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SAN ANTONIO -- Patients with early breast cancer who skipped axillary lymph node dissection (ALND) lived just as long as those who underwent sentinel lymph node biopsy (SLNB), the randomized INSEMA trial showed.

The estimated 5-year invasive disease-free survival (IDFS) rate was 91.9% in patients who omitted ALND and 91.7% for those who had SLNB. The small difference met prespecified noninferiority criteria for ALND omission versus SLNB. An analysis of first primary events showed a higher axillary recurrence rate in patients who omitted ALND but a lower death rate.

Patients randomized to ALND omission had less lymphedema, better arm mobility, and less pain with arm and shoulder movement as compared with patients who underwent SLNB, reported Toralf Reimer, PhD, of the University of Rostock in Germany, at the San Antonio Breast Cancer Symposium.

"The ... significantly demonstrated that complete omission of sentinel lymph node biopsy in clinical node-negative patients with early breast cancer and scheduled for breast-conserving therapy did not result in inferior outcomes," said Reimer. "Patients recruited for the INSEMA trial had a very good overall survival, with 97% versus 98% at 5 years, according to the treatment arms."

"This de-escalation concept, avoiding complete axillary surgery, is suitable for patients with an age 50 years and older and with low tumor characteristics, like low or immediate tumor grading and hormone receptor-positive subtype and a tumor size up to 2 cm," he noted.

The study was published simultaneously in the .

Option for Selected Patients

The INSEMA study added to existing evidence that SLNB can be omitted in select patients and results in excellent survival and low rates of recurrence, said invited discussant Puneet Singh, MD, of the University of Texas MD Anderson Cancer Center in Houston. The results are consistent with those of the recently published study, which involved a similar patient population. SOUND showed 5-year distant disease-free survival and overall survival (OS) rates of about 98% with or without SLNB.

"I think [omission of SLNB] is appropriate for smaller tumors, those that are 2 cm or smaller, as we know that higher rates of sentinel node positivity exist with larger tumors, and that has implications for adjuvant therapies," said Singh. "[INSEMA] had a very low percentage of non-hormone receptor-positive/HER2-negative tumors, so we really don't know what to do with small HER2-positive or triple-negative breast cancers that are undergoing upfront surgery."

"The role of preoperative imaging is also still a question. While at my institution, we do it routinely for everyone, that may not be standard workflow for everyone," she continued. "How does that fit in if we're going to omit [SLNB]? There was a low percentage of lobular-histology tumors and we know these are hard to detect on imaging."

Eliminating SLNB has several implications for breast cancer management, Singh said. A positive sentinel lymph node influences adjuvant therapy decision making, including systemic therapies and radiotherapy. Chemotherapy or CDK4/6 inhibitors might be recommended for premenopausal patients, and radiotherapy options might be limited in the absence of axillary staging, with respect to partial breast irradiation and enrollment into clinical trials.

"I think [SLNB] is still a staging modality that is necessary for many patients," noted Singh. "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. We now have additional data on omitting surgical treatment in low-risk populations -- even though there are questions that remain -- that bring us closer to individualizing and optimizing the care of patients with breast cancer."

The author of an that accompanied the study said trials such as INSEMA and SOUND, as well as ongoing studies, "provide a glimpse into the future."

"Sentinel lymph node biopsy is associated with low but measurable morbidity, and elimination of the procedure decreases the treatment burden on patients," wrote Monica Morrow, MD, of Memorial Sloan Kettering Cancer Center in New York City. "But if the omission compromises recommendations for adjuvant therapy and leads to whole-breast irradiation in a candidate for partial-breast irradiation or to the omission of CDK4/6 inhibitor therapy because of uncertainty about nodal status, is this the most appropriate course?"

"Successful de-escalation of any therapeutic approach requires multidisciplinary consideration of the effects on the entire treatment plan; INSEMA and SOUND data provide a strong foundation for consideration of how to incorporate the elimination of sentinel-lymph-node biopsy into practice," she added.

Background, Results

Axillary lymph node status has a long history of providing prognostic information and guiding systemic therapy and radiotherapy for breast cancer. The American College of Surgeons Oncology Group Z0011 trial provided the basis for subsequent studies evaluating treatment de-escalation for early breast cancer, demonstrating noninferiority of SLNB to ALND.

INSEMA and SOUND are among four trials designed to evaluate omission of SLNB in patients with clinically node-negative early breast cancer. The and studies are ongoing.

INSEMA involved 5,502 patients with newly diagnosed, clinically node-negative stage T1 or 2 breast cancer, enrolled at centers throughout Germany and Austria. The patients were randomized 3:1 to SLNB or no axillary surgery. The per-protocol analysis included 4,858 patients, 962 assigned to no axillary surgery and 3,896 to SLNB. Patients who had positive SLNB results were randomized a second time to complete ALND or no further axillary surgery. Reimer reported only the results from the first randomization.

The primary endpoint was IDFS, and the trial had the statistical power to demonstrate noninferiority of no axillary surgery versus SLNB within the range of 85% to 95% for the no-surgery group. After a median follow-up of 73.6 months, the data showed a 5-year IDFS rate of about 92% in both treatment groups.

An analysis of first primary-outcome events (occurrence or recurrence of invasive disease or death) showed a slightly higher rate of axillary recurrence in the no-surgery group (1% vs 0.3%) but lower mortality (1.4% vs 2.4%).

A safety analysis showed that surgery omission was associated with a reduced 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%).