Skip to main content


Log in

Oncologic Outcomes in Nipple-sparing Mastectomy with Immediate Reconstruction and Total Mastectomy with Immediate Reconstruction in Women with Breast Cancer: A Machine-Learning Analysis

  • Global Health Services Research
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript



This study used a single-institution cohort, the Severance dataset, validated the results by using the surveillance, epidemiology, and end results (SEER) database, adjusted with propensity-score matching (PSM), and analyzed by using a machine learning method.

To determine whether the 5-year, disease-free survival (DFS) and overall survival (OS) of patients undergoing nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) are not inferior to those of women treated with total mastectomy/skin-sparing mastectomy (TM/SSM).


The Severance dataset enrolled 611 patients with early, invasive breast cancer from 2010 to 2017. The SEER dataset contained data for 485,245 patients undergoing TM and 14,770 patients undergoing NSM between 2000 and 2018. All patients underwent mastectomy and IBR. Intraoperative, frozen-section biopsy for the retro-areolar tissue was performed in the NSM group. The SEER dataset was extracted by using operation types, including TM/SSM and NSM. The primary outcome was DFS for the Severance dataset and OS for the SEER dataset. PSM analysis was applied. Survival outcomes were analyzed by using the Kaplan-Meier method and Cox proportional hazard (Cox PH) regression model. We implemented XGBSE to predict mortality with high accuracy and evaluated model prediction performance using a concordance index. The final model inspected the impact of relevant predictors on the model output using shapley additive explanation (SHAP) values.


In the Severance dataset, 151 patients underwent NSM with IBR and 460 patients underwent TM/SSM with IBR. No significant differences were found between the groups. In multivariate analysis, NSM was not associated with reduced oncologic outcomes. The same results were observed in PSM analysis. In the SEER dataset, according to the SHAP values, the individual feature contribution suggested that AJCC stage ranks first. Analyses from the two datasets confirmed no impact on survival outcomes from the two surgical methods.


NSM with IBR is a safe and feasible procedure in terms of oncologic outcomes. Analysis using machine learning methods can be successfully applied to identify significant risk factors for oncologic outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others


  1. Freeman BS. Subcutaneous mastectomy for benign breast lesions with immediate or delayed prosthetic replacement. Plast Reconstr Surg Transplant Bull. 1962;30:676–82.

    Article  CAS  PubMed  Google Scholar 

  2. Toth BA, Lappert P. Modified skin incisions for mastectomy: the need for plastic surgical input in preoperative planning. Plast Reconstr Surg. 1991;87(6):1048–53.

    Article  CAS  PubMed  Google Scholar 

  3. Agha RA, Al Omran Y, Wellstead G, et al. Systematic review of therapeutic nipple-sparing versus skin-sparing mastectomy. BJS Open. 2019;3(2):135–45.

    Article  CAS  PubMed  Google Scholar 

  4. Bailey CR, Ogbuagu O, Baltodano PA, et al. Quality-of-life outcomes improve with nipple-sparing mastectomy and breast reconstruction. Plast Reconstr Surg. 2017;140(2):219–26.

    Article  CAS  PubMed  Google Scholar 

  5. Sherman KA, Woon S, French J, Elder E. Body image and psychological distress in nipple-sparing mastectomy: the roles of self-compassion and appearance investment. Psychooncology. 2017;26(3):337–45.

    Article  CAS  PubMed  Google Scholar 

  6. Gerber B, Krause A, Dieterich M, Kundt G, Reimer T. The oncological safety of skin sparing mastectomy with conservation of the nipple-areola complex and autologous reconstruction: an extended follow-up study. Ann Surg. 2009;249(3):461–8.

    Article  PubMed  Google Scholar 

  7. Peled AW, Duralde E, Foster RD, et al. Patient-reported outcomes and satisfaction after total skin-sparing mastectomy and immediate expander-implant reconstruction. Ann Plast Surg. 2014;72(Suppl 1):S48-52.

    Article  CAS  PubMed  Google Scholar 

  8. (2021) NCCN. Version 5; 2021, pp. 1–245.

  9. Mota BS, Riera R, Ricci MD, et al. Nipple- and areola-sparing mastectomy for the treatment of breast cancer. Cochrane Database Syst Rev. 2016.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Han W, Lee HB. Recurrence at the nipple-areola complex and safety of nipple-sparing mastectomy. JAMA Surg. 2020;155(4):364–5.

    Article  PubMed  Google Scholar 

  11. Conde DM, Torresan RZ. Nipple-sparing mastectomy: what is the frontier between oncologic safety and cosmetic outcome? J Plast Reconstr Aesthet Surg. 2013;66(5):734–5.

    Article  PubMed  Google Scholar 

  12. De La Cruz L, Moody AM, Tappy EE, Blankenship SA, Hecht EM. Overall survival, disease-free survival, local recurrence, and nipple-areolar recurrence in the setting of nipple-sparing mastectomy: a meta-analysis and systematic review. Ann Surg Oncol. 2015;22(10):3241–9.

    Article  PubMed  Google Scholar 

  13. Benediktsson KP, Perbeck L. Survival in breast cancer after nipple-sparing subcutaneous mastectomy and immediate reconstruction with implants: a prospective trial with 13 years median follow-up in 216 patients. Eur J Surg Oncol. 2008;34(2):143–8.

    Article  CAS  PubMed  Google Scholar 

  14. Wu ZY, Kim HJ, Lee JW, et al. Long-term oncologic outcomes of immediate breast reconstruction vs. conventional mastectomy alone for breast cancer in the setting of neoadjuvant chemotherapy. JAMA Surg. 2020;155(12):1142–50.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kim HJ, Park EH, Lim WS, et al. Nipple areola skin-sparing mastectomy with immediate transverse rectus abdominis musculocutaneous flap reconstruction is an oncologically safe procedure: a single center study. Ann Surg. 2010;251(3):493–8.

    Article  PubMed  Google Scholar 

  16. Headon HL, Kasem A, Mokbel K. The oncological safety of nipple-sparing mastectomy: a systematic review of the literature with a pooled analysis of 12,358 procedures. Arch Plast Surg. 2016;43(4):328–38.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Weissler EH, Naumann T, Andersson T, et al. The role of machine learning in clinical research: transforming the future of evidence generation. Trials. 2021;22(1):537.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Zhang MJ. Cox proportional hazards regression models for survival data in cancer research. Cancer Treat Res. 2002;113:59–70.

    Article  PubMed  Google Scholar 

  19. Won SY, Park HS, Kim EK, et al. Survival rates of breast cancer patients aged 40 to 49 years according to detection modality in Korea: screening ultrasound versus mammography. Korean J Radiol. 2021;22(2):159–67.

    Article  PubMed  Google Scholar 

  20. Chen T, Guestrin C. XGBoost: a scalable tree boosting system. Presented at: Proceedings of the 22nd ACM SIGKDD international conference on knowledge discovery and data mining; 2016; San Francisco, California, USA.

  21. Team. LDS. XGBSE: XGBoost survival embeddings. Accessed 30 Mar 2021.

  22. Wu ZY, Han HH, Kim HJ, et al. A propensity score-matched analysis of long-term oncologic outcomes after nipple-sparing versus conventional mastectomy for locally advanced breast cancer. Ann Surg. 2020.

    Article  PubMed  Google Scholar 

  23. Paepke S, Schmid R, Fleckner S, et al. Subcutaneous mastectomy with conservation of the nipple-areola skin: Broadening the indications. Ann Surg. 2009;250(2):288–92.

    Article  PubMed  Google Scholar 

  24. Mallon P, Feron JG, Couturaud B, et al. The role of nipple-sparing mastectomy in breast cancer: a comprehensive review of the literature. Plast Reconstr Surg. 2013;131(5):969–84.

    Article  CAS  PubMed  Google Scholar 

  25. Kim S, Lee S, Bae Y, Lee S. Nipple-sparing mastectomy for breast cancer close to the nipple: a single institution’s 11-year experience. Breast Cancer. 2020;27(5):999–1006.

    Article  PubMed  Google Scholar 

  26. Alsharif E, Ryu JM, Choi HJ, et al. Oncologic outcomes of nipple-sparing mastectomy with immediate breast reconstruction in patients with tumor-nipple distance less than 2.0 cm. J Breast Cancer. 2019;22(4):613–23.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Wu ZY, Kim HJ, Lee JW, et al. Breast cancer recurrence in the nipple-areola complex after nipple-sparing mastectomy with immediate breast reconstruction for invasive breast cancer. JAMA Surg. 2019;154(11):1030–7.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Jensen JA, Orringer JS, Giuliano AE. Nipple-sparing mastectomy in 99 patients with a mean follow-up of 5 years. Ann Surg Oncol. 2011;18(6):1665–70.

    Article  PubMed  Google Scholar 

  29. Wang F, Peled AW, Garwood E, et al. Total skin-sparing mastectomy and immediate breast reconstruction: an evolution of technique and assessment of outcomes. Ann Surg Oncol. 2014;21(10):3223–30.

    Article  PubMed  Google Scholar 

Download references


This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2022R1C1C1010441) and a faculty research grant of Yonsei University College of Medicine (6-2021-0239).

Author information

Authors and Affiliations


Corresponding author

Correspondence to Hyung Seok Park MD, PhD.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cho, JH., Park, J.M., Park, H.S. et al. Oncologic Outcomes in Nipple-sparing Mastectomy with Immediate Reconstruction and Total Mastectomy with Immediate Reconstruction in Women with Breast Cancer: A Machine-Learning Analysis. Ann Surg Oncol 30, 7281–7290 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: