Abstract
Purpose
The aim of this review was to examine the incidence of nipple-areola complex (NAC) involvement, the rates of NAC recurrence, and the data regarding the role of radiation therapy (RT) following nipple-sparing mastectomy (NSM).
Methods
A literature review was performed using the PubMed search engine, with articles selected based on standardized criteria. Additional articles included those known to the authors and those obtained by review of references from key studies.
Results
The reported incidence of NAC involvement ranges from 0 to 58 %. The most commonly associated factors with NAC involvement include tumor-to-NAC distance, tumor size, central location of the primary tumor, multicentricity/multifocality, and positive axillary lymph nodes. Following NSM, in the setting of proper patient selection, rates of NAC recurrence are generally low, with the majority of studies reporting rates ranging from 0 to 4 %. There is a paucity of data evaluating the role of RT after NSM and a lack of level I evidence, with the largest series documenting low rates of local recurrence with RT but failing to provide a control arm without radiotherapy.
Conclusions
Optimal preoperative patient selection for NSM and intraoperative assessment of the NAC result in acceptably low rates of NAC involvement/recurrence. NSM alone is not adequate justification for post-mastectomy radiation. NSM should be taken into consideration to inform radiation decision making only when preoperative imaging, clinical features, or pathologic findings suggest higher risk for NAC involvement.
Similar content being viewed by others
References
Maddox WA, Carpenter JT Jr, Laws HL, et al. A randomized prospective trial of radical (Halsted) mastectomy versus modified radical mastectomy in 311 breast cancer patients. Ann Surg. 1983;198:207–12.
Forrest AP, Stewart HJ, Everington D, et al. Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial. Lancet. 1996;348:708–13.
Liljegren G, Holmberg J, Bergh A, et al. 10-year results after sector resection with or without postoperative radiotherapy for stage I breast cancer: a randomized trial. J Clin Oncol. 1999;17:2326–33.
van Dongen JA, Voogd AC, Fentiman IS, et al. Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 Trial. J Natl Cancer Inst. 2000;92:1143–50.
Veronesi U, Marubini E, Mariani L, et al. Radiotherapy after breast-conserving surgery in small breast carcinoma: long-term results of a randomized trial. Ann Oncol. 2001;12:997–1003.
Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347:1233–41.
Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347:1227–32.
Holli K, Hietanen P, Saaristo R, Huhtala H, Hakama M, Joensuu H. Radiotherapy after segmental resection of breast cancer with favorable prognostic features: 12-year follow-up results of a randomized trial. J Clin Oncol. 2009;27:927–32.
Dragun AE, Huang B, Tucker TC, Spanos WJ. Increasing mastectomy rates among all age groups for early stage breast cancer: a 10-year study of surgical choice. Breast J. 2012;18:318–25.
Sappey PC. Anatomie, physiologie, pathologie des vaisseaux lymphatiques considere chez l’homme et les vertebres. Paris: Leconsier; 1885.
Didier F, Radice D, Gandini S, et al. Does nipple preservation in mastectomy improve satisfaction with cosmetic results, psychological adjustment, body image and sexuality? Breast Cancer Res Treat. 2009;118:623–33.
Smith J, Payne WS, Carney JA. Involvement of the nipple and areola in carcinoma of the breast. Surg Gynecol Obstet. 1976;143:546–8.
Parry RG, Cochran TC Jr, Wolfort FG. When is there nipple involvement in carcinoma of the breast? Plast Reconstr Surg. 1977;59:535–7.
Andersen JA, Pallesen RM. Spread to the nipple and areola in carcinoma of the breast. Ann Surg. 1979;189:367–72.
Lagios MD, Gates EA,Westdahl PR, Richards V, Alpert BS. 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;138:135–41.
Wertheim U, Ozzello L. Neoplastic involvement of nipple and skin flap in carcinoma of the breast. Am J Surg Pathol. 1980;4:543–9.
Quinn RH, Barlow JF. Involvement of the nipple and areola by carcinoma of the breast. Arch Surg. 1981;116:1139–40.
Morimoto T, Komaki K, Inui K, Umemoto A, Yamamoto H, Harada K, et al. Involvement of the nipple and areola in early breast cancer. Cancer. 1985;55:2459–63.
Lüttges J, Kalbfleisch H, Prinz P. Nipple involvement and multicentricity in breast cancer. A study on whole organ sections. J Cancer Res Clin Oncol. 1987;113:481–7.
Santini D, Taffurelli M, Gelli MC, Grassigli A, Giosa F, Marrano D, et al. Neoplastic involvement of nipple-areolar complex in invasive breast cancer. Am J Surg. 1989;158:399–403.
Menon RS, van Geel AN. Cancer of the breast with nipple involvement. Br J Cancer. 1989;59:81–4.
Verma GR, Kumar A, Joshi K. Nipple involvement in peripheral breast carcinoma: a prospective study. Indian J Cancer. 1997;34:1–5.
Vyas JJ, Chinoy RF, Vaidya JS. Prediction of nipple and areola involvement in breast cancer. Eur J Surg Oncol. 1998;24:15–16.
Laronga C, Kemp B, Johnston D, Robb G, Singletary SE. The incidence of occult nipple-areola complex involvement in breast cancer patients receiving a skin-sparing mastectomy. Ann Surg Oncol. 1999;6:609–13.
Lambert PA, Kolm P, Perry RR. Parameters that predict nipple involvement in breast cancer. J Am Coll Surg. 2000;191:354–9.
Simmons RM, Brennan M, Christos P, King V, Osborne M. Analysis of nipple/areolar involvement with mastectomy: can the areola be preserved? Ann Surg Oncol. 2002;9:165–8.
Brachtel EF, Rusby JE, Michaelson JS, Chen LL, Muzikansky A, Smith BL, et al. Occult nipple involvement in breast cancer: clinicopathologic findings in 316 consecutive mastectomy specimens. J Clin Oncol. 2009;27:4948–54.
Weidong L, Wang S, Guo X, et al. Nipple involvement in breast cancer: retrospective analysis of 2,323 consecutive mastectomy specimens. Int J Surg Pathol. 2011;19:328–34.
Wang J, Xiao X, Wang J, et al. Predictors of nipple-areola complex involvement by breast carcinoma: histopathologic analysis of 787 consecutive therapeutic mastectomy specimens. Ann Surg Oncol. 2012;19:1174–80.
D’Alonzo M, Martincich L, Biglia N, et al. Clinical and radiological predictors of nipple-areola complex involvement in breast cancer patients. Eur J Cancer. 2012;48:2311–8.
Billar JAY, Dueck AC, Gray RJ, Wasif N, Pockaj BA. Preoperative predictors of nipple-areola complex involvement for patients undergoing mastectomy for breast cancer. Ann Surg Oncol. 2011;18:3123–8.
Sakamoto N, Tozaki M, Hoshi K, Fukuma E. Is MRI useful for the prediction of nipple involvement? Breast Cancer. 2013;20:316–22.
Schecter AK, Freeman MB, Giri D, Sabo E, Weinzweig J. Applicability of the nipple-areola complex-sparing mastectomy: a prediction model using mammography to estimate risk of nipple-areola complex imvolvement in breast cancer patients. Ann Plast Surg. 2006;56:498–504.
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;131:969–84.
Bishop CC, Singh S, Nash AG. Mastectomy and breast reconstruction preserving the nipple. Ann R Coll Surg Engl. 1990;72:87–9.
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;34:143–8.
Crowe JP, Patrick RJ, Yetman RJ, Djohan R. Nipple-sparing mastectomy update: one hundred and forty-nine procedures and clinical outcomes. Arch Surg. 2008;143:1106-10.
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.
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.
Cheung KL, Blamey RW, Robertson JF, Elston CW, Ellis IO. Subcutaneous mastectomy for primary breast cancer and ductal carcinoma in situ. Eur J Surg Oncol. 1997;23:343–7.
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;238:120–7.
Petit JY, Veronesi U, Orecchia R, et al. Nipple sparing mastectomy with nipple areola intraoperative radiotherapy: one thousand and one cases of a five years experience at the European Institute of Oncology of Milan (EIO). Breast Cancer Res Treat. 2009;117:333–8.
Garcia-Etienne CA, Cody Iii HS 3rd, Disa JJ, Cordiero P, Sacchini V. Nipple-sparing mastectomy: initial experience at the Memorial Sloan-Kettering Cancer Center and a comprehensive review of the literature. Breast J. 2009;15:440–9.
Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. N Engl J Med. 1997;337:949–55.
Overgaard M, Jensen MB, Overgaard J, et al. Postoperative radiotherapy in high-risk postmenopausal breast cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c Randomized Trial. Lancet. 1999;353:1641–8.
Ragaz J, Olivotto IA, Spinelli JJ, et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst. 2005;97:116–26.
Abi-Raad R, Boutrus R, Wang R, Niemierko A, Macdonald S, Smith B, et al. Patterns and risk factors of locoregional recurrence in T1-T2 node negative breast cancer patients treated with mastectomy: implications for postmastectomy radiotherapy. Int J Radiat Oncol Biol Phys. 2011;81:151–7.
Yildirim E, Berberoglu U. Can a subgroup of node-negative breast carcinoma patients with T1-2 tumor who may benefit from postmastectomy radiotherapy be identified? Int J Radiat Oncol Biol Phys. 2007;68:1024–9.
Jagsi R, Raad RA, Goldberg S. Locoregional recurrence rates and prognostic factors for failure in node-negative patients treated with mastectomy: implications for postmastectomy radiation. Int J Radiat Oncol Biol Phys. 2005;62:1035–9.
Truong PT, Lesperance M, Culhaci A, Kader HA, Speers CH, Olivotto IA. Patient subsets with T1-T2, node-negative breast cancer at high locoregional recurrence risk after mastectomy. Int J Radiat Oncol Biol Phys. 2005;62:175–82.
Financial Disclosures
None.
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gomez, C., Shah, C., McCloskey, S. et al. The Role of Radiation Therapy after Nipple-Sparing Mastectomy. Ann Surg Oncol 21, 2237–2244 (2014). https://doi.org/10.1245/s10434-013-3446-z
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1245/s10434-013-3446-z