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Nomogram for predicting axillary upstaging in clinical node-negative breast cancer patients receiving neoadjuvant chemotherapy

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Abstract

Purpose

The prediction of axillary lymph node status after neoadjuvant chemotherapy (NAC) becoming critical because of the advocation of the de-escalation of axillary management. We investigate associated factors of axillary upstaging in clinical node-negative (cN0) breast cancer patients receiving NAC to develop and validate an accurate prediction nomogram.

Methods

We retrospectively analyzed 1892 breast cancer patients with stage of cT1-3N0 treated by NAC and subsequent surgery between 2010 and 2020 in twenty hospitals across China. Patients randomly divided into a training set and validation set (3:1). Univariate and multivariate logistic regression analysis were performed, after which a nomogram was constructed and validated.

Results

In total, pathologic node negativity (ypN0) achieved in 1406 (74.3%) patients and another 486 (25.7%) patients upstaged to pathologic node positive (ypN+). Breast pathologic complete response (bpCR) was achieved in 445 (23.5%) patients and non-bpCR in 1447 (76.5%) patients. A nomogram was established by ER, tumor histology, HER2 status, cycle of NAC treatment, and the bpCR, which were confirmed by multivariate logistic analysis as independent predictors of nodal upstaging in the training cohort (n = 1419). The area under the receiver operating characteristic curve (AUC) of the training cohort and validation cohort (n = 473) were 0.73 (95% CI 0.693–0.751) and 0.77 (95% CI 0.723–0.812) respectively.

Conclusion

We present a nomogram with a nationwide large sample data which can effectively predict axillary upstaging after neoadjuvant chemotherapy to give better advice for individualized axillary lymph node management of breast cancer.

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Availability of data and material

All data during the study are proprietary in nature and may only be provided with restrictions (e.g. anonymized data).

References

  • Andersson Y et al (2018) Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes. Breast Cancer Res Treat 171(2):359–369

    Article  PubMed  Google Scholar 

  • Asaoka M et al (2020) Neoadjuvant chemotherapy for breast cancer: past, present, and future. Breast Cancer (auckl) 14:1178223420980377

    PubMed  Google Scholar 

  • Barrio AV et al (2016) How often is treatment effect identified in axillary nodes with a pathologic complete response after neoadjuvant chemotherapy? Ann Surg Oncol 23(11):3475–3480

    Article  PubMed  PubMed Central  Google Scholar 

  • Barron AU et al (2018) Association of low nodal positivity rate among patients with ERBB2-positive or triple-negative breast cancer and breast pathologic complete response to neoadjuvant chemotherapy. JAMA Surg 153(12):1120–1126

    Article  PubMed  PubMed Central  Google Scholar 

  • Boér K et al (2021) Pathologic complete response rates after neoadjuvant pertuzumab and trastuzumab with chemotherapy in early stage HER2-positive breast cancer - increasing rates of breast conserving surgery: a real-world experience. Pathol Oncol Res 27:1609785

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen P et al (2021) Laboratory indicators predict axillary nodal pathologic complete response after neoadjuvant therapy in breast cancer. Future Oncol 17(19):2449–2460

    Article  CAS  PubMed  Google Scholar 

  • Corsi F et al (2021) Development of a novel nomogram-based online tool to predict axillary status after neoadjuvant chemotherapy in cN+ breast cancer: a multicentre study on 1,950 patients. Breast 60:131–137

    Article  PubMed  PubMed Central  Google Scholar 

  • Eisenhauer EA et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247

    Article  CAS  PubMed  Google Scholar 

  • Feng K et al (2022) A review of studies on omitting surgery after neoadjuvant chemotherapy in breast cancer. Am J Cancer Res 12(8):3512–3531

    PubMed  PubMed Central  Google Scholar 

  • Fisher CS et al (2020) The landmark series: axillary management in breast cancer. Ann Surg Oncol 27(3):724–729

    Article  PubMed  Google Scholar 

  • Foldi J et al (2021) Optimal management for residual disease following neoadjuvant systemic therapy. Curr Treat Options Oncol 22(9):79

    Article  PubMed  Google Scholar 

  • Gebruers N et al (2015) Incidence and time path of lymphedema in sentinel node negative breast cancer patients: a systematic review. Arch Phys Med Rehabil 96(6):1131–1139

    Article  PubMed  Google Scholar 

  • Giuliano AE et al (2016) Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: long-term follow-up from the american college of surgeons oncology group (Alliance) ACOSOG Z0011 randomized trial. Ann Surg 264(3):413–420

    Article  PubMed  Google Scholar 

  • Goldhirsch A et al (2011) Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22(8):1736–1747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gradishar WJ et al (2022) Breast cancer, version 3.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 20(6):691–722

    Article  PubMed  Google Scholar 

  • Gu J et al (2022) Deep learning radiomics of ultrasonography for comprehensively predicting tumor and axillary lymph node status after neoadjuvant chemotherapy in breast cancer patients: a multicenter study. Cancer 129:356–366

    Article  PubMed  Google Scholar 

  • Guo R et al (2020) A nomogram for predicting axillary pathologic complete response in hormone receptor-positive breast cancer with cytologically proven axillary lymph node metastases. Cancer 126(Suppl 16):3819–3829

    Article  CAS  PubMed  Google Scholar 

  • Hammond JB et al (2022) Characterizing occult nodal disease within a clinically node-negative, neoadjuvant breast cancer population. Clin Breast Cancer 22(2):186–190

    Article  CAS  PubMed  Google Scholar 

  • Haque W et al (2018) Response rates and pathologic complete response by breast cancer molecular subtype following neoadjuvant chemotherapy. Breast Cancer Res Treat 170(3):559–567

    Article  CAS  PubMed  Google Scholar 

  • Hersh EH, King TA (2022) De-escalating axillary surgery in early-stage breast cancer. Breast 62(Suppl 1):S43-s49

    Article  PubMed  Google Scholar 

  • Hwang HW et al (2019) A nomogram to predict pathologic complete response (pCR) and the value of tumor-infiltrating lymphocytes (TILs) for prediction of response to neoadjuvant chemotherapy (NAC) in breast cancer patients. Breast Cancer Res Treat 173(2):255–266

    Article  CAS  PubMed  Google Scholar 

  • Jin X et al (2016) A nomogram for predicting the pathological response of axillary lymph node metastasis in breast cancer patients. Sci Rep 6:32585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang YJ et al (2022) A nomogram for predicting three or more axillary lymph node involvement before breast cancer surgery. Sci Rep 12(1):12141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kong X et al (2022) Advances in imaging in evaluating the efficacy of neoadjuvant chemotherapy for breast cancer. Front Oncol 12:816297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krag DN et al (2007) Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial. Lancet Oncol 8(10):881–888

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Tarruella S et al (2022) How we treat HR-positive, HER2-negative early breast cancer. Future Oncol 18(8):1003–1022

    Article  CAS  PubMed  Google Scholar 

  • Luo Y et al (2023) Axillary Downstaging and the impact of clinical axillary status on efficacy of neoadjuvant therapy for HER2-positive breast cancer: a network meta-analysis. Technol Cancer Res Treat 22:15330338221150324

    Article  PubMed  PubMed Central  Google Scholar 

  • Montagna G et al (2020) Selecting node-positive patients for axillary downstaging with neoadjuvant chemotherapy. Ann Surg Oncol 27(11):4515–4522

    Article  PubMed  PubMed Central  Google Scholar 

  • Montemurro F, Nuzzolese I, Ponzone R (2020) Neoadjuvant or adjuvant chemotherapy in early breast cancer? Expert Opin Pharmacother 21(9):1071–1082

    Article  PubMed  Google Scholar 

  • Moorman AM, Rutgers EJT, Kouwenhoven EA (2022) Omitting SLNB in breast cancer: is a nomogram the answer? Ann Surg Oncol 29(4):2210–2218

    Article  CAS  PubMed  Google Scholar 

  • Pilewskie M, Morrow M (2017) Axillary nodal management following neoadjuvant chemotherapy: a review. JAMA Oncol 3(4):549–555

    Article  PubMed  PubMed Central  Google Scholar 

  • Pilewskie M et al (2022) How often do sentinel lymph node biopsy results affect adjuvant therapy decisions among postmenopausal women with early-stage HR(+)/HER2(-) breast cancer in the post-RxPONDER era? Ann Surg Oncol 29(10):6267–6273

    Article  PubMed  Google Scholar 

  • Reimer T et al (2020) Avoiding axillary sentinel lymph node biopsy after neoadjuvant systemic therapy in breast cancer: rationale for the prospective, multicentric EUBREAST-01 trial. Cancers (basel) 12(12):3698

    Article  CAS  PubMed  Google Scholar 

  • Samiei S et al (2020) Correlation between pathologic complete response in the breast and absence of axillary lymph node metastases after neoadjuvant systemic therapy. Ann Surg 271(3):574–580

    Article  PubMed  Google Scholar 

  • Samiei S et al (2021) Axillary pathologic complete response after neoadjuvant systemic therapy by breast cancer subtype in patients with initially clinically node-positive disease: a systematic review and meta-analysis. JAMA Surg 156(6):e210891

    Article  PubMed  PubMed Central  Google Scholar 

  • Tadros AB et al (2017) Identification of patients with documented pathologic complete response in the breast after neoadjuvant chemotherapy for omission of axillary surgery. JAMA Surg 152(7):665–670

    Article  PubMed  PubMed Central  Google Scholar 

  • Verbelen H et al (2019) Long-term morbidity after a negative sentinel node in breast cancer patients. Eur J Cancer Care (engl) 28(5):e13077

    Article  PubMed  Google Scholar 

  • Weiss A et al (2021) Factors associated with nodal pathologic complete response among breast cancer patients treated with neoadjuvant chemotherapy: results of CALGB 40601 (HER2+) and 40603 (triple-negative) (alliance). Ann Surg Oncol 28(11):5960–5971

    Article  PubMed  PubMed Central  Google Scholar 

  • Yu CC et al (2022) Factors associated with axillary lymph node status in clinically node-negative breast cancer patients undergoing neoadjuvant chemotherapy. Cancers (Basel) 14(18):4451

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank the member units of CSBrS for data collection and the Institutional Foundation of The First Affiliated Hospital of Xi’an Jiaotong University (2022YQPY08) for supporting this work.

Funding

This work is supported by the Institutional Foundation of The First Affiliated Hospital of Xi’an Jiaotong University (2022YQPY08) for supporting this work.

Author information

Authors and Affiliations

  1. Department of Breast Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Road, Xi’an, 710061, Shaanxi Province, China

    Amina Maimaitiaili, Heyan Chen, Peiling Xie, Jianjun He & Huimin Zhang

  2. Department of Breast Disease, Henan Breast Cancer Center, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Dongming Road, Zhengzhou, 450008, Henan Province, China

    Zhenzhen Liu

  3. Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, Shaanxi, China

    Rui Ling

  4. Surgical Oncology Department, Shengjing Hospital of China Medical University, Shenyang, 110022, Liaoning Province, China

    Yi Zhao

  5. Department of Breast Surgery, Institute of Basic Medicine and Cancer (IBMC), The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang Province, China

    Hongjian Yang

  6. Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 052360, Hebei Province, China

    Yunjiang Liu

  7. Fourth Department of Breast Surgery, Jilin Cancer Hospital, Changchun, 130012, Jilin Province, China

    Ke Liu

  8. Department of Breast Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang Province, China

    Jianguo Zhang

  9. Department of Breast Surgery, Affiliated Wudang Hospital of Guizhou Medical University, Guiyang, 550009, Guizhou Province, China

    Dahua Mao

  10. Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, Shandong Province, China

    Zhigang Yu

  11. Breast Disease Center, Peking University First Hospital, Beijing, 100034, China

    Yinhua Liu

  12. Department of Breast Surgery, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China

    Peifen Fu

  13. Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, 100852, China

    Jiandong Wang

  14. Department of Breast Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China

    Hongchuan Jiang

  15. Department of Breast Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, Liaoning Province, China

    Zuowei Zhao

  16. Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong Province, China

    Xingsong Tian

  17. Department of Thyroid, Breast, Hernia Surgery, The Inner Mongolia Autonomous Region People’s Hospital, Hohhot, 010017, Inner Mongolia Autonomous Region, China

    Zhongwei Cao

  18. Department of Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200433, China

    Kejin Wu

  19. Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730000, Gansu Province, China

    Ailin Song

  20. Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, 110002, Liaoning Province, China

    Feng Jin

  21. Department of Breast Surgery, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin Province, China

    Zhimin Fan

Authors
  1. Amina Maimaitiaili
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  2. Heyan Chen
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  3. Peiling Xie
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  4. Zhenzhen Liu
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  5. Rui Ling
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  6. Yi Zhao
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  7. Hongjian Yang
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  8. Yunjiang Liu
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  9. Ke Liu
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  10. Jianguo Zhang
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  11. Dahua Mao
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  12. Zhigang Yu
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  13. Yinhua Liu
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  14. Peifen Fu
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  15. Jiandong Wang
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  16. Hongchuan Jiang
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  17. Zuowei Zhao
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  18. Xingsong Tian
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  19. Zhongwei Cao
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  20. Kejin Wu
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  21. Ailin Song
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  22. Feng Jin
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  23. Jianjun He
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  24. Zhimin Fan
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  25. Huimin Zhang
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Contributions

Conceptualization: HZ, JH, ZF and AM. Data curation: HC, PX, ZL, RL, YZ, HY, YL, KL, JZ, DM, ZY, YL, PF, JW, HJ, ZZ, XT, ZC, KW, AS, FJ, JH and ZF. Methodology: AM. Formal analysis: AM. Funding acquisition: HZ. Investigation: AM, HC, PX. Writing-original draft preparation: AM. Writing-review and editing: HZ, JH, ZF and HC. Final approval of manuscript: all authors. All authors read and approved the manuscript.

Corresponding authors

Correspondence to Jianjun He, Zhimin Fan or Huimin Zhang.

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Conflict of interest

The authors have declared that no competing interest existed.

Ethics approval and consent to participate

The study was performed in accordance with the Declaration of Helsinki and was approved by the Ethical Review Committee of the First Hospital of Jilin University (No. 2021-066). Since this study was retrospective and all data analysis was conducted anonymously, there was no informed consent of patients.

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Not applicable.

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Maimaitiaili, A., Chen, H., Xie, P. et al. Nomogram for predicting axillary upstaging in clinical node-negative breast cancer patients receiving neoadjuvant chemotherapy. J Cancer Res Clin Oncol 149, 8769–8778 (2023). https://doi.org/10.1007/s00432-023-04817-9

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  • DOI: https://doi.org/10.1007/s00432-023-04817-9

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