Does the Rapid Acceptance of ACOSOG Z0011 Compromise Selection of Systemic Therapy

The acceptance of sentinel lymph node (SLN) biopsy as standard care in cN0 breast cancer is one of the great success stories in contemporary surgical oncology and is supported by the results of at least 69 observational studies, 7 randomized trials, and extensive literature covering all aspects of the procedure. The logical next question in the evolution of axillary staging is to ask whether all SLNpositive patients require axillary lymph node dissection (ALND), and it is clear that for many American surgeons they do not. In a retrospective study from the National Cancer Data Base, Bilimoria et al. report on 97,314 SLNpositive patients treated nationwide between 1998 and 2006. They show 23 % of patients with SLN macrometastases ([2 mm, pN1) and 55 % with SLN micrometastases (0.2–2 mm, pN1mi) did not have ALND, yet for both pN1 and pN1mi SLN disease, axillary local recurrence and 5-year relative survival were the same with or without ALND. These suggestive results are of course subject to selection bias, but are confirmed by ACOSOG Z0011, a unique and visionary prospective trial that randomized 813 SLNpositive patients with clinical stage T1-2N0 breast cancer to ALND vs no further surgery. All patients were SLNpositive by routine H&E (not immunohistochemical) staining, and all had breast conservation including wholebreast RT. Patients with 3 or more positive SLN (or with matted nodes) were excluded, and formal axillary RT was not allowed. Additional positive nodes were found in 27 % of the patients who had ALND, but at 6 years’ follow-up there were no differences between the ALND and noALND arms in local (3.6 % vs 1.9 %), regional (0.5 % vs 0.9 %), or overall locoregional recurrence (4.1 % vs 2.8 %), nor were there any differences in disease-free or overall survival. Over the last 2 years many institutions and surgeons in the United States (and to a lesser extent in Europe and worldwide) have found the results of Z0011 to be persuasive and practice-changing, incorporating into their treatment guidelines a policy of ‘‘no-ALND’’ for SLN-positive patients who meet the Z0011 selection criteria. In this issue of the Annals, Montemurro and colleagues ask whether the growing acceptance of Z0011 may have been premature. Among 321 of their own SLN-positive breast cancer patients who matched the Z0011 selection criteria, all of whom had ALND, they ask how often the results of ALND were sufficient to change the systemic therapy. In their study design, 2 medical oncologists retrospectively reviewed each patient’s chart twice, first making a recommendation for systemic therapy based on SLN status alone, and then incorporating the results of the ALND. They found that the information gained from the ALND changed the recommended treatment in 16 % of patients, most of them ER-positive/her2-negative (luminal A and B) and most in the direction of ‘‘ACT’’ (doxorubicin, cyclophosphamide, and paclitaxel) chemotherapy. They conclude by suggesting that to avoid undertreatment ALND may be appropriate for some, if not all, SLNpositive patients meeting the Z0011 criteria. Their argument deserves serious consideration, but I do not share their concerns, for the following reasons. First, the subtext of their study is the hypothesis that there are node-positive patients who do not require chemotherapy. This is expressed obliquely in the 2011 St. Gallen Consensus document: ‘‘the Panel did not believe that node positivity per se was an indication for use of chemotherapy, though a strong majority would use it if more than 3 lymph nodes were involved.’’ This fits with the authors’ observation that ALND changed therapy primarily by finding additional positive nodes in those SLNSociety of Surgical Oncology 2012