Judy C. Boughey, MD, on Changes in Axillary Surgical Management: An I-SPY2 Analysis

The goal of this study was to look at changes in axillary management in patients treated with neoadjuvant chemotherapy over the last 11 years. To accomplish this, we looked at all patients enrolled in the I-SPY2 clinical trial, which is a prospective platform trial using adaptive randomization to enroll patients with tumors of 2.5 centimeters or greater that are of high genomic risk, and these patients are treated with neoadjuvant chemotherapy, which on this trial includes multiple different novel agents.The primary endpoint of the study is to look at the pathologic complete response rate. There have been a lot of changes in the way that we manage the axilla in patients treated with neoadjuvant chemotherapy, most notably in the end of 2012 and through 2013, the presentation of the 1071 and SENTINA studies showing the use of sentinel lymph node surgery after neoadjuvant chemotherapy is feasible for patients with no positive breast cancer. Then more recently, the Alliance 11102 clinical trial, we were asking the question whether we can omit axial lymph node dissection in patients that are shown to have pathologically-positive lymph nodes after neoadjuvant chemotherapy. So that was the backdrop as to why we wanted to look over the last 11 years at the changes in surgical management of the axilla in patients treated with neoadjuvant chemotherapy. Within the I-SPY2 clinical trial from January of 2011 to December of 2021, we identified 1,578 patients. The majority of these patients had hormone receptor-positive, HER2-negative breast cancer accounting for 43% of the population, with 35% having hormone receptor-negative, HER2-negative, and 22% having HER2-positive disease. Overall, the vast majority of patients in this cohort underwent sentinel lymph node surgery only, and that was 62% of patients, with about 30% of patients having an axial lymph node dissection only, and 8% having sentinel lymph node surgery and axillary lymph node dissection. When we look at the total cohort over time, we saw a significant increase in the use of sentinel lymph node surgery only and a significant decrease in the use of axillary lymph node dissection only. Breaking this down by the patient's clinical nodal status at the time of their initial diagnosis with breast cancer, 732 patients had clinically node-negative disease and 846 patients had clinically node-positive disease. In the clinically node negative patients, the dominant axillary surgery was sentinel lymph node only, and this increased from 70% in 2011 to 88% in 2021, with the use of axillary lymph node dissection only decreasing in the same time period from 20% to 6%. What's even more striking is in the patients that were clinically node-positive at presentation, which was 846 patients, and in the first half of the time period of this study, we saw that the dominant surgical procedure was axillary lymph node dissection only, with 71% of patients in 2011 going to straight to axillary lymph node dissection. This decreased dramatically over the 11-year study period to 30% of patients in 2021 undergoing axial lymph node dissection. Along with this, we saw an increase in the use of sentinel lymph node surgery only, increasing from 15% to 57%. This seems to be a reflection of the incorporation of the SENTINA and the Z1071 studies that were presented and published in late 2013. When we look at the patients that were clinically node-positive at presentation, in the group that were sentinel lymph node positive, 68 patients went onto a completion axillary lymph node dissection, and 41 of those patients, or 60%, had additional positive nodes on the axillary lymph node dissection. Switching now to look at the management of patients based on their pathologic stage at surgery, two-thirds of the cohort, 1,053, were pathologically node-negative at surgery and most of these patients had sentinel lymph node surgery and this increased over time. When we look at the patients, however, that had node-positive disease at surgery, we again saw a decrease in the use of axillary lymph node dissection only, from 69% to 39% with an increase in the use of sentinel lymph node surgery only, showing that in 2021, 39% of patients actually had omission of axial lymph node dissection in the setting of pathologically node-positive disease. Overall, when we look at the results of this study, we see that there has been a significant dramatic change in the axillary surgery performed in patients treated with neoadjuvant chemotherapy. Mostly, we're seeing an increase in the use of sentimental lymph node surgery and a decrease in the use of axillary lymph node dissection. For those patients that present with clinically node-negative disease, sentinel lymph node surgery is the main axillary surgical staging procedure being performed. Interestingly, in clinically node-positive disease, we have seen the adoption of sentinel lymph node surgery after neoadjuvant chemotherapy for this patient population as sentinel lymph node surgery is being used to stage the response to neoadjuvant chemotherapy. Furthermore, when we look at patients based on the pathologic findings in the lymph nodes at surgery, for those patients that have a positive lymph node at surgery, we've seen an increase over time in the omission of axle lymph node dissection. It's important, however, to note that in those patients that do have a completion dissection, the rate of additional positive nodes is high at 60%, and thus it's important that we await the outcome data and results from prospective cohorts as well as prospective trials, such as the Alliance 11102 and [inaudible 00:05:54] study. There is some future important work that needs to be done with this cohort. We do plan to look at the resection of the clip node at the time of sentinel lymph node surgery, and it will be critically important to look at the local regional recurrences and survival outcomes of this cohort by axillary management.