Axillary lymph node dissection (ALND) for patients with breast cancer has the potential to cause side-effects, including pain, numbness or paresthesia, arm/shoulder mobility restriction, and lymphedema . Arm lymphedema has been documented in 7 to 77% of patients who undergo ALND [2, 3]. The incidence of lymphedema depends on whether ALND has been combined with subsequent radiotherapy, but also on the definition of ALND used.
Sentinel lymph node biopsy (SLNB) represents the standard of care for axillary node staging in patients with early-stage, clinically node-negative breast cancer (cT1 to 2N0). The goals of SLNB are to reduce the morbidity from breast-cancer surgery by avoiding unnecessary ALND and to improve staging of the regional LNs. However, in a selected group of patients, ALND is still indicated.
Axillary reverse mapping (ARM) is a recently developed technique that enables surgeons to discriminate the lymphatic drainage pattern of the breast from that of the upper limb. The concept of ARM is to map the drainage of the upper limb to determine the anatomical variation in these lymphatics and thus create a road map for their preservation. If lymphedema is caused by removing the lymphatics and nodes of the upper limb, the possibility of identifying these lymphatics would enable surgeons to preserve them . The ARM technique can be performed by using blue dye, fluorescent dye, or a radioisotope. In the past few years, several groups have reported their first experiences with this relatively new technique [5–13]. A review by Ngochi on this topic  clearly described the ARM techniques that are currently available. Studies on ARM using blue dye reported identification rates varying between 50 and 89% [5–10], and for isotope and fluorescent dyes, these rates are 91 to 100% [11, 13] and 88%  respectively. The latter two visualization techniques have the advantage of not leaving a ‘blue tattoo’ on the patient’s skin. However, there is limited information on the use of isotopes and fluorescent dyes, and they require the use of expensive equipment during surgery.
Between October 2009 and June 2011, we performed a pilot study using blue dye for visualizing LN drainage of the upper limb . Patients with invasive breast cancer and an indication for ALND were enrolled in the study, and these comprised 50 patients with a tumor-positive SLN and 43 patients who had axillary LN metastases proven by pre-operative cytology. During surgery, ARM nodes were identified and removed first, followed by ALND (at least level I to II). No significant differences were seen in the visualization rate of ARM nodes between the groups (86 and 94% respectively, P = 0.196). In the group of patients with a positive SLN, none of the ARM nodes contained metastases, whereas 11 (22%) of the ARM nodes in the group with axillary metastases proven by pre-operative cytology contained metastases (P = 0.001). Patients receiving neoadjuvant chemotherapy had a significantly lower risk of additional axillary LN metastases (24.6 versus 44.4%, P = 0.046). These results are largely in accordance with other studies. Boneti et al. , Thompson et al. , and Casbona et al.  found no tumor deposits in the ARM nodes even when the patients had positive axillary nodes in the initial series. However, Nos et al.  found metastases in 14% of the ARM nodes (3 of 21 patients), all of which were associated with extensive axillary LN metastasis. Noguchi et al.  found ARM node metastases in three of seven patients who underwent ALND, and all three patients had a clinically positive axilla (N1/N2). Based on our results and those from the literature, we conclude that the ARM procedure using blue dye is technically feasible and has a high visualization rate, and that its use might be considered in patients with a positive SLN. Nevertheless, more research is needed to determine the safety of ARM in patients with clinically positive LNs.
Despite these promising results, there are some problems that need to be considered before ARM can be used in routine clinical practice. The currently available techniques are insufficient to identity the upper-limb LNs in some patients. The relevance of the ARM procedure is based on the assumption that the lymphatic pathways from the upper limb are not involved in metastasis of the primary breast cancer ; however, in a minority of patients, the SLN draining of the breast may be the same as the ARM node draining the upper limb. This may explain why the ARM nodes may be involved with metastatic foci in patients with clinically axillary LN metastases. These issues may represent an important drawback for the implementation of the ARM procedure.
Boneti et al. recently published a phase II trial of ARM with promising results . The study showed that preserving the ARM nodes in a clinically negative axilla is safe, and results in a low incidence of post-operative lymphedema in patients undergoing ALND and SLNB. However, further studies are needed before this technique can be adopted as a standard procedure during complementary ALND (cALND) in the surgical treatment of breast cancer.
In this paper, we present the design for a multicenter randomized controlled trial to determine the clinical relevance and safety of selectively sparing upper-limb axillary LNs and their corresponding lymphatics by means of ARM. To minimize the risk of under-treatment due to non-removal of possible ARM node metastases, we will only include patients based on a tumor-positive SLN.