PHILADELPHIA (FRONTLINE MEDICAL NEWS) – The safety of sentinel lymph node biopsy (SLNB) alone without axillary lymph node dissection (ALND) had been established for patients with cT1-2N0 cancer with one or two positive sentinel lymph nodes who undergo breast conservation therapy, but concerns about omitting axillary lymph node dissection and the role of radiation therapy have remained.

A large, prospective, 5-plus-year study at Memorial Sloan Kettering Cancer Center has shown that these patients do not require axillary lymph node dissection.

“Axillary dissection can no longer be considered standard management for women with clinical T1 and T2 [human epidermal growth factor receptor]–negative breast cancers undergoing breast conservation and found to have sample node metastases,” Monica Morrow, MD , said at the 137th annual meeting of the American Surgical Association here. The study involved 793 women, who were found to have sentinel node metastases, undergoing breast-conserving surgery at Memorial Sloan Kettering Cancer Center (MSKCC) in New York from September 2010 to March 2016.

Dr. Morrow explained that, in August 2010, the breast surgery service at MSKCC adopted the guidelines that arose from the American College of Surgeons Oncology Group’s multicenter Z0011 trial and abandoned routine use of ALND in eligible patients. The goal of the study, she reported, was to determine how frequently axillary dissection was avoided in a consecutive, otherwise unselected, series of patients and to determine the incidence of local regional recurrence after SLNB alone in a population treated with known radiotherapy fields.

Eligible subjects had T1 or T2 node-negative breast cancer, were undergoing breast-conserving surgery with planned whole-breast irradiation, and were found to have hematoxylin-eosin-detected sentinel node metastases. Patients receiving neoadjuvant chemotherapy or requiring conversion to mastectomy, or those in whom partial breast irradiation or no radiotherapy was planned, were ineligible. Axillary imaging was not used in select patients. Criteria for axillary dissection were metastases in three or more sentinel nodes or the presence of matted nodes identified intraoperatively. The researchers did not use the MSKCC nomogram to predict the likelihood of non–sentinel node metastases.

Median patient age was 58 years and median tumor size 1.7 cm. With regard to tumor pathology, 87% had infiltrating ductal tumors, 94% had grade 2 or 3 disease, and the most common subtype was HR+, HER2– disease in 84%. “In this node-positive cohort of patients, 98% received adjuvant systemic therapy, most commonly both chemotherapy and endocrine therapy (received by 65%), and 93% completed radiotherapy,” Dr. Morrow said.

In the entire patient cohort, 84% (663) were treated with SLNB alone, Dr. Morrow said. Among the 130 patients requiring ALND, 68% (88) had metastases in three or more nodes, 26% (34) were found to have had matted nodes intraoperatively, and 6% (8) were eligible for SLNB alone but opted for ALND or had it recommended by their surgeon. “All of these occurred early in our experience, and this has not been repeated since,” Dr. Morrow said.

Among the SLNB-only patients, the 5-year event-free survival was 93%. “There were no isolated axillary recurrences,” Dr. Morrow said. The study reported four combined breast and axillary recurrences, three in nonradiated patients, and four combined nodal and distant recurrences, only one of which involved the axillary nodes. “The median time to any nodal recurrence was 25 months,” Dr. Morrow added. Among 484 patients who had 1 year or more of follow-up, 58% (280) received conventional supine breast tangents, 21% were treated prone – “meaning their axilla received essentially no radiotherapy,” Dr. Morrow said – and 21% had node field irradiation.

“If we compare patient characteristics based on radiotherapy fields treated, it’s clear that the patients who received nodal irradiation were a higher-risk group,” Dr. Morrow said. While all three groups had a median of one positive sentinel node, that “skewed towards two” in the nodal irradiation group, she said. This group also had higher rates of lymphovascular invasion (72% vs. 56% and 49% in the supine and prone groups, respectively) and extracapsular extension (41% vs. 31% and 25%).

The rates of nodal relapse were not statistically significant among the three groups: 1% in the prone group, 1.4% in the supine group, and 0% in the node irradiation group.

“Factors associated with a higher risk of distant metastases, such as young patient age, estrogen receptor negativity, or HER2 over-expression, were not associated with the need for axillary dissection and should not be used as priority selection criteria,” Dr. Morrow said. “Nodal recurrence was uncommon in the absence of routine nodal radiation therapy, and no isolated nodal failures were observed.

In his comments, Armando Giuliano, MD , of Cedars Sinai Medical Center in Los Angeles, principal investigator of the Z0011 trial , said the MSKCC study “extends and informs” the Z0011 findings. He noted that the prone treatment group in the MSKCC trial had a low rate of axillary recurrence. “Can you speculate how such excellent results are achieved without resection or irradiation?” he asked Dr. Morrow. “To me it appears that no irradiation provides very little benefit to this selected group of patients.”

The patients in the prone group were in the lowest-risk category of the study, Dr. Morrow said, but the fact that not all nodal disease becomes clinically evident, even in patients who do not receive radiotherapy or systemic therapy, along with the high use of systemic therapy in this group, may explain the low rates of axillary recurrence. “What I think we still need to find out, though, is whether or not failure to irradiate the nodes at all is in any way associated with decreased survival, as would be suggested in the MA.20 trial, ” she said. “I think we will find that out from ongoing trials looking at no axillary dissection in mastectomy patients.”

Dr. Morrow and Dr. Giuliano reported no financial disclosures.

The complete manuscript of this study and its presentation at the American Surgical Association’s 137th Annual Meeting, April 2017, in Philadelphia, Pennsylvania, is to be published in Annals of Surgery pending editorial review.