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

NCT ID: NCT00003830

Last Updated: 2017-12-13

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

5611 participants

Study Classification

INTERVENTIONAL

Study Start Date

1999-05-31

Study Completion Date

2014-02-28

Brief Summary

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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

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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.

Conditions

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Breast Cancer

Keywords

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stage I breast cancer stage II breast cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I: Conventional axillary dissection

Sentinel node resection immediately followed by axillary dissection

Group Type ACTIVE_COMPARATOR

conventional surgery

Intervention Type PROCEDURE

Sentinel node resection immediately followed by axillary dissection.

Arm II: Sentinel node resection followed by node examination

Sentinel node resection followed by node examination then axillary dissection if positive sentinel node.

Group Type EXPERIMENTAL

Sentinel node resection followed by node examination

Intervention Type PROCEDURE

Sentinel node resection followed by node examination then axillary dissection if positive sentinel node. No axillary dissection for negative sentinel node.

Interventions

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conventional surgery

Sentinel node resection immediately followed by axillary dissection.

Intervention Type 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.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

NSABP Foundation Inc

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Norman Wolmark, MD

Role: PRINCIPAL_INVESTIGATOR

NSABP Foundation Inc

Locations

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MBCCOP - Gulf Coast

Mobile, Alabama, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Sutter Breast Cancer Group

Sacramento, California, United States

Site Status

Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego

San Diego, California, United States

Site Status

Stanford Cancer Center at Stanford University Medical Center

Stanford, California, United States

Site Status

Hartford Hospital

Hartford, Connecticut, United States

Site Status

MBCCOP - Howard University Cancer Center

Washington D.C., District of Columbia, United States

Site Status

Halifax Medical Center

Daytona Beach, Florida, United States

Site Status

Baptist Regional Cancer Institute - Jacksonville

Jacksonville, Florida, United States

Site Status

University of Miami Sylvester Cancer Center

Miami, Florida, United States

Site Status

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

Sarasota Memorial Hospital

Sarasota, Florida, United States

Site Status

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States

Site Status

MBCCOP-Cook County Hospital

Chicago, Illinois, United States

Site Status

Creticos Cancer Center at Advocate Illinois Masonic Medical Center

Chicago, Illinois, United States

Site Status

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

Site Status

Methodist Cancer Center at Methodist Hospital

Indianapolis, Indiana, United States

Site Status

CCOP - Northern Indiana CR Consortium

South Bend, Indiana, United States

Site Status

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, United States

Site Status

CCOP - Wichita

Wichita, Kansas, United States

Site Status

Stanley S. Scott Cancer Center at Louisiana State University Medical Center - New Orleans

New Orleans, Louisiana, United States

Site Status

Tulane University Medical Center

New Orleans, Louisiana, United States

Site Status

Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

Franklin Square Hospital Center

Baltimore, Maryland, United States

Site Status

Cancer Research Center at Boston Medical Center

Boston, Massachusetts, United States

Site Status

University of Massachusetts Memorial Medical Center - University Campus

Worcester, Massachusetts, United States

Site Status

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, United States

Site Status

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Michigan State University

East Lansing, Michigan, United States

Site Status

CCOP - Grand Rapids

Grand Rapids, Michigan, United States

Site Status

CCOP - Kalamazoo

Kalamazoo, Michigan, United States

Site Status

CCOP - Beaumont

Royal Oaks, Michigan, United States

Site Status

Providence Cancer Institute at Providence Hospital

Southfield, Michigan, United States

Site Status

CCOP - Kansas City

Kansas City, Missouri, United States

Site Status

CCOP - Montana Cancer Consortium

Billings, Montana, United States

Site Status

Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha

Omaha, Nebraska, United States

Site Status

Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Site Status

New York Oncology Hematology, P.C. - Albany Regional Cancer Center

Albany, New York, United States

Site Status

CCOP - Southeast Cancer Control Consortium

Winston-Salem, North Carolina, United States

Site Status

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, United States

Site Status

CCOP - Merit Care Hospital

Fargo, North Dakota, United States

Site Status

Akron City Hospital

Akron, Ohio, United States

Site Status

Aultman Hospital Cancer Center at Aultman Health Foundation

Canton, Ohio, United States

Site Status

Jewish Hospital of Cincinnati, Incorporated

Cincinnati, Ohio, United States

Site Status

Charles M. Barrett Cancer Center at University Hospital

Cincinnati, Ohio, United States

Site Status

Ireland Cancer Center

Cleveland, Ohio, United States

Site Status

CCOP - Columbus

Columbus, Ohio, United States

Site Status

CCOP - Dayton

Kettering, Ohio, United States

Site Status

CCOP - Columbia River Oncology Program

Portland, Oregon, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Reading Hospital and Medical Center

Reading, Pennsylvania, United States

Site Status

CCOP - MainLine Health

Wynnewood, Pennsylvania, United States

Site Status

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Utah Valley Regional Medical Center - Provo

Provo, Utah, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Vermont Cancer Center at University of Vermont

Burlington, Vermont, United States

Site Status

Virginia Oncology Associates - Newport News

Newport News, Virginia, United States

Site Status

MBCCOP - Massey Cancer Center

Richmond, Virginia, United States

Site Status

Puget Sound Oncology Consortium

Seattle, Washington, United States

Site Status

CCOP - Northwest

Tacoma, Washington, United States

Site Status

Camcare Health

Charleston, West Virginia, United States

Site Status

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Saint John Regional Hospital

Saint John, New Brunswick, Canada

Site Status

Toronto Sunnybrook Regional Cancer Centre

Toronto, Ontario, Canada

Site Status

St. Michael's Hospital - Toronto

Toronto, Ontario, Canada

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada

Site Status

Royal Victoria Hospital - Montreal

Montreal, Quebec, Canada

Site Status

Jewish General Hospital - Montreal

Montreal, Quebec, Canada

Site Status

St. Mary's Hospital Center

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire de Quebec

Québec, Quebec, Canada

Site Status

MBCCOP - San Juan

San Juan, , Puerto Rico

Site Status

Countries

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United States Canada Puerto Rico

References

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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.

Reference Type BACKGROUND
PMID: 17991930 (View on PubMed)

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.

Reference Type RESULT
PMID: 19730364 (View on PubMed)

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.

Reference Type RESULT

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.

Reference Type RESULT

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.

Reference Type RESULT

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.

Reference Type RESULT
PMID: 17851130 (View on PubMed)

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.

Reference Type RESULT

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.

Reference Type RESULT
PMID: 17024757 (View on PubMed)

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.

Reference Type RESULT
PMID: 15621990 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21247310 (View on PubMed)

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.

Reference Type DERIVED
PMID: 20863759 (View on PubMed)

Other Identifiers

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U10CA012027

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000066987

Identifier Type: -

Identifier Source: secondary_id

NSABP B-32

Identifier Type: -

Identifier Source: org_study_id