Response-guided axillary treatment using an approach known as the MARI protocol can safely spare many women with node-positive breast cancer from axillary lymph node dissection (ALND) after neoadjuvant systemic therapy, a large Dutch study has found.

In the MARI protocol, a single biopsy-proven positive axillary node is marked with a radioactive iodine seed before primary systemic therapy and then selectively removed after primary therapy to gauge response.

The new study found that, among the 39% of patients who experienced a pathologic complete response (pCR) in the MARI-marked node and received no further axillary treatment, only one patient (0.7%) had an axillary recurrence. Overall, 98% of patients in this group were alive at 5 years.

Even among patients who had residual disease in the MARI node and received radiation, the axillary recurrence rate was low: 2.3%.

“These findings suggest that response-guided axillary treatment based on the MARI protocol for patients with limited nodal disease was associated with a very low risk of axillary recurrence and should be considered in patients with node-positive breast cancer who experienced nodal pCR after [primary systemic therapy],” lead author Marie-Jeanne Vrancken Peeters, MD, PhD, of the Department of Surgical Oncology, the Netherlands Cancer Institute, Amsterdam, the Netherlands, and colleagues concluded.

Overall, ALND has fallen out of favor in the US in lieu of more limited axillary surgery for many patients with breast cancer, Abram Recht, MD, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, told Medscape Medical News.

“This important study from the Netherlands Cancer Institute adds to a growing body of information suggesting that most patients with a limited axillary tumor burden on pretreatment evaluation are unlikely to benefit sufficiently from ALND to outweigh its morbidity,” Recht wrote in an editorial accompanying the study in JAMA Oncology.

Ongoing Uncertainty

Since 2022, the MARI procedure has been incorporated into the Dutch breast cancer guidelines, resulting in a “huge de-escalation of axillary treatment” in clinically node-positive patients treated with primary therapy, Vrancken Peeters told Medscape Medical News.

Previous smaller studies have found that using a MARI-guided approach can help patients with breast cancer avoid ALND. The current analysis aimed to assess the axillary recurrence rate, invasive disease-free survival, and overall survival among patients receiving MARI-guided care in a larger patient population.

The study involved 350 patients with breast cancer with one to three positive nodes who underwent primary systemic therapy using the MARI protocol. Patients with limited node involvement and a pCR in the MARI-marked node received no further axillary treatment, while those with residual disease in the MARI node underwent locoregional axillary radiotherapy.

Overall, 39% of all patients (n = 135) had a pCR in the MARI node and received no further axillary treatment, while the remaining 61% (n = 215) with residual disease in the MARI node received locoregional radiotherapy.

After a median follow-up of 49 months, only one patient (0.7%) with a pCR in the MARI node had an axillary recurrence. In this group, 5-year overall survival was 98%, and 5-year invasive disease-free survival was 93%.

For patients who had residual disease in the MARI node and received radiation, the axillary recurrence rate was 2.3%. However, all five patients also experienced concurrent distant metastases. Among this group, 5-year invasive disease-free survival was 87%, and overall survival was 93%.

The data suggest that ALND is unlikely to sufficiently benefit patients who have isolated tumor cells only or a limited number of micrometastases, particularly when uninvolved nodes are also recovered, Recht said.

But Recht provided some notes of caution.

It remains unclear how best to tailor axillary treatment in patients undergoing neoadjuvant chemotherapy who have residual nodal disease and whether certain patient subgroups are at substantially greater risk for axillary recurrence with limited axillary surgery plus radiation than with ALND, Recht explained. Caution is needed, for instance, when considering omission of ALND in patients with several macrometastases, axillary soft tissue involvement, and triple-negative cancers.

“Patients who have triple-negative disease maybe are really the ones where we have to worry,” Recht said, adding that these patients may still need an axillary dissection.

Another potential caveat is the use of the MARI protocol.

“While effective, MARI raises issues because you’re dealing with this radioactive node — very low activity, but still there’re radiation considerations,” Recht said.

MARI is one of several less invasive axillary techniques that have been developed over the years. Others include sentinel lymph node biopsy and targeted axillary dissection, which combines sentinel lymph node biopsy with removal of a marked node, as well as other node-marking alternatives such as radiofrequency chips.

While several ongoing randomized controlled trials should provide more guidance for clinicians on the need for ALND and when it can be omitted, “for now, each multidisciplinary group should create its own internal guidelines and protocols,” Recht wrote in the editorial. “If nothing else, this will reduce patient confusion when speaking to different specialists.”

The study was supported by the Reggeborgh Foundation, the Herja Foundation, and the AVL Foundation. Vrancken Peeters and Recht reported having no relevant disclosures.