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. 2022 May;193(1):37-48.
doi: 10.1007/s10549-022-06545-z. Epub 2022 Mar 3.

Three-year follow-up of de-escalated axillary treatment after neoadjuvant systemic therapy in clinically node-positive breast cancer: the MARI-protocol

Ariane A van Loevezijn  1   2 , Marieke E M van der Noordaa  1 , Marcel P M Stokkel  3 , Erik D van Werkhoven  4 , Emma J Groen  5 , Claudette E Loo  6 , Paula H M Elkhuizen  7 , Gabe S Sonke  8 , Nicola S Russell  7 , Frederieke H van Duijnhoven  1 , Marie-Jeanne T F D Vrancken Peeters  9   10
Affiliations

Three-year follow-up of de-escalated axillary treatment after neoadjuvant systemic therapy in clinically node-positive breast cancer: the MARI-protocol

Ariane A van Loevezijn et al. Breast Cancer Res Treat. 2022 May.

Abstract

Purpose: In clinically node-positive (cN+) breast cancer patients, evidence supporting response-guided treatment after neoadjuvant systemic therapy (NST) instead of axillary lymph node dissection (ALND) is increasing, but follow-up results are lacking. We assessed three-year axillary recurrence-free interval (aRFI) in cN+ patients with response-adjusted axillary treatment according to the 'Marking Axillary lymph nodes with Radioactive Iodine seeds' (MARI)-protocol.

Methods: We retrospectively assessed all stage II-III cytologically proven cN+ breast cancer patients who underwent the MARI-protocol between July 2014 and November 2018. Pre-NST axillary staging with FDG-PET/CT (less- or more than four suspicious axillary nodes; cALN < 4 or cALN ≥ 4) and post-NST pathological axillary response measured in the pre-NST largest tumor-positive axillary lymph node marked with an iodine seed (MARI-node; ypMARI-neg or ypMARI-pos) determined axillary treatment: no further treatment (cALN < 4, ypMARI-neg), axillary radiotherapy (ART) (cALN < 4, ypMARI-pos and cALN ≥ 4, ypMARI-neg) or ALND plus ART (cALN ≥ 4, ypMARI-pos).

Results: Of 272 women included, the MARI-node was tumor-negative in 56 (32%) of 174 cALN < 4 patients and 43 (44%) of 98 cALN ≥ 4 patients. According to protocol, 56 (21%) patients received no further axillary treatment, 161 (59%) received ART and 55 (20%) received ALND plus ART. Median follow-up was 3.0 years (IQR 1.9-4.1). Five patients (one no further treatment, four ART) had axillary metastases. Three-year aRFI was 98% (95% CI 96-100). The overall recurrence risk remained highest for patients with ALND (HR 4.36; 95% CI 0.95-20.04, p = 0.059).

Conclusions: De-escalation of axillary treatment according to the MARI-protocol prevented ALND in 80% of cN+ patients with an excellent three-year aRFI of 98%.

Keywords: Axillary lymph node dissection; Breast cancer; Neoadjuvant therapy; Tailored treatment.

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Conflict of interest statement

GS received institutional research support from AstraZeneca, Merck, Novartis, and Roche outside the scope of this manuscript. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Patient inclusion. MARI Marked axillary lymph node with radioactive iodine seed, FDG-PET/CT fluorodeoxyglucose—positron emission tomography/computed tomography; ALNs Axillary lymph nodes, FS frozen section, ALND axillary lymph node dissection, cALN < 4 less than four FDG-PET/CT-positive axillary lymph nodes, cALN ≥ 4 more than four FDG-PET/CT positive axillary lymph nodes, ART axillary radiotherapy
Fig. 2
Fig. 2
Tailored adjuvant axillary treatment strategy according to the MARI protocol. FNAC fine needle aspiration cytology, cALN < 4 less than four FDG-PET/CT-positive axillary lymph nodes, cALN ≥ 4 more than four FDG-PET/CT positive axillary lymph nodes, MARI marked axillary lymph node with radioactive iodine seed, pCR pathological complete response, ALN Axillary lymph node, ALND axillary lymph node dissection, ART axillary radiotherapy
Fig. 3
Fig. 3
Overall recurrence-free interval by axillary staging and treatment. cALN < 4 less than four FDG-PET/CT-positive axillary lymph nodes, cALN ≥ 4 more than four FDG-PET/CT positive axillary lymph nodes, MARI marked axillary lymph node with radioactive iodine seed, ypMARI-neg/ypMARI-pos pathology analysis of MARI-node after neoadjuvant systemic therapy tumor-negative/tumor-positive, ART axillary radiotherapy, ALND axillary lymph node dissection
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