Surgery to Remove Sentinel Lymph Nodes With or Without Removing Lymph Nodes in the Armpit in Treating Women With Breast Cancer

A Randomized, Phase III Clinical Trial to Compare Sentinel Node Resection to Conventional Axillary Dissection in Clinically Node-Negative Breast Cancer Patients

RATIONALE: Removing the sentinel lymph nodes and examining them under a microscope may help plan more effective surgery for breast cancer. It is not yet known if surgery to remove the sentinel lymph nodes is more effective with or without removal of the lymph nodes in the armpit in treating breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of surgery to remove the sentinel lymph nodes with or without removal of lymph nodes in the armpit in treating women who have breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: conventional surgery; Procedure: Sentinel node resection followed by node examination

Detailed Description

OBJECTIVES:

• Compare the long term control of regional disease by sentinel node resection vs sentinel node resection followed by conventional axillary dissection in women with breast cancer who are clinically node negative and pathologically sentinel node negative.
• Compare the effect of these two regimens on the overall and disease-free survival of these patients.
• Compare the morbidity associated with these two regimens in these patients.
• Compare the prognostic value of these two regimens in patients who are sentinel node negative or positive by pathology.
• Determine whether a more detailed pathology investigation can identify a group of patients with a potentially increased risk of systemic recurrence who are node negative by pathology.
• Determine the technical success rate of sentinel node dissection and the variability of technical success rate in a broad population of surgeons.
• Determine the sensitivity of the sentinel node to determine the presence of nodal metastases in these patients.

Objectives of quality of life questionnaire in sentinel node-negative patients:

• Compare the severity of self-assessed symptoms and activity limitations of patients treated with these two regimens.
• Compare the severity of self-assessed symptoms and activity limitations after breast cancer surgery in patients whose surgery was on the dominant side vs patients whose surgery was on the non-dominant side.
• Compare the impact of arm edema, range of motion, and sensory neuropathy on self-assessed measures of daily functioning, symptoms, and overall quality of life of patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are stratified according to the surgical treatment plan (lumpectomy vs mastectomy), age (49 and under vs 50 and over), and clinical tumor size (no greater than 2.0 cm vs 2.1-4.0 cm vs at least 4.1 cm). Patients are randomized to one of two surgery arms.

All patients receive technetium (Tc 99m) sulfur colloid injected into normal breast tissue within 1 cm of the primary tumor or biopsy cavity and an intradermal injection of technetium (Tc 99m) sulfur colloid, approximately 0.5-8 hours before surgery. Patients also receive an injection of isosulfan blue dye around the tumor or biopsy cavity after a hot spot is identified with a gamma detector. If a hot spot is not identified, the blue dye is injected after a saline bolus injection.

• Arm I: Patients undergo sentinel node resection immediately followed by conventional axillary dissection.
• Arm II: Patients undergo sentinel node resection and an intraoperative examination of sentinel nodes.

Patients with positive sentinel nodes undergo axillary dissection after sentinel node resection.

Patients with cytologically negative sentinel nodes do not undergo axillary dissection.

Patients with cytologically negative but histologically positive sentinel nodes return to surgery for axillary dissection.

Patients with histologically positive sentinel nodes and those in whom the sentinel node is not identified undergo axillary dissection after sentinel node resection.

Patients with pathologically positive, nonaxillary sentinel nodes undergo axillary dissection after sentinel node resection.

Patients with evidence of tumor remaining after surgery undergo a total mastectomy.

Quality of life is assessed at baseline, at weeks 1-3, and then every 6 months for 3 years or until recurrence.

Patients are followed at 1 and 3 weeks, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 5,400 patients will be accrued for this study within 4 years.

• Study Type: Interventional
• Enrollment (Actual): 5611
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Saint John Regional Hospital
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Toronto Sunnybrook Regional Cancer Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital - Toronto
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Royal Victoria Hospital - Montreal
    • Montreal, Quebec, Canada, H2L-4M1
      • Centre Hospitalier de l'Universite de Montreal
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital - Montreal
    • Montreal, Quebec, Canada, H3T 1M5
      • St. Mary's Hospital Center
    • Quebec City, Quebec, Canada, G1R 2J6
      • Centre Hospitalier Universitaire de Quebec
• Puerto Rico
  • San Juan, Puerto Rico, 00927-5800
    • MBCCOP - San Juan
• United States
  • Alabama
    • Mobile, Alabama, United States, 36688
      • MBCCOP - Gulf Coast
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • Loma Linda, California, United States, 92354
      • Loma Linda University Cancer Institute at Loma Linda University Medical Center
    • Sacramento, California, United States, 95819-5156
      • Sutter Breast Cancer Group
    • San Diego, California, United States, 92120
      • Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego
    • Stanford, California, United States, 94305-5408
      • Stanford Cancer Center at Stanford University Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06102-5037
      • Hartford Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • MBCCOP - Howard University Cancer Center
  • Florida
    • Daytona Beach, Florida, United States, 32114
      • Halifax Medical Center
    • Jacksonville, Florida, United States, 32207
      • Baptist Regional Cancer Institute - Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Cancer Center
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii
  • Illinois
    • Chicago, Illinois, United States, 60657
      • Creticos Cancer Center at Advocate Illinois Masonic Medical Center
    • Chicago, Illinois, United States, 60612
      • MBCCOP-Cook County Hospital
    • Peoria, Illinois, United States, 61602
      • CCOP - Illinois Oncology Research Association
  • Indiana
    • Indianapolis, Indiana, United States, 46206-1367
      • Methodist Cancer Center at Methodist Hospital
    • S. Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
  • Iowa
    • Des Moines, Iowa, United States, 50309-1016
      • CCOP - Iowa Oncology Research Association
  • Kansas
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Medical Center
    • New Orleans, Louisiana, United States, 70112
      • Stanley S. Scott Cancer Center at Louisiana State University Medical Center - New Orleans
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Franklin Square Hospital Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Cancer Research Center at Boston Medical Center
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center - University Campus
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Hospital
    • E. Lansing, Michigan, United States, 48824
      • Michigan State University
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Kalamazoo, Michigan, United States, 49007-3731
      • CCOP - Kalamazoo
    • Royal Oaks, Michigan, United States, 48073-6769
      • CCOP - Beaumont
    • Southfield, Michigan, United States, 48075-9975
      • Providence Cancer Institute at Providence Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Cancer Institute Of New Jersey
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology, P.C. - Albany Regional Cancer Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27104-4241
      • CCOP - Southeast Cancer Control Consortium
    • Winston-Salem, North Carolina, United States, 27157-1082
      • Comprehensive Cancer Center at Wake Forest University
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • CCOP - Merit Care Hospital
  • Ohio
    • Akron, Ohio, United States, 44312
      • Akron City Hospital
    • Canton, Ohio, United States, 44710
      • Aultman Hospital Cancer Center at Aultman Health Foundation
    • Cincinnati, Ohio, United States, 45267-0502
      • Charles M. Barrett Cancer Center at University Hospital
    • Cincinnati, Ohio, United States, 45236
      • Jewish Hospital of Cincinnati, Incorporated
    • Cleveland, Ohio, United States, 44106-5065
      • Ireland Cancer Center
    • Columbus, Ohio, United States, 43206
      • CCOP - Columbus
    • Kettering, Ohio, United States, 45429
      • CCOP - Dayton
  • Oregon
    • Portland, Oregon, United States, 97213
      • CCOP - Columbia River Oncology Program
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-2001
      • Geisinger Medical Center
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • Pittsburg, Pennsylvania, United States, 15212-4772
      • Allegheny General Hospital
    • Reading, Pennsylvania, United States, 19612-6052
      • Reading Hospital and Medical Center
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - MainLine Health
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
  • Texas
    • San Antonio, Texas, United States, 78284-7811
      • University of Texas Health Science Center at San Antonio
  • Utah
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Vermont
    • Burlington, Vermont, United States, 05401-3498
      • Vermont Cancer Center at University of Vermont
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Virginia Oncology Associates - Newport News
    • Richmond, Virginia, United States, 23298-0037
      • MBCCOP - Massey Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Puget Sound Oncology Consortium
    • Tacoma, Washington, United States, 98405-0986
      • CCOP - Northwest
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • Camcare Health
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Resectable invasive adenocarcinoma of the breast, confirmed by 1 of the following:

  • Histologically confirmed by core or open biopsy
  • Confirmed by fine needle aspiration cytology AND positive clinical breast examination and ultrasound or mammography

• Clinically negative lymph nodes

  • No positive ipsilateral axillary lymph nodes
  • No prior removal of ipsilateral axillary lymph nodes
  • No suspicious palpable nodes in the contralateral axilla or palpable supraclavicular or infraclavicular nodes, unless proven nonmalignant by biopsy

• No ulceration, erythema, infiltration of the skin or underlying chest wall (complete fixation), peau d'orange, or skin edema of any magnitude

  • Tethering or dimpling of the skin or nipple inversion allowed
• No bilateral malignancy or mass in the opposite breast that is suspicious for malignancy, unless proven nonmalignant by biopsy
• No diffuse tumors or multiple malignant tumors in different quadrants of the breast
• No other prior breast malignancy except lobular carcinoma in situ
• No prior or concurrent breast implants

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 years and older

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• Not specified

Life expectancy:

• At least 10 years (excluding diagnosis of cancer)

Hematopoietic:

• Not specified

Hepatic:

• No hepatic systemic disease

Renal:

• No renal systemic disease

Cardiovascular:

• No cardiovascular systemic disease

Other:

• No prior malignancy within past 5 years except:

  • Effectively treated squamous cell or basal cell skin cancer
  • Surgically treated carcinoma in situ of the cervix
  • Surgically treated lobular carcinoma in situ of the ipsilateral or contralateral breast
• No concurrent psychiatric or addictive disorder

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior immunotherapy for this cancer

Chemotherapy:

• No prior chemotherapy for this cancer, including neoadjuvant chemotherapy

Endocrine therapy:

• No prior hormonal therapy for this cancer

Radiotherapy:

• No prior radiotherapy for this cancer

Surgery:

• See Disease Characteristics
• No prior breast reduction surgery
• Prior excisional biopsy or lumpectomy allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I: Conventional axillary dissection; Sentinel node resection immediately followed by axillary dissection	Procedure: conventional surgery; Sentinel node resection immediately followed by axillary dissection.
Experimental: Arm II: Sentinel node resection followed by node examination; Sentinel node resection followed by node examination then axillary dissection if positive sentinel node.	Procedure: Sentinel node resection followed by node examination; Sentinel node resection followed by node examination then axillary dissection if positive sentinel node. No axillary dissection for negative sentinel node.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morbidity - Number of Participants With Residual Shoulder Abduction Deficit	Morbidity as measured by residual shoulder abduction deficit. Shoulder Abduction Deficit definition: Shoulder range of motion decreased by greater than or equal to 10% as compared with that measured prior to surgery.	Before and after surgery (within 30 days of randomization)
Morbidity - Number of Participants With Residual Arm Volume Difference	Morbidity as measured by residual arm volume difference. Residual Arm Volume Difference definition: Arm volume differences greater than or equal to 10% as compared with that measured prior to surgery	before and after surgery (within 30 days of randomization)
Morbidity - Number of Participants With Residual Arm Numbness	Morbidity as measured by residual arm numbness	before and after surgery (within 30 days of randomization)
Morbidity - Number of Participants With Residual Arm Tingling	Morbidity as measured by residual arm tingling	before and after surgery (within 30 days of randomization)
Overall Survival	Measured at the time from randomization to any death to determine the percentage of patients alive at 8 years	8 years
Disease-free Survival as Measured by Breast Cancer Recurrence, Any Second Primary Cancer, and Death From Any Cause in Patients Without a Prior Event.	Measured at time from randomization to recurrence, second primary, or death to determine the percentage of patients disease free at 8 years.	8 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathology Investigation of Sentinel Nodes in Sentinel Node Negative Patients to Identify a Group Who Were Potentially at Increased Risk of Systemic Recurrence	Percentage of patients distant disease-free at 5 years. Sentinel node definition: Sentinel nodes are the first few lymph nodes into which a tumor drains. Sentinel node biopsy requires injecting a tracer material to help a surgeon locate sentinel nodes during surgery.	From the time of randomization until 5 years
Pathology Investigation of Sentinel Nodes in Sentinel Node Negative Patients to Identify a Group Who Were Potentially at Increased Risk of Systemic Recurrence	Measured at time from randomization to any distant cancer or death to determine percentage of patients distant disease free at 5 years. Sentinel node definition: Sentinel nodes are the first few lymph nodes into which a tumor drains. Sentinel node biopsy requires injecting a tracer material to help a surgeon locate sentinel nodes during surgery.	From the time of randomization until 5 years
The Percentage of Technically Successful Sentinel Node Resections as Measured by the Proportion of Patients for Whom at Least One Sentinel Node is Identified.	Sentinel node definition: Sentinel nodes are the first few lymph nodes into which a tumor drains. Sentinel node biopsy requires injecting a tracer material to help a surgeon locate sentinel nodes during surgery.	At time of surgery (within 30 days of randomization)
Sensitivity of the Sentinel Node to Determine Presence of Nodal Metastases.	Sentinel node definition: Sentinel nodes are the first few lymph nodes into which a tumor drains. Sentinel node biopsy requires injecting a tracer material to help a surgeon locate sentinel nodes during surgery.	At time of surgery (within 30 days of randomization)

Collaborators and Investigators

• Sponsor: NSABP Foundation Inc
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Land SR, Ritter MW, Costantino JP, Julian TB, Cronin WM, Haile SR, Wolmark N, Ganz PA. Compliance with patient-reported outcomes in multicenter clinical trials: methodologic and practical approaches. J Clin Oncol. 2007 Nov 10;25(32):5113-20. doi: 10.1200/JCO.2007.12.1749.
• Weaver DL, Le UP, Dupuis SL, Weaver KA, Harlow SP, Ashikaga T, Krag DN. Metastasis detection in sentinel lymph nodes: comparison of a limited widely spaced (NSABP protocol B-32) and a comprehensive narrowly spaced paraffin block sectioning strategy. Am J Surg Pathol. 2009 Nov;33(11):1583-9. doi: 10.1097/PAS.0b013e3181b274e7.
• Land SR, Kopec JA, Lee M, et al.: Quality of life in breast cancer patients receiving sentinel-node (SN) biopsy alone or with axillary dissection (AD): results from NSABP protocol B-32. [Abstract] J Clin Oncol 26 (Suppl 15): A-9533, 2008.
• Julian TB, Anderson SJ, Fourchotte V, et al.: Is completion axillary dissection always required after a positive sentinel node biopsy? NSABP B-32. [Abstract] Breast Cancer Res Treat 106 (1): A-51, S15, 2007.
• Julian TB, Anderson SJ, Fourchotte V, et al.: Is intraoperative cytology of sentinel nodes useful and predictive for non-sentinel axillary nodes? NSABP B-32. [Abstract] Breast Cancer Res Treat 106 (1): A-3001, 2007.
• Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Ashikaga T, Weaver DL, Miller BJ, Jalovec LM, Frazier TG, Noyes RD, Robidoux A, Scarth HM, Mammolito DM, McCready DR, Mamounas EP, Costantino JP, Wolmark N; National Surgical Adjuvant Breast and Bowel Project. Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial. Lancet Oncol. 2007 Oct;8(10):881-8. doi: 10.1016/S1470-2045(07)70278-4.
• Julian B, Fourchotte V, Anderson S, et al.: Predictive factors that identify patients not requiring a sentinel node biopsy: continued analysis of the NSABP B-32 sentinel node trial. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-2003, S80-1, 2006.
• Weaver DL, Krag DN, Manna EA, Ashikaga T, Waters BL, Harlow SP, Bauer KD, Julian TB. Detection of occult sentinel lymph node micrometastases by immunohistochemistry in breast cancer. An NSABP protocol B-32 quality assurance study. Cancer. 2006 Aug 15;107(4):661-7. doi: 10.1002/cncr.22074.
• Harlow SP, Krag DN, Julian TB, Ashikaga T, Weaver DL, Feldman SA, Klimberg VS, Kusminsky R, Moffat FL Jr, Noyes RD, Beitsch PD. Prerandomization Surgical Training for the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 trial: a randomized phase III clinical trial to compare sentinel node resection to conventional axillary dissection in clinically node-negative breast cancer. Ann Surg. 2005 Jan;241(1):48-54. doi: 10.1097/01.sla.0000149429.39656.94.
• Weaver DL, Ashikaga T, Krag DN, Skelly JM, Anderson SJ, Harlow SP, Julian TB, Mamounas EP, Wolmark N. Effect of occult metastases on survival in node-negative breast cancer. N Engl J Med. 2011 Feb 3;364(5):412-21. doi: 10.1056/NEJMoa1008108. Epub 2011 Jan 19.
• Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino JP, Ashikaga T, Weaver DL, Mamounas EP, Jalovec LM, Frazier TG, Noyes RD, Robidoux A, Scarth HM, Wolmark N. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol. 2010 Oct;11(10):927-33. doi: 10.1016/S1470-2045(10)70207-2.

Study record dates

Study Major Dates

• Study Start: May 1, 1999
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 27, 2003
• First Posted (Estimate): January 28, 2003

Study Record Updates

• Last Update Posted (Actual): December 13, 2017
• Last Update Submitted That Met QC Criteria: November 14, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: stage II breast cancer; stage I breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: NSABP B-32; U10CA012027 (U.S. NIH Grant/Contract); CDR0000066987