A Clinical Trial Of Internal Mammary Sentinel Lymph Node Biopsy In Breast Cancer Patients

Objective:In addition to the axillary lymph node (ALN), the internal mammary lymph node(IMLN) drainage is another important lymphatic channel of the breast, the status of IMLNalso provides important prognostic information for breast cancer patients. Patients withIMLN metastases had a worse prognosis than patients who did not, independent of theiraxillary status. Many researchers found that the survival outcomes for patients with IMLNmetastases only were similar to those for patients with axillary metastases only; suggestingthat regional disease in either nodal chain has the same prognostic relevance. However,there still lack a minimally invasive method to evaluate the status of IMLN so far. Althoughthe necessity of a mandatory axillary dissection is currently under question in certainpatients by the ACOSOG Z0011results, the importance and validity of a sentinel lymphnode biopsy (SLNB) is not being questioned. The technical evolvements of SLNB andlymphoscintigraphy provided a less invasive method for assessing IMLN than surgicaldissection, and this might affect the decision-making for the local-regional and systemictherapy. As the technique developed over time, it was discovered that superficial injectionof radiotracer was unable to identify internal mammary sentinel lymph node (IM-SLN) butthat intraparenchymal injection (peritumoral, intratumoral, or subtumoral) was morereliable. Unfortunately, with this injection method, the internal mammary hotspots inlymphoscintigraphy were seen only in a small proportion of patients (range from13to 37%), which has been the restriction for internal mammary sentinel lymph node biopsy(IM-SLNB) to date.In the present study, we tried injecting radiotracer with different technique. Theprimary purpose of this study is to develop a new injection technique which is useful forthe detection of the IM-SLN in breast cancer patients and to determine the impact ofIM-SLNB on the systemic and locoregional treatment plan. The secondary purpose is toestimate the risk factors for IM-SLN metastasis, successful rate and complication ofIM-SLNBMethods:From November2011to March2013,190patients from Shandong cancer hospitalwith biopsy-proven T1-T2invasive breast cancer and clinically negative axilla wereenrolled into this prospective study. The mean age was46years (range,26~80). Patientswere divided into two groups: group A (n=58), the patients received the radiotracerinjection only into the tumor quadrant; group B (n=132), the radiotracer was injected intotwo quadrants of the breast (at the6and12o’clock positions2.0~3.0cm from nipples).Then, we separated the group B into two groups: group B1(n=41), the radiotracer wasinjected in a low volume (<0.5ml/point); group B2(n=91), the radiotracer was injected in ahigh volume (≥0.5ml/point). For every patients,99mTc-labeled sulfur colloid was injectedunder the ultrasonographic guidance3~24hours before surgery. All patients underwent apreoperative lymphoscintigraphy30min before surgery. The visualization rate of theIM-SLN was compared between the two groups, and the relevant factors were analyzed.Then, IM-SLNB will be performed for all patients with IM-SLN visualized onpreoperative lymphoscintigraphy and/or detected by intraoperative gamma probe. All theSLNs are sectioned at least2levels and permanent H&E stained slides were taken for eachlevel. The metastatic deposits were classified as according to the criterion of the7th editionof the American Joint Committee on Cancer. The adjuvant systemic therapy is determinedby the treating physician according to the most recent National Comprehensive CancerNetwork Clinical Practice Guidelines and St Gallen Consensus. The successful rate and complication of IM-SLNB and its impact on the systemic and locoregional treatment planwould be analyzed.Results:The visualization rate of SLN was improved with intraoperative gamma probecompare to lymphoscintigraphy: group A (axilla77.6%â†'98.3%, P=0.001; internalmammary13.8%â†'15.5%, P=0.794) and group B (axilla84.8%â†'98.5%, P=0.000; internalmammary71.2%â†'76.5%, P=0.328).Group B (two-quadrant injection) was associated with a significantly highervisualization rate (76.5%,101/132) of IM-SLN compared with group A (one-quadrantinjection)(15.5%,9/58)(P=0.000), both techniques had the same visualization rate in theaxilla (98.5%vs.98.3%, P=0.915). In addition, the internal mammary hotspots were morecommon seen in patients who were injected with a higher volume of radiotracer(≥0.5ml/point)(86.8%vs.53.7%, P=0.000). The visualization rate of IM-SLN was relatedwith the patient’s age (P=0.037) and injection volume (P=0.000).In Group B, the IM-SLN was identified by intraoperative gamma probe in101patients; the IM-SLNB was performed in52patients (51.5%,52/101); in48/52(92.3%)exploration was successful and the mean number of removed IM-SLN was1.7(total82;range1~4). The IM-SLNs were concentrated in the2th and3th intercostal space (84.1%,69/82). A small additional horizontal incision was necessary in2patients (4.2%,2/48) forbreast conserving therapy and lateral tumor. A small pleural lesion was notedintraoperatively in4patients (8.3%,4/48) and no pneumothorax was seen postoperativelywith chest X-rays. Intraoperative bleeding from the internal mammary artery occurred in4patients (8.3%,4/48), but was stopped successfully.In our study,4patients (8.3%,4/48) the IM-SLN was tumor positive with a successfulIM-SLNB. Of these4patients2had positive ALN and2had positive IM-SLN only. In thepatients who underwent IM-SLNB, lymph staging was changed in8.3%patients, systemictreatment was changed only in2.1%patients; however, radiotherapy treatment waschanged in33.3%patients. For the patients with upper inner quadrant tumor, lymph staging was changed in21.1%patients, systemic and radiotherapy treatment was changed in5.3%and80%patients.Conclusions:1. Qiu’s injection of radiotracer (two-quadrant, high volume and ultrasonographicguidance) could significantly improve the visualization rate of IM-SLN. Our findingsshould make the IM-SLNB widely implemented and provide an effective technique toevaluate the status of IMLN.2. Preoperative lymphoscintigraphy is not a prerequisite for axillary SLNB, but it isnecessary for IM-SLNB. The visualization rate of SLN would be improved withintraoperative gamma probe.3. After finish20surgeries, IM-SLNB is suitable to be performed as its highsuccessful rate and low complication.4. We suggested that IM-SLNB should be performed routinely in breast cancerpatients, espacilly in the patients with upper inner quadrant tumor, for it could lead to agreater degree of staging accuracy and provide the accurate indication of radiation to theinternal mammary area.5. As IMLN metastases are mostly found concomitantly with ALN metastases, theIM-SLNB should be encouraged in the clinically positive ALN patients (Clinicaltrials.gov,ID: NCT01668914).