Annals of Surgical Oncology

, 18:3102 | Cite as

Prophylactic and Therapeutic Mastectomy in BRCA Mutation Carriers: Can the Nipple Be Preserved?

  • Carol Reynolds
  • Jennifer A. Davidson
  • Noralane M. Lindor
  • Katrina N. Glazebrook
  • James W. Jakub
  • Amy C. Degnim
  • Nicole P. Sandhu
  • Molly F. Walsh
  • Lynn C. Hartmann
  • Judy C. Boughey
American Society of Breast Surgeons



Use of nipple-sparing mastectomy (NSM) is increasing. We sought to look at the role of NSM in BRCA mutation carriers.


Tissue from women with a BRCA1 or BRCA2 mutation who underwent mastectomy between March 1987 and June 2009 at a single institution was reviewed. The entire nipple–areolar complex (NAC) was excised and histologically evaluated. The presence of terminal duct lobular units (TDLUs) and premalignant or malignant lesions in the NAC was noted.


Sixty-two NACs from 33 women (25 BRCA1, 8 BRCA2) were studied. TDLUs were present in 15 (24%) NAC specimens. No evidence of atypical hyperplasia, carcinoma in situ, or invasive carcinoma was found in any of the 33 prophylactic mastectomy specimens. Among the 29 breasts with cancer and available tissue, 2 (7%) had malignant findings and 1 (3%) had atypia in the NAC. One woman who underwent bilateral mastectomy for bilateral invasive carcinoma had one nipple with tumor within lymphatics, and her contralateral nipple had atypical lobular hyperplasia. A second woman had ductal carcinoma in situ involving a single major lactiferous duct.


The probability of nipple involvement by premalignant or malignant lesions in the NAC of BRCA mutation carriers is low at time of prophylactic mastectomy, but higher (10%) in women undergoing therapeutic mastectomy. NSM may be appropriate and oncologically safe for selected women with BRCA mutations. However, 24% of NACs contained TDLUs, with only 8% found in the nipple papilla; the significance of this for long-term risk is unknown.



I (C.R.) would like to acknowledge and extend my heartfelt gratitude to Dr. David L. Page, Vanderbilt University, for his inspiration in this work and his encouragement and support over the years.


  1. 1.
    Brekelmans CT, Seynaeve C, Bartels CC, et al. Effectiveness of breast cancer surveillance in BRCA1/2 gene mutation carriers and women with high familial risk. J Clin Oncol. 2001;19(4):924–30.PubMedGoogle Scholar
  2. 2.
    Scheuer L, Kauff N, Robson M, et al. Outcome of preventive surgery and screening for breast and ovarian cancer in BRCA mutation carriers. J Clin Oncol. 2002;20(5):1260–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Pierce LJ, Levin AM, Rebbeck TR, et al. Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol. 2006;24(16):2437–43.PubMedCrossRefGoogle Scholar
  4. 4.
    Metcalfe K, Lynch HT, Ghadirian P, et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2004;22(12):2328–35.PubMedCrossRefGoogle Scholar
  5. 5.
    Graeser MK, Engel C, Rhiem K, et al. Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2009;27(35):5887–92.PubMedCrossRefGoogle Scholar
  6. 6.
    Tercyak KP, Peshkin BN, Brogan BM, et al. Quality of life after contralateral prophylactic mastectomy in newly diagnosed high-risk breast cancer patients who underwent BRCA1/2 gene testing. J Clin Oncol. 2007;25(3):285–91.PubMedCrossRefGoogle Scholar
  7. 7.
    Mai PL, Lagos VI, Palomares MR, et al. Contralateral risk-reducing mastectomy in young breast cancer patients with and without genetic cancer risk assessment. Ann Surg Oncol. 2008;15(12):3415–21.PubMedCrossRefGoogle Scholar
  8. 8.
    Stolier AJ, Wang J. Terminal duct lobular units are scarce in the nipple: implications for prophylactic nipple-sparing mastectomy: terminal duct lobular units in the nipple. Ann Surg Oncol. 2008;15(2):438–42.PubMedCrossRefGoogle Scholar
  9. 9.
    Petit JY, Veronesi U, Rey P, et al. Nipple-sparing mastectomy: risk of nipple-areolar recurrences in a series of 579 cases. Breast Cancer Res Treat. 2009;114(1):97–101.PubMedCrossRefGoogle Scholar
  10. 10.
    Wellisch DK, Schain WS, Noone RB, et al. The psychological contribution of nipple addition in breast reconstruction. Plast Reconstr Surg. 1987;80(5):699–704.PubMedCrossRefGoogle Scholar
  11. 11.
    Chagpar AB. Skin-sparing and nipple-sparing mastectomy: preoperative, intraoperative, and postoperative considerations. Am Surg. 2004;70(5):425–32.PubMedGoogle Scholar
  12. 12.
    Rusby JE, Brachtel EF, Taghian A, et al. George Peters Award. Microscopic anatomy within the nipple: implications for nipple-sparing mastectomy. Am J Surg. 2007;194(4):433–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Simmons RM, Brennan M, Christos P, et al. Analysis of nipple/areolar involvement with mastectomy: can the areola be preserved? Ann Surg Oncol. 2002;9(2):165–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Vyas JJ, Chinoy RF, Vaidya JS. Prediction of nipple and areola involvement in breast cancer. Eur J Surg Oncol. 1998;24(1):15–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Laronga C, Kemp B, Johnston D, et al. The incidence of occult nipple-areola complex involvement in breast cancer patients receiving a skin-sparing mastectomy. Ann Surg Oncol. 1999;6(6):609–13.PubMedCrossRefGoogle Scholar
  16. 16.
    Menon RS, van Geel AN. Cancer of the breast with nipple involvement. Br J Cancer. 1989;59(1):81–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Santini D, Taffurelli M, Gelli MC, et al. Neoplastic involvement of nipple-areolar complex in invasive breast cancer. Am J Surg. 1989;158(5):399–403.PubMedCrossRefGoogle Scholar
  18. 18.
    Quinn RH, Barlow JF. Involvement of the nipple and areola by carcinoma of the breast. Arch Surg. 1981;116(9):1139–40.PubMedGoogle Scholar
  19. 19.
    Luttges J, Kalbfleisch H, Prinz P. Nipple involvement and multicentricity in breast cancer. A study on whole organ sections. J Cancer Res Clin Oncol. 1987;113(5):481–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Morimoto T, Komaki K, Inui K, et al. Involvement of nipple and areola in early breast cancer. Cancer. 1985;55(10):2459–63.PubMedCrossRefGoogle Scholar
  21. 21.
    Lagios MD, Gates EA, Westdahl PR, et al. A guide to the frequency of nipple involvement in breast cancer. A study of 149 consecutive mastectomies using a serial subgross and correlated radiographic technique. Am J Surg. 1979;138(1):135–42.PubMedCrossRefGoogle Scholar
  22. 22.
    Wertheim U, Ozzello L. Neoplastic involvement of nipple and skin flap in carcinoma of the breast. Am J Surg Pathol. 1980;4(6):543–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Parry RG, Cochran TC, Jr., Wolfort FG. When is there nipple involvement in carcinoma of the breast? Plast Reconstr Surg. 1977;59(4):535–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Smith J, Payne WS, Carney JA. Involvement of the nipple and areola in carcinoma of the breast. Surg Gynecol Obstet. 1976;143(4):546–8.PubMedGoogle Scholar
  25. 25.
    Andersen JA, Pallesen RM. Spread to the nipple and areola in carcinoma of the breast. Ann Surg. 1979;189(3):367–72.PubMedCrossRefGoogle Scholar
  26. 26.
    Vlajcic Z, Zic R, Stanec S, et al. Nipple-areola complex preservation: predictive factors of neoplastic nipple-areola complex invasion. Ann Plast Surg. 2005;55(3):240–4.PubMedCrossRefGoogle Scholar
  27. 27.
    Schecter AK, Freeman MB, Giri D, et al. Applicability of the nipple-areola complex-sparing mastectomy: a prediction model using mammography to estimate risk of nipple-areola complex involvement in breast cancer patients. Ann Plast Surg. 2006;56(5):498–504; discussion 504.PubMedCrossRefGoogle Scholar
  28. 28.
    Rusby JE, Brachtel EF, Othus M, et al. Development and validation of a model predictive of occult nipple involvement in women undergoing mastectomy. Br J Surg. 2008;95(11):1356–61.PubMedCrossRefGoogle Scholar
  29. 29.
    Miki Y, Swensen J, Shattuck-Eidens D, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994;266(5182):66–71.PubMedCrossRefGoogle Scholar
  30. 30.
    Wooster R, Bignell G, Lancaster J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995;378(6559):789–92.PubMedCrossRefGoogle Scholar
  31. 31.
    Brose MS, Rebbeck TR, Calzone KA, et al. Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst. 2002;94(18):1365–72.PubMedGoogle Scholar
  32. 32.
    Thompson D, Easton DF. Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002;94(18):1358–65.PubMedGoogle Scholar
  33. 33.
    King MC, Wieand S, Hale K, et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA. 2001;286(18):2251–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Hartmann LC, Sellers TA, Schaid DJ, et al. Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst. 2001;93(21):1633–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Meijers-Heijboer H, van Geel B, van Putten WL, et al. Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2001;345(3):159–64.PubMedCrossRefGoogle Scholar
  36. 36.
    Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2004;22(6):1055–62.PubMedCrossRefGoogle Scholar
  37. 37.
    Kaas R, Verhoef S, Wesseling J, et al. Prophylactic mastectomy in BRCA1 and BRCA2 mutation carriers: very low risk for subsequent breast cancer. Ann Surg. 2010;251(3):488–92.PubMedCrossRefGoogle Scholar
  38. 38.
    Little JW, III. Nipple-areola reconstruction. Clin Plast Surg. 1984;11(2):351–64.PubMedGoogle Scholar
  39. 39.
    Rosen PP, Tench W. Lobules in the nipple. Frequency and significance for breast cancer treatment. Pathol Annu. 1985;20 Pt 2:317–22.PubMedGoogle Scholar
  40. 40.
    Brachtel EF, Rusby JE, Michaelson JS, et al. Occult nipple involvement in breast cancer: clinicopathologic findings in 316 consecutive mastectomy specimens. J Clin Oncol. 2009;27(30):4948–54.PubMedCrossRefGoogle Scholar
  41. 41.
    Kissin MW, Kark AE. Nipple preservation during mastectomy. Br J Surg. 1987;74(1):58–61.PubMedCrossRefGoogle Scholar
  42. 42.
    Verma GR, Kumar A, Joshi K. Nipple involvement in peripheral breast carcinoma: a prospective study. Indian J Cancer. 1997;34(1):1–5.PubMedGoogle Scholar
  43. 43.
    Cense HA, Rutgers EJ, Lopes Cardozo M, et al. Nipple-sparing mastectomy in breast cancer: a viable option? Eur J Surg Oncol. 2001;27(6):521–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Gerber B, Krause A, Dieterich M, et al. 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.PubMedCrossRefGoogle Scholar
  45. 45.
    Caruso F, Ferrara M, Castiglione G, et al. Nipple sparing subcutaneous mastectomy: sixty-six months follow-up. Eur J Surg Oncol. 2006;32(9):937–40.PubMedCrossRefGoogle Scholar
  46. 46.
    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.PubMedCrossRefGoogle Scholar
  47. 47.
    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(5):704–14.PubMedCrossRefGoogle Scholar
  48. 48.
    Sookhan N, Boughey JC, Walsh MF, et al. Nipple-sparing mastectomy–initial experience at a tertiary center. Am J Surg. 2008;196(4):575–7.PubMedCrossRefGoogle Scholar
  49. 49.
    El-Tamer M, Russo D, Troxel A, et al. Survival and recurrence after breast cancer in BRCA1/2 mutation carriers. Ann Surg Oncol. 2004;11(2):157–64.PubMedCrossRefGoogle Scholar
  50. 50.
    Denewer A, Farouk O. Can nipple-sparing mastectomy and immediate breast reconstruction with modified extended latissimus dorsi muscular flap improve the cosmetic and functional outcome among patients with breast carcinoma? World J Surg. 2007;31:1169–77.PubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2011

Authors and Affiliations

  • Carol Reynolds
    • 1
  • Jennifer A. Davidson
    • 1
  • Noralane M. Lindor
    • 2
  • Katrina N. Glazebrook
    • 3
  • James W. Jakub
    • 4
  • Amy C. Degnim
    • 4
  • Nicole P. Sandhu
    • 5
  • Molly F. Walsh
    • 6
  • Lynn C. Hartmann
    • 7
  • Judy C. Boughey
    • 4
  1. 1.Department of PathologyMayo Clinic, Division of Anatomic PathologyRochesterUSA
  2. 2.Department of Medical GeneticsMayo ClinicRochesterUSA
  3. 3.Department of Diagnostic RadiologyMayo ClinicRochesterUSA
  4. 4.Department of SurgeryMayo ClinicRochesterUSA
  5. 5.Department of General Internal MedicineMayo ClinicRochesterUSA
  6. 6.Division of Plastic SurgeryMayo ClinicRochesterUSA
  7. 7.Department of Medical OncologyMayo ClinicRochesterUSA

Personalised recommendations