“Reverse axillary mapping in early stage breast cancer Is it oncologically safe? A feasibity study

Background: Arm lymphatics draining through the axilla are frequently disrupted during surgery for carcinoma breast leading to lymphedema. Techniques for differential identification of arm lymphatics might enable their preservation, and probable reduction in lymphedema. Aims: To evaluate the efficacy and oncological safety of reverse axillary mapping (RAM) in patients with early stage breast carcinoma and to correlate with post operative pathological nodal status. Methods and Material: It is a prospective pilot study, conducted at a tertiary care cancer speciality hospital, among patients with early stage breast cancer ( cT1/T2 cN1M0) planned for straight surgery, consenting to be part of the study. Patients were subjected to injection of blue dye (total 1 ml) at the time of surgery. During axillary dissection, lymphnodes taking up blue dye, were identified, dissected out and sent separately for pathological assessment . Results: RAM technique with blue dye identified arm lymphatic in ipsilateral axilla in 72.22%. Blue lymph nodes were identified in 61.11%. Postoperatively 13 out of 18 patients were staged as pN0, two as pN1, and three as pN3. RAM identified arm lymph nodes were free of diseases in all the patients with pN0,pN1 patients, only one of the three pN3 patients showed metastatic involvement . ( all pN3 patients could be identified as suspicious of having high nodal disease intraoperatively) Conclusions: Reverse axillary mapping can be used to identify the arm lymphatics in the ipsilateral axilla and these nodes are found to be free of metastatic disease in early stage breast cancer. I. Background Lymphatic drainage of the breast and ipsilateral upper limb is through the axilla. Majority of the cases, the two lymphatic pathways are different[1] Technique, that can differentially identify the upper limb lymphatic in the axilla can help preventing disruption of arm lymphatics at the time of axillary dissection for breast cancer. This may help reduce lymphedema, the most significant morbidity associated with surgical management of breast cancer. Reverse axillary mapping (RAM) technique, is a recent development, aimed at identifying the arm lymphatics in axilla at the time of axillary surgery for carcinoma breast. Various techniques have been described for the same using blue dye ,radioisotope or fluorescence imaging[2–5]. Although arm and breast lymphatics have been postulated to have differential drainage crossover has been documented in 2-18% [1,5–7] with pathologically proven involvement of nodes draining the arm by metastatic carcinoma from breast in 043%[5,7–11]. Most common complication associated with this procedure has been local tattoing lasting from few weeks to as long as 6 months. We aim to evaluate the efficacy of identification of arm lymphatic using low volume methylene blue injection (1-1.5 ml) and the degree of involvement of RAM identified nodes by metastatic disease among women with early stage breast cancer. II. Methods The study was conducted as a prospective non randomised study. It was conducted in the Division of breast oncology, Department of Surgical oncology at our tertiary care centre. Subjects Female patients with early stage breast cancer (cT1/T2) satisfying the exclusion criteria, with soft clinically palpable node (cN1) after routine metastatic work up , consenting to be a part of study were included in the study. Written informed consent , explaining the procedure and possible complications were taken from the patients in local language. A total of 18 patients were included in the study. “Reverse axillary mapping in early stage breast cancer Is it oncologically safe ? A feasibity study” DOI: 10.9790/0853-160701110115 ww.iosrjournals.org 111 | Page Exclusion criteria: Age < 18 yrs and more than 70 years Patients medically unfit for surgery Patients not consenting to be a part of the study Patients with history of previous surgery to ipsilateral axilla or arm. Patients with clinically N2/N3 nodes Technique Reverse axillary mapping protocol: Patients included in the study were subjected to injection of methylene blue to a total volume of 1-1.5 ml (a combination of intradermal and subcutaneous injection) , given under general anaesthesia , prior to commencement of surgery . Intradermal injection was given using an insulin syringe, and subcutaneous injection using 2 ml syringe with 26 gauze needle. All injections were given at the intermuscular groove in the medial aspect at the junction upper and middle third of the arm. Time from injection to the time of axillary dissection was noted. Careful and meticulous search for blue lymphatics were done at the start of axillary dissection to identify arm lymphatics. The position of the lymphatics/nodes were documented in relation to axillary vein, thoraco dorsal pedicle and intercostobrachial nerve. Blue nodes were dissected out and separately sent for histopathological analysis and routine axillary dissection was done to include levels 1,2 and 3, limiting dissection to tissue below the axillary vein. Intraoperative assessment of the extent of axillary nodal disease was done to identify extensive disease and was correlated with post operative histopathology. Postoperative morbidity associated with the procedure was recorded . Patients were stratified based on the postoperative nodal status and degree of involvement of arm lymph nodes by metastatic disease assessed for each category (pNO,pN1,pN2,pN3). Statistical Analysis: Statistical analysis was performed using the SPSS Statistical Software (version 17). III. Results The median age of patients included was 51.44 years (34-60 years). Three of the 18 patients had underwent excision biopsy outside. Thirteen patients has clinically T2 lesion and 3 patients had clinically T1 lesions. Based on location of the primary tumour, upper outer quadrant (11) was the most common location, followed by upper inner quadrant (4), lower outer quadrant (1), lower inner quadrant(1) and central sector(1). Preoperative diagnosis of malignancy was available for all the patients (fine aspiration cytology (4), core needle biopsy (11) and slide review (3)). Intra ductal carcinoma NOS was the most common histology, one with neuroendocrine differentiation one with poorly differentiated carcinoma with neuro endocrine differentiation. Sixteen patients had grade 3 tumours, 2 patients with grade 2 tumours (Table 1). Modified radical mastectomy was performed in 15 of 18 patients, breast conservation surgery in 2 patients and axillary lymph node dissection(ALND) alone in one patient . Mean time from injection to axillary dissection was 41.07 minutes. Mean lymph node yield was 17.9 (range 11-32). Five patients had positive nodes in axilla on final histopathological assessment [pN1 in two ( one and two nodes positive ), pN3 in 3 patients(10,12 and 16 nodes positive)].All the three patients with pN3 could be identified intra operatively as suspicious of having high nodal involvement. Blue lymphatics(RAM lymphatics) were identified in 13 out of 18 patients (72.22%) and blue lymphnodes were identified in 11 of 18 patients (61.11%).Mean duration between the injection and start of axillary dissection was41.27 minutes. The blue nodes/lymphatics were most commonly located within a centimetre below the axillary vein , just lateral to thoracodorsal pedicle (9/11 patients) , anterior to the axillary vein(1) and just inferior to the vein (1).(Fig 1) Mean yield of blue lymph node was 1.83 (range 1-3). The size of the blue lymphnode was variable ranging from 4 mm to 1.7 cm . Only one of the 11 patients in whom RAM lymph node was identified and removed, was positive for metastatic disease( had a high axillary nodal disease, pN3) (Fig 2) .Four of the 18 patients had minimal staining at the injection site, two patients complained of minimal pain at first review (2 weeks post surgery), one had a superficial epidermal loss and at the injection site . IV. Discussion Globally breast cancer is the most common cancer among women. The management of breast cancer has evolved over the years from most radical Halstead’s Radical mastectomy through breast conservation surgery to sentinel node biopsy (SLNB), with a significant reduction in the morbidity associated with the procedure. The status of axilla is one of the most important predictors of disease outcome. Most important morbidity associated with breast cancer surgery is ipsilateral lymphedema. Lymphedema incidence has a direct relationship to the extent of axillary lymph node dissection(ALND), varying from 58.4 % with radical mastectomy [12] to as low as 5 %with sentinel lymph node techniques[13].Though Z0011 trial showed that SLNB alone without ALND was not inferior in terms of local recurrence and survival [14], still the standard “Reverse axillary mapping in early stage breast cancer Is it oncologically safe ? A feasibity study” DOI: 10.9790/0853-160701110115 ww.iosrjournals.org 112 | Page practice is to perform an axillary dissection in women with positive SLNB. Cadaveric studies tracing the lymphatic of upper limb , has shown that there are two pathways, a superficial and deep pathway , most of which drain into a single sentry node in the axilla[15]. Post ALND, most of these pathways become fibrosed, impairing lymphatic drainage of he upper limb, with opening of new lymphatics in some patients[16]. Lymphatics from the ipsilateral upper limb and breast in breast cancer patients draining into the axilla, were found to be different in 86.7 % cases, in patients undergoing ALND[1]. A number of techniques have been described in literature for the identification of arm lymphatics in the axilla, using blue dye [4,6,8], radio isotope [9] and fluorescence[17]. Rate of Identification of arm lymphatics varies from 33.3% in initial studies to as high as 91% with use of radio isotopes, [8,9]. In our study, using methylene blue dye injection, at the start of surgery, blue lymphatics were identified