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After Chemotherapy, Sentinel Lymph Node Surgery Demonstrated Accuracy in Nodal Staging

by Bidita Debnath on  December 08, 2012 at 6:19 PM Research News   - G J E 4
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In 84 percent of patients with node-positive breast cancer, sentinel lymph node surgery correctly identified nodal status after treatment with neoadjuvant chemotherapy.
 After Chemotherapy, Sentinel Lymph Node Surgery Demonstrated Accuracy in Nodal Staging
After Chemotherapy, Sentinel Lymph Node Surgery Demonstrated Accuracy in Nodal Staging

And this could therefore provide a less invasive option than axillary lymph node dissection for nodal staging in this population, according to data from the American College of Surgeons Oncology Group (ACOSOG) Z1071 study.

These results were presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8.

Most women with breast cancer that has spread to their lymph nodes undergo an axillary lymph node dissection (ALND). However, treatment with chemotherapy before surgery, or neoadjuvant chemotherapy, can eradicate disease in the lymph nodes of some patients, converting them to node-negative status.

Sentinel lymph node (SLN) surgery is routinely used for patients initially diagnosed with node-negative disease. Judy C. Boughey, M.D., associate professor of surgery at the Mayo Clinic in Rochester, Minn., and her colleagues evaluated whether this technique could be safe for patients with node-positive breast cancer who undergo neoadjuvant chemotherapy.

In the case of node-positive breast cancer, "the question arises as to whether removal of the lymph nodes with an ALND is needed, or whether less invasive surgery, with a sampling of the nodes by SLN surgery alone, would reliably identify which patients still have disease in the lymph nodes and which patients have negative lymph nodes," said Boughey.

The researchers conducted a multicenter study of 756 women with node-positive breast cancer who received neoadjuvant chemotherapy and underwent surgery. The study was performed through the American College of Surgeons Oncology Group (ACOSOG) and supported by the NCI.

Of these patients, 637 underwent both SLN surgery with identification and removal of the sentinel nodes under the arm and ALND to remove most of the lymph nodes in the axilla. SLN surgery correctly identified nodal status in 91 percent of patients, including 255 patients now with node-negative breast cancer and 326 patients with continuing node-positive disease.

Boughey and her colleagues also found that 40 percent of the patients for which an SLN could be identified showed a complete pathological response in the lymph nodes, or eradication of active disease in the lymph nodes.

"If SLN surgery is accurate for evaluating the lymph nodes after neoadjuvant chemotherapy, it potentially could allow patients to avoid ALND and undergo SLN for axillary staging and only require an ALND if the SLN is positive," Boughey said.

Boughey noted a false-negative rate of 12.6 percent.

"This rate is lower with use of dual tracer (blue dye and radiolabelled colloid) to identify the SLN, and the false-negative rate is lower the more SLNs are removed. Therefore, technical factors are important to minimize incorrect nodal staging," she said.

# # #

The mission of the 2012 CTRC-AACR San Antonio Breast Cancer Symposium is to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for patients with breast cancer. The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR) and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. This collaboration utilizes the clinical strengths of the CTRC and Baylor and the AACR''s scientific prestige in basic, translational and clinical cancer research to expedite the delivery of the latest scientific advances to the clinic.

Abstract:
Publication Number: S2-1

Title: The role of sentinel lymph node surgery in patients presenting with node positive breast cancer (T0-T4, N1-2) who receive neoadjuvant chemotherapy results from the ACOSOG Z1071 trial

Judy C Boughey1, Vera J Suman1, Elizabeth A Mittendorf2, Gretchen M Ahrendt3, Lee G Wilke4, Bret Taback5, A M Leitch6, Teresa S Flippo-Morton7, David R Byrd8, David W Ollila9, Thomas B Julian10, Sarah A McLaughlin11, Linda McCall12, W F Symmans2, Huong T Le-Petross2, Bruce G Haffty13, Thomas A Buchholz2 and Kelly K Hunt2. 1Mayo Clinic, Rochester, MN; 2MD Anderson Cancer Center, Houston, TX; 3Magee-Womens Surgical Associates, Pittsburgh, PA; 4University of Wisconsin-Madison, WI; 5Columbia University Medical Center, New York, NY; 6University of Texas Southwestern Medical Center, Dallas, TX; 7Carolinas Medical Center, Charlotte, NC; 8University of Washington Medical Center, Seattle, WA; 9University of North Carolina - Chapel Hill, NC; 10Allegheny General Hospital, Pittsburgh, PA; 11Mayo Clinic, Jacksonville, FL; 12Duke University Medical Center, Durham, NC and 13The Cancer Institute of New Jersey, New Brunswick, NJ.

Body: Background: The utility of sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in patients presenting with node-positive breast cancer has not been determined. The American College of Surgeons Oncology Group (ACOSOG) Z0171 trial was designed to evaluate SLN surgery after NAC in women presenting with node positive disease.

Methods: ACOSOG Z1071 enrolled women with clinical T0-4, N1-2, M0 breast cancer receiving NAC. At the time of surgery, all patients were to undergo SLN surgery followed by axillary lymph node dissection (ALND). The primary endpoint was false negative rate (FNR) in women with cN1 disease with 2 or more SLNs reviewed. Positive SLNs were defined as metastases >0.2mm on H&E. The protocol encouraged dual tracer technique. A Bayesian study design with a non-informative prior was chosen to assess whether the probability that the SLN surgery FNR is greater than 10%.

Results: From July 2009 to July 2011, 756 patients were enrolled from 136 institutions. Fifteen women were ineligible and 33 withdrew. Of 708 evaluable pts (668 cN1, 40 cN2), 643 had a SLN identified and an ALND (607 cN1, with indeterminate SLN results in 2); 52 pts (48 cN1) had no SLN identified and had ALND; 11 underwent ALND only (all cN1), and 2 pts had SLN only (both cN1). In patients with SLN and ALND, the SLN identification rate was 92.5% (92.7% in cN1, 90% in cN2). SLN correctly identified nodal status in 84% of the 695 pts [258 of pathologically node negative and 327 of pathologically node positive; cN1: 83.8% (549/655), cN2: 90.0% (36/40)]. Of the 643 pts with a SLN identified there was a complete pathologic response in 40.3% (40.3 % for cN1 and 50% for cN2). Of the pts with a positive SLN, the SLN was the only site of disease in 40%. For pts with cN1 disease with 2+ SLNs identified with residual nodal disease, the SLN FNR was 12.8%. In pts with dual tracer technique the FNR was 11.1%. There were no FN results among pts with cN2 disease with 2+ SLNs reviewed. Of the 40 pts with a false negative SLN of the 528 cN1 patients with 2+ SLNs examined, the number of positive nodes at ALND was 1 (50.0%); 2 (25%); 3 (10.0%) and 4-9 (15.0%).

Conclusions: NAC resulted in eradication of lymph node disease in 40% of node positive breast cancer patients. SLN surgery after NAC in node positive breast cancer pts correctly identified nodal status in 84% of all patients and was associated with a FNR of 12.8%. The FNR of SLN is higher than the prespecified study endpoint of 10%. Further analysis of factors associated with FNR such as clinical response, histological findings and axillary ultrasound findings is warranted prior to widespread use of SLN in these patients.

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