Clinical trial NCT00003830: Surgery to Remove Sentinel Lymph Nodes With or Without Removing Lymph Nodes in the Armpit in Treating Women With Breast Cancer
Official title: A Randomized, Phase III Clinical Trial to Compare Sentinel Node Resection to Conventional Axillary Dissection in Clinically Node-Negative Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: stage I breast cancer
stage II breast cancer
Lead sponsor: NSABP Foundation Inc
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-28
Enrollment: 5611
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Morbidity - Number of Participants With Residual Shoulder Abduction Deficit
timeFrame: Before and after surgery (within 30 days of randomization)
measure: Morbidity - Number of Participants With Residual Arm Volume Difference
timeFrame: before and after surgery (within 30 days of randomization)
measure: Morbidity - Number of Participants With Residual Arm Numbness
timeFrame: before and after surgery (within 30 days of randomization)
measure: Morbidity - Number of Participants With Residual Arm Tingling
timeFrame: before and after surgery (within 30 days of randomization)
measure: Overall Survival
timeFrame: 8 years
measure: Disease-free Survival as Measured by Breast Cancer Recurrence, Any Second Primary Cancer, and Death From Any Cause in Patients Without a Prior Event.
timeFrame: 8 years
Secondary outcomes:
measure: Pathology Investigation of Sentinel Nodes in Sentinel Node Negative Patients to Identify a Group Who Were Potentially at Increased Risk of Systemic Recurrence
timeFrame: From the time of randomization until 5 years
measure: Pathology Investigation of Sentinel Nodes in Sentinel Node Negative Patients to Identify a Group Who Were Potentially at Increased Risk of Systemic Recurrence
timeFrame: From the time of randomization until 5 years
measure: The Percentage of Technically Successful Sentinel Node Resections as Measured by the Proportion of Patients for Whom at Least One Sentinel Node is Identified.
timeFrame: At time of surgery (within 30 days of randomization)
measure: Sensitivity of the Sentinel Node to Determine Presence of Nodal Metastases.
timeFrame: At time of surgery (within 30 days of randomization)
Other outcomes:
Locations:
city: Mobile
country: United States
facility: MBCCOP - Gulf Coast
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Cancer Institute at Loma Linda University Medical Center
state: California
city: Sacramento
country: United States
facility: Sutter Breast Cancer Group
state: California
city: San Diego
country: United States
facility: Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center at Stanford University Medical Center
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Washington
country: United States
facility: MBCCOP - Howard University Cancer Center
state: District of Columbia
city: Daytona Beach
country: United States
facility: Halifax Medical Center
state: Florida
city: Jacksonville
country: United States
facility: Baptist Regional Cancer Institute - Jacksonville
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Cancer Center
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: MBCCOP-Cook County Hospital
state: Illinois
city: Chicago
country: United States
facility: Creticos Cancer Center at Advocate Illinois Masonic Medical Center
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Indianapolis
country: United States
facility: Methodist Cancer Center at Methodist Hospital
state: Indiana
city: S. Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: New Orleans
country: United States
facility: Stanley S. Scott Cancer Center at Louisiana State University Medical Center - New Orleans
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University Medical Center
state: Louisiana
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: Franklin Square Hospital Center
state: Maryland
city: Boston
country: United States
facility: Cancer Research Center at Boston Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center - University Campus
state: Massachusetts
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: E. Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Royal Oaks
country: United States
facility: CCOP - Beaumont
state: Michigan
city: Southfield
country: United States
facility: Providence Cancer Institute at Providence Hospital
state: Michigan
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Omaha
country: United States
facility: Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha
state: Nebraska
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology, P.C. - Albany Regional Cancer Center
state: New York
city: Winston-Salem
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Fargo
country: United States
facility: CCOP - Merit Care Hospital
state: North Dakota
city: Akron
country: United States
facility: Akron City Hospital
state: Ohio
city: Canton
country: United States
facility: Aultman Hospital Cancer Center at Aultman Health Foundation
state: Ohio
city: Cincinnati
country: United States
facility: Jewish Hospital of Cincinnati, Incorporated
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Kettering
country: United States
facility: CCOP - Dayton
state: Ohio
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Pittsburg
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Reading
country: United States
facility: Reading Hospital and Medical Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - MainLine Health
state: Pennsylvania
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Burlington
country: United States
facility: Vermont Cancer Center at University of Vermont
state: Vermont
city: Newport News
country: United States
facility: Virginia Oncology Associates - Newport News
state: Virginia
city: Richmond
country: United States
facility: MBCCOP - Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: Puget Sound Oncology Consortium
state: Washington
city: Tacoma
country: United States
facility: CCOP - Northwest
state: Washington
city: Charleston
country: United States
facility: Camcare Health
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Saint John
country: Canada
facility: Saint John Regional Hospital
state: New Brunswick
city: Toronto
country: Canada
facility: Toronto Sunnybrook Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital - Toronto
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Montreal
country: Canada
facility: Royal Victoria Hospital - Montreal
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital - Montreal
state: Quebec
city: Montreal
country: Canada
facility: St. Mary's Hospital Center
state: Quebec
city: Quebec City
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
state: Quebec
city: San Juan
country: Puerto Rico
facility: MBCCOP - San Juan
Study officials:
affiliation: NSABP Foundation Inc
name: Norman Wolmark, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.