Extending ACOSOG Z0011 to Encompass Mastectomy: What Happens Without RT?

Abstract

The initial premise of sentinel lymph node (SLN) biopsy for breast cancer, that patients with negative SLN could safely avoid axillary lymph node dissection (ALND), is well established. A substantial worldwide literature documents low rates of axillary node recurrence (0.3 %), and five randomized trials show no difference between ALND and SLN biopsy in local, regional, or distant control of node-negative disease. 1-4Could subsets of SLN-positive patients also avoid ALND? In fact, a policy of selective non-ALND dates back almost to the advent of SLN biopsy. Bilimoria et al. retrospectively analyzed 403,167 stage I to III breast cancer patients in the National Cancer Data Base (1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005) and found that 23 % of those with SLN macrometastases (pN1) and 36 % of those with SLN micrometastases (pN1mi) did not have ALND; uncorrected for selection bias, there was no adverse effect on axillary local recurrence or 5-year relative survival. 5Two randomized trials are more definitive, ACOSOG Z0011 was performed for hematoxylin and eosin-detected SLN metastases (cT1-2N0 patients with 1 to 2 positive SLN treated by breast conservation with whole-breast radiotherapy [WBRT]). 6,7 International Breast Cancer Study Group (IBCSG) 23-01 was performed for SLN micrometastases (cT1-2N0 patients with SLN micrometastases \2 mm).8 Each study randomized SLN biopsy alone versus SLN biopsy plus ALND and found no differences in 5-year local, regional, or distant disease-free survival. These results were particularly striking in that ALND identified residual axillary disease in 27 % of the Z0011 and in 13 % of the IBCSG 23-01 patients, yet axillary recurrence at 5 years developed in only 0.9 and 1 %, respectively, of the SLN-only arms. Both trials have been practice changing; at our own institution, 84 % of patients who met the Z0011 selection criteria were able to avoid ALND, and in Europe, ALND is no longer routine for patients with SLN micrometastases. Although Z0011 required WBRT without nodal radiotherapy (RT), a lingering concern is that the excellent results may reflect the use of ''high tangents'' to extend the breast RT field into the axilla. Indeed, an audit of the RT fields in a subset of the Z0011 patients confirmed that about half received high tangents, 17-21 % had supraclavicular RT, and 6-10 % had a posterior axillary boost. (These protocol violations were equally distributed between the study arms). 10Can ALND be avoided for SLN-positive patients outside the Z0011 selection criteria, specifically those who are treated by mastectomy without RT? My colleagues and I first addressed this question in 2012, comparing outcomes in SLN-positive breast cancer patients treated by mastectomy (n = 210) or breast conservation (n = 325) without any axillary-specific treatment.11 At a median follow-up of 5 years, there were no significant differences in the rates of local (1.7 vs. 1.4 %) or regional node recurrence (1.2 vs. 1.0 %) even though 94 % of the breast conservation patients had received WBRT. The...

Role of sentinel node biopsy in breast cancer: a review

“…These data and others from the MD Anderson Center [65] suggest that avoiding ALND could be reasonable for a low-risk subset of patients with SN-positive disease who will not receive postmastectomy radiotherapy. What is more, according to the AMAROS trial [56], we know that axillary radiotherapy and ALND are equally effective.…”

Analyzing non-sentinel axillary metastases in patients with T3–T4 cN0 early breast cancer and tumor-involved sentinel lymph nodes undergoing breast-conserving therapy or mastectomy

“…It is the aim to identify further patient populations in which a reduced axillary surgery is possible without comprising oncological outcome. The application of the clinical recommendations based on ACOSOG Z0011 also to patients with higher tumor stages (T3-T4) and to patients undergoing mastectomy are being discussed [20] and to some extent are already being implemented in the clinical routine for SLNpositive patients [21,22].…”