The Memorial Sloan-Kettering Cancer Center (MSKCC
The Memorial Sloan-Kettering Cancer Center (MSKCC
The purpose of this study is to prospectively evaluate the combined use of the MSKCC nomogram
 (Memorial Sloan-Kettering Cancer Center) and Tenon score to select, in patients with
 metastatic sentinel lymph node (SN), those at low risk of metastatic non-SN in whom
 additional axillary lymph node dissection (ALND) could be avoided.
EXPERIMENTAL PLAN AND COURSE OF STUDY This is a prospective non-randomized non-interventional
 multicenter study including the respect of a quality charter and involving a prospective
 registration of clinical and histological data to test the hypothesis of a proportion of
 false negative rate (=rate of metastatic SN) of 5% +/- 5% within the population at low risk
 by the combined use of the MSKCC nomogram and Tenon score. No modification therapy will be
 conducted because the scores will not be provided to operators.

 6.1 Conduct of the study 6.1.1 Before and during surgery Every surgeon agreeing to
 participate in the study - and thus to respect the quality charter - will make the inclusion
 of his eligible patients with an e-CRF which will generate automatically a number of
 anonymity. A form of inclusion specifying the number of anonymity of the patient, the
 initials of the name and the first name as well as the date of birth of the patient will be
 send back by e-mail by the study coordinator and clinical study technician (CST) of the
 URC-Est. The surgeon will have at his disposal 60 boards of labels of anonymity elaborated by
 the CST of the URC-Est corresponding to 30 patients (2 boards of labels by patient). The
 resupplying of labels will be managed by the CST.

 A label will contain i) the number of anonymity, ii) the address and phone number of the
 surgeon, iii) the address and phone number of the pathology laboratory, iv) the address and
 phone number of the study coordinator including fax number where pathological results should
 be send.

 During the first intervention, the surgeon will send the histological specimen (i.e.
 lumpectomy or mastectomy, SN, and possibly non-SN in case the ALND is completed during the
 first surgical procedure with a board of labels of anonymity.

 In case of additional surgical procedure to complete ALND, the histological specimen (i.e.
 non-SN) will be sent to the pathology laboratory with the second board of label of anonymity
 corresponding to this patient.

 The laboratory of pathology will have to label with anonymity labels all histological reports
 that should be sent to the study coordinator. To eventually calculate combined prediction
 (MSKCC nomogram and Tenon score) and ensure respect of the quality charter, specific data
 must appear in the pathology report:

 -  Clinical information: age of the patient, the location of the primitive tumor (upper
 outer quadrant, SUPERO-medial, INFERO-lateral, INFERO-internal retroareolar or other),
 palpable tumor or not, the results of histological or cytological diagnosis performed
 preoperatively.

 -  Regarding the number of lumpectomy: size of invasive cancer (largest diameter),
 histologic type, associated intra ductal carcinoma (type and percentage), existence of
 vascular or lymphatic emboli, estrogen receptor status, progesterone receptor status,
 HER-2-neu status, SCAFF and Bloom-Richardson grade or equivalent, if realized, the level
 of expression of antigen Ki 67; regarding sentinel lymph nodes: number of SN harvested ;
 for each metastatic SN: type of metastasis: macrometastasis, micrometastasis, isolated
 cells, method of intraoperative diagnosis of metastasis (if performed): frozen section,
 cytology, RT-PCR. Final pathologic exam: routine H&E, serial sectioning H&E, IHC.
 Regarding non-sentinel lymph nodes: number of non-SN

 -  number of metastatic non-SN, postoperative TNM. 6.1.2 Collection of histological results
 from the pathology laboratories The study data will be informed through pathology
 reports. Ten weeks after receiving the e-CRF, the CST of the URC-EST under the
 responsibility of the study coordinator will contact the pathology laboratory. The
 latter will label with anonymity labels all histology reports corresponding to the first
 and possibly, if an additional ALND has further been done, and will fax reports to the
 study coordinator(fax number on the label).

 6.2 Procedure to calculate the risk of non-SN involvement A calculation of the probability of
 metastatic non-SN using the MSKCC nomogram and the the Tenon score will be performed for all
 patients. Calculations will be implemented under the responsibility of coordinating doctor.

 The result of these calculations will not be communicated to surgeons. 6.2.1 Calculating the
 score of Tenon

 -  Variable 1: Existence of macrometastasis in a non-SN: if macrometastases, 2 points are
 assigned, 0 otherwise.

 -  Variable 2: histological size of invasive tumor: 3 points if the tumor is greater than
 20 mm, 1.5 points if the size is in 10 and 20 mm and 0 points if less than 10 mm.

 -  Variable 3: Ratio between the number of metastatic SN (whatever the type of metastasis
 (macrometastasis, micrometastasis or isolated tumor cells)) and the number of SN
 harvested: 2 points if the ratio is 1; 1 point if between 0.5 and 1, and 0 points if
 less than 0.5.

 The scores for the 3 variables are then added together to calculate the score of Tenon.

 6.2.2 Calculation of risk by the MSKCC nomogram This calculation involves 8 variables: 1)
 histological type associated with SBR grade (infiltrating ductal carcinoma grade 1, grade 2,
 grade 3 and invasive lobular carcinoma (ILC)), 2) the existence of a LYMPHO-vascular invasion
 (LVI) (yes, no), 3) the multifocal nature of the tumor (yes, no), 4) status of estrogen
 receptor (present, absent), 4) the number of non-metastatic SN (0 to 14), 5) the number of
 metastatic SN (from 1 to 7), 6) the size of the tumor (from 0 to 9 cm), 7) method of
 detecting metastases in the SN. For the latter, there are 2 different situations: when using
 the technique CRYOCONGELATION, 4 items were proposed (CRYOCONGELATION analysis, analysis by
 H&E : routine H&E and serial sectioning H&E, and IHC), and in the absence of use of
 technology by cryocongelation only 3 items were proposed (analysis by H&E : routine H&E and
 serial sectioning H&E, and IHC).

 1. The calculation must be done using the calculator developed by the authors and easily
 accessible on the website http://www.mskcc.org/MSKCC/htlm/5794.cfm.

 -  First Row "Performed Frozen Section. The item must be checked if the pathologist
 has performed frozen section intra-operatively. Otherwise, the item must not be
 checked.

 -  Second line "Pathological size (cm)" must refer the histological size of the
 largest tumor diameter in centimeters.

 -  Third line "Tumor type and grade": you must select the corresponding item from the
 4 items offered: ductal I (for infiltrating ductal carcinoma (TCC) grade 1), ductal
 II (for TCC grade 2), ductal III (for TCC grade 3) and lobular (for infiltrating
 lobular carcinoma).

 -  Fourth line "Number of Positive Sentinel Lymph Nodes" must report the number of
 metastatic SN, whatever the type of flooding (by macrometastasis a micrometastasis
 or isolated cells).

 -  Fifth line "SN Method of Detection": you must select the item. Two scenarios:

 1. In the first line item "Frozen Section Performed" was checked: 4 item are then
 offered: Frozen (if the metastasis was diagnosed at the frozen section).
 However, this scenario can not produce it because in this case, the patient
 has received ALND in the same operation as the procedure of SN; Routine (if
 the metastasis was diagnosed by analyzing routine H&E), Serial (if the
 metastasis was diagnosed after serial sectioning in H&E), IHC (if the
 metastasis was diagnosed by IHC)

 2. the first line item "Frozen Section Performed" was not checked: 3 item are
 then proposed: Routine (if the metastasis was diagnosed by analyzing routine
 H&E), Serial (if the metastasis was diagnosed after serial sectioning in H&E),
 IHC (if the metastasis was diagnosed by IHC).

 -  Sixth row "Number of Negative Sentinel Lymph Nodes': the number of non-metastatic
 SN.

 -  Seventh row "Lymphovascular Invasion." The item must be checked in case of
 lymphatic or vascular emboli.

 -  Eighth row "Multifocality. The item must be checked in case of multifocality.

 -  Ninth Line "Estrogen Receptor Positive". The item must be checked if the tumor
 estrogen receptors.

 2. The use of the nomogram (defined as the graphical representation of the model) is not
 recommended because the calculation is less precise than the web interface.

 6.2.3 Risk calculation combining the MSKCC nomogram and the Tenon score

 -  Group at low risk of metastatic non-SN: probability with the MSKCC nomogram of ≤ 10% and
 a score of Tenon ≤ 3.5.

 -  Group at risk of metastatic non-SN: probability with the MSKCC nomogram of > 10% and/or
 Tenon score > 3.5.

 6.3 Monitoring of patients included in the study The study evaluates the combined use of two
 predictors at baseline. It does not require monitoring. However, all patients will be
 monitored regularly for any breast cancer and adjuvant treatment of breast cancer will remain
 unchanged by this study.

 6.4 Total time of research The recruitment and the opening of study centers is planned over a
 period of 6 months. Inclusion of patients is planned over a period of 18 months. The total
 duration of the study is 24 months.
Inclusion Criteria:

 -  Patients aged over 18 years old with invasive breast cancer with an indication of SN
 procedure as recommended by Saint-Paul de VENCE in 2005 amended in 2009

 -  T1-2 breast cancer

 -  Patients having social security coverage.

 Exclusion Criteria:

 -  Patient under the age of 18.

 -  Patient who had neoadjuvant chemotherapy.

 -  Patient who had had radiotherapy to the ipsilateral axilla or breast.

 -  Pregnant patient.

 -  Patients who do not speak French.

 -  Patients refusing to participate in the study.

 -  Simultaneous participation in another research period of exclusion