Annals of Surgical Oncology

, Volume 21, Issue 5, pp 1583–1588 | Cite as

MRI Volumetric Analysis of Breast Fibroglandular Tissue to Assess Risk of the Spared Nipple in BRCA1 and BRCA2 Mutation Carriers

  • Heather L. Baltzer
  • Olivier Alonzo-Proulx
  • James G. Mainprize
  • Martin J. Yaffe
  • Kelly A. Metcalfe
  • Steve A. Narod
  • Ellen Warner
  • John L. Semple
Breast Oncology



Prophylactic nipple-areolar complex (NAC)-sparing mastectomy (NSM) in BRCA1/2 mutation carriers is controversial over concern regarding residual fibroglandular tissue (FGT) with malignant potential. The objective of this study was to model the volume of FGT in the NAC at a standard retroareolar margin (5 mm) and examine the change in this amount with a greater retroareolar margin or areola-sparing technique.


A segmentation protocol was applied to breast MRIs from 105 BRCA1/2 patients to quantify volumes of FGT for total breast and NAC. The proportion of FGT in the NAC relative to the breast was calculated as the primary outcome and was compared for 5 mm versus 10 mm retroareolar depths. The proportion of FGT in the areola was compared with the NAC.


At 5 mm retroareolar thickness, residual NAC FGT comprised 1.3 % of the total breast FGT. This amount was not significantly greater than the proportion in the areola (p = 0.3, d = 0.1). Increasing the retroareolar thickness to 10 mm led to a statistically and possibly clinically significant increase in the amount of NAC FGT (p < 0.001, d = 1.1).


The proportion of FGT remaining in the spared NAC with a 5 mm margin is extremely small, suggesting that leaving the entire NAC would create very little added risk. Doubling the retroareolar margin may translate into a clinically meaningful increase. Overall, our findings support the safety of the current trend toward increased rates of prophylactic NSM performed in this high-risk population.



Dr. Semple is supported by the Canadian Breast Cancer Foundation (Ontario Chapter).


The authors have no conflicts of interest to declare.


  1. 1.
    Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72(5):1117–30.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007;25(11):1329–33.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The breast cancer linkage consortium. Am J Hum Genet. 1998;62(3):676–89.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Hartmann LC, Sellers TA, Schaid DJ, Frank TS, Soderberg CL, Sitta DL, 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
  5. 5.
    Kaas R, Verhoef S, Wesseling J, Rookus MA, Oldenburg HS, Peeters MJ, 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
  6. 6.
    Meijers-Heijboer H, van Geel B, van Putten WL, Henzen-Logmans SC, Seynaeve C, Menke-Pluymers MB, 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
  7. 7.
    Semple J, Metcalfe KA, Lynch HT, Kim-Sing C, Senter L, Pal T, et al. International rates of breast reconstruction after prophylactic mastectomy in BRCA1 and BRCA2 mutation carriers. Ann Surg Oncol. 2013;20(12):3817–22.PubMedCrossRefGoogle Scholar
  8. 8.
    Carlson GW, Bostwick J 3rd, Styblo TM, Moore B, Bried JT, Murray DR, et al. Skin-sparing mastectomy. Oncologic and reconstructive considerations. Ann Surg. 1997;225(5):570–5; discussion 575-8.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Craig ES, Walker ME, Salomon J, Fusi S. Immediate nipple reconstruction utilizing the DIEP flap in areola-sparing mastectomy. Microsurgery. 2013;33(2):125–9.PubMedCrossRefGoogle Scholar
  10. 10.
    de Alcantara Filho P, Capko D, Barry JM, Morrow M, Pusic A, Sacchini VS. Nipple-sparing mastectomy for breast cancer and risk-reducing surgery: the Memorial Sloan-Kettering Cancer Center experience. Ann Surg Oncol. 2011;18(11):3117–22.PubMedCrossRefGoogle Scholar
  11. 11.
    Didier F, Arnaboldi P, Gandini S, Maldifassi A, Goldhirsch A, Radice D, et al. Why do women accept to undergo a nipple sparing mastectomy or to reconstruct the nipple areola complex when nipple sparing mastectomy is not possible? Breast Cancer Res Treat. 2012;132(3):1177–84.PubMedCrossRefGoogle Scholar
  12. 12.
    Petit JY, Veronesi U, Lohsiriwat V, Rey P, Curigliano G, Martella S, et al. Nipple-sparing mastectomy–is it worth the risk? Nat Rev Clin Oncol. 2011;8(12):742–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Sinno H, Izadpanah A, Thibaudeau S, Christodoulou G, Lin SJ, Dionisopoulos T. An objective assessment of the perceived quality of life of living with bilateral mastectomy defect. Breast. 2013;22(2):168–72.PubMedCrossRefGoogle Scholar
  14. 14.
    Didier F, Radice D, Gandini S, Bedolis R, Rotmensz N, Maldifassi A, et al. Does nipple preservation in mastectomy improve satisfaction with cosmetic results, psychological adjustment, body image and sexuality? Breast Cancer Res Treat. 2009;118(3):623–33.PubMedCrossRefGoogle Scholar
  15. 15.
    Djohan R, Gage E, Gatherwright J, Pavri S, Firouz J, Bernard S, et al. Patient satisfaction following nipple-sparing mastectomy and immediate breast reconstruction: an 8-year outcome study. Plast Reconstr Surg. 2010;125(3):818–29.PubMedCrossRefGoogle Scholar
  16. 16.
    Wellisch DK, Schain WS, Noone RB, Little JW 3rd. The psychological contribution of nipple addition in breast reconstruction. Plast Reconstr Surg. 1987;80(5):699–704.PubMedCrossRefGoogle Scholar
  17. 17.
    Metcalfe KA, Semple JL, Narod SA. Time to reconsider subcutaneous mastectomy for breast-cancer prevention? Lancet Oncol. 2005;6(6):431–4.PubMedCrossRefGoogle Scholar
  18. 18.
    Jabor MA, Shayani P, Collins DR Jr, Karas T, Cohen BE. Nipple-areola reconstruction: satisfaction and clinical determinants. Plast Reconstr Surg. 2002;110(2):457–63; discussion 464–5.PubMedCrossRefGoogle Scholar
  19. 19.
    Reynolds C, Davidson JA, Lindor NM, Glazebrook KN, Jakub JW, Degnim AC, et al. Prophylactic and therapeutic mastectomy in BRCA mutation carriers: can the nipple be preserved? Ann Surg Oncol. 2011;18(11):3102–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Hartmann LC, Schaid DJ, Woods JE, Crotty TP, Myers JL, Arnold PG, et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med. 1999;340(2):77–84.PubMedCrossRefGoogle Scholar
  21. 21.
    Spear SL, Willey SC, Feldman ED, Cocilovo C, Sidawy M, Al-Attar A, et al. Nipple-sparing mastectomy for prophylactic and therapeutic indications. Plast Reconstr Surg. 2011;128(5):1005–14.PubMedCrossRefGoogle Scholar
  22. 22.
    Temple WJ, Lindsay RL, Magi E, Urbanski SJ. Technical considerations for prophylactic mastectomy in patients at high risk for breast cancer. Am J Surg. 1991;161(4):413–5.PubMedCrossRefGoogle Scholar
  23. 23.
    Kroll SS, Schusterman MA, Tadjalli HE, Singletary SE, Ames FC. Risk of recurrence after treatment of early breast cancer with skin-sparing mastectomy. Ann Surg Oncol. 1997;4(3):193–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Ma G, Richardson H, Pacella SJ, Codner MA. Single-stage breast reconstruction following areola-sparing mastectomy. Plast Reconstr Surg. 2009;123(5):1414–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Simmons RM, Hollenbeck ST, Latrenta GS. Two-year follow-up of areola-sparing mastectomy with immediate reconstruction. Am J Surg. 2004;188(4):403–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Simmons RM, Hollenbeck ST, Latrenta GS. Areola-sparing mastectomy with immediate breast reconstruction. Ann Plast Surg. 2003;51(6):547–51.PubMedCrossRefGoogle Scholar
  27. 27.
    Schnitt SJ, Goldwyn RM, Slavin SA. Mammary ducts in the areola: implications for patients undergoing reconstructive surgery of the breast. Plast Reconstr Surg. 1993;92(7):1290–3.PubMedGoogle Scholar
  28. 28.
    Stolier AJ, Grube BJ. Areola-sparing mastectomy: defining the risks. J Am Coll Surg. 2005;201(1):118–24.PubMedCrossRefGoogle Scholar
  29. 29.
    Vlajcic Z, Zic R, Stanec Z. Has the time come to change the breast-conserving treatment for skin and nipple-areola complex-sparing mastectomy? Plast Reconstr Surg. 2010;125(3):1043–4; author reply 1044–5.PubMedCrossRefGoogle Scholar
  30. 30.
    Algaithy ZK, Petit JY, Lohsiriwat V, Maisonneuve P, Rey PC, Baros N, et al. Nipple sparing mastectomy: can we predict the factors predisposing to necrosis? Eur J Surg Oncol. 2012;38(2):125–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Harness JK, Vetter TS, Salibian AH. Areola and nipple-areola-sparing mastectomy for breast cancer treatment and risk reduction: report of an initial experience in a community hospital setting. Ann Surg Oncol. 2011;18(4):917–22.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Petit JY, Veronesi U, Rey P, Rotmensz N, Botteri E, Rietjens M, 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
  33. 33.
    Stolier AJ, Levine EA. Reducing the risk of nipple necrosis: technical observations in 340 nipple-sparing mastectomies. Breast J. 2013;19(2):173–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Stolier AJ, Sullivan SK, Dellacroce FJ. Technical considerations in nipple-sparing mastectomy: 82 consecutive cases without necrosis. Ann Surg Oncol. 2008;15(5):1341–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Jensen JA, Orringer JS, Giuliano AE. Nipple-sparing mastectomy in 99 patients with a mean follow-up of 5 years. Ann Surg Oncol. 2011 June;18(6):1665–70.PubMedCrossRefGoogle Scholar
  36. 36.
    Passaperuma K, Warner E, Causer PA, Hill KA, Messner S, Wong JW, et al. Long-term results of screening with magnetic resonance imaging in women with BRCA mutations. Br J Cancer. 2012;107(1):24–30.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Ortiz CG, Martel AL. Automatic atlas-based segmentation of the breast in MRI for 3D breast volume computation. Med Phys. 2012;39(10):5835–48.PubMedCrossRefGoogle Scholar
  38. 38.
    Thompson DJ, Leach MO, Kwan-Lim G, Gayther SA, Ramus SJ, Warsi I, et al. Assessing the usefulness of a novel MRI-based breast density estimation algorithm in a cohort of women at high genetic risk of breast cancer. The UK MARIBS Study. Breast Cancer Res. 2009;11(6):R80.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Hauben DJ, Adler N, Silfen R, Regev D. Breast-areola-nipple proportion. Ann Plast Surg. 2003;50(5):510–3.PubMedCrossRefGoogle Scholar
  40. 40.
    Sanuki J, Fukuma E, Uchida Y. Morphologic study of nipple-areola complex in 600 breasts. Aesthetic Plast Surg. 2009;33(3):295–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Murthy V, Chamberlain RS. Nipple-sparing mastectomy in modern breast practice. Clin Anat. 2013;26(1):56–65.PubMedCrossRefGoogle Scholar
  42. 42.
    Livingston EH, Elliot A, Hynan L, Cao J. Effect size estimation: a necessary component of statistical analysis. Arch Surg. 2009;144(8):706–12.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Heather L. Baltzer
    • 1
  • Olivier Alonzo-Proulx
    • 2
    • 3
  • James G. Mainprize
    • 2
  • Martin J. Yaffe
    • 2
    • 3
  • Kelly A. Metcalfe
    • 4
    • 5
  • Steve A. Narod
    • 4
  • Ellen Warner
    • 2
    • 6
  • John L. Semple
    • 1
    • 4
  1. 1.Division of Plastic and Reconstructive SurgeryUniversity of TorontoTorontoCanada
  2. 2.Sunnybrook Research InstituteTorontoCanada
  3. 3.Department of Medical BiophysicsUniversity of TorontoTorontoCanada
  4. 4.Women’s College Research InstituteTorontoCanada
  5. 5.Lawrence S. Bloomberg Faculty of NursingUniversity of TorontoTorontoCanada
  6. 6.Division of Medical Oncology, Department of MedicineSunnybrook Health Sciences CentreTorontoCanada

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