Medico-economic Study of Three Strategies of Sentinel Lymph Node Analysis in Operable Breast Cancer
Medico-economic Study of Three Strategies of Sentinel Lymph Node Analysis in Operable Breast Cancer
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.
Today, standard treatment for early Breast carcinoma starts with a surgical step consisting
 of the tumor resection and sentinel lymph-node (SLN) detection, in order to select patients
 to be proposed for complementary axillary lymphadenectomy. This requested information may be
 obtained during the same operation time by intra operative examination, or after surgery with
 the consequence of a second surgical procedure when lymphadenectomy appears to be indicated.
 In France, three strategies are currently used for the management of sentinel lymph nodes:

 -  intra operative pathological frozen section examination followed by final pathological
 diagnosis,

 -  intra operative molecular biology using the OSNA technique (One Step Nuclear Acid
 analysis)

 -  no intra operative examination, but the final pathological examination. Each of these 3
 strategies has advantage and drawbacks and their own cost. With more than 50000 new
 cases per year in France, Breast carcinoma, thanks to population screening, more and
 more small tumors are detected where such information about sentinel LN invasion is
 needed.

 Our proposed study is a prospective, cost-effectiveness and comparative non randomised study
 where three strategies are evaluated in the current practice of the participating teams.

 Main Objective :

 • to evaluate in each of these 3 strategies for sentinel LN diagnosis, cost-effectiveness and
 cost-utility (QALY), Quality of Life,…

 Secondary Objectives :

 -  rate of second surgery needed

 -  rate of mico-metastases or macro-metastases detected to build a decision score,

 -  follow-up of non re-operated patient despite positive sentinel LN,

 -  RNA collection from the crushed and blended sentinel LN

 -  Quality of Life evaluation through the surgical times using QLQ C30 and Br 23 scales.

 Medical section :

 At pre-operative consultation, patients will be informed to consent participating in our
 observational study, without any change in their treatment strategy. Inclusion parameters are
 strictly the same in the three groups.

 At the time of surgery, if intra operative examination is planned, patient will be informed
 that a complete axillary dissection could be indicated.

 Included patients will be followed 15 days after surgery and at 3 and 9 months. Then every 6
 months during 2 years, then yearly.

 Economical section :

 Main objective of " SAGE " study is to light up decision maker in striking the balance of
 each strategy (induced costs and prevented costs) and results in terms of health as expressed
 by individuals preference depending on different health status, treatment strategies and
 clinical practice in French centers.

 In our study, the medico-economical evaluation on such a quite National scale (17 different
 centers) takes place in a practice standardization prospect.

 General methodology :

 In each participating center, one of the 3 strategies for the sentinel LN analysis is
 currently used (with or without extemporaneous procedure).

 Cost-effect evaluation will inventory all undertaken costs in each strategy and all induced
 positive or negative consequences, both at a qualitative and quantitative level using micro
 costing and macro costing evaluations. Evaluation of Quality of Life adjusted to health will
 be included to the cost effect analysis.

 In our study, population studied with a localized breast carcinoma, are women aged between 18
 and 65 years old and likely to be active : inclusion criteria are strictly the same in the 3
 strategies studied.

 In our study, we will consider Hospital and Health Insurance point of view. Hospital prospect
 will identify and value the cost paid by health institution due to the use of any of these 3
 techniques.

 Insurance Health prospect will value the costs of each treatment strategy including direct
 costs related to private medical care and not only those to be reimbursed to the hospital.

 The study starts at the time of the sentinel LN excision and ends 9 months later, including
 the post-operative complications and the possible second surgery for axillary LN excision.

 At all 920 patients will be included in the 20 participating team.
Inclusion Criteria:

 1. Infiltrating breast carcinoma histologically proven (lobular, ...)

 2. unifocal,

 3. T <3 cm (clinical), palpable or non-palpable tumor (smaller than a centimetre
 allowed),

 4. N0 clinical axillary

 5. Conservative surgery,

 6. GS detection by isotopic or combined method,

 7. Age <65 (for more frequent activity), and> 18 years.

 8. Social protection

 9. Signed Informed consent

 Exclusion Criteria:

 1. Recurrence of breast carcinoma,

 2. History of ipsilateral breast reduction surgery,

 3. Radical surgery.

 4. History of lumpectomy

 5. Neoadjuvant chemotherapy

 6. Multi-focality

 7. Neoadjuvant hormone therapy

 8. < 18 years old

 9. Pregnant or nursing patient or of childbearing age without effective contraception,

 10. Legal incapacity or limited legal capacity. Medical or psychological conditions not
 allowing the subject to understand the study and sign the consent.