Partial axillary lymph node dissection inferior to the intercostobrachial nerves complements sentinel node biopsy in patients with clinically node-negative breast cancer

As preservation of the ICBNs does not affect patient survival but significantly ameliorates the sensory deficit and other long-term symptoms [13], this procedure potentially provides a new anatomic landmark in axillary lymph nodes dissection. In our previous study investigating the anatomic localization of SLNs in relation to the ICBN, we found that the majority of SLNs were located inferior to the ICBN using a dye-tracer technique, and axillary lymph nodes metastases progress from the inferior to the superior axillary as divided by ICBN [9]. This is similar to the findings by Clough et al. who discovered that nearly 89 % SLNs were inferior to the ICBN and few were located superior to ICBN and at the outside of the subscapular artery when traced by the combined method [14]. A recent study demonstrated that the node draining the arm lymph vessels was localized in the lateral pillar of the axillary, and was always found superior to or at the level of the second ICBN [15]. These findings indicate that the localization of nodes draining the breast and the arm lymphatic vessels is not overlapping and is largely divided by ICBN. Theoretically, postoperative arm lymphedema is preventable if the tissue and nodes superior to ICBN are preserved. PALND, which only involves dissection of nodes inferior to ICBN, should have similar lymphedema occurrence rate with SLNB but lower rate than ALND. In the present study, no postoperative severe arm lymphedema was found after one year follow-up in the SLNB and PALND groups with over 15 % of severe lymphedema in the ALND group, suggesting PALND has the same protective effect as SLNB on arm lymphedema and is superior to ALND because the lymphatic drainage of the arm was preserved. The high level of chemotherapy, later clinical stage, and the poorer clinicopathological subtypes in the ALND group may have also contributed to the lymphedema observed in this group.

We carried out survival analysis according to the types of axillary intervention. There was no difference among the SLNB, PALND and ALND groups in DFS with a zero recurrence rate in all groups. Patients in the ALND group might have benefited from chemotherapy and radiotherapy. Our findings are consistent with a study by Kodama et al. who compared overall 5-year survival rates in patients undergoing PALND and historical controls undergoing conventional dissection [16]. Thus, there is sufficient evidence to suggest that PALND can significantly prevent arm lymphedema with a satisfying DFS.

Blue dye is so far the first choice for SLNB in China because it is cheap, safe without the need for nuclear medicine department and gamma probes. However, although blue dye alone technique is generally considered as a valid and acceptable tool to assess axillary nodes status and staging [17], there is growing evidence suggesting the combined technique of blue dye plus radioactive tracer is more superior. In a randomized study by Radovanovic et al., the false rate of blue dye was 17.6 % and accuracy was 68 % [7]. Other studies in the literature showed the similar false-negative rates for the blue dye alone method which were generally higher than the recommended 5 % rate [18, 19]. The combined blue dye and radioactive tracer had a significantly lower FNR (4.5 %) with higher accuracy [7]. In the present study, the FNR of blue dye technique was as high as 43 % and the accuracy rate was only 58 %, which appeared to be unexpected and unacceptable. We believe that the practice of performing SLN mapping/SLNB after tumorectoy is largely responsible for the high FNR and low accuracy rate as open incision and the tumor removal procedure are potentially destroy breast lymphatic network, thus reduce breast lymphatic drainage towards axilla. The lack of other intensive node exploration technique (e.g. continuous multiple sections and lymph node imprint) in the present study may have also been a contributor. Different from western countries where malignance of a tumor is determined by preoperative biopsy and surgical plan is normally determined preoperatively, such practice is common in China where malignance of a tumor is largely identified by intraoperative instant frozen histology and the therapeutic plan is determined intraoperatively. With unknown biological behaviour of a tumor and uncertain time frame before the result of intraoperative frozen histology was available, it appeared inappropriate to perform SLNB prior to tumorectomy. Our study showed an unacceptably higher FNR using blue dye alone under such circumstances.

We found that 48 (30.4 %) patients who showed either failed SLNB (33.3 %) or negative SLNB (30.2 %) using blue dye were found additional positive nodes by PALND. These data demonstrated that there may be an over 30 % chance of leaving behind positive nodes for those with failed or negative SLNB using blue dye alone. In a country where blue dye is the only option for SLNB and intraoperative instant frozen histology is the major method for primary diagnosis of breast cancer, PALND can be considered as a good complementary procedure to SLNB in patients with clinically-negative node breast cancer. Our findings are in keeping with an Indian study which showed low axillary sampling is accurate in predicting axillary nodes status in women with clinically node negative operable breast cancer [20]. In the light of the high FNR of SLNB, we are now trialling SLNB prior to tumorectomy to minimise the effect of open incision on breast lymphatic drainage in all patients with suspected breast cancer. The FNR and accuracy rate are yet to be evaluated.

Recently, a presentation and related publications of the American College of Surgeons Oncology Group (ACOSOG) Z0011 have provoked controversy around the world regarding the need for ALND in patients with SLN-positive breast cancer [21‐23]. It seems that less than or equal to two positive nodes does not warrant dissection. In our study, all the patients with less than or equal to two positive SLNs had all their metastatic nodes located inferior to the ICBN. Only three patients with more than two metastatic nodes had nodes found superior to the ICBNs. Therefore, PALND is considered as a way of biopsy for clinically node-negative breast cancer: if there are two or fewer positive nodes, then ALND is not necessary and the PALND is sufficient; if there are more than two positive nodes, then ALND is necessary. A recent study reported that for patients with positive nodes who do not undergo ALND, adjuvant therapy can have the same effect on overall survival as the ALND procedure performed on similar node-positive patients [24]. However, the presence of positive nodes is one of the important factors to be taken into account when considering radiotherapy and chemotherapy. Perhaps in the near future we can develop a novel imaging technique instead of SLNB for the assessment of ALNs, we will enter a new era when the axillary surgery is not necessary. However, at the present time, PALND could be considered as a procedure complementary to SLNB in clinically node-negative breast cancer, especially in China where the combined technique is not available for SALN detection. This technique is so simple that a surgeon could easily perform without the need of complicated equipment. In fact, we prefer the name “functional axillary lymph node dissection (FALND) to PALND, a term which is coined when SLNs are not located. Our further investigation is ongoing on the clinical difference between FALND and ALND when there are two or fewer positive nodes and the results will be available in the near future.

In conclusion, there are considerable differences in the practice of breast cancer diagnosis and treatment between China and western developed countries. In a country where blue dye is the only technique for SLNB and intraoperative SLNB is normally performed after tumorectomy, the FNR of SLNB is unacceptably high. Under such circumstances specific to China, axillary node dissection inferior to the ICBN is a good complementary procedure following SLNB in clinically node-negative breast cancer because it provides better assessment of nodes status, reduces the occurrence rate for postoperative arm lymphedema with satisfying long-term disease free survival.