Z-11 trial and rethinking axillary reverse mapping.

Abstract

Axillary lymph node dissection (ALND) was an integral part of the surgical procedure of breast cancer in the era of radical mastectomy. However, a randomized clinical trial has demonstrated that it does not reduce systemic recurrence or improve survival. Therefore, ALND was regarded as a surgical procedure for assessing nodal status and preventing axillary recurrence. Recently, sentinel lymph node (SLN) biopsy has become a standard method for assessing nodal status in breast cancer. Several randomized studies confirmed that SLN biopsy achieves the same survival and regional control as ALND in SLN-negative patients with invasive breast cancer. This procedure can avoid unnecessary ALND in SLN-negative patients, thereby minimizing arm lymphedema. However, SLNpositive patients who undergo ALND do not benefit from SLN biopsy. In 2011, the American College of Surgeons Oncology Group (ACOSOG) reported the results of the Z-11 trial. This trial was designed to address whether ALND is necessary in SLN-positive patients who underwent breastconserving surgery (BCS) with whole-breast irradiation and systemic therapy [1]. The results indicated a remarkably low rate of axillary recurrence in SLN-positive patients who did not undergo ALND. At a median followup of 6.3 years, axillary recurrence rates were similar between each arm with 4 (0.9 %) patients in the SLN biopsy group compared with 2 (0.5 %) in the ALND group, and there was no trend towards improvement of diseasefree or overall survival with ALND. Morrow et al. [2] stated that ALND could be safely omitted in selected women with T1-2, clinically node-negative (cN0) breast cancer who undergo SLN biopsy and BCS with wholebreast irradiation and appropriate systemic therapy. The Z-11 trial is a landmark study. Even in patients with positive SLNs, ALND is not a critical component of surgical therapy. In ACOSOG Z-11, regional recurrence after SLNB alone was \0.1 %, despite the fact that 27 % of patients randomized to the ALND arm of the study had additional metastases identified [1]. However, this trial did not lead to the abandonment of SLN biopsy itself in cN0 patients, even if ALND can be avoided irrespective of the SLN status. It demonstrated that SLN biopsy with wholebreast irradiation and systemic therapy can replace ALND in preventing axillary recurrence in patients with macrometastatic SLNs. Thus, a combination therapy of surgical resection and irradiation is effective not only for the primary breast cancer but also for the axillary metastases. Obviously, ALND should not be omitted in patients who underwent total mastectomy, patients who received neoadjuvant therapy, and patients who underwent BCS without breast radiotherapy. Currently, nippleor skin-sparing mastectomy with immediate breast reconstruction using breast implant has become increasingly popular for patients with multicentric and multifocal tumors. However, either breast or axillary irradiation would not be preferable for these patients because of the increasing rate of capsular contracture. Therefore, ALND remains the standard procedure of treating regional disease in these patients. Nevertheless, conventional ALND is frequently associated with morbidities, including arm lymphedema, seroma, disturbance of shoulder movement and sensory loss. Arm This study was presented at the Breast Service Conference in the Memorial Sloan-Kettering Cancer Center, October 14th, 2014, New York, NY, USA.