Clinical trial NCT00636467: Axillary Sentinel Lymph Node Detection in Breast Cancers > 2 cm
Official title: Evaluation of the Technique of Axillary Sentinel Lymph Node (SLN) Detection in Breast Cancers > 2 cm
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Breast cancer (tumors> 2 cm)
Detection
Axillary sentinel lymph node
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
Collaborators: name: PHRC 2007: financial support
First posted: 2008-03-14
Enrollment: 249
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to evaluate the quality criteria of the SLN detection technique in breast cancer patients with a tumor size (clinical measurement) greater than 2 centimeters (rate of false negatives, rate of detection).

Eligible patients will only be registered (no randomization). The estimated inclusion period is approximately 24 months. The duration of the research is 25 months (24 months for patient inclusion + 1 month for reception of results). The maximum participation duration of each patient is 1 month.

The number of patients required in this multicentric and prospective study is 240 (16 participating centers).

Detailed description: Axillary node extension is one of the major prognostic factors in breast cancer. Axillary dissection of Berg level I and II nodes is the validated method to obtain information on lymph node invasion, but it is associated with important morbidity.

Sentinel lymph node assessment (SLN) was developed to select patients likely not to have axillary node extension using a technique less invasive than conventional dissection. Axillary dissection is restricted to patients with undetected or metastatic SLN.

SLN detection involves subareolar or peri-tumoral injection of lymphotropic contrast agents which map the regional lymphatic drainage pattern of the tumor.

This technique allows an optimization of histopathological analysis: the pathologist must analyze only two nodes on average (instead of 10-15), allowing the examination of numerous tissue sections and the development of specific techniques such as immunohistochemistry.

The principal indicators of success for the technique are the detection rate, the false negative rate and the number of SLN sampled.

The assessment of feasibility is based on concomitant histopathological analysis of the SLN and of complementary lymph nodes.

There is no consensus in the literature on the SLN technique to be used for tumors with clinical size superior to 2 cm in diameter.

The aim of this prospective, multicentric study is to evaluate the performance of the SLN technique, in terms of detection rate and false negative rate, for patients with tumors greater than 2 cm (clinical measurement).

A homogeneous technique with "combined", colorimetric and isotopic SLN detection with subareolar or peri-tumoral injection will be used. This consensus "combined" technique has been validated by all investigators. The histopathological procedure will also be homogeneous, and validated within the group of pathologists of the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC). Breast surgery will either be a mastectomy or conservative treatment.

The primary objective of the study is to evaluate the quality criteria of the SLN detection technique in breast cancer patients with a tumor size (clinical measurement) greater than 2 centimeters (rate of false negatives, rate of detection).

The secondary objectives are:

* Evaluation of the number of SLN sampled per patient,
* Lymphoscintigraphic evaluation of the pattern of lymphatic drainage in breast tumors \> 2 centimeters,
* Precise histopathological description of the SLN sampled and of axillary nodes of levels I and II.

Evaluation criteria:

The primary criterion is the rate of false negatives, determined by the ratio of the number of patients with detected but negative SLN to the total number of positive non-sentinel nodes at the time of axillary dissection of levels I and II (patients classified as N+ according to the TNM system).

This rate will be determined after calculation of the detection rate, determined by the ratio of the number of patients evaluated on the total number of patients.

In agreement with international recommendations, the expected rate of false negatives should be \< 5 % with a detection rate \> 85 %.

Secondary criteria include:

* Total number of sampled SLN per patient,
* Lymphoscintigraphy: detection of SLN by means of extra-axillary markings,
* Histopathological results:

  * SLN: metastases, capsular breach, micro metastases, isolated cells,
  * Dissection: number of positive nodes.

Eligibility criteria: Inclusion Criteria:

* Female, age ≥ 18 years
* Patient with invasive unifocal breast cancer with tumor size \> 2 cm at initial examination (clinical examination and/or imaging)
* Preoperative histological diagnosis of infiltrating mammary carcinoma
* No lymph node at clinical examination
* No treatment for this cancer before surgery
* Mandatory affiliation with a social security system
* Written, signed informed consent

Exclusion Criteria:

* No invasive breast cancer
* Breast tumor =\< 2 cm
* Preoperative histological diagnosis other than infiltrating mammary carcinoma
* Multifocal breast cancer
* Inflammatory breast cancer
* Metastatic cancer
* History of homolateral breast surgery
* History of allergic disorders
* History of homolateral breast cancer
* Difficult follow-up
* Pregnant or lactating woman
* Previous inclusion in the trial

Primary outcomes:
measure: Quality criteria of the SLN detection technique
timeFrame: 1 month
Secondary outcomes:
measure: Total number of sampled SLN per patient
timeFrame: 1 month
measure: Detection of SLN by means of extra-axillary markings (lymphoscintigraphy)
timeFrame: 1 month
measure: Histopathological results (SLN)
timeFrame: 1 month
measure: Histopathological results (dissection)
timeFrame: 1 month
Other outcomes:
Locations:
city: Angers
country: France
facility: Centre Paul Papin
city: Bordeaux
country: France
facility: Institut Bergonié
city: Boulogne Sur Mer
country: France
facility: CH Boulogne sur Mer
city: Calais
country: France
facility: CH Calais
city: Coquelles
country: France
facility: Clinique des 2 Caps
city: Cucq
country: France
facility: Clinique des Acacias
city: Guilherand Granges
country: France
facility: Clinique Pasteur
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Hôtel Dieu
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: Centre Val d'Aurelle
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Rang Du Fliers
country: France
facility: CH Arrondissement Montreuil sur Mer
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Cloud
country: France
facility: Centre René Huguenin
city: Saint Etienne
country: France
facility: CHRU Saint Etienne
city: Saint Herblain
country: France
facility: Centre René Gauducheau
city: Saint Martin Boulogne
country: France
facility: CMCO
city: Toulouse
country: France
facility: Institut Claudius Régaud
city: Vandoeuvre Les Nancy
country: France
facility: Centre Alexis Vautrin
Study officials:
affiliation: Centre Leon Berard, Lyon
name: Hervé MIGNOTTE, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bonadonna G, Valagussa P, Moliterni A, Zambetti M, Brambilla C. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med. 1995 Apr 6;332(14):901-6. doi: 10.1056/NEJM199504063321401.
citation: Ivens D, Hoe AL, Podd TJ, Hamilton CR, Taylor I, Royle GT. Assessment of morbidity from complete axillary dissection. Br J Cancer. 1992 Jul;66(1):136-8. doi: 10.1038/bjc.1992.230.
citation: Ververs JM, Roumen RM, Vingerhoets AJ, Vreugdenhil G, Coebergh JW, Crommelin MA, Luiten EJ, Repelaer van Driel OJ, Schijven M, Wissing JC, Voogd AC. Risk, severity and predictors of physical and psychological morbidity after axillary lymph node dissection for breast cancer. Eur J Cancer. 2001 May;37(8):991-9. doi: 10.1016/s0959-8049(01)00067-3.
citation: Kissin MW, Querci della Rovere G, Easton D, Westbury G. Risk of lymphoedema following the treatment of breast cancer. Br J Surg. 1986 Jul;73(7):580-4. doi: 10.1002/bjs.1800730723.
citation: Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994 Sep;220(3):391-8; discussion 398-401. doi: 10.1097/00000658-199409000-00015.
citation: Krag DN, Weaver DL, Alex JC, Fairbank JT. Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg Oncol. 1993 Dec;2(6):335-9; discussion 340. doi: 10.1016/0960-7404(93)90064-6.
citation: Glass EC, Essner R, Giuliano AE. Sentinel node localization in breast cancer. Semin Nucl Med. 1999 Jan;29(1):57-68. doi: 10.1016/s0001-2998(99)80030-0.
citation: Turner RR, Ollila DW, Krasne DL, Giuliano AE. Histopathologic validation of the sentinel lymph node hypothesis for breast carcinoma. Ann Surg. 1997 Sep;226(3):271-6; discussion 276-8. doi: 10.1097/00000658-199709000-00006.
citation: McMasters KM, Tuttle TM, Carlson DJ, Brown CM, Noyes RD, Glaser RL, Vennekotter DJ, Turk PS, Tate PS, Sardi A, Cerrito PB, Edwards MJ. Sentinel lymph node biopsy for breast cancer: a suitable alternative to routine axillary dissection in multi-institutional practice when optimal technique is used. J Clin Oncol. 2000 Jul;18(13):2560-6. doi: 10.1200/JCO.2000.18.13.2560.
citation: Weaver DL, Krag DN, Ashikaga T, Harlow SP, O'Connell M. Pathologic analysis of sentinel and nonsentinel lymph nodes in breast carcinoma: a multicenter study. Cancer. 2000 Mar 1;88(5):1099-107.
citation: Tafra L, McMasters KM, Whitworth P, Edwards MJ. Credentialing issues with sentinel lymph node staging for breast cancer. Am J Surg. 2000 Oct;180(4):268-73. doi: 10.1016/s0002-9610(00)00466-9.
citation: McMasters KM, Wong SL, Chao C, Woo C, Tuttle TM, Noyes RD, Carlson DJ, Laidley AL, McGlothin TQ, Ley PB, Brown CM, Glaser RL, Pennington RE, Turk PS, Simpson D, Edwards MJ; University of Louisville Breast Cancer Study Group. Defining the optimal surgeon experience for breast cancer sentinel lymph node biopsy: a model for implementation of new surgical techniques. Ann Surg. 2001 Sep;234(3):292-9; discussion 299-300. doi: 10.1097/00000658-200109000-00003.
citation: Orr RK, Hoehn JL, Col NF. The learning curve for sentinel node biopsy in breast cancer: practical considerations. Arch Surg. 1999 Jul;134(7):764-7. doi: 10.1001/archsurg.134.7.764.
citation: Bedrosian I, Reynolds C, Mick R, Callans LS, Grant CS, Donohue JH, Farley DR, Heller R, Conant E, Orel SG, Lawton T, Fraker DL, Czerniecki BJ. Accuracy of sentinel lymph node biopsy in patients with large primary breast tumors. Cancer. 2000 Jun 1;88(11):2540-5. doi: 10.1002/1097-0142(20000601)88:113.0.co;2-a.
citation: Chung MH, Ye W, Giuliano AE. Role for sentinel lymph node dissection in the management of large (> or = 5 cm) invasive breast cancer. Ann Surg Oncol. 2001 Oct;8(9):688-92. doi: 10.1007/s10434-001-0688-y.
citation: Lelievre L, Houvenaeghel G, Buttarelli M, Brenot-Rossi I, Huiart L, Tallet A, Tarpin C, Jacquemier J. Value of the sentinel lymph node procedure in patients with large size breast cancer. Ann Surg Oncol. 2007 Feb;14(2):621-6. doi: 10.1245/s10434-006-9232-4. Epub 2006 Nov 12.
citation: Schwartz GF, Giuliano AE, Veronesi U; Consensus Conference Committee. Proceedings of the consensus conference on the role of sentinel lymph node biopsy in carcinoma of the breast, April 19-22, 2001, Philadelphia, Pennsylvania. Cancer. 2002 May 15;94(10):2542-51. doi: 10.1002/cncr.10539. No abstract available.
citation: Lyman GH, Giuliano AE, Somerfield MR, Benson AB 3rd, Bodurka DC, Burstein HJ, Cochran AJ, Cody HS 3rd, Edge SB, Galper S, Hayman JA, Kim TY, Perkins CL, Podoloff DA, Sivasubramaniam VH, Turner RR, Wahl R, Weaver DL, Wolff AC, Winer EP; American Society of Clinical Oncology. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol. 2005 Oct 20;23(30):7703-20. doi: 10.1200/JCO.2005.08.001. Epub 2005 Sep 12.
citation: Edwards M, Giuliano A, Reintgen D, Tafra L. Consensus statement on guidelines for performance of sentinel lymph node biopsy for breast cancer. Am Soc Breast Surg Q. Press Release, 1998 ;Fall :3