Medico-economic Study of Three Strategies of Sentinel Lymph Node Analysis in Operable Breast Cancer

NCT02056886 | Completed DMC

• 2 other identifiers: ICO-N-2012-082012-A01504-39
• Study Type: interventional
• Target: 858
• Locations: 1 country
• Sites: 17

Brief Summary

Breast carcinoma requires frequently an adjuvant therapy after surgical excision: in this way, one of the major criteria indicating the need of adjuvant chemotherapy is the diagnosis of a metastatic lymph-node invasion, mainly in the axillary field. Axillary surgery is therefore mandatory at the diagnosis of breast carcinoma. For many years, in order to avoid unnecessary complications due to extensive axillary surgery (for instance, arm enlargement by lymphedema), a limited surgery is frequently performed on the first supposed invaded lymph-nodes (LN) called "sentinel" LN technique; if the sentinel LN are not invaded, extensive axillary surgery can be omitted. To decide it during the surgery, removed sentinel LN are cut in 3 to 4 slices which are examined immediately as smears (cytology) or frozen slices (pathology). However, due to hazard in cutting the LN, micro-metastases can be misdiagnosed. That is why a recent molecular biology method has been developed in which the total LN are crushed and blended, then analyzed by OSNA technique (One Step Nuclear Acid analysis) so as to amplify and detect the mRNA coding for cytokeratin-19 protein witnessing the LN metastatic invasion. A standardized automated technique is available with a mean time of 30 to 50 minutes according to the number of analyzed LN. In 12 international studies (2830 cases) the consistency between OSNA technique and final pathology is of 91 to 98% and the sensitivity seems higher. Less than 5% of all breast carcinomas cells don't express CK-19 protein. The use of OSNA technique requires a dedicated machine and a skilled pathologist, increasing slightly the operation time; however it allows to avoid the immediate and long-term complications due to the radical LN axillary surgery in case of negativity of the sentinel LN procedure. To date, the three techniques including extemporaneous examinations (OSNA or classical methods) or not (classical pathological analysis) have their own advantages and drawbacks. "SAGE" study main objective is to compare these three techniques in terms of direct costs and Quality of Life impacts. The superiority of any of these three techniques is not the purpose of SAGE study, but the economic burden of OSNA technique in comparison with the 2 others in the standard setting in France. Quality of Life and Pain evaluations will be performed immediately after surgery and during the 6 months after.

Conditions

Breast Cancer; Surgery

Keywords

breast cancer, sentinel lymph node, extemporaneous, OSNA

Outcome Measures

Primary Outcomes (1)

• Medico-economic study : medical cost between 3 different sentinel lymph node analysis (histological analysis or molecular biology) in the management of patients treated for invasive breast carcinoma.

  Several phases are differences to compare the costs of three strategies: * surgery * hospitalization * follow-up

  from surgery to 9 mounths later

Study Arms (3)

OSNA

EXPERIMENTAL

Intra operative sentinel lymph-node sampling. In this experimental arm, the molecular biology technique is only used through the OSNA technique (One Step Nuclear Acid analysis), and no other classical pathology's diagnosis method such as formalin fixation, then parraffin embedding before slices cutting, hematoxylin-eosin-safran staining or any other immunohistochemical stainings. According to the results of the staging procedure, the treatment in this arm is decided in conformity with local and national guidelines in breast cancer treatments. SLN detection +/- complementary axillary lymphadenectomy is immediately decided if a tumor invasion is detected within the sentinel LN material.

Procedure: SLN detection +/- complementary axillary lymphadenectomy

PATHOLOGICAL ANALYSIS

OTHER

No intra operative examination is performed in this arm, but the final pathological examination: In this arm, the classical pathology's diagnosis method is starting with a formalin fixation of suspected invaded lymph-nodes sampling at least 24Hrs; then parraffin embedding before slices cutting; then hematoxylin-eosin-safran staining or any other immunohistochemical stainings. According to the results of the staging procedure, the treatment in this arm is decided in conformity with local and national updated guidelines in breast cancer treatments. SLN detection +/- complementary axillary lymphadenectomy: is decided in a second surgical step when the pathologic analysis has detected a tumor invasion

Procedure: SLN detection +/- complementary axillary lymphadenectomy

EXTEMPORANEOUS

OTHER

"Intra-operative" pathological frozen sections of sentinel LN samples are coloured and examined immediately by the pathologist, allowing an immediate result at the disposal of the surgeon who can decide to complete by an axillary LN dissection or not. Then the remaining material will be prepared similarly as in the pathological classical method (Arm B), ie formalin fixation, then parraffin embedding, then slices cutting, then HES staining or ImmunoHistochemistry for a final diagnosis. SLN detection +/- complementary axillary lymphadenectomy: is decided immediately when the tumor invasion is detected in the sentinel LN material.

Procedure: SLN detection +/- complementary axillary lymphadenectomy

Interventions

SLN detection +/- complementary axillary lymphadenectomy PROCEDURE

breast cancer surgery with SLN detection +/- complementary axillary lymphadenectomy Whatever the detection method used in the lab (Arm A: OSNA; Arm B: Pathological Examination; Arm C: Extemporaneous) to assess the positivity of sentinel lymph-node invasion, if negative result (no tumor invasion in the sentinel LN), a complementary lymph-node dissection is not mandatory if positive result (tumor invasion in the sentinel LN), a complementary lymph-node dissection is performed, either immediately (Arm A and C) or in a second surgical procedure (Arm B)

Also known as: Surgical complementary dissection of axillary lymph-node.

EXTEMPORANEOUS; OSNA; PATHOLOGICAL ANALYSIS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Infiltrating breast carcinoma histologically proven (lobular, ...)
• unifocal,
• T \<3 cm (clinical), palpable or non-palpable tumor (smaller than a centimetre allowed),
• N0 clinical axillary
• Conservative surgery,
• GS detection by isotopic or combined method,
• Age \<65 (for more frequent activity), and\> 18 years.
• Social protection
• Signed Informed consent

You may not qualify if:

• Recurrence of breast carcinoma,
• History of ipsilateral breast reduction surgery,
• Radical surgery.
• History of lumpectomy
• Neoadjuvant chemotherapy
• Multi-focality
• Neoadjuvant hormone therapy
• \< 18 years old
• Pregnant or nursing patient or of childbearing age without effective contraception,
• Legal incapacity or limited legal capacity. Medical or psychological conditions not allowing the subject to understand the study and sign the consent.

Sponsors & Collaborators

• Institut Cancerologie de l'Ouest: lead

Study Sites (17)

ICO Paul Papin

Angers, 49000, France

Location

Institut Bergonie

Bordeaux, 33000, France

Location

Jean Perrin

Clermont-Ferrand, 63011, France

Location

Institut du Sein -Clinique Saint-Amé

Lambres-lez-Douai, 59552, France

Location

Oscar Lambret

Lille, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

HEGP

Paris, 75015, France

Location

Institut Curie

Paris, 75248, France

Location

CHU

Pierre-Bénite, 69495, France

Location

Eugène Marquis

Rennes, France

Location

Henri BECQUEREL

Rouen, 76038, France

Location

Institut Curie

Saint-Cloud, 92210, France

Location

Clinique Mutualiste

Saint-Etienne, 42013, France

Location

Jean-Marc cancérologie CLASSE

Saint-Herblain, 44800, France

Location

CHU

Saint-Priest-en-Jarez, 42277, France

Location

IUCT-O

Toulouse, 31052, France

Location

Institut de Cancérlogie de Lorraine

Vandœuvre-lès-Nancy, 54511, France

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Virginie BORDES, MD

  Institut de Cancérologie de l'Ouest (ICO) - Nantes, France

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2014
• First Posted: February 6, 2014
• Study Start: October 21, 2013
• Primary Completion: January 2, 2018
• Study Completion: February 15, 2022
• Last Updated: April 29, 2022

Record last verified: 2022-04

Locations

FR (17)