Miriam E. Tucker

October 07, 2013

WASHINGTON, DC — Sentinel lymph node (SLN) staging could be considered a reliable alternative to full axillary lymph node dissection (ALND) for women in whom 3 or more sentinel nodes can be identified, according to a recent American College of Surgeons Oncology Group (ACOSOG) trial. The study was conducted in women with invasive breast cancer with histologically or cytologically conformed node-positive status who had undergone neoadjuvant systemic chemotherapy.

Findings from the ACOSOG Z1071 trial, by Judy C. Boughey, MD, associate professor of surgery at the Mayo Clinic, Rochester, Minnesota, and colleagues, were published online October 7 in JAMA. Dr. Boughey will be discussing the results here at the American College of Surgeons (ACS) 2013 Annual Clinical Congress.

ACOSOG Z1071 results were first presented in December 2012 at the San Antonio Breast Cancer Symposium. At the time, the investigators concluded that some women with node-positive breast cancer who receive neoadjuvant chemotherapy might not need to automatically undergo ALND. Instead, it might be possible for some to undergo a less invasive SLN biopsy. With the publication of the results, the investigators provide more details on which women might be suitable for this regimen.

The trial did not meet its prespecified primary end point of a false-negative rate for SLN surgery of 10% or less after chemotherapy. However, this end point was met by a subset of women with 3 or more resected SLNs.

"There are a lot of things from this study that provide information that will help us change the way we treat patients in the future," Dr. Boughey told Medscape Medical News in an interview. She noted that the false-negative rate was lower — although not below 10% — when dual mapping agents were used instead of just 1 agent.

"This will not be a one size fits all. This will be trying to identify the subgroups that will benefit from this. This is a high-risk patient population and we want to do this safely, not take all comers on board," she told Medscape Medical News.

There is significant morbidity associated with ALND, Dr. Boughey noted. "We're trying to improve our selection of women who would do just as well with either surgery or radiation, and try to make sure we're treating women with the most effective options but not overtreating them," she explained.

A More Conservative View

In an accompanying editorial, Monica Morrow, MD, and Chau T. Dang, MD, from the Memorial Sloan-Kettering Cancer Center in New York City, take a more conservative look at the data.

This is not something that is dramatically practice-changing, because it only applies to about a quarter of women. Dr. Monica Morrow

"This procedure is only accurate if you get 3 or more sentinel lymph nodes, and many women do not have 3 or more sentinel lymph nodes," Dr. Morrow told Medscape Medical News.

The average SLN count in this patient group is 2; only about 25% of women have 3 SLNs. "We have to make sure we do it safely.... This is not something that is dramatically practice-changing, because it only applies to about a quarter of women," she noted.

In addition, in the neoadjuvant setting, where the chemotherapy has already been given, any residual positive nodes are likely to be more resistant to drugs, she pointed out. "It's important that women understand that if they start out with involved lymph nodes under the arms and undergo chemotherapy, the most likely thing that will happen is that they will still need to have all of their lymph nodes removed," Dr. Morrow told Medscape Medical News.

Is It Safe to Skip ALND?

Of the 756 patients with clinical stage T0 to T4, N1 or N2 disease from 136 institutions enrolled over a 2-year period, 687 underwent both SLN surgery and subsequent ALND. Most (79%) had the SLN mapping done with both blue dye and radiolabeled colloid; 21% had only one or the other.

In 525 patients with cN1 disease, 2 or more SLNs were identified and excised in the 84 days after chemotherapy. In 215 (41%) of these patients, pathologic examinations of SLN and ALND samples were negative. In the remaining 310 patients, residual nodal disease was found with both SLN biopsy and ALND in 163 (31%), with SLN surgery in 108 (21%), and with ALND in 39 (7%).

Thus, the false-negative rate was 39 of 310 (12.6%). That did not meet the prespecified primary end point of 10% or less, which was based on the false-negative rate typically seen with SLN staging in women initially presenting with clinically negative axillary lymph nodes, the investigators note.

Of the 26 women with cN2 disease who had at least 2 SLNs excised, residual nodal disease was found with either SLN biopsy or ALND in 12 (46%). In the remaining 14 patients, residual nodal disease was found with both SLN biopsy and ALND in 8 (31%) patients and with SLN surgery in 6 (23%), with 0% false negatives.

Dr. Boughey and colleagues point out that in the cN1 group, the false-negative rate was significantly lower when both blue dye and radiolabeled colloid were used for SLN mapping than when only 1 method was used (10.8% vs 20.0%; P = .05). The rate was also lower when 3 or more SLNs were examined than when 2 SNLs were examined (9.1% vs 21.0%; P = .007).

"Taking this piece of information can help us identify both surgical and patient factors to help us select the best patients for whom this can be utilized," Dr. Boughey told Medscape Medical News.

She pointed out that this information will become more relevant with advances in systemic chemotherapy. In the past, only 10% to 15% of previously positive lymph nodes would become negative after chemotherapy; current success rates range from 40% to even 70% with some of the newer targeted therapies.

"When you look at the big picture of taking care of women with breast cancer, as we get better with our systemic chemotherapy and targeted therapies, it's time for the surgeons and radiation oncologists to re-evaluate whether we need to be maximally invasive. Or, if we have a patient who has a very responsive tumor, who has gotten great systemic therapy and has had a great response, can we be less aggressive in what we're doing with our local management," Dr. Boughey said.

However, Dr. Morrow cautioned that with chemotherapy, the tumor cells in the breast don't die uniformly, but rather in a "patchy fashion," which would likely be the pattern in the lymph nodes as well. "It might be that the SLN procedure isn't well suited to this setting," she told Medscape Medical News.

Dr. Morrow acknowledged that SLN staging with the aim of finding at least 3 SLNs might be worth a try in selected patients who have had a good response in the primary tumor. But, she added, surgeons must be "rigorous" in finding 3 "real" sentinel nodes. "You can't just find 1 or 2 and then pick out 2 or 3 other nodes. We don't know that that's accurate."

The study was funded by a grant from the National Cancer Institute awarded to the American College of Surgeons Oncology Group.

JAMA. Published online October 7, 2013. Abstract, Editorial


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