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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003830
• Other study ID #: NSABP B-32
• Secondary ID: U10CA012027CDR00
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: November 14, 2017
• Start date: May 1999
• Est. completion date: February 2014

Study information

• Verified date: November 2017
• Source: NSABP Foundation Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5611
• Est. completion date: February 2014
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Procedure:
• conventional surgery
Sentinel node resection immediately followed by axillary dissection.
• 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.

Locations

Country	Name	City	State
Canada	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	Jewish General Hospital - Montreal	Montreal	Quebec
Canada	Royal Victoria Hospital - Montreal	Montreal	Quebec
Canada	St. Mary's Hospital Center	Montreal	Quebec
Canada	Centre Hospitalier Universitaire de Quebec	Quebec City	Quebec
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	St. Michael's Hospital - Toronto	Toronto	Ontario
Canada	Toronto Sunnybrook Regional Cancer Centre	Toronto	Ontario
Puerto Rico	MBCCOP - San Juan	San Juan
United States	Akron City Hospital	Akron	Ohio
United States	New York Oncology Hematology, P.C. - Albany Regional Cancer Center	Albany	New York
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Franklin Square Hospital Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Cancer Research Center at Boston Medical Center	Boston	Massachusetts
United States	Vermont Cancer Center at University of Vermont	Burlington	Vermont
United States	Aultman Hospital Cancer Center at Aultman Health Foundation	Canton	Ohio
United States	Camcare Health	Charleston	West Virginia
United States	Creticos Cancer Center at Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	MBCCOP-Cook County Hospital	Chicago	Illinois
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Jewish Hospital of Cincinnati, Incorporated	Cincinnati	Ohio
United States	Ireland Cancer Center	Cleveland	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Halifax Medical Center	Daytona Beach	Florida
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Michigan State University	E. Lansing	Michigan
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Hartford Hospital	Hartford	Connecticut
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Methodist Cancer Center at Methodist Hospital	Indianapolis	Indiana
United States	Baptist Regional Cancer Institute - Jacksonville	Jacksonville	Florida
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	CCOP - Dayton	Kettering	Ohio
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California
United States	University of Miami Sylvester Cancer Center	Miami	Florida
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	MBCCOP - Gulf Coast	Mobile	Alabama
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Stanley S. Scott Cancer Center at Louisiana State University Medical Center - New Orleans	New Orleans	Louisiana
United States	Tulane University Medical Center	New Orleans	Louisiana
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Virginia Oncology Associates - Newport News	Newport News	Virginia
United States	Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha	Omaha	Nebraska
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburg	Pennsylvania
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	Reading Hospital and Medical Center	Reading	Pennsylvania
United States	MBCCOP - Massey Cancer Center	Richmond	Virginia
United States	CCOP - Beaumont	Royal Oaks	Michigan
United States	CCOP - Northern Indiana CR Consortium	S. Bend	Indiana
United States	Sutter Breast Cancer Group	Sacramento	California
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego	San Diego	California
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	Puget Sound Oncology Consortium	Seattle	Washington
United States	Providence Cancer Institute at Providence Hospital	Southfield	Michigan
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Stanford Cancer Center at Stanford University Medical Center	Stanford	California
United States	CCOP - Northwest	Tacoma	Washington
United States	MBCCOP - Howard University Cancer Center	Washington	District of Columbia
United States	CCOP - Wichita	Wichita	Kansas
United States	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center - University Campus	Worcester	Massachusetts
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
NSABP Foundation Inc	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

References & Publications (9)

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 — View 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.

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 — View 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.

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. Review. — View 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( — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	Morbidity - Number of Participants With Residual Arm Numbness	Morbidity as measured by residual arm numbness	before and after surgery (within 30 days of randomization)
Primary	Morbidity - Number of Participants With Residual Arm Tingling	Morbidity as measured by residual arm tingling	before and after surgery (within 30 days of randomization)
Primary	Overall Survival	Measured at the time from randomization to any death to determine the percentage of patients alive at 8 years	8 years
Primary	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	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
Secondary	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
Secondary	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)
Secondary	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)