patients received treatment with neoadjuvant chemotherapy before definitive surgical treatment. At definitive operation, 41 (98%) of 42 patients in this group received a CALND. One patient opted for an SLN biopsy after treatment and did not undergo a CALND. This patient had a micrometastatic tumor apparent on cytokeratin staining only and refused further axillary surgery.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Patient characteristics broken down into group 1 (no SLN biopsy before neoadjuvant chemotherapy; n = 42) and group 2 (SLN biopsy before chemotherapy; n = 47)
 
The average number of axillary lymph nodes removed on CALND was 15. Eleven (26%) of 42 patients had a complete pathologic axillary conversion, and no metastatic tumor was found in the axillary lymph nodes. Thirty-one (74%) of 42 had residual axillary disease (Table 1Go).

Group 2: Patients With SLN Biopsy Before Treatment
Forty-seven patients with LABC and clinically negative nodes were treated with neoadjuvant chemotherapy. These patients underwent lymphatic mapping of the breast with the combination technique. One (2.1%) of 47 patients experienced mapping failure and went on to CALND, whereas in 46 (98%) of 47, an SLN was identified by either blue staining or a sufficient radioactive count with the gamma probe. SLN biopsy before neoadjuvant chemotherapy found 7 (15%) of 47 patients with a negative SLN and 40 (85%) of 47 with a positive SLN. One case had positive results with cytokeratin staining only and went on to undergo CALND, whereas the remaining 39 patients had positive SLNs on standard H&E staining.

After preoperative chemotherapy, a CALND was performed on the 40 patients with positive SLNs before treatment and the 1 patient with a failed mapping. An average of 13 lymph nodes were removed upon CALND. Response to preoperative chemotherapy was assessed for those with positive SLNs and the individual with an SLN biopsy failure. Thirteen (33%) of 40 patients had a pCRAX, and 27 (67%) of 40 had residual disease in the axilla. Four patients (10%) had a complete response in the primary tumor, because no residual tumor was identified upon definitive operation (Table 1Go).

Seven patients (15%) who underwent SLN biopsy before surgery were found to have negative SLNs. None of these patients received a CALND after neoadjuvant chemotherapy, and response was measured with regard to only the primary tumor. Two (29%) of seven patients had a complete pathologic tumor response. One patient had six lymph nodes removed upon definitive operation at the discretion of the surgeon; however, none of the axillary lymph nodes removed was positive for metastatic carcinoma. Moreover, all of these patients were staged T3 and N0 and were stage IIB overall.

Group Comparison
Overall, 27 (30%) of 89 patients received breast-conserving therapy in the form of lumpectomy at the time of definitive operation (Table 2Go). Neoadjuvant chemotherapy changed the surgical options for these 27 patients from mastectomy to lumpectomy in the overall group. Fewer patients in group 2 were converted to lumpectomy (Table 2Go). This finding may be related to factors of patient choice versus tumor biology or other unknown factors. Finally, patients who had a pCRAX had a significantly longer overall survival (P = .020) and disease-free survival (P = .023) than patients with residual disease (Fig. 1Go).


View this table:
[in this window]
[in a new window]
  		TABLE 2. Number of patients in groups 1 and 2 who received breast-conserving therapy after neoadjuvant chemotherapy
 

Figure 1
View larger version (18K):
[in this window]
[in a new window]
  		FIG. 1. Overall survival comparison (A) and disease-free survival comparison (B) for patients who had a complete axillary response and patients who had residual disease in their axilla after neoadjuvant chemotherapy.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
The incontrovertible goals of the surgical management of breast cancer are (1) performing accurate staging, (2) providing prognostic indicators for patient stratification, (3) collecting prognostic tissue markers, and (4) controlling local disease. The premise of this study is an attempt to maximize these goals. Accurate identification of nodal involvement in patients with LABC was accomplished in 47% of the patients with clinically evident axillary disease by core or FNA biopsy, whereas 53% of patients with clinically negative axillae were evaluated by SLN biopsy. Of these, 15% were spared axillary dissection when the SLN was negative.

The hope that SLN biopsy after neoadjuvant therapy could potentially eliminate CALND in 23% of patients who have a pCRAX to therapy presupposes that all cases are documented to have positive nodes before treatment and that in all cases the SLN biopsy, after therapy, would accurately reflect the entire basin. Conflicting studies report on the efficacy of SLN biopsy after treatment with neoadjuvant chemotherapy, reporting a 0% to 33% false-negative rate (FNR) when SLN biopsy is used to stage the axilla after treatment14–28 (Table 3Go). The higher FNRs were demonstrated in several of these trials in which large tumors (>3.5 cm) were present before neoadjuvant chemotherapy, whereas low FNRs were seen in patients with tumors ≤3.5 cm. Therefore, it remains questionable whether a complete pathologic response in the SLN truly represents the status of the remaining axilla after neoadjuvant therapy (Table 3Go).


View this table:
[in this window]
[in a new window]
  		TABLE 3. Studies reporting on SLN mapping after treatment with neoadjuvant chemotherapy
 
The validity of SLN biopsy has been shown with respect to large tumors without neoadjuvant chemotherapy, and lymphatic mapping success rates are very similar to those seen in patients with smaller tumors. Therefore, LABC is not a contraindication for SLN biopsy when performed before neoadjuvant chemotherapy. The failure rate for locating the SLN in our study was 1 (2.1%) in 47, which is considerably lower than the average failure rate of 10.6% reported in other studies (Table 3Go) that conducted SLN biopsy after neoadjuvant chemotherapy.18,19,24,25,28,29 These studies show a range of failure rates of 2.4% to 18%. The higher end of the range may be due, in part, to structural changes in lymphatic drainage that may be caused by treatment.

FNRs when SLN biopsy is performed after treatment in patients receiving neoadjuvant chemotherapy range from 0% to 33%17–28 (Table 3Go). Many of the studies reporting an FNR of 0% were conducted in patients with a smaller average tumor size. Piato et al.26 reported an FNR of 17% with average tumor sizes of <5 cm. The study by Bear et al. was conducted on a subset of the National Surgical Adjuvant Breast and Bowel Project B-27 trial, which we know from published data has a mean tumor size of 4.5 cm.8 However, the average tumor size for the 428-patient subset that received SLN mapping after neoadjuvant chemotherapy was not available. The studies that report a higher FNR consist of patients with larger tumors. The high variability in the reporting of FNRs raises concerns about the predictive value of SLN biopsy after treatment with neoadjuvant chemotherapy. The predictive value of SLN biopsy in patients with small (<4.5-cm) breast tumors is very high, and rarely is an SLN negative (false negative) for meta-static disease when further non-SLNs are positive.30

Some advocate noninvasive techniques to provide axillary staging of patients with LABC before treatment. Noninvasive axillary staging techniques are inaccurate and do not provide a high-enough sensitivity to be used as viable tools. Magnetic resonance imaging has been used to evaluate the axillary nodes for the presence of metastases; however, the sensitivity is 73% to 83%, even though overall accuracy is high.31,32 One technique evaluates the axilla with ultrasonography; determination by size alone helps to increase sensitivity, but there is a corresponding low specificity. Determination by echo characteristics of malignant involvement shows high specificity but low sensitivity.33 FNA biopsy has been combined with the above-mentioned technique to improve on the results, and specificity approaches 100%, but the sensitivity is approximately 80%.33 Although all of these techniques show potential for noninvasive axillary staging, the sensitivity of these techniques is lower and less specific than that of SLN biopsy.

Structural changes in lymphatic drainage in the breast can occur as a result of treatment with neoadjuvant chemotherapy, thus causing SLN biopsy failure rates to increase after treatment.28 Not all axillary nodes may respond equally to neoadjuvant chemotherapy, and SLNs may be cleared of axillary disease while other non-SLNs may still harbor cancerous cells. This nonidentical response to neoadjuvant chemotherapy would adversely affect the predictive value of SLN biopsy after neoadjuvant chemotherapy. Therefore, posttreatment SLN mapping may not be a reliable assessment of the axillary basin, particularly in patients with large tumors, with relative rates of positivity of approximately 75%.10

Some patients with LABC have clinically negative nodes that are also negative upon SLN biopsy before treatment. Fifteen percent of patients who had their axilla staged with SLN biopsy before treatment had node-negative disease in this series. These patients did not receive a CALND or axillary radiation after treatment, and none has presented with either local or distant recurrence at 33 months’ follow-up. This represents a significant subset of patients who do not require a CALND after treatment. Furthermore, by identification of the negative SLN before neoadjuvant chemotherapy, those who would not benefit from axillary radiotherapy are clearly defined. In this series, these 15% were appropriately stratified for not needing axillary radiotherapy or CALND.

Axillary staging in patients undergoing neoadjuvant treatments is necessary according to the study conducted by Kuerer et al.,5 in which all patients had cytologically or histologically documented axillary lymph node metastasis before neoadjuvant chemotherapy. If accurate nodal staging is required for patient accrual to neoadjuvant studies, then pretreatment SLN biopsy can greatly improve axillary staging when the axilla is clinically negative. In our series, more than half of the patients had nonpalpable nodes. Patients with positive SLNs before neoadjuvant chemotherapy can undergo a CALND after treatment, and those few with negative SLNs can be spared a CALND with a very low probability of further axillary metastases.1 The effectiveness of neoadjuvant chemotherapy in this group of clinically and pathologically node-negative patients, however, can be assessed by the pathologic tumor response to neoadjuvant chemotherapy. The concept of the SLN is to assess the true status of the axilla, and it has been shown that this concept of the SLN may not hold true when alterations occur as a result of treatment with neoadjuvant chemotherapy.28

Our findings maintain that patients with a pCRAX have a significantly greater overall survival rate than those with residual disease after neoadjuvant chemotherapy. Kuerer and colleagues’ results,5 along with this study, document a significant difference in survival (both overall and disease-free survival) between complete and partial responses to neoadjuvant chemotherapy.34 This study substantiates the finding that patients with a pCRAX have a significantly improved prognosis.


   CONCLUSIONS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
Patients with LABC (stage II >4.5 cm; stage IIIA and B without inflammatory changes) should have axillary staging performed before treatment with neoadjuvant chemotherapy. Mapping the SLN of these patients with clinically node-negative disease before neoadjuvant chemotherapy is accurate, sensitive, and specific. Neoadjuvant treatment of patients with confirmed nodal disease was increased by 53% when SLN biopsy was performed on cN0 patients before neoadjuvant treatment. SLN biopsy in patients with LABC increased by 53% those who were accurately stratified by axillary response to neoadjuvant chemotherapy, spared 15% a CALND, and appropriately excluded the need for axillary radiotherapy. Mapping patients before or after neoadjuvant chemotherapy is accurate, sensitive, and specific for patients with smaller tumors (<4.5 cm) but begs the question as to why the patient is receiving neoadjuvant chemotherapy, because studies have validated no survival advantage with neoadjuvant treatment for this subset of patients.

This study proposes the abandonment of post-treatment SLN mapping for LABC and the application of only pretreatment SLN mapping. This study validates the M. D. Anderson study5 and suggests pretreatment lymphatic SLN mapping of patients with nonpalpable (cN0) disease while eliminating CALND for patients with negative SLNs. The recommended approach to cN0 patients with LABC (tumor sizes ≥ 4.5 cm) includes incisional biopsy of the tumor, SLN biopsy, and placement of a vascular access device before neoadjuvant chemotherapy. This provides an excellent opportunity to accurately stage patients before chemotherapy; to collect appropriate samples for standard treatment markers (estrogen and progesterone receptor status and HER-2/neu), prognostic biomarkers (signal transducer and activator of transcription, Ki-67, and epidermal growth factor receptor), prognostic microarray analysis of the tumor or nodal metastasis, and bone marrow; and, finally, to determine prognostic stratification as a response to chemotherapy. The primary goals of the surgical management of breast cancer remain accurate staging, providing prognostic indicators for patient stratification, collecting tissues for prognostic markers, and controlling local disease: these are all maximized by the above-described approach.

Received for publication March 25, 2005. Accepted for publication October 19, 2005.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Nwariaku FE, Euhus DM, Beitsch PD, et al. Sentinel lymph node biopsy, an alternative to elective axillary dissection for breast cancer. Am J Surg 1998; 176:529– 31.[CrossRef][Medline]
  2. Canavese G, Gipponi M, Catturich A, et al. Sentinel lymph node mapping in early-stage breast cancer: technical issues and results with vital blue dye mapping and radioguided surgery. J Surg Oncol 2000; 74:61– 8.[Medline]
  3. Veronesi U, Galimberti V, Zurrida S, et al. Sentinel lymph node biopsy as an indicator for axillary dissection in early breast cancer. Eur J Cancer 2001; 37:454– 8.[CrossRef][Medline]
  4. Feggi LM, Querzoli P, Prandini N, et al. Sentinel node study in early breast cancer. Tumori 2000; 86:314– 6.[Medline]
  5. Kuerer HM, Singletary SE, Buzdar AU, et al. Surgical conservation planning after neoadjuvant chemotherapy for stage II and operable stage III breast carcinoma. Am J Surg 2001; 182:601– 8.[CrossRef][Medline]
  6. Cance WG, Carey LA, Calvo BF, et al. Long-term outcome of neoadjuvant therapy for locally advanced breast carcinoma: effective clinical downstaging allows breast preservation and predicts outstanding local control and survival. Ann Surg 2002; 236:295– 302; discussion 302–3.[CrossRef][Medline]
  7. Smith IC, Heys SD, Hutcheon AW, et al. Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol 2002; 20:1456– 66.[Abstract/Free Full Text]
  8. Bear HD, Anderson S, Brown A, et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project protocol B-27. J Clin Oncol 2003; 21:1– 10.[Free Full Text]
  9. Merajver SD, Weber BL, Cody R, et al. Breast conservation and prolonged chemotherapy for locally advanced breast cancer: the University of Michigan experience. J Clin Oncol 1997; 15:2873– 81.[Abstract]
  10. Chung MH, Ye W, Giuliano AE. Role for sentinel lymph node dissection in the management of large (> or = 5 cm) invasive breast cancer. Ann Surg Oncol 2001; 8:688– 92.[Abstract/Free Full Text]
  11. Bedrosian I, Reynolds C, Mick R, et al. Accuracy of sentinel lymph node biopsy in patients with large primary breast tumors. Cancer 2000; 88:2540– 5.[CrossRef][Medline]
  12. Schrenk P, Hochreiner G, Fridrik M, Wayand W. Sentinel node biopsy performed before preoperative chemotherapy for axillary lymph node staging in breast cancer. Breast J 2003; 9:282– 7.[Medline]
  13. Diaz N, Minton S, Cox C, et al. Activation of staff in primary tumors from high-risk breast cancer patients is associated with elevated levels of activated SRC and survivin expression. Clin Cancer Res 2006; 12:20–28.[Abstract/Free Full Text]
  14. Schwartz GF, Meltzer AJ. Accuracy of axillary sentinel lymph node biopsy following neoadjuvant (induction) chemotherapy for carcinoma of the breast. Breast J 2003; 9:374– 9.[CrossRef][Medline]
  15. Kang SH, Kim SK, Kwon Y, et al. Decreased identification rate of sentinel lymph node after neoadjuvant chemotherapy. World J Surg 2004; 28:1019– 24.[Medline]
  16. Lang JE, Esserman LJ, Ewing CA, et al. Accuracy of selective sentinel lymphadenectomy after neoadjuvant chemotherapy: effect of clinical node status at presentation. J Am Coll Surg 2004; 199:855– 62.[CrossRef]
  17. Tafra L, Verbanac KM, Lannin DR. Preoperative chemotherapy and sentinel lymphadenectomy for breast cancer. Am J Surg 2001; 182:312– 5.[CrossRef][Medline]
  18. Miller AR, Thomason VE, Yeh IT, et al. Analysis of sentinel lymph node mapping with immediate pathologic review in patients receiving preoperative chemotherapy for breast carcinoma. Ann Surg Oncol 2002; 9:243– 7.[Abstract/Free Full Text]
  19. Haid A, Tausch C, Lang A, et al. Is sentinel lymph node biopsy reliable and indicated after preoperative chemotherapy in patients with breast carcinoma? Cancer 2001; 92:1080– 4.[CrossRef][Medline]
  20. Julian TB, Dusi D, Wolmark N. Sentinel node biopsy after neoadjuvant chemotherapy for breast cancer. Am J Surg 2002; 184:315– 7.[Medline]
  21. Brady EW. Sentinel lymph node mapping following neoadjuvant chemotherapy for breast cancer. Breast J 2002; 8:97– 100.[Medline]
  22. Balch GC, Mithani SK, Richards KR, Beauchamp RD, Kelley MC. Lymphatic mapping and sentinel lymphadenectomy after preoperative therapy for stage II and III breast cancer. Ann Surg Oncol 2003; 10:616– 21.[Abstract/Free Full Text]
  23. Mamounas EP. Sentinel lymph node biopsy after neoadjuvant systemic therapy. Surg Clin North Am 2003; 83:931–42.[CrossRef][Medline]
  24. Breslin TM, Cohen L, Sahin A, et al. Sentinel lymph node biopsy is accurate after neoadjuvant chemotherapy for breast cancer. J Clin Oncol 2000; 18:3480– 6.[Abstract/Free Full Text]
  25. Stearns V, Ewing CA, Slack R, Penannen MF, Hayes DF, Tsangaris TN. Sentinel lymphadenectomy after neoadjuvant chemotherapy for breast cancer may reliably represent the axilla except for inflammatory breast cancer. Ann Surg Oncol 2002; 9:235– 42.[Abstract/Free Full Text]
  26. Piato JR, Barros AC, Pincerato KM, Sampaio AP, Pinotti JA. Sentinel lymph node biopsy in breast cancer after neoadjuvant chemotherapy. A pilot study. Eur J Surg Oncol 2003; 29:118– 20.[Medline]
  27. Fernandez A, Cortes M, Benito E, et al. Gamma probe sentinel node localization and biopsy in breast cancer patients treated with a neoadjuvant chemotherapy scheme. Nucl Med Commun 2001; 22:361– 6.[CrossRef][Medline]
  28. Nason KS, Anderson BO, Byrd DR, et al. Increased false negative sentinel node biopsy rates after preoperative chemotherapy for invasive breast carcinoma. Cancer 2000; 89: 2187– 94.[CrossRef][Medline]
  29. Cohen LF, Breslin TM, Kuerer HM, Ross MI, Hunt KK, Sahin AA. Identification and evaluation of axillary sentinel lymph nodes in patients with breast carcinoma treated with neoadjuvant chemotherapy. Am J Surg Pathol 2000; 24: 1266– 72.[Medline]
  30. Albertini J, Lyman GH, Cox C, Yeatman T. Lymphatic mapping and sentinel node biopsy in the patient with breast cancer. JAMA 1996; 276:1818– 22.[Abstract]
  31. Yoshimura G, Sakurai T, Oura S, et al. Evaluation of axillary lymph node status in breast cancer with MRI. Breast Cancer 1999; 6:249– 58.[Medline]
  32. Michel SC, Keller TM, Frohlich JM, et al. Preoperative breast cancer staging: MR imaging of the axilla with ultrasmall superparamagnetic iron oxide enhancement. Radiology 2002; 225:527– 36.[Abstract/Free Full Text]
  33. Bonnema J, van Geel AN, van Ooijen B, et al. Ultrasound-guided aspiration biopsy for detection of nonpalpable axillary node metastases in breast cancer patients: new diagnostic method. World J Surg 1997; 21:270– 4.[CrossRef][Medline]
  34. Kuerer HM, Sahin A, Hunt KK, et al. Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy. Ann Surg Oncol 1999; 230:72– 8.



This article has been cited by other articles:


Home page
 Ann. Surg. Oncol.Home page
K. E. Kilbride, M. C. Lee, A. V. Nees, V. M. Cimmino, K. M. Diehl, M. S. Sabel, D. F. Hayes, A. F. Schott, C. G. Kleer, A. E. Chang, et al.
Axillary Staging Prior to Neoadjuvant Chemotherapy for Breast Cancer: Predictors of Recurrence
Ann. Surg. Oncol., November 1, 2008; 15(11): 3252 - 3258.
[Abstract] [Full Text] [PDF]

Home page
 Arch SurgHome page
B. J. Grube, C. J. Christy, D. Black, M. Martel, L. Harris, J. Weidhaas, M. P. DiGiovanna, G. Chung, M. M. Abu-Khalaf, K. D. Miller, et al.
Breast Sentinel Lymph Node Dissection Before Preoperative Chemotherapy
Arch Surg, July 1, 2008; 143(7): 692 - 700.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
P. Gimbergues, C. Abrial, X. Durando, G. Le Bouedec, F. Cachin, F. Penault-Llorca, M. A. Mouret-Reynier, F. Kwiatkowski, J. Maublant, A. Tchirkov, et al.
Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy Is Accurate in Breast Cancer Patients with a Clinically Negative Axillary Nodal Status at Presentation
Ann. Surg. Oncol., May 1, 2008; 15(5): 1316 - 1321.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
E. A. Newman, M. S. Sabel, A. V. Nees, A. Schott, K. M. Diehl, V. M. Cimmino, A. E. Chang, C. Kleer, D. F. Hayes, and L. A. Newman
Sentinel Lymph Node Biopsy Performed After Neoadjuvant Chemotherapy is Accurate in Patients with Documented Node-Positive Breast Cancer at Presentation
Ann. Surg. Oncol., October 1, 2007; 14(10): 2946 - 2952.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cox, C. E.
Right arrow Articles by Minton, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cox, C. E.
Right arrow Articles by Minton, S.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS