Avoid common mistakes on your manuscript.
Past
In breast cancer patients with pathological complete response (pCR) of the breast after neoadjuvant systemic therapy (NST), the therapeutic effect of surgery is questionable. The detection of pCR without surgery, however, is challenging. Imaging techniques, including MRI and FDG-PET/CT, have not been able to reliably identify patients with pCR after NST.1 Therefore, several studies were initiated, aiming to identify pCR with the use of biopsies. Exploratory analyses showed promising results with false-negative rates (FNRs) of 0–5% for detecting pCR with large vacuum-assisted biopsies.2 However, none of these studies selected patients with radiological response using MRI, the most accurate diagnostic modality for this purpose, and sample sizes were small. In the MICRA trial,3 we aimed to identify pCR of the breast in patients with good MRI response using eight ultrasound-guided minimally invasive 14G core biopsies of the pre-NST marked tumor area.
Present
Currently, the prospect of eliminating breast surgery in early-stage breast cancer patients with pCR after NST is a much-discussed topic. The results of the MICRA trial were presented simultaneously with results of three other studies aiming to identify breast pCR without surgery: a multi-institutional pooled analysis, the RESPONDER trial, and the NRG-BR005 trial.4,5 All four studies differed in biopsy technique (vacuum-assisted or core-cut, either stereotactic or ultrasound-guided), the number and size of the biopsies (14G–7G), and radiological response assessment. None of the studies achieved a FNR below 10% in the entire study population. As for the MICRA trial, the relatively small 14G biopsies mainly missed small lesions and DCIS in patients with radiological complete response on MRI.3
Future
Breast cancer patients with residual disease after NST could benefit from adjuvant systemic therapy (e.g., T-DM1), and reliable assessment of residual disease is therefore essential when considering omission of surgery. The risk of sampling error in future biopsy studies may be reduced by obtaining at least six large and pathologically representative vacuum-assisted biopsies under optimal imaging conditions.5,6 In addition, adequate patient selection is important. Biomarkers such as tumor-infiltrating lymphocytes in combination with advanced MRI analysis could be used to develop a response prediction model which may even outperform biopsies in detecting pCR in selected patients in the near future. Furthermore, pCR of the breast does not guarantee pCR of the lymph nodes, which is an important prognostic factor for disease recurrence and should therefore be investigated as well.
References
Sheikhbahaei S, Trahan TJ, Xiao J, et al. FDG-PET/CT and MRI for evaluation of pathologic response to neoadjuvant chemotherapy in patients with breast cancer: a meta-analysis of diagnostic accuracy studies. Oncologist 2016;21(8):931–39.
Kuerer HM, Vrancken Peeters M, Rea DW, et al. Nonoperative management for invasive breast cancer after neoadjuvant systemic therapy: conceptual basis and fundamental international feasibility clinical trials. Ann Surg Oncol 2017; 24(10):2855–2862.
van Loevezijn AA, van der Noordaa MEM, van Werkhoven ED et al. Minimally invasive complete response assessment of the breast after neoadjuvant systemic therapy for early breast cancer (MICRA trial): interim analysis of a multicenter observational cohort study. Ann Surg Oncol 2020. https://doi.org/10.1245/s10434-020-09273-0.
General Session 5. San Antonio Breast Cancer Symposium 2019. Available at: Abstracts retrieved from: https://www.abstractsonline.com/pp8/#!/7946/session/86. Accessed December 23, 2019.
Tasoulis MK, Lee HB, Yang W, et al. Accuracy of post-neoadjuvant chemotherapy image-guided breast biopsy to predict residual cancer. JAMA Surg 2020:e204103.
Heil J, Kuerer HM, Pfob A, et al. Eliminating the breast cancer surgery paradigm after neoadjuvant systemic therapy: current evidence and future challenges. Ann Oncol 2020;31(1):61–71.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Disclosure
This work was supported by research grants from the Dutch Cancer Society (KWF, Project NKI 2016-8210, Pink Ribbon 2016-206) and the Dutch Innovation Fund Health insurers (IFZ, Project 3.642).
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
van Loevezijn, A.A., van Duijnhoven, F.H. & Vrancken Peeters, MJ.T.F.D. ASO Author Reflections: The Pursuit of Eliminating Surgery after Neoadjuvant Systemic Therapy in Breast Cancer Patients. Ann Surg Oncol 28, 3254–3255 (2021). https://doi.org/10.1245/s10434-020-09324-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1245/s10434-020-09324-6