Skip to main content
Top
Published in: Breast Cancer 6/2019

01-11-2019 | Mastectomy | Original Article

A novel nipple–areola complex involvement predictive index for indicating nipple-sparing mastectomy in breast cancer patients

Authors: Hirohito Seki, Takashi Sakurai, Shodai Mizuno, Toshiki Tokuda, Takuji Kaburagi, Minako Seki, Tsuyoshi Karahashi, Kenichiro Nakajima, Ken Shimizu, Hiromitsu Jinno

Published in: Breast Cancer | Issue 6/2019

Login to get access

Abstract

Background

Nipple-sparing mastectomy (NSM) is increasingly used in breast cancer patients, as it offers better cosmetic outcomes and improves quality of life. Nipple–areola complex (NAC) involvement must be accurately determined to identify which patients may be candidates for NSM. We aimed to identify the predictors of NAC involvement and develop a clinical predictive model to determine the patients for whom NAC preservation may be considered.

Patients and methods

Patients (n = 168) with primary operable breast cancer who underwent subcutaneous mastectomy for breast reconstruction at Saitama Medical Center from July 2013 to December 2017 were selected from the hospital’s surgical database.

Results

The clinicopathological factors of tumor size ≧ 4 cm (p < 0.001), nipple-to-tumor distance (NTD) < 1 cm by mammography (p = 0.002), NTD < 1 cm by magnetic-resonance imaging (MRI) (p < 0.001), nipple contrast findings by MRI (p < 0.001), tumor in central portion (p < 0.001), multicentric/focal lesion (p < 0.001), and clinical node involvement (p = 0.014) were significantly associated with the presence of NAC involvement. Each predictor was scored 0 or 1. A score of 0–3 points was defined as low risk, 4 points as intermediate risk, and 5–7 points as high risk. Using these classification criteria, NAC involvement rate was determined to be 3.5% in low-risk, 68.7% in intermediate-risk, and 90.0% in high-risk specimens. A significant correlation was observed between the risk group and NAC involvement (p < 0.001).

Conclusion

This nipple–areola complex involvement predictive index can be used to determine the appropriate indication for NSM in breast cancer patients who request NAC preservation with more oncological safety.
Appendix
Available only for authorised users
Literature
1.
go back to reference Fisher B, Anderson S, Redmond CK, Wolmark N, Wickerham DL, Cronin WM. Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med. 1995;333:1456–61.CrossRefPubMed Fisher B, Anderson S, Redmond CK, Wolmark N, Wickerham DL, Cronin WM. Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med. 1995;333:1456–61.CrossRefPubMed
2.
go back to reference Arriagada R, Le MG, Rochard F, Contesso G. Conservative treatment versus mastectomy in early breast cancer: patterns of failure with 15 years of follow-up data. Institut Gustave-Roussy Breast Cancer Group. J Clin Oncol. 1996;14:1558–64.CrossRefPubMed Arriagada R, Le MG, Rochard F, Contesso G. Conservative treatment versus mastectomy in early breast cancer: patterns of failure with 15 years of follow-up data. Institut Gustave-Roussy Breast Cancer Group. J Clin Oncol. 1996;14:1558–64.CrossRefPubMed
3.
go back to reference 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;4:193–7.CrossRefPubMed 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;4:193–7.CrossRefPubMed
4.
go back to reference Simmons RM, Fish SK, Gayle L, La Trenta GS, Swistel A, Christos P, et al. Local and distant recurrence rates in skin-sparing mastectomies compared with non-skin-sparing mastectomies. Ann Surg Oncol. 1999;6:676–81.CrossRefPubMed Simmons RM, Fish SK, Gayle L, La Trenta GS, Swistel A, Christos P, et al. Local and distant recurrence rates in skin-sparing mastectomies compared with non-skin-sparing mastectomies. Ann Surg Oncol. 1999;6:676–81.CrossRefPubMed
5.
go back to reference Toth BA, Forley BG, Calabria R. Retrospective study of the skin-sparing mastectomy in breast reconstruction. Plast Reconstr Surg. 1999;104:77–84.CrossRefPubMed Toth BA, Forley BG, Calabria R. Retrospective study of the skin-sparing mastectomy in breast reconstruction. Plast Reconstr Surg. 1999;104:77–84.CrossRefPubMed
6.
go back to reference Toth BA, Lappert P. Modified skin incisions for mastectomy: the need for plastic surgical input in preoperative planning. Plast Reconstr Surg. 1991;87:1048–53.CrossRefPubMed Toth BA, Lappert P. Modified skin incisions for mastectomy: the need for plastic surgical input in preoperative planning. Plast Reconstr Surg. 1991;87:1048–53.CrossRefPubMed
7.
go back to reference Newman LA, Kuerer HM, Hunt KK, Kroll SS, Ames FC, Ross MI, et al. Presentation, treatment, and outcome of local recurrence afterskin-sparing mastectomy and immediate breast reconstruction. Ann Surg Oncol. 1998;5:620–6.CrossRefPubMed Newman LA, Kuerer HM, Hunt KK, Kroll SS, Ames FC, Ross MI, et al. Presentation, treatment, and outcome of local recurrence afterskin-sparing mastectomy and immediate breast reconstruction. Ann Surg Oncol. 1998;5:620–6.CrossRefPubMed
8.
go back to reference Slavin SA, Schnitt SJ, Duda RB, Houlihan MJ, Koufman CN, Morris DJ, et al. Skin-sparing mastectomy and immediate reconstruction: oncologic risks and aesthetic results in patients with early-stage breast cancer. Plast Reconstr Surg. 1998;102:49–62.CrossRefPubMed Slavin SA, Schnitt SJ, Duda RB, Houlihan MJ, Koufman CN, Morris DJ, et al. Skin-sparing mastectomy and immediate reconstruction: oncologic risks and aesthetic results in patients with early-stage breast cancer. Plast Reconstr Surg. 1998;102:49–62.CrossRefPubMed
9.
go back to reference Kroll SS, Khoo A, Singletary SE, Ames FC, Wang BG, Reece GP, et al. Local recurrence risk after skin-sparing and conventional mastectomy: a 6-year follow-up. Plast Reconstr Surg. 1999;104:421–5.CrossRefPubMed Kroll SS, Khoo A, Singletary SE, Ames FC, Wang BG, Reece GP, et al. Local recurrence risk after skin-sparing and conventional mastectomy: a 6-year follow-up. Plast Reconstr Surg. 1999;104:421–5.CrossRefPubMed
10.
go back to reference Petit JY, Veronesi U, Luini A, Orecchia R, Rey PC, Martella S, et al. When mastectomy becomes inevitable: the nipple-sparing approach. Breast. 2005;14:527–31.CrossRefPubMed Petit JY, Veronesi U, Luini A, Orecchia R, Rey PC, Martella S, et al. When mastectomy becomes inevitable: the nipple-sparing approach. Breast. 2005;14:527–31.CrossRefPubMed
11.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
12.
go back to reference Wellisch DK, Schain WS, Noone RB, Little JW 3rd. The psychological contribution of nipple addition in breast reconstruction. Plast Reconstr Surg. 1987;80:699–704.CrossRefPubMed Wellisch DK, Schain WS, Noone RB, Little JW 3rd. The psychological contribution of nipple addition in breast reconstruction. Plast Reconstr Surg. 1987;80:699–704.CrossRefPubMed
13.
go back to reference Petit JY, Veronesi U, Orecchia R, Rey P, Martella S, Didier F, 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.CrossRefPubMed Petit JY, Veronesi U, Orecchia R, Rey P, Martella S, Didier F, 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.CrossRefPubMed
14.
go back to reference 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;114:97–101.CrossRefPubMed 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;114:97–101.CrossRefPubMed
15.
go back to reference Garcia-Etienne CA, Cody Iii HS 3rd, Disa JJ, Cordeiro P, Sacchini V. Nipple-sparing mastectomy: initial experience at the Memorial Sloan-Kettering Cancer Center and a comprehensive review of literature. Breast J. 2009;15:440–9.CrossRefPubMed Garcia-Etienne CA, Cody Iii HS 3rd, Disa JJ, Cordeiro P, Sacchini V. Nipple-sparing mastectomy: initial experience at the Memorial Sloan-Kettering Cancer Center and a comprehensive review of literature. Breast J. 2009;15:440–9.CrossRefPubMed
17.
go back to reference Jensen JA, Orringer JS, Giuliano AE. Nipple-sparing mastectomy in 99 patients with a mean follow-up of 5 years. Ann Surg Oncol. 2011;18:1665–70.CrossRefPubMed Jensen JA, Orringer JS, Giuliano AE. Nipple-sparing mastectomy in 99 patients with a mean follow-up of 5 years. Ann Surg Oncol. 2011;18:1665–70.CrossRefPubMed
18.
go back to reference Verma GR, Kumar A, Joshi K. Nipple involvement in peripheral breast carcinoma: a prospective study. Indian J Cancer. 1997;34:1–5.PubMed Verma GR, Kumar A, Joshi K. Nipple involvement in peripheral breast carcinoma: a prospective study. Indian J Cancer. 1997;34:1–5.PubMed
19.
go back to reference Moon JY, Chang YW, Lee EH, Seo DY. Malignant invasion of the nipple-areolar complex of the breast: usefulness of breast MRI. AJR Am J Roentgenol. 2013;201:448–55.CrossRefPubMed Moon JY, Chang YW, Lee EH, Seo DY. Malignant invasion of the nipple-areolar complex of the breast: usefulness of breast MRI. AJR Am J Roentgenol. 2013;201:448–55.CrossRefPubMed
20.
go back to reference Byon W, Kim E, Kwon J, Park YL, Park C. Magnetic resonance imaging and clinicopathological factors for the detection of occult nipple involvement in breast cancer patients. J Breast Cancer. 2014;17:386–92.CrossRefPubMedPubMedCentral Byon W, Kim E, Kwon J, Park YL, Park C. Magnetic resonance imaging and clinicopathological factors for the detection of occult nipple involvement in breast cancer patients. J Breast Cancer. 2014;17:386–92.CrossRefPubMedPubMedCentral
21.
go back to reference Karamchandani DM, Chetlen AL, Riley MP, Schetter S, Hollenbeak CS, Mack J. Pathologic-radiologic correlation in evaluation of retroareolar margin in nipple-sparing mastectomy. Virchows Arch. 2015;466:279–87.CrossRefPubMed Karamchandani DM, Chetlen AL, Riley MP, Schetter S, Hollenbeak CS, Mack J. Pathologic-radiologic correlation in evaluation of retroareolar margin in nipple-sparing mastectomy. Virchows Arch. 2015;466:279–87.CrossRefPubMed
22.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
23.
go back to reference Loewen MJ, Jennings JA, Sherman SR, Slaikeu J, Ebrom PA, Davis AT, et al. Mammographic distance as a predictor of nipple-areola complex involvement in breast cancer. Am J Surg. 2008;195:391–4 (discussion 4–5).CrossRefPubMed Loewen MJ, Jennings JA, Sherman SR, Slaikeu J, Ebrom PA, Davis AT, et al. Mammographic distance as a predictor of nipple-areola complex involvement in breast cancer. Am J Surg. 2008;195:391–4 (discussion 4–5).CrossRefPubMed
24.
go back to reference Yamashiro N, Tozaki M, Ogawa T, Kawano N, Suzuki T, Ozaki S, et al. Preoperative MRI marking technique for the planning of breast-conserving surgery. Breast Cancer. 2009;16:223–8.CrossRefPubMed Yamashiro N, Tozaki M, Ogawa T, Kawano N, Suzuki T, Ozaki S, et al. Preoperative MRI marking technique for the planning of breast-conserving surgery. Breast Cancer. 2009;16:223–8.CrossRefPubMed
25.
go back to reference 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 involvement in breast cancer patients. Ann Plast Surg. 2006;56:498–504 (discussion).CrossRefPubMed 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 involvement in breast cancer patients. Ann Plast Surg. 2006;56:498–504 (discussion).CrossRefPubMed
26.
go back to reference Paepke S, Schmid R, Fleckner S, Paepke D, Niemeyer M, Schmalfeldt B, et al. Subcutaneous mastectomy with conservation of the nipple-areola skin: broadening the indications. Ann Surg. 2009;250:288–92.CrossRefPubMed Paepke S, Schmid R, Fleckner S, Paepke D, Niemeyer M, Schmalfeldt B, et al. Subcutaneous mastectomy with conservation of the nipple-areola skin: broadening the indications. Ann Surg. 2009;250:288–92.CrossRefPubMed
27.
go back to reference Chattopadhyay D, Gupta S, Jash PK, Murmu MB, Gupta S. Skin sparing mastectomy with preservation of nipple areola complex and immediate breast reconstruction in patients with breast cancer: a single centre prospective study. Plast Surg Int. 2014;2014:589068.PubMedPubMedCentral Chattopadhyay D, Gupta S, Jash PK, Murmu MB, Gupta S. Skin sparing mastectomy with preservation of nipple areola complex and immediate breast reconstruction in patients with breast cancer: a single centre prospective study. Plast Surg Int. 2014;2014:589068.PubMedPubMedCentral
28.
go back to reference Crowe JP Jr, Kim JA, Yetman R, Banbury J, Patrick RJ, Baynes D. Nipple-sparing mastectomy: technique and results of 54 procedures. Arch Surg. 2004;139:148–50.CrossRefPubMed Crowe JP Jr, Kim JA, Yetman R, Banbury J, Patrick RJ, Baynes D. Nipple-sparing mastectomy: technique and results of 54 procedures. Arch Surg. 2004;139:148–50.CrossRefPubMed
29.
go back to reference Luo D, Ha J, Latham B, Ingram D, Connell T, Hastrich D, et al. The accuracy of intraoperative subareolar frozen section in nipple-sparing mastectomies. Ochsner J. 2010;10:188–92.PubMedPubMedCentral Luo D, Ha J, Latham B, Ingram D, Connell T, Hastrich D, et al. The accuracy of intraoperative subareolar frozen section in nipple-sparing mastectomies. Ochsner J. 2010;10:188–92.PubMedPubMedCentral
30.
go back to reference Kneubil MC, Lohsiriwat V, Curigliano G, Brollo J, Botteri E, Rotmensz N, et al. Risk of locoregional recurrence in patients with false-negative frozen section or close margins of retroareolar specimen in nipple-sparing mastectomy. Ann Surg Oncol. 2012;19:4117–23.CrossRefPubMed Kneubil MC, Lohsiriwat V, Curigliano G, Brollo J, Botteri E, Rotmensz N, et al. Risk of locoregional recurrence in patients with false-negative frozen section or close margins of retroareolar specimen in nipple-sparing mastectomy. Ann Surg Oncol. 2012;19:4117–23.CrossRefPubMed
31.
go back to reference Eisenberg RE, Chan JS, Swistel AJ, Hoda SA. Pathological evaluation of nipple-sparing mastectomies with emphasis on occult nipple involvement: the Weill-Cornell experience with 325 cases. Breast J. 2014;20:15–21.CrossRefPubMed Eisenberg RE, Chan JS, Swistel AJ, Hoda SA. Pathological evaluation of nipple-sparing mastectomies with emphasis on occult nipple involvement: the Weill-Cornell experience with 325 cases. Breast J. 2014;20:15–21.CrossRefPubMed
32.
go back to reference Duarte GM, Tomazini MV, Oliveira A, Moreira L, Tocchet F, Worschech A, et al. Accuracy of frozen section, imprint cytology, and permanent histology of sub-nipple tissue for predicting occult nipple involvement in patients with breast carcinoma. Breast Cancer Res Treat. 2015;153:557–63.CrossRefPubMed Duarte GM, Tomazini MV, Oliveira A, Moreira L, Tocchet F, Worschech A, et al. Accuracy of frozen section, imprint cytology, and permanent histology of sub-nipple tissue for predicting occult nipple involvement in patients with breast carcinoma. Breast Cancer Res Treat. 2015;153:557–63.CrossRefPubMed
33.
go back to reference Morales Piato JR, Aguiar FN, Mota BS, Ricci MD, Doria MT, Alves-Jales RD, et al. Improved frozen section examination of the retroareolar margin for prediction of nipple involvement in breast cancer. Eur J Surg Oncol. 2015;41:986–90.CrossRefPubMed Morales Piato JR, Aguiar FN, Mota BS, Ricci MD, Doria MT, Alves-Jales RD, et al. Improved frozen section examination of the retroareolar margin for prediction of nipple involvement in breast cancer. Eur J Surg Oncol. 2015;41:986–90.CrossRefPubMed
34.
go back to reference Ponzone R, Maggiorotto F, Carabalona S, Rivolin A, Pisacane A, Kubatzki F, et al. MRI and intraoperative pathology to predict nipple-areola complex (NAC) involvement in patients undergoing NAC-sparing mastectomy. Eur J Cancer. 2015;51:1882–9.CrossRefPubMed Ponzone R, Maggiorotto F, Carabalona S, Rivolin A, Pisacane A, Kubatzki F, et al. MRI and intraoperative pathology to predict nipple-areola complex (NAC) involvement in patients undergoing NAC-sparing mastectomy. Eur J Cancer. 2015;51:1882–9.CrossRefPubMed
35.
go back to reference Alperovich M, Choi M, Karp NS, Singh B, Ayo D, Frey JD, et al. Nipple-sparing mastectomy and sub-areolar biopsy: to freeze or not to freeze? Evaluating the role of sub-areolar intraoperative frozen section. Breast J. 2016;22:18–23.CrossRefPubMed Alperovich M, Choi M, Karp NS, Singh B, Ayo D, Frey JD, et al. Nipple-sparing mastectomy and sub-areolar biopsy: to freeze or not to freeze? Evaluating the role of sub-areolar intraoperative frozen section. Breast J. 2016;22:18–23.CrossRefPubMed
36.
go back to reference Chan SE, Liao CY, Wang TY, Chen ST, Chen DR, Lin YJ, et al. The diagnostic utility of preoperative breast magnetic resonance imaging (MRI) and/or intraoperative sub-nipple biopsy in nipple-sparing mastectomy. Eur J Surg Oncol. 2017;43:76–84.CrossRefPubMed Chan SE, Liao CY, Wang TY, Chen ST, Chen DR, Lin YJ, et al. The diagnostic utility of preoperative breast magnetic resonance imaging (MRI) and/or intraoperative sub-nipple biopsy in nipple-sparing mastectomy. Eur J Surg Oncol. 2017;43:76–84.CrossRefPubMed
37.
go back to reference Lambert PA, Kolm P, Perry RR. Parameters that predict nipple involvement in breast cancer. J Am Coll Surg. 2000;191:354–9.CrossRefPubMed Lambert PA, Kolm P, Perry RR. Parameters that predict nipple involvement in breast cancer. J Am Coll Surg. 2000;191:354–9.CrossRefPubMed
38.
go back to reference 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;138:135–42.CrossRefPubMed 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;138:135–42.CrossRefPubMed
39.
go back to reference Morimoto T, Komaki K, Inui K, Umemoto A, Yamamoto H, Harada K, et al. Involvement of nipple and areola in early breast cancer. Cancer. 1985;55:2459–63.CrossRefPubMed Morimoto T, Komaki K, Inui K, Umemoto A, Yamamoto H, Harada K, et al. Involvement of nipple and areola in early breast cancer. Cancer. 1985;55:2459–63.CrossRefPubMed
Metadata
Title
A novel nipple–areola complex involvement predictive index for indicating nipple-sparing mastectomy in breast cancer patients
Authors
Hirohito Seki
Takashi Sakurai
Shodai Mizuno
Toshiki Tokuda
Takuji Kaburagi
Minako Seki
Tsuyoshi Karahashi
Kenichiro Nakajima
Ken Shimizu
Hiromitsu Jinno
Publication date
01-11-2019
Publisher
Springer Japan
Published in
Breast Cancer / Issue 6/2019
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-019-00987-y

Other articles of this Issue 6/2019

Breast Cancer 6/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine