Oncologic outcomes in breast cancer patients with metastatic nodes and pathological nodal response following neoadjuvant chemotherapy without axillary dissection: a literature review.

Review Article Page 1 of 8 Oncologic outcomes in breast cancer patients with metastatic nodes and pathological nodal response following neoadjuvant chemotherapy without axillary dissection: a literature review Geok Hoon Lim1,2^, Lester Chee Hao Leong3 1 Breast Department, KK Women’s and Children’s Hospital, Singapore, Singapore; 2Duke-NUS Medical School, Singapore, Singapore; 3Department of Diagnostic Radiology, Singapore General Hospital, Singapore, Singapore Contributions: (I) Conception and design: GH Lim; (II) Administrative support: None; (III) Provision of study materials or patients: Both authors; (IV) Collection and assembly of data: Both authors; (V) Data analysis and interpretation: Both authors; (VI) Manuscript writing: Both authors; (VII) Final approval of manuscript: Both authors. Correspondence to: Geok Hoon Lim, FRCS. Breast Department, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore. Email: . Background and Objective: With promising nodal pathological complete response (pCR) after neoadjuvant chemotherapy, the role of axillary lymph node dissection (ALND) was questioned. While there is much data on the accuracy of axillary staging after neoadjuvant chemotherapy to predict nodal pCR, limited data on the oncological safety of omitting ALND exists. We aim to review the oncological safety of omitting ALND in patients with initially metastatic nodes achieving nodal pCR, based on axillary staging, following neoadjuvant chemotherapy. Methods: A PubMed search of relevant articles from 1 st January 2013 to 15 th September 2022 was performed. Studies with duplication of patients, ALND only, no oncological details, initially N0 patients only and patients without nodal pCR were excluded. Key Content and Findings: Fifteen studies with 1,515 eligible patients (range, 29–242 patients) were analysed. There was heterogeneity of patients among the included studies and patients had varying TN staging, making selection criteria for omission of ALND inconclusive. Sentinel lymph node biopsy (SLNB) was the most studied mode of axillary staging in 1,416 (93.5%) patients, though 35.7% had <3 SLN harvested. On average median follow-up of 52.8 months (range, 9–110 months), axillary recurrence ranged from 0% to 3.4%. There was limited data on survival outcomes. Conclusions: In node positive breast cancer patients who achieved nodal pCR after neoadjuvant chemotherapy, the axillary recurrence rate was low without ALND. However, survival data was limited. The selection criteria and ideal axillary staging technique for patients, who are suitable for axillary preservation, are unclear. More prospective studies with longer follow-up, providing survival data, are needed. Keywords: Breast cancer; neoadjuvant chemotherapy; sentinel lymph node biopsy (SLNB); survival; axillary recurrence Submitted Oct 09, 2022. Accepted for publication Feb 19, 2023. Published online Mar 09, 2023. doi: 10.21037/atm-22-4961 View this article at: https://dx.doi.org/10.21037/atm-22-4961 ^ ORCID: 0000-0002-5296-3437. © Annals of Translational Medicine. All rights reserved. Ann Transl Med 2023;11(5):218 | https://dx.doi.org/10.21037/atm-22-4961 Page 2 of 8 Lim and Leong. Outcomes of patients with pathological nodal response Introduction For node positive (N+) breast cancer patients with no systemic metastasis, axillary lymph node dissection (ALND) used to be the treatment of choice. However, with the promising results of nodal pathological complete response (pCR) with neoadjuvant chemotherapy (1), axillary staging, in the form of sentinel lymph node biopsy (SLNB) alone (2) or combined with clipped node excision via targeted axillary dissection (TAD) (3) or clipped node alone (4) have been reported. Depending on the results of the axillary staging, an ALND could potentially be omitted. While there was much data on the various types of localising agents used for clipping the node (5) and the accuracy of SLNB or TAD in predicting nodal pCR for this group of patients (3,6), there is limited data on the oncologic safety of omitting ALND following neoadjuvant chemotherapy in patients with initial metastatic nodes. We aim to perform a narrative review of the axillary recurrence and survival rates in this group of patients with nodal pCR after neoadjuvant chemotherapy, who underwent SLNB, TAD or clipped node staging only. This is the first such reported review, to the best of our knowledge. We present the following article in accordance with the Narrative Review reporting checklist (available at https://atm. amegroups.com/article/view/10.21037/atm-22-4961/rc). Methods A PubMed search was conducted for relevant publications dated between 1st January 2013 to 15th September 2022, using the following search terms: breast cancer, neoadjuvant chemotherapy, SLNB, TAD, survival, axillary recurrence, clipped node (Table 1). Publications were only searched from the year of 2013 because the concept of axillary staging after neoadjuvant chemotherapy without ALND for patients with initially metastatic nodes, was only introduced around that time (7). Only publications in the English language consisting of female patients were included. Publications without an abstract, such as editorials and letters to the editor were excluded. This review included patients with initially N+ disease who underwent only SLNB/TAD/clipped node following neoadjuvant chemotherapy and achieved ypN0 based on histological axillary staging, to follow-up on their oncologic outcomes. We excluded publications with duplication of the study population, patients who underwent ALND or had no recurrence data. Patients with no clinical or pathological © Annals of Translational Medicine. All rights reserved. nodal metastasis prior to neoadjuvant chemotherapy were excluded too. The PubMed search was conducted independently by two authors. The abstract was first assessed for its relevance. If found to be relevant, the full article was retrieved for the extraction of relevant details. For relevant publications, the references in the publications were also assessed for relevance to add to the review. For any relevant publication, a PubMed search was also conducted to look for similar related articles. In cases of discordance, the two authors would reassess the article again to reach a consensus. Results A total of 22 studies were found relevant to this review. However, 7 studies had to be excluded as 2 studies (8,9) had duplication of patients. For such duplicated cases, studies with a longer follow-up (10,11) were included instead. Another publication (12) included patients from 2 centres, of which there was duplication of the patients from one of the centres with another study (11). Since the patients from the various centres in the study could not be differentiated, this study (12) was excluded. In addition, though the multicentre study by Kang et al. (13) demonstrated in their subgroup analysis that ypN0 patients under (...truncated)