CHICAGO (FRONTLINE MEDICAL NEWS) – Women with clinical early-stage breast cancer and a positive sentinel lymph node who receive breast-conserving therapy can safely skip an axillary lymph node dissection (ALND), and therefore avoid its associated morbidity, confirms long-term follow-up of the Z0011 trial conducted by the American College of Surgeons Oncology Group and the Alliance for Clinical Trials in Oncology.

The phase III trial enrolled 891 women with clinical T1-2,N0,M0 disease who underwent lumpectomy and were found to have sentinel node involvement. They were randomized to ALND or no further surgery, followed by whole-breast radiation therapy and, in most cases, systemic adjuvant therapy.

The trial was closed early because of low rates of accrual and events. Results at 6.3 years of follow-up showed that compared with peers who had an ALND, the women who skipped this surgery did not have inferior 5-year rates of locoregional recurrence or overall survival ( JAMA. 2011;305:569-75 ).

“The study, however, like most breast cancer studies, contained mostly postmenopausal women with hormone receptor–positive tumors who are known to have late recurrences, and it was criticized for short follow-up,” commented first author Armando E. Giuliano , MD, executive vice chair of surgical oncology in the department of surgery, and associate director of surgical oncology in the Samuel Oschin Comprehensive Cancer Institute, Los Angeles.

In an update of the findings, now with a median follow-up of 9.3 years, the groups were statistically indistinguishable with respect to 10-year rates of the same outcomes, he reported at the annual meeting of the American Society of Clinical Oncology.

“This study… shows that sentinel node biopsy alone provides excellent 10-year locoregional control and survival comparable to completion axillary lymph node dissection for these patients, even with long-term follow-up,” he maintained. “Routine use of axillary lymph node dissection should be abandoned.”

“This was designed as a noninferiority trial, and I would suggest that based on the data we have seen, even if they had hit their target accrual, the outcomes would not be different,” said invited discussant Elizabeth A. Mittendorf , MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston. “Clearly, even before today’s presentation, Z0011 has been identified as a practice-changing trial, as evidenced by the NCCN guidelines.”

In fact, a study last year showed that among patients in the general U.S. population meeting the trial’s enrollment criteria, the use of sentinel lymph node dissection alone has increased significantly since the Z0011 results were first reported ( J Am Coll Surg. 2015;221:71-81 ).

“However, I would highlight that we have also seen an increase in omission of axillary lymph node dissection for patients who do not meet the Z0011 criteria to include those not planned for radiotherapy, those receiving APBI [accelerated partial breast irradiation], and those undergoing mastectomy,” she added. “I highlight these examples specifically because it’s been suggested that one of the reasons the patients on the trial have outstanding regional control is because of the radiation administered as part of their breast-conserving therapy.”

“We will obtain additional data on the locoregional management of these early-stage patients with clinically node-negative breast cancer,” Dr. Mittendorf predicted, pointing to the similar POSNOC trial (which is comparing systemic therapy with versus without axillary treatment) and SOUND trial (which is comparing sentinel node dissection versus no axillary surgery).

In Z0011, all women had tumor in sentinel nodes detected with hematoxylin and eosin staining. Those with sentinel node tumor detected only by immunohistochemistry were excluded, as were those who had matted nodes, three or more involved sentinel nodes, or planned third-field (nodal) irradiation.

Overall, 27.4% of the patients in the ALND group had additional positive nodes removed beyond their sentinel nodes. “There is no reason to suspect that women with sentinel node biopsy [only] had fewer involved nodes than the women treated with axillary lymph node dissection,” Dr. Giuliano commented; thus, a similar share of the former group likely had residual axillary disease that went unresected.

The updated findings showed that the women received ALND and the women who did not were statistically indistinguishable with respect to the 10-year rate of locoregional recurrence (6.2% and 5.3%). Of note, only a single regional recurrence was seen after the initial 5 years of follow-up, and it occurred in the group that did not have ALND.

The groups treated with and without ALND were also statistically indistinguishable with respect to 10-year rates of disease-free survival (78.2% and 80.2%), locoregional recurrence–free survival (81.2% and 83.0%), and overall survival (83.6% and 86.3%).

In multivariate analysis, omission of ALND did not significantly predict locoregional recurrence or overall survival, reported Dr. Giuliano. Additionally, stratified analysis showed that the lack of difference in overall survival between study groups was the same whether tumors had hormone receptors or not.

In a related analysis of radiation protocol deviations in a subset of women from the trial, 11% did not receive any radiation therapy, while 18.9% received third-field radiation, with equal distribution of the latter between study groups ( J Clin Oncol. 2014;32:3600-6 ). Omission of radiation was associated with an increased risk of local recurrence and death, but it did not affect nodal recurrences. Receipt of third-field radiation did not influence survival.