Management of axillary lymph node metastasis in breast cancer: making progress.

LESS IS MORE”—SO GOES THE ADAGE, AND THAT CERtainly has been the case for breast cancer. Forty years ago, the standard treatment for this disease was the Halsted radical mastectomy, an aggressive operation that involved removal of not only the breast but also the adjacent musculature and axillary lymph nodes. Better understanding of breast cancer biology revealed that aggressive surgical therapy alone was inadequate. As treatment approaches evolved away from extensive surgery, axillary lymph node dissection (ALND) remained part of the treatment regimen to detect nodal disease. Axillary lymph node metastases were considered an indicator that systemic disease was present, identifying a need for chemotherapy. Women with breast cancer have benefitted greatly from a series of carefully performed randomized controlled trials. Each successive trial showed that less surgery was better, in that outcomes were the same and less surgical intervention resulted in fewer surgical complications. In the first major study, the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-04 trial, which began in 1971, 1765 women with breast cancer were randomized into 5 treatment groups. Those with palpable lymph nodes were randomized to receive a Halsted radical mastectomy or a total mastectomy (removal of the breast only without the underlying muscle or lymph nodes) along with regional radiation therapy. Women with breast cancer without palpable axillary lymph nodes were randomized into 1 of 3 study groups: Halsted radical mastectomy with ALND, total mastectomy with regional radiation treatment, or mastectomy alone with delayed ALND if nodal recurrences were observed. There was a 40% incidence of occult nodal metastasis in the radical mastectomy group. Despite an axillary recurrence failure rate of 19% in the total mastectomy group, the survival was similar between the groups after 25 years of follow-up. In general, women with clinically palpable axillary lymph nodes had worse survival than those without clinically evident lymph nodes. Local treatment of occult cancer in axillary lymph nodes had no effect on overall survival. Recognition of the waning utility of ANLD led to the development of sentinel lymph node dissection (SLND). This technique involves injecting dye into the primary tumor and selectively resecting lymph nodes that take up the dye and thus indicate that they are the nodes draining the tumor mass. SLND has supplanted ALND for staging the axilla in early breast cancer, because less aggressive axillary surgery results in less arm stiffness, pain, paresthesia, and risk of lymphedema. A recently published single-institution study with 10-year follow-up randomized 516 patients with breast cancer to undergo both SLND and ALND or SLND alone with ALND only if the sentinel lymph nodes (SLNs) contained cancer; that study showed better arm mobility and less pain in the SLND-alone group. At a median follow-up of 102 months, the regional failure rate in the SLND-alone group was 0.77%. There was no significant difference in diseasefree survival between the groups, suggesting that ALND is not beneficial. Retrospective analyses add indirect evidence regarding the lack of utility of ALND. These studies are not definitive because, as with all retrospective evaluations, it is difficult to control for selection bias and treatment bias. In general, these analyses show low axillary recurrence rates in women with minimal axillary disease and with positive SLNs who did not have completion ALND. These patients tended to be older; had small, low-grade tumors with micrometastatic ( 2 mm) nodal disease; and underwent breast conservation surgery. Predictors of non-SLN metastasis include tumor size, size of SLN metastatic deposit, number of SLNs involved, tumor lymphovascular invasion, and extranodal extension. In an effort to identify patients who might benefit from ALND, nomograms using these characteristics have been developed to predict who should undergo ALND. Despite increasing evidence disfavoring ALND, it remains part of widely recognized guidelines for breast cancer care. However, the apparent lack of utility of ALND has influenced clinicians treating breast cancer because the performance of ALND following SLND has declined. In this issue of JAMA, Giuliano and colleagues from the American College of Surgeons Oncology Group report results of the Z0011 randomized trial comparing SLND alone with ALND in women with breast cancer and SLN metas-