Sentinel Node Biopsy and Axillary Sampling in Operable Breast Cancer
Sentinel Node Biopsy and Axillary Sampling in Operable Breast Cancer
The advent of mammography and increased awareness of breast cancer has resulted in detection
 of smaller tumors, the majority of which would not have had metastasized to the axillary
 lymph nodes. The sentinel node (SN) is presumably the first echelon node in the axillary
 basin to become involved with metastatic breast cancer cells. Sentinel node biopsy (SNB) in
 operable breast cancer has gained popularity since it promises to avoid treatment of the
 axilla when the nodes are negative for metastasis. Advances in technology (radio-guided SNB)
 is associated with a risk of false negative SN reporting in 4-12%. The consequence of leaving
 behind untreated positive non-sentinel nodes in the axilla is a potential risk for axillary
 recurrence. Axillary sampling is a simple and inexpensive procedure in which level I nodes
 are removed by a blind dissection. The investigators critically analyzed the efficacy of both
 the procedures separately in consecutive pilot studies i.e., targeted SNB versus blind
 axillary sampling. The current study is planned as a prospective comparison study where a
 patient undergoes both the procedures in the same surgical intervention and thus provides an
 immediate comparison of the two techniques with respect to their effectiveness.
Axillary node dissection in operable breast cancer provides an accurate way of staging the
 disease. With increased popularity of screening and earlier diagnosis, most women do not
 harbor axillary metastases, in which case, axillary lymph node dissection could be avoided.
 Sentinel node biopsy (SNB) gained rapid popularity because the technique could predict the
 presence of metastases in downstream lymph nodes, so that surgery and its associated
 morbidity could be safely avoided. SNB can be performed with injection of isosulphan blue
 subdermally and peritumorally alone or in combination with radio-guidance with technetium-99
 labeled colloid injection. Radio-guided SNB is superior to the blue dye in identifying the
 SN, and a combined technique is still better. However, it failed to accomplish its objective
 in a proportion of cases where the sentinel node could not be identified even with expensive
 gadgetry like gamma probes. An overview of sentinel node studies showed that the node was
 found in only 85-90% of patients and the overall sensitivity in correctly predicting the
 negative axilla by sentinel node biopsy was only 94%. There was a false negative rate of 6.2%
 wherein the sentinel node was reported negative in presence of metastasis to non-sentinel
 nodes in axilla.

 Axillary sampling was a forerunner to the targeted sentinel node biopsy. The main objective
 of axillary sampling at that time was to detect a positive axilla. More recently it is being
 tested as an accurate predictor of axillary status for absence of metastasis.

 There is a definite learning curve in SNB with higher non-detection rates and false negative
 rate in the earlier phases of the study compared to the later part. This learning curve is
 absent in axillary sampling, which requires no specialized training or expensive equipment
 and has a 100% detection rate. The mean number of sentinel nodes that were identified, as
 reported in various SNB studies, was 2.13 (with a range of mean numbers of SN dissected being
 1.3-3.1). The actual range of number of sentinel nodes dissected was 1 - 8, which is quite
 comparable to the average 4 -5 nodes that are required to be sampled for accurately
 predicting the axilla. Badwe and Mittra have concluded that sentinel node biopsy is expensive
 and is driven by lure for technology and fashion, and has little advantage over axillary node
 sampling in predicting a negative axilla.

 There is a validation study of lower axillary sampling versus total axillary clearance
 reported by Steele et al in 1985 with a sensitivity of 100% and an accuracy of 99.5%. The
 more recent validation study of 5-node axillary sampling compared to level I-II dissection
 was reported from Stockholm on 416 operable breast cancer patients. The noteworthy finding
 was that in this study node sampling had a 100% yield, 97.3% sensitivity and a negative
 predictive value of 98.5% with a false negative rate of 2.7% in predicting the axilla. The
 comparative figures for SNB in the world overview are 94% sensitivity, 97% negative
 predictive value and a false negative rate of 6.5%.

 Preliminary studies of SNB and axillary sampling at TMH Sentinel node biopsy by Isosulphan
 blue injection was performed as a validation pilot study at the Breast unit in TMH between
 April 1999 to November 2000 in 100 women with clinically node negative operable breast
 cancer. SN was found in 77% cases with a false negative rate of 16.6% and sensitivity of
 76.1%. The procedure had a negative predictive value of 90.4% cases in predicting the rest of
 the axilla. The number of sentinel nodes dissected was 1-6 with an average of 1.4.

 Axillary sampling was subsequently performed as a pilot study between May 2001 to August 2002
 in 97 women with a similar clinical stage as above. Nodes were found in all patients (100%)
 in level I with a false negative reporting in 11% cases, sensitivity of 88.9%, negative
 predictive value of 100% and an average of 4 nodes dissected (range from 1-9).

 In developing countries with limited resources, it may not be feasible for every institution
 to acquire a gamma probe. Axillary sampling may thus be a comparably cheaper and practical
 alternative to SNB. Axillary sampling and sentinel node biopsy should, however, be compared
 with respect to the resultant morbidity and false negative rates before adopting either
 method as standard clinical practice.

 The Nottingham group have recently published the results of a prospective study to find out
 the value of adding SNB to 4-node axillary sampling (4NAS) within the same patient. Two
 hundred patients were accrued and 4NAS was found to have a lower false negative rate compared
 to SNB. We propose to compare the two procedures in a clinical trial with a comparison of
 respective false negative rates and sensitivity as the immediate end points.

 Methodology:

 Eligible women will be recruited in the study after obtaining an informed consent and
 centrally registered at the Clinical Research Secretariat at the Tata Memorial Hospital,
 Mumbai.

 The radiolabeled Tc-99 colloid or phytate (500 Mbq) will be injected into the primary tumor 2
 hours before surgery. A localized scintiscan will then be performed to confirm the
 radiolabeling of the sentinel node before surgery and for documentation. Isosulphan blue dye
 will be injected subdermal (0.5ml) over the tumor and intraparenchymal (3-4ml) towards the
 axilla 10-15mins before incision.

 Axillary sampling will be performed first. A 2 cm incision will be made in the middle third
 of the proposed axillary clearance incision below the axillary hairline. All axillary fat and
 tissue in an area of 2cm diameter will be dissected out. The anterior limit of dissection is
 the posterior border of pectoralis major, the posterior limit of dissection is the anterior
 border of latissimus dorsi muscle, upper limit of dissection is the intercostobrachial nerve,
 and base is serratus anterior muscle on lateral chest wall. In those cases that undergo a
 mastectomy, the tissue in the axillary tail will be identified first and then removed as
 specified above.

 After completion of sampling procedure, the remaining axillary tissue will be checked for any
 other node showing a blue discoloration or radioactivity and the same will be documented as
 found outside of axillary sampling. Axillary clearance will then be separately completed in
 all patients by standard technique after extending the incision without waiting for the
 frozen section report.
Inclusion Criteria:

 -  Clinically node negative operable breast cancer

 -  No prior incision or excision biopsy

 Exclusion Criteria:

 -  Palpable axillary lymph nodes

 -  Contraindications for injecting radiocolloid