Annals of Surgical Oncology

, Volume 22, Issue 10, pp 3241–3249 | Cite as

Overall Survival, Disease-Free Survival, Local Recurrence, and Nipple–Areolar Recurrence in the Setting of Nipple-Sparing Mastectomy: A Meta-Analysis and Systematic Review

  • Lucy De La Cruz
  • Alison M. Moody
  • Erryn E. Tappy
  • Stephanie A. Blankenship
  • Eric M. Hecht
Breast Oncology



Nipple-sparing mastectomy (NSM) is an increasingly common procedure; however, concerns exist regarding its oncological safety due to the potential for residual breast tissue to harbor occult malignancy or future cancer.


A systematic literature review was performed. Studies with internal comparison arms evaluating therapeutic NSM versus skin-sparing mastectomy (SSM) and/or modified radical mastectomy (MRM) were included in a meta-analysis of overall survival (OS), disease-free survival (DFS), and local recurrence (LR). Studies lacking comparison arms were only included in the systematic review to evaluate mean OS, DFS, LR, and nipple–areolar recurrence (NAR).


The search yielded 851 articles. Twenty studies with 5594 patients met selection criteria. The meta-analysis included eight studies with comparison arms. Seven studies that compared OS found a 3.4 % risk difference between NSM and MRM/SSM, five studies that compared DFS found a 9.6 % risk difference between NSM and MRM/SSM, and eight studies that compared LR found a 0.4 % risk difference between NSM and MRM/SSM. Risk differences for all outcomes were not statistically significant. The systematic review included all 20 studies and evaluated OS, DFS, LR, and NAR. Studies with follow-up intervals of <3 years, 3–5 years, and >5 years had mean OS of 97.2, 97.9, and 86.8 %; DFS of 93.1, 92.3, and 76.1 %; LR of 5.4, 1.4, and 11.4 %; and NAR of 2.1, 1.0, and 3.4 %, respectively.


This study did not detect adverse oncologic outcomes of NSM in carefully selected women with early-stage breast cancer. Use of prospective data registries, notably the Nipple-Sparing Mastectomy Registry, will add clarity to this important clinical question.


Overall Survival Local Recurrence Invasive Ductal Carcinoma Nipple Risk Difference 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This manuscript includes preliminary data presented at the 16th Annual Meeting of the American Society of Breast Surgeons, and incorporates additional analyses that have undergone peer review. The authors would like to thank Dr. Beth-Ann Lesnikoski for reviewing our initial abstract presented at the meeting.

Author Contribution

Lucy De La Cruz conceptualized and designed the project. Eric Hecht, Stephanie Blankenship, Alison Moody, and Erryn Tappy drafted the initial manuscript. All authors reviewed, revised, and approved the final manuscript as submitted and agree to be accountable for all aspects of the work.


No external funding was secured for this study. Lucy De La Cruz, Alison M. Moody, Erryn E. Tappy, Stephanie A. Blankenship, and Eric M. Hecht have no financial relationships or conflicts of interest to disclose that are relevant to this article.

Supplementary material

10434_2015_4739_MOESM1_ESM.docx (85 kb)
Supplementary material 1 (DOCX 85 kb)


  1. 1.
    American Cancer Society. Cancer facts and figures 2015. Accessed 22 Feb 2015.
  2. 2.
    Laronga C, Lewis JD, Smith PD. The changing face of mastectomy: an oncologic and cosmetic perspective. Cancer Control. 2012;19(4):286–94.PubMedGoogle Scholar
  3. 3.
    Agarwal S, Agarwal S, Neumayer L, Agarwal JP. Therapeutic nipple-sparing mastectomy: trends based on a national cancer database. Am J Surg. 2014;208(1):93–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Lanitis S, Tekkis PP, Sgourakis G, Dimopoulous N, Al Mufti R, Hadjiminas DJ. Comparison of skin-sparing mastectomy versus non-skin-sparing mastectomy for breast cancer: a meta-analysis of observational studies. Ann Surg. 2010;251(4):632–9.CrossRefPubMedGoogle Scholar
  5. 5.
    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.CrossRefPubMedGoogle Scholar
  6. 6.
    National Comprehensive Cancer Network. NCCN Guidelines For Patients®. Version 1.2014. Stages I and II breast cancer. Accessed 22 Feb 2015.
  7. 7.
    Adam H, Bygdeson M, de Boniface J. The oncological safety of nipple-sparing mastectomy: a Swedish matched cohort study. Eur J Surg Oncol. 2014;40(10):1209–15.CrossRefPubMedGoogle Scholar
  8. 8.
    Boneti C, Yuen, J Santiago C, et al. Oncologic safety of nipple skin-sparing or total skin-sparing mastectomies with immediate reconstruction. J Am Coll Surg. 2011;212:686–93.CrossRefPubMedGoogle Scholar
  9. 9.
    Burdge EC, Yuen J, Hardee M, et al. Nipple skin-sparing mastectomy is feasible for advanced disease. Ann Surg Oncol. 2013;20(10):3294–302.CrossRefPubMedGoogle Scholar
  10. 10.
    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):461–68.CrossRefPubMedGoogle Scholar
  11. 11.
    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.CrossRefPubMedGoogle Scholar
  12. 12.
    Poruk KE, Ying J, Chidester JR, Olson JR, Matsen CB, Neumayer L, et al. Breast cancer recurrence after nipple-sparing mastectomy: one institution’s experience. Am J Surg. 2015;209(1):212–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Sakurai T, Zhang N, Suzuma T, Umemura T, Yoshimura G, Sakurai T, et al. Long-term follow-up of nipple-sparing mastectomy without radiotherapy: a single center study at a Japanese institution. Med Oncol. 2013;30(1):481.CrossRefPubMedGoogle Scholar
  14. 14.
    Shi A, Wu D, Li X, et al. Subcutaneous nipple-sparing mastectomy and immediate breast reconstruction. Breast Care (Basel). 2012;7(2):131–136.CrossRefGoogle Scholar
  15. 15.
    Alperovich M, Tanna N, Samra F, et al. Nipple-sparing mastectomy in patients with a history of reduction mammaplasty or mastopexy: how safe is it? Plast Reconstr Surg. 2013;131(5):962–7.CrossRefPubMedGoogle Scholar
  16. 16.
    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):143–148.CrossRefPubMedGoogle Scholar
  17. 17.
    Caruso F, Ferrara M, Castiglione G, Trombetta G, De Meo L, Catanuto G, et al. Nipple sparing subcutaneous mastectomy: sixty-six months follow-up. Eur J Surg Oncol. 2006:32;937–40.CrossRefPubMedGoogle Scholar
  18. 18.
    Crowe JP, Patrick RJ, Yetman RJ, Djohan R. Nipple-sparing mastectomy update: one hundred forty-nine procedures and clinical outcomes. Arch Surg. 2008;143(11):1106–10; discussion 1110.CrossRefPubMedGoogle Scholar
  19. 19.
    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.CrossRefPubMedGoogle Scholar
  20. 20.
    Nava MB, Ottolenghi J, Pennati A, et al. Skin/nipple sparing mastectomies and implant-based breast reconstruction in patients with large and ptotic breast: oncological and reconstructive results. Breast. 2012;21(3):267–71.CrossRefPubMedGoogle Scholar
  21. 21.
    Paepke S, Schmid R, Fleckner S, et al. Subcutaneous mastectomy with conservation of the nipple–areolar skin. Ann Surg. 2009;250: 288–92.CrossRefPubMedGoogle Scholar
  22. 22.
    Sacchini V, Pinotti JA, Barros AC, et al. Nipple-sparing mastectomy for breast cancer and risk reduction: oncologic or technical problem? J Am Coll Surg. 2006;203:704–14.CrossRefPubMedGoogle Scholar
  23. 23.
    Sood S, Elder E, French J. Nipple-sparing mastectomy with implant reconstruction: the Westmead experience. ANZ J Surg. 2015;85(5):363–67.CrossRefPubMedGoogle Scholar
  24. 24.
    Sookhan N, Boughey JC, Walsh MF. Nipple-sparing mastectomy: initial experience at a tertiary center. Am J Surg. 2008;196(4):575–77.CrossRefPubMedGoogle Scholar
  25. 25.
    Tancredi A, Ciuffreda L, Petito L, Natale F, Murgo R. Nipple-areola-complex sparing mastectomy: five years of experience in a single centre. Updates Surg. 2013;65(4):289–94.CrossRefPubMedGoogle Scholar
  26. 26.
    Voltura AM, Tsangaris TN, Rosson GD, et al. Nipple-sparing mastectomy: critical assessment of 51 procedures and implications for selection criteria. Ann Surg Oncol. 2008;15(12):3396–401.CrossRefPubMedGoogle Scholar
  27. 27.
    Gilliland MD, Barton RM, Copeland EM III. The implications of local recurrence of breast cancer as the first site of therapeutic failure. Ann Surg. 1983;197:284–87.PubMedCentralCrossRefPubMedGoogle Scholar
  28. 28.
    Donegan WL, Perez-Mesa CM, Watson FR. A biostatistical study of locally recurrent breast carcinoma. Surg Gynecol Obstet. 1966;122:529–540.PubMedGoogle Scholar
  29. 29.
    Moran MS, Schnitt SJ, Giuliano AE, et al. Society of Surgical OncologyAmerican Society for Radiation Oncology Consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. Int J Radiation Oncol Biol Phys. 2014;88(3):553–64.CrossRefGoogle Scholar
  30. 30.
    Gerber B, Krause A, Reimer T, et al. Skin-sparing mastectomy with conservation of the nipple-areola complex and autologous reconstruction is an oncologically safe procedure. Ann Surg. 2003;238(1):120–7.PubMedCentralPubMedGoogle Scholar
  31. 31.
    Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration. Accessed 22 Feb 2015.

Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • Lucy De La Cruz
    • 1
  • Alison M. Moody
    • 2
  • Erryn E. Tappy
    • 2
  • Stephanie A. Blankenship
    • 2
  • Eric M. Hecht
    • 3
  1. 1.Department of SurgeryUniversity of Miami Miller School of MedicineMiamiUSA
  2. 2.University of Miami Miller School of MedicineMiamiUSA
  3. 3.Department of Public Health SciencesUniversity of Miami Miller School of MedicineMiamiUSA

Personalised recommendations