Omitting Axillary Lymph Node Dissection in Early Breast Cancer

Recently, omission of axillary lymph node dissection among patients with early breast cancer has been found to have no detrimental effect on outcomes in most cases, continuing a trend toward less aggressive management.

Historically, treatment for breast cancer has been aggressive, with surgery, chemotherapy, and radiotherapy used to optimize outcomes.

“But the burden for patients was high,” noted Monica Morrow, MD, of Memorial Sloan Kettering Cancer Center in New York City, at the recent San Antonio Breast Cancer Symposium (SABCS). “Based on prospective randomized trials over the years, we came to learn that we could replace mastectomy with breast conservation for many patients, replace axillary dissection with sentinel [lymph] node biopsy [SLNB], give less radiotherapy in the form of partial breast irradiation or give it over a shorter period of time with hypofractionation, and that targeted therapies actually work just as well, if not better, than chemotherapy.”

In the setting of hormone receptor (HR)-positive, HER2-negative breast cancer, most postmenopausal women can be spared axillary surgery, contended Elizabeth Mittendorf, MD, PhD, of Dana-Farber Cancer Institute in Boston. She presented her institution’s criteria for omission of surgical dissection of the axilla that were informed by recent results from the SOUND and INSEMA trials, as well as real-world experience.

SOUND Trial

The phase III SOUND trial randomized patients with early breast cancer and a negative axillary ultrasound to SLNB or no axillary surgery. In the SLNB arm, 13.7% had positive axillary nodes, 5.1% had micrometastases, and 8.6% had macrometastases. Only four patients had four or more positive nodes.

The 5-year distant disease-free survival rate was about 98% in both study arms, meeting the primary endpoint of noninferiority. The rates of axillary recurrence were low in both arms, at 0.4% in each.

INSEMA Trial

In the INSEMA trial, patients with newly diagnosed, clinically node-negative stage T1-2 breast cancer were randomized to SLNB or no axillary surgery. After a median follow-up of 73.6 months, the 5-year invasive disease-free survival rate was about 92% in both treatment groups. There was a slightly higher rate of axillary recurrence in the no-surgery group versus the SLNB group (1% vs 0.3%), but fewer deaths (1.4% vs 2.4%).

Omission of surgery was associated with reductions in the incidence of lymphedema (1.8% vs 5.7%), restricted arm/shoulder movement (2% vs 3.5%), and pain with arm/shoulder movement (2% vs 4.2%).

Real-World Experience

Following the publication of SOUND, Mittendorf’s group looked at 3,972 patients with HR-positive, HER2-negative breast cancer to examine clinicopathologic characteristics, disease burden, adjuvant treatment, and oncologic outcomes. Of these patients, 544 underwent axillary ultrasound, and 312 met SOUND eligibility criteria.

“Because we had already incorporated the Choosing Wisely recommendations into our practice, 96 had SLNB omitted, and this was primarily women 70 and older,” Mittendorf said. (The Choosing Wisely campaign recommends omission of SLNB in patients ages 70 and older.)

Some 88% of patients in the real-world cohort were node-negative compared with 85% in SOUND. Less than 1% had four or more positive nodes, and about 80% received hormone therapy only, similar to patients in SOUND.

“I would note that nodal status did not impact adjuvant therapy considerations in our postmenopausal patients. Our follow-up is limited as I acknowledge, but we so far have excellent oncologic outcomes,” Mittendorf said. With a median follow-up of 26 months, rates of locoregional recurrence, as well as distant metastases, are low.

Implications of SOUND and INSEMA

INSEMA investigator Toralf Reimer, MD, PhD, of the University of Rostock in Germany, said that avoidance of complete axillary surgery as treatment de-escalation is suitable for women ages 50 and older with HR-positive breast cancer and a tumor size ≤2 cm.

Puneet Singh, MD, of the University of Texas MD Anderson Cancer Center in Houston, who was an invited discussant for the INSEMA trial at SABCS, noted that omission of SLNB for tumors ≤2 cm is appropriate “as we know that higher rates of sentinel node positivity exist with larger tumors, and that has implications for adjuvant therapies.”

The data from INSEMA, however, do not make clear the appropriate strategy for women with non-HR-positive/HER2-negative tumors undergoing upfront surgery.

“The role of preoperative imaging is also still a question,” said Singh. “While at my institution, we do it routinely for everyone, that may not be standard workflow for everyone.”

“I think [SLNB] is still a staging modality that is necessary for many patients,” she added. “The take-home point is that shared decision-making with patients and the multidisciplinary team is critical when determining who we can omit the sentinel node biopsy without compromising their care.”

A series of multidisciplinary discussions at Dana Farber resulted in criteria they use to omit surgical staging of the axilla. These criteria include:

• Ages 60-69 years
• Clinical T1N0 tumors
• Ductal histology
• Grade 1-2 disease
• Estrogen receptor >10%, HER2-negative tumors
• No lymphovascular invasion
• Negative axillary ultrasound findings

“I would suggest that this is probably fairly conservative implementation criteria,” said Mittendorf. “We were trying to identify a patient population that our radiation oncologists would still feel comfortable considering partial breast irradiation, even with the omission of SLNB.”

These criteria are similar, but a bit more restrictive, to those used at Memorial Sloan Kettering Cancer Center and the Mayo Clinic in Jacksonville, she noted.

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