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Nipple-sparing Mastectomy with Immediate Implant-based Reconstruction for Patients with Pure Ductal Carcinoma in Situ

Mastectomia preservadora demamilo com reconstrução imediata baseada em implante para pacientes com carcinoma ductal puro in situ

Antônio Luiz Frasson Ana Beatriz Falcone Isabela Miranda Alessandra Borba Anton de Souza Betina Vollbrecht Fernanda Barbosa Mônica Adriana Rodriguez Martinez Frasson Martina Lichtenfels About the authors

Abstract

Objective

The presence of an extensive intraductal component is associated to an increasing risk of relapse in the nipple-areola complex. The aim of the present study was to evaluate the outcomes of patients diagnosed with ductal carcinoma in situ (DCIS) who underwent nipple-sparing mastectomy (NSM) with immediate breast reconstruction using silicone implants.

Methods

We retrospectively analyzed the postoperative complications and oncological safety of 67 breast cancer patients diagnosed with pure DCIS who underwent NSM with immediate breast reconstruction using silicone implants between 2004 and 2018.

Results

Among the 127 NSM procedures performed, 2 hematomas (1.5%) and 1 partial nipple necrosis (0.7%) were observed. After a mean follow-up of 60months, the local recurrence rate was of 8.9%, the disease-free survival rate was of 90%, and 1 of the patients died.

Conclusion

Despite the local recurrence rate, we showed that NSM with immediate breast reconstruction using silicone implants is a feasible surgical approach, with a low rate of complications and high survival rates for patients with a diagnosis of pure DCIS when breast-conserving surgery is not an option.

Keywords:
breast cancer; intraductal noninfiltrating carcinoma; subcutaneous mastectomy

Resumo

Objetivo

A presença de componente intraductal extenso é associada ao risco aumentado de recorrência no complexo aréolo-mamilar. O objetivo deste estudo foi avaliar os resultados de pacientes diagnosticados com carcinoma ductal in situ (CDIS)submetidas a adenomastectomia (nipple-sparing mastectomy, NSM, em inglês) com reconstrução mamária imediata utilizando prótese de silicone.

Métodos

Restrospectivamente, foramanalisadas as complicações pós-operatórias e a segurança oncológica de 67 pacientes com câncer de mama diagnosticadas com CDIS puro, e submetidas a NSM com reconstrução mamária imediata utilizando prótese de silicone, entre 2004 e 2018.

Resultados

Entre os 127 procedimentos realizados, 2 hematomas (1,5%) e 1 necrose parcial de mamilo (0,7%) foram observados. Após um período médio de 60 meses de seguimento, a taxa de recorrência local foi de 8,9%, a sobrevida livre de doença, de 90%, e apenas 1 paciente foi a óbito.

Conclusão

Apesar da taxa de recorrência local, demostrou-se que NSM com reconstrução mamária imediata comprótese de silicone é umprocedimento viável, combaixa taxa de complicação e alta sobrevida para pacientes com diagnóstico de CDIS puro quando a cirurgia conservadora da mama não é uma opção.

Palavras-chave:
neoplasias da mama; carcinoma ductal de mama; mastectomia subcutânea

Introduction

Nipple-sparing mastectomy (NSM) has been successfully performed in the treatment of breast cancer, with excellent results.11 Petit JY, Veronesi U, Orecchia R, Curigliano G, Rey PC, Botteri E, et al. Risk factors associated with recurrence after nipple-sparing mastectomy for invasive and intraepithelial neoplasia. Ann Oncol. 2012;23(08):2053-2058. Doi: 10.1093/annonc/mdr566
https://doi.org/10.1093/annonc/mdr566...
22 De La Cruz L, Moody AM, Tappy EE, Blankenship SA, Hecht EM. Overall survival, disease-free survival, local recurrence, and nipple- areolar recurrence in the setting of nipple-sparing mastectomy: a meta-analysis and systematic review. Ann Surg Oncol. 2015;22(10):3241-3249. Doi: 10.1245/s10434-015-4739-1
https://doi.org/10.1245/s10434-015-4739-...
33 Orzalesi L, Casella D, Santi C, Cecconi L, Murgo R, Rinaldi S, et al. Nipple sparing mastectomy: Surgical and oncological outcomes from a national multicentric registry with 913 patients (1006 cases) over a six year period. Breast. 2016;25:75-81. Doi: 10.1016/j.breast.2015.10.010
https://doi.org/10.1016/j.breast.2015.10...
44 Smith BL, Tang R, Rai U, Plichta JK, Colwell AS, Gadd MA, et al. Oncologic safety of nipple-sparing mastectomy in women with breast cancer. J Am Coll Surg. 2017;225(03):361-365. Doi: 10.1016/j.jamcollsurg.2017.06.013
https://doi.org/10.1016/j.jamcollsurg.20...
The indications for NSM include invasive breast cancer and ductal carcinoma in situ (DCIS) for patients in whom breast-conserving surgery (BCS) may not be performed.55 Hieken TJ, Boolbol SK, Dietz JR. Nipple-sparing mastectomy: indications, contraindications, risks, benefits, and techniques. Ann Surg Oncol. 2016;23(10):3138-3144. Doi: 10.1245/s10434- 016-5370-5 Some contraindications to BCS include larger tumor sizes, multifocal and multicentric tumors, contraindications to radiotherapy (RT), a potentially-poor cosmetic outcome due to the tumor/breast relationship, and patient choice.55 Hieken TJ, Boolbol SK, Dietz JR. Nipple-sparing mastectomy: indications, contraindications, risks, benefits, and techniques. Ann Surg Oncol. 2016;23(10):3138-3144. Doi: 10.1245/s10434- 016-5370-566 Galimberti V, Vicini E, Corso G, Morigi C, Fontana S, Sacchini V, et al. Nipple-sparing and skin-sparing mastectomy: Review of aims, oncological safety and contraindications. Breast. 2017;34 (Suppl 1):S82-S84. Doi: 10.1016/j.breast.2017.06.034
https://doi.org/10.1016/j.breast.2017.06...
Currently, some authors77 Jadeja P, Ha R, Rohde C, Ascherman J, Grant R, Chin C, et al. Expanding the criteria for nipple-sparing mastectomy in patients with poor prognostic features. Clin Breast Cancer. 2018;18(03): 229-233. Doi: 10.1016/j.clbc.2017.08.010
https://doi.org/10.1016/j.clbc.2017.08.0...
suggest expanding NSM indications to include patients with large tumors who have undergone neoadjuvant chemotherapy, and patients with local recurrence after BCS followed by RT. The presence of an extensive intraductal component is strongly associated to an increasing risk of relapse in the nipple-areola complex.88 Wu ZY, Kim HJ, Lee JW, Chung IY, Kim JS, Lee SB, et al. Breast cancer recurrence in the nipple-areola complex after nipple-sparingmastectomy with immediate breast reconstruction. JAMA Surg. 2019; 154(11):1030-1037. Doi: 10.1001/jamasurg.2019.2959
https://doi.org/10.1001/jamasurg.2019.29...
Previous studies33 Orzalesi L, Casella D, Santi C, Cecconi L, Murgo R, Rinaldi S, et al. Nipple sparing mastectomy: Surgical and oncological outcomes from a national multicentric registry with 913 patients (1006 cases) over a six year period. Breast. 2016;25:75-81. Doi: 10.1016/j.breast.2015.10.010
https://doi.org/10.1016/j.breast.2015.10...
99 Manning AT, Sacchini VS. Conservative mastectomies for breast cancer and risk-reducing surgery: the Memorial Sloan Kettering Cancer Center experience. Gland Surg. 2016;5(01):55-62. Doi: 10.3978/j.issn.2227-684X.2015.10.02
https://doi.org/10.3978/j.issn.2227-684X...
1010 Leclère FM, Panet-Spallina J, Kolb F, Garbay JR, Mazouni C, Leduey A, et al. Nipple-sparing mastectomy and immediate reconstruction in ductal carcinoma in situ: a critical assessment with 41 patients. Aesthetic Plast Surg. 2014;38(02):338-343. Doi: 10.1007/s00266-013-0236-8
https://doi.org/10.1007/s00266-013-0236-...
have reported low rates of recurrence in the nipple-areola complex, ranging from 1.4% to 3.2%, in patients diagnosed with in situ tumors, and have highlighted the oncological safety of the preservation of the nipple-areola complex for patients with a negative intraoperative retroareolar frozen section. Many studies11 Petit JY, Veronesi U, Orecchia R, Curigliano G, Rey PC, Botteri E, et al. Risk factors associated with recurrence after nipple-sparing mastectomy for invasive and intraepithelial neoplasia. Ann Oncol. 2012;23(08):2053-2058. Doi: 10.1093/annonc/mdr566
https://doi.org/10.1093/annonc/mdr566...
33 Orzalesi L, Casella D, Santi C, Cecconi L, Murgo R, Rinaldi S, et al. Nipple sparing mastectomy: Surgical and oncological outcomes from a national multicentric registry with 913 patients (1006 cases) over a six year period. Breast. 2016;25:75-81. Doi: 10.1016/j.breast.2015.10.010
https://doi.org/10.1016/j.breast.2015.10...
99 Manning AT, Sacchini VS. Conservative mastectomies for breast cancer and risk-reducing surgery: the Memorial Sloan Kettering Cancer Center experience. Gland Surg. 2016;5(01):55-62. Doi: 10.3978/j.issn.2227-684X.2015.10.02
https://doi.org/10.3978/j.issn.2227-684X...
evaluating the outcomes of patients who underwent NSM were performed with heterogeneous samples, including patients with invasive and intraepithelial tumors, and focusing on NSM with immediate breast reconstruction using prosthetic implants (saline-filled implants or tissue expanders) and autologous tissue flaps.1010 Leclère FM, Panet-Spallina J, Kolb F, Garbay JR, Mazouni C, Leduey A, et al. Nipple-sparing mastectomy and immediate reconstruction in ductal carcinoma in situ: a critical assessment with 41 patients. Aesthetic Plast Surg. 2014;38(02):338-343. Doi: 10.1007/s00266-013-0236-8
https://doi.org/10.1007/s00266-013-0236-...
1111 Lago V, Maisto V, Gimenez-Climent J, Vila J, Vazquez C, Estevan R. Nipple-sparingmastectomy as treatment for patients with ductal carcinoma in situ: A 10-year follow-up study. Breast J. 2018;24 (03):298-303. Doi: 10.1111/tbj.12947
https://doi.org/10.1111/tbj.12947...
1212 Wu ZY, Kim HJ, Lee J, Chung IY, Kim JS, Lee SB, et al. Recurrence outcomes after nipple-sparing mastectomy and immediate breast reconstruction in patients with pure ductal carcinoma in situ. Ann Surg Oncol. 2020;27(05):1627-1635. Doi: 10.1245/s10434-019-08184-z
https://doi.org/10.1245/s10434-019-08184...
1313 Galimberti V, Morigi C, Bagnardi V, Corso G, Vicini E, Fontana SK, et al. Oncological outcomes of nipplesparing mastectomy: a single-center experience of 1989 patients. Ann Surg Oncol. 2018;25(13):3849-3857. Doi: 10.1245/s10434-018-6759-0
https://doi.org/10.1245/s10434-018-6759-...
The recovery of breast reconstruction following mastectomy is a concern for surgeons. Kim et al.1414 Kim SW, Lee HK, Kang SM, Kang TH, Yoon CS, Ko SS, et al. Shortterm outcomes of immediate breast reconstruction using an implant or tissue expander after mastectomy in breast cancer patients. Breast Cancer. 2016;23(02):279-285. Doi: 10.1007/ s12282-014-0570-y showed that NSM with immediate breast reconstruction with implants is a safe and feasible procedure associated with good cosmetic results. In 2017, most of the NSM performed in Italy were reconstructed using prothesis and direct-to-implant reconstruction was gaining acceptance.1515 Casella D, Calabrese C, Orzalesi L, Gaggelli I, Cecconi L, Santi C, et al. Current trends and outcomes of breast reconstruction following nipple-sparing mastectomy: results from a national multicentric registry with 1006 cases over a 6-year period. Breast Cancer. 2017;24(03):451-457. Doi: 10.1007/s12282-016-0726-z
https://doi.org/10.1007/s12282-016-0726-...
The aim of the present study was to retrospectively evaluate the oncological safety, complications and survival rates of patients diagnosed with pure DCIS who underwent NSM with immediate breast reconstruction with prostheses.

Methods

The present retrospective study was performed according to ethical guidelines, and received approval from the Ethics in Research Committee of Hospital São Lucas and Hospital Albert Einstein. Patients with complete medical records were included, and all of them had beene operated on by the main author of the present study. Informed consent was waived by the institutional review board because of the retrospective nature of the study.

Between January 2004 and December 2018, 345 NSMs with immediate breast reconstruction were performed, 77 for in situ tumors. We excluded 5 patients who underwent reconstruction with tissue expanders, 4 patients with recurrence after BCS for invasive cancer, and 2 patients due to loss to follow-up (less than 3 months of follow-up). Patients who underwent risk-reduction NSM with an accidental finding of DCIS were included in the study. The tumor-to-nipple distance and tumor size were not exclusion criteria. Sentinel lymph node biopsy (SLNB) was performed for all patients in the affected breast. All patients were operated on by the same surgeon. The data was retrospectively evaluated through the medical charts, and the follow-up of the patients was updated during the appointments.

We analyzed 67 patients diagnosed with pure DCIS who underwent NSM with immediate implant-based reconstruction. The indications for NSM were risk-reduction breast surgery with an accidental finding of DCIS (n = 4; 6%), multifocal disease (n = 16; 23.9%), compromised margins after BCS (n = 11; 16.4%), tumors ≥ 40 mm (n = 16; 23.9%), and unfavorable relationships between tumor size and breast size or patient preference (n = 20; 29.8%). The postoperative complications were defined as hematoma requiring drainage, infection, prolonged seroma formation, skin necrosis, partial nipple necrosis, total nipple necrosis, and prothesis extrusion.

The patients were followed by means of clinical examinations every six to twelve months for the first five years, followed by yearly exams thereafter. Imaging exams, such as ultrasonography, magnetic resonance, or mammography, were required based on patient complaints and after a physical examination.

The recurrences were diagnosed in clinical examinations or imaging exams, and all of the breast and axillary recurrences were biopsied and sent to pathology to confirm the diagnosis. Invasive or in situ local recurrence was defined as recurrence in the same breast and/or ipsilateral axilla.

All procedures were performed under general anesthesia using a periareolar, vertical, or inframammary incision. The NSM skin incision was chosen in accordance with breast type and method of reconstruction, and the majority of them were in the inframammary fold. The glandular tissue was removed respecting the plane of the subcutaneous fascia, carefully resecting breast tissue but leaving a sufficient amount of fat tissue to preserve blood flow and avoid flap necrosis. It is important to highlight that flap thickness varies among patients, since it is based on the amount of subcutaneous fat present in the breast.

An intraoperative histopathological examination of frozen sections of the retroareolar tissue was performed to confirm the absence of DCIS in the retroareolar margin, and all the patients presented tumor-negative margins. No cutoffs for margin status were used, and the postoperative histopathological examination confirmed that all samples were tumor-free.

Patients with DCIS were submitted to SLNB, but not in the breast that underwent contralateral mastectomy. Immediate breast reconstruction was performed using subpectoral definitive prosthetic implants in every patient (Figs. 1,2,3,4,5,6,7,8). None of these patients required the use of acellular dermal matrix implants.

Fig. 1
Preoperative bilateral NSM.

Fig. 2
Inframammary skin incision.

Fig. 3
All breast tissue removed.

Fig. 4
Inclusion of silicone implant.

Fig. 5
Breast reconstructed with silicone implant.

Fig. 6
Postoperative bilateral NSM with immediate breast reconstruction with permanent silicone implants.

Fig. 7
Preoperative imaging exam.

Fig. 8
Postoperative imaging exam of the reconstructed breast with permanent silicone implants.

The statistical analysis was performed with information from 67 patients. Descriptive statistics was used to summarize the characteristics of the patients. The quantitative variables were expressed as means and ranges, while the categorical variables were expressed as absolute and relative frequencies. Disease-free survival (DFS) was summarized using the Kaplan-Meier method and displayed graphically. The significance level for statistical differences was set at 0.05. The statistical analysis was performed using the SAS (SAS Institute, Inc., Cary, NC, US) statistical software, version 9.4.

Results

We analyzed 67 patients who were diagnosed with pure DCIS and underwent 127 NSMs with implant-based immediate reconstruction between 2004 and 2018. The mean age of the patients was 46.8 years (range 30–75 years). The clinicopathological characteristics and treatment are listed in Table 1.

Table 1
Patient, tumor, and treatment characteristics (n = 67)

Bilateral procedures were performed in 60 (89.5%) patients, and 7 (10.5%) surgeries were unilateral. In total, 2 (3.4%) patients underwent bilateral surgery due to the diagnosis of DCIS in both breasts, 10 (16.7%) patients presented a diagnosis of atypical hyperplasia in the contralateral breast, 7 (11.7%) patients were mutation carriers with high risk of developing breast cancer, and 41 (68.2%) patients underwent bilateral NSM by choice, looking for better symmetry and a better esthetic result. All patients underwent SLNB in the affected breast, and the lymph node was free of metastasis in every case. Unifocal lesions were found in 36 (53.7%) patients, and multifocal tumors were found in 31 (46.3%) cases. Most of the tumors were high-grade; 38.9% were grade-2, and 47.8%, grade-3. Only 10.4% of the tumors were grade-1 and data was missing from from 2 (2.9%) tumors. A total of 36 (53.7%) patients presented estrogen-receptor-positive (ER + ) tumors, 17 (25.4%), ER-negative (ER-) tumors, and data was missing from 14 (20.9%) tumors. Out of the 36 patients with ER+ tumors, 14 (38.9%) underwent hormone therapy (HT), and for the others patients the treatment was not indicated based on the risk/benefit of the hormonal treatment.

Immediate breast reconstruction was performed with silicone-filled implants for all patients. Frozen sections of the areolar flap's undersurface was performed for every patient, and the samples were tumor-free in the final analysis.

In the 69 procedures performed for DCIS, 3 (4.3%) complications occurred, including 2 (2.9%) cases of hematomas that required drainage, and 1 (1.4%) partial nipple necrosis. Full-thickness necrosis was defined as necrosis in the entire dermis requiring surgical intervention, such as debridement, delayed repair, and skin grafting, and partial nipple necrosis was defined as injuries that heal with conservative wound care, since they do not extend to the entire thickness of the dermis.

Adjuvant hormone therapy was administered to 14 patients (20.9%), and RT was administered to 12 patients (18%): because of the large extent of the superficial distribution of the DCIS, even with free margins. For one patient, the RT data were missing, and one patient chose not to undergo it. None of the patients submitted to RT presented complications. The patient with partial nipple necrosis presented type-1 diabetes.

During the mean follow-up of 60 months (range: 3 to 183 months), 6 (8.9%) patients presented local recurrence, and 2 (2.95%) cases occurred in the nipple-areola complex. From the 6 relapses, 4 were DCIS and 2 were invasive ductal carcinoma (IDC). None of the patients who presented local recurrence underwent RT, and only 1 patient was older than 50 years old.

Details regarding local recurrence are shown in Table 2 and Table 3. None of the patients presented metastasis. The DFS rate was of 90% (Fig. 9), and all patients were alive at the end of the 60-month follow-up.

Fig. 9
Disease-free survival (n = 67).

Table 2
Local recurrence rates

Table 3
Characteristics of the local recurrence

Discussion

Nipple-sparing mastectomy is a conservative approach for breast cancer with good rates of esthetic satisfaction from the patients.1616 Howard MA, Sisco M, Yao K, Winchester DJ, Barrera E, Warner J, et al. Patient satisfaction with nipple-sparing mastectomy: A prospective study of patient reported outcomes using the BREAST-Q. J Surg Oncol. 2016;114(04):416-422. Doi: 10.1002/ jso.243641717 Bailey CR, Ogbuagu O, Baltodano PA, Simjee UF, Manahan MA, Cooney DS, et al. Quality-of-life outcomes improve with nipplesparing mastectomy and breast reconstruction. Plast Reconstr Surg. 2017;140(02):219-226. Doi: 10.1097/PRS.000000000 0003505
https://doi.org/10.1097/PRS.000000000...
The main concerns regarding the use of NSM are nipple necrosis and local and nipple recurrences. Different authors11 Petit JY, Veronesi U, Orecchia R, Curigliano G, Rey PC, Botteri E, et al. Risk factors associated with recurrence after nipple-sparing mastectomy for invasive and intraepithelial neoplasia. Ann Oncol. 2012;23(08):2053-2058. Doi: 10.1093/annonc/mdr566
https://doi.org/10.1093/annonc/mdr566...
33 Orzalesi L, Casella D, Santi C, Cecconi L, Murgo R, Rinaldi S, et al. Nipple sparing mastectomy: Surgical and oncological outcomes from a national multicentric registry with 913 patients (1006 cases) over a six year period. Breast. 2016;25:75-81. Doi: 10.1016/j.breast.2015.10.010
https://doi.org/10.1016/j.breast.2015.10...
99 Manning AT, Sacchini VS. Conservative mastectomies for breast cancer and risk-reducing surgery: the Memorial Sloan Kettering Cancer Center experience. Gland Surg. 2016;5(01):55-62. Doi: 10.3978/j.issn.2227-684X.2015.10.02
https://doi.org/10.3978/j.issn.2227-684X...
1111 Lago V, Maisto V, Gimenez-Climent J, Vila J, Vazquez C, Estevan R. Nipple-sparingmastectomy as treatment for patients with ductal carcinoma in situ: A 10-year follow-up study. Breast J. 2018;24 (03):298-303. Doi: 10.1111/tbj.12947
https://doi.org/10.1111/tbj.12947...
1818 Shimo A, Tsugawa K, Tsuchiya S, Yoshie R, Tsuchiya K, Uejima T, et al. Oncologic outcomes and technical considerations of nipplesparing mastectomies in breast cancer: experience of 425 cases from a single institution. Breast Cancer. 2016;23(06):851-860. Doi: 10.1007/s12282-015-0651-6
https://doi.org/10.1007/s12282-015-0651-...
1919 Headon HL, Kasem A, Mokbel K. The oncological safety of nipplesparing mastectomy: a systematic review of the literature with a pooled analysis of 12,358 procedures. Arch Plast Surg. 2016;43 (04):328-338. Doi: 10.5999/aps.2016.43.4.328
https://doi.org/10.5999/aps.2016.43.4.32...
have reported rates of local and nipple-areola-complex recurrence after NSM ranging from 0% to 11.6% and 0.7% to 4.8% respectively. The reported incidence of nipple necrosis after NSM ranges from 1.4% to 5.9%.33 Orzalesi L, Casella D, Santi C, Cecconi L, Murgo R, Rinaldi S, et al. Nipple sparing mastectomy: Surgical and oncological outcomes from a national multicentric registry with 913 patients (1006 cases) over a six year period. Breast. 2016;25:75-81. Doi: 10.1016/j.breast.2015.10.010
https://doi.org/10.1016/j.breast.2015.10...
1818 Shimo A, Tsugawa K, Tsuchiya S, Yoshie R, Tsuchiya K, Uejima T, et al. Oncologic outcomes and technical considerations of nipplesparing mastectomies in breast cancer: experience of 425 cases from a single institution. Breast Cancer. 2016;23(06):851-860. Doi: 10.1007/s12282-015-0651-6
https://doi.org/10.1007/s12282-015-0651-...
1919 Headon HL, Kasem A, Mokbel K. The oncological safety of nipplesparing mastectomy: a systematic review of the literature with a pooled analysis of 12,358 procedures. Arch Plast Surg. 2016;43 (04):328-338. Doi: 10.5999/aps.2016.43.4.328
https://doi.org/10.5999/aps.2016.43.4.32...
However, most of the published studies analyzed the rates of complications and recurrence after NSM in heterogeneous samples with invasive and noninvasive tumors.11 Petit JY, Veronesi U, Orecchia R, Curigliano G, Rey PC, Botteri E, et al. Risk factors associated with recurrence after nipple-sparing mastectomy for invasive and intraepithelial neoplasia. Ann Oncol. 2012;23(08):2053-2058. Doi: 10.1093/annonc/mdr566
https://doi.org/10.1093/annonc/mdr566...

The increasing number of NSMs has expanded the classic indications, and the number of NSMs for patients with DCIS has been increasing. Most of the studies1010 Leclère FM, Panet-Spallina J, Kolb F, Garbay JR, Mazouni C, Leduey A, et al. Nipple-sparing mastectomy and immediate reconstruction in ductal carcinoma in situ: a critical assessment with 41 patients. Aesthetic Plast Surg. 2014;38(02):338-343. Doi: 10.1007/s00266-013-0236-8
https://doi.org/10.1007/s00266-013-0236-...
1111 Lago V, Maisto V, Gimenez-Climent J, Vila J, Vazquez C, Estevan R. Nipple-sparingmastectomy as treatment for patients with ductal carcinoma in situ: A 10-year follow-up study. Breast J. 2018;24 (03):298-303. Doi: 10.1111/tbj.12947
https://doi.org/10.1111/tbj.12947...
1212 Wu ZY, Kim HJ, Lee J, Chung IY, Kim JS, Lee SB, et al. Recurrence outcomes after nipple-sparing mastectomy and immediate breast reconstruction in patients with pure ductal carcinoma in situ. Ann Surg Oncol. 2020;27(05):1627-1635. Doi: 10.1245/s10434-019-08184-z
https://doi.org/10.1245/s10434-019-08184...
available in the literature regarding the rates of nipple complications and the oncological safety of NSM for patients diagnosed with pure DCIS used different techniques of breast reconstruction, such as prosthetic implants or an autologous tissue flap. Complications related to breast reconstruction after mastectomy are still a concern. The use of immediate implant-based reconstruction after NSM seems to be safe and feasible, and has been growing worldwide.1414 Kim SW, Lee HK, Kang SM, Kang TH, Yoon CS, Ko SS, et al. Shortterm outcomes of immediate breast reconstruction using an implant or tissue expander after mastectomy in breast cancer patients. Breast Cancer. 2016;23(02):279-285. Doi: 10.1007/ s12282-014-0570-y1515 Casella D, Calabrese C, Orzalesi L, Gaggelli I, Cecconi L, Santi C, et al. Current trends and outcomes of breast reconstruction following nipple-sparing mastectomy: results from a national multicentric registry with 1006 cases over a 6-year period. Breast Cancer. 2017;24(03):451-457. Doi: 10.1007/s12282-016-0726-z
https://doi.org/10.1007/s12282-016-0726-...
A retrospective study2020 Radovanovic Z, Ranisavljevic M, Radovanovic D, Vicko F, Ivkovic- Kapicl T, Solajic N. Nipple-sparing mastectomy with primary implant reconstruction: surgical and oncological outcome of 435 breast cancer patients. Breast Care (Basel). 2018;13(05): 373-378. Doi: 10.1159/000489317
https://doi.org/10.1159/000489317...
with 435 patients who underwent NSM for invasive and in situ tumors with primary implant reconstruction reported a rate of 5.9% of skin flap ischemia/necrosis. In the present study, we pnly analyzed patients with immediate implant-based reconstruction, and we found a rate of 1.4% of nipple necrosis, which is lower than the rates in most of the previous reports of NSM for DCIS, including a large series1313 Galimberti V, Morigi C, Bagnardi V, Corso G, Vicini E, Fontana SK, et al. Oncological outcomes of nipplesparing mastectomy: a single-center experience of 1989 patients. Ann Surg Oncol. 2018;25(13):3849-3857. Doi: 10.1245/s10434-018-6759-0
https://doi.org/10.1245/s10434-018-6759-...
published in 2018 that reported a rate of nipple-areola-complex necrosis of 2.2% for in situ cancer. Our cumulative complication rates were also lower than those reported in previous studies, with only 4.3% of complications in 69 NSM procedures performed for DCIS. Leclère et al.1010 Leclère FM, Panet-Spallina J, Kolb F, Garbay JR, Mazouni C, Leduey A, et al. Nipple-sparing mastectomy and immediate reconstruction in ductal carcinoma in situ: a critical assessment with 41 patients. Aesthetic Plast Surg. 2014;38(02):338-343. Doi: 10.1007/s00266-013-0236-8
https://doi.org/10.1007/s00266-013-0236-...
reported a rate of 17% of nipple-areola-complex necrosis and 5.3% of local recurrence in the long-term follow-up of 41 patients diagnosed with DCIS who underwent NSM. Despite the high rate of nipple-areola-complex necrosis, the locoregional recurrence rate for DCIS was low; however, the loss of patients over the mean follow-up period of 7.1 years (only 46% completed the follow-up) and the subsequent small sample size were limitations of the study.1010 Leclère FM, Panet-Spallina J, Kolb F, Garbay JR, Mazouni C, Leduey A, et al. Nipple-sparing mastectomy and immediate reconstruction in ductal carcinoma in situ: a critical assessment with 41 patients. Aesthetic Plast Surg. 2014;38(02):338-343. Doi: 10.1007/s00266-013-0236-8
https://doi.org/10.1007/s00266-013-0236-...
In 2018, Lago et al.1111 Lago V, Maisto V, Gimenez-Climent J, Vila J, Vazquez C, Estevan R. Nipple-sparingmastectomy as treatment for patients with ductal carcinoma in situ: A 10-year follow-up study. Breast J. 2018;24 (03):298-303. Doi: 10.1111/tbj.12947
https://doi.org/10.1111/tbj.12947...
evaluated the oncological safety of NSM for DCIS in 69 patients with a 10-year follow-up. The authors reported a rate of local relapse of 11.6%, and a low rate of nipple-areola-complex recurrence (1.4%). They did not observe cases of nipple necrosis after surgery either.1111 Lago V, Maisto V, Gimenez-Climent J, Vila J, Vazquez C, Estevan R. Nipple-sparingmastectomy as treatment for patients with ductal carcinoma in situ: A 10-year follow-up study. Breast J. 2018;24 (03):298-303. Doi: 10.1111/tbj.12947
https://doi.org/10.1111/tbj.12947...
The current study evidenced a rate of locoregional recurrence (LRR) of 4.5%, and a rate of nipple-areola-complex recurrence of 3% in the 10-year follow-up. The authors demonstrated that characteristics such as negative progesterone receptor status, and tumor size ≥ 4 cm were related to an increased risk of developing LRR. Interestingly, margin status presented no statistical significance associated with LRR.1212 Wu ZY, Kim HJ, Lee J, Chung IY, Kim JS, Lee SB, et al. Recurrence outcomes after nipple-sparing mastectomy and immediate breast reconstruction in patients with pure ductal carcinoma in situ. Ann Surg Oncol. 2020;27(05):1627-1635. Doi: 10.1245/s10434-019-08184-z
https://doi.org/10.1245/s10434-019-08184...

At a mean follow-up of 60 months, our local recurrence rate of 8.9%, including the nipple-areola-complex recurrence rate of 2.95%, was higher when compared with that of previous studies (Chart 1).

Chart 1
Outcomes of NSM patients in previous studies

All of the relapses in the tumor bed and nipple areola complex were cases of DCIS, and the two recurrences in another quadrant in the same breast were IDCs. We consider all patients with no involvement of the skin or nipple areola complex candidates for NSM; therefore, the characteristics of our patients, such as young age, tumors larger than 40 mm, multifocal tumors, and no criteria for the distance between the lesion and the skin or the nipple areola complex (since all margins were free) might have influenced the increased rate of local relapse found in the present study. Wu et al.1212 Wu ZY, Kim HJ, Lee J, Chung IY, Kim JS, Lee SB, et al. Recurrence outcomes after nipple-sparing mastectomy and immediate breast reconstruction in patients with pure ductal carcinoma in situ. Ann Surg Oncol. 2020;27(05):1627-1635. Doi: 10.1245/s10434-019-08184-z
https://doi.org/10.1245/s10434-019-08184...
reported that tumor size ≥ 4 cm was risk factor for LRR in the univariate analysis; however, in the multivariate analysis, the statistical significance was borderline (p = 0.064).1212 Wu ZY, Kim HJ, Lee J, Chung IY, Kim JS, Lee SB, et al. Recurrence outcomes after nipple-sparing mastectomy and immediate breast reconstruction in patients with pure ductal carcinoma in situ. Ann Surg Oncol. 2020;27(05):1627-1635. Doi: 10.1245/s10434-019-08184-z
https://doi.org/10.1245/s10434-019-08184...
We observed a tendency of tumor multifocality to be a risk factor for local recurrence (p = 0.061); however, due to the small sample size of the present study, we found no statistical difference when analyzing correlations between local recurrence and the clinicopathological characteristics and treatments. No cases of distant metastasis were observed in our patients.

For patients who underwent NSM, the benefit of RT has not been confirmed yet. However, a Cochrane review2121 Goodwin A, Parker S, Ghersi D, Wilcken N. Post-operative radiotherapy for ductal carcinoma in situ of the breast. Cochrane Database Syst Rev. 2013;(11):CD000563. Doi: 10.1002/ 14651858.CD000563.pub7 confirmed the benefit of RT for all patients diagnosed with DCIS and submitted to BCS. Therefore, we chose to apply RT in patients with larger tumors. None of the patients who relapsed underwent RT after the first surgery. Radiotherapy was performed after the recurrence, and only one patient presented a new recurrence after it. Radiotherapy after BCS is the gold standard treatment for cases of early breast cancer, including DCIS. We hypothesize a possible relationship between RT and a reduced risk of developing ipsilateral breast cancer recurrence after NSM for DCIS, but new studies are necessary to confirm this potential benefit.2121 Goodwin A, Parker S, Ghersi D, Wilcken N. Post-operative radiotherapy for ductal carcinoma in situ of the breast. Cochrane Database Syst Rev. 2013;(11):CD000563. Doi: 10.1002/ 14651858.CD000563.pub7

As observed in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17 and B-24 randomized clinical trials for DCIS,2222 Wapnir IL, Dignam JJ, Fisher B, Mamounas EP, Anderson SJ, Julian TB, et al. Long-termoutcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst. 2011;103(06): 478-488. Doi: 10.1093/jnci/djr027
https://doi.org/10.1093/jnci/djr027...
young patients with DCIS have an increased risk of developing invasive ipsilateral breast tumor recurrence; in the present study, only 1 patient who prsented relapse was older than 50 years of age. In our population, there were 48 patients aged ≤ 50 years, and analyzing only this population, we found a local recurrence rate of 10.4%. Approximately 19% of the young patients underwent RT; however, none of the patients who presented relapse underwent RT. The use of RT for local control in these patients might be an option.

The use of hormone receptors (ER, progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2]) as prognostic biomarkers is still controversial for DCIS. Some authors have observed an association between HER2 positive and ER- DCIS with increased risk of recurrence, whereas in other studies these associations have not observed.2323 Williams KE, Barnes NLP, Cramer A, Johnson R, Cheema K,Morris J, et al. Molecular phenotypes of DCIS predict overall and invasive recurrence. Ann Oncol. 2015;26(05):1019-1025. Doi: 10.1093/ annonc/mdv0622424 Rakovitch E, Nofech-Mozes S, HannaW, Narod S, ThiruchelvamD, Saskin R, et al. HER2/neu and Ki-67 expression predict noninvasive recurrence following breast-conserving therapy for ductal carcinoma in situ. Br J Cancer. 2012;106(06):1160-1165. Doi: 10.1038/bjc.2012.41
https://doi.org/10.1038/bjc.2012.41...
2525 Zhang X, Dai H, Liu B, Song F, Chen K. Predictors for local invasive recurrence of ductal carcinoma in situ of the breast: a metaanalysis. Eur J Cancer Prev. 2016;25(01):19-28. Doi: 10.1097/ CEJ.00000000000001312626 Poulakaki N, Makris GM, Battista MJ, Böhm D, Petraki K, Bafaloukos D, et al. Hormonal receptor status, Ki-67 and HER2 expression: Prognostic value in the recurrence of ductal carcinoma in situ of the breast? Breast. 2016;25:57-61. Doi: 10.1016/j.breast.2015.10.007
https://doi.org/10.1016/j.breast.2015.10...
Endocrine therapy is indicated after BCS for patients with ER+ DCIS aiming to reduce the risk of local relapse and contralateral breast recurrence.2222 Wapnir IL, Dignam JJ, Fisher B, Mamounas EP, Anderson SJ, Julian TB, et al. Long-termoutcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst. 2011;103(06): 478-488. Doi: 10.1093/jnci/djr027
https://doi.org/10.1093/jnci/djr027...
In the sample of the present study, HT was not indicated for all patients with ER+ tumors: ∼ 40% were treated with the hormone treatment. All patients that relapsed presented ER+ tumors, and half of them underwent hormone treatment. We evaluated the risk/benefit of hormone treatment for each patient presenting ER+ DCIS, considering the side effects and the risk of recurrence based on tumor size, grade, and young age. Indeed, since of all these patients were submitted to NSM and most of them underwent bilateral procedures, we considered that the risk of local and contralateral recurrence was diminished, and did not indicate HT for all ER+ patients

In the present study, all patients were alive by the end of the follow-up, and this result is consistent with the NSM findings reported by Lago et al.,1111 Lago V, Maisto V, Gimenez-Climent J, Vila J, Vazquez C, Estevan R. Nipple-sparingmastectomy as treatment for patients with ductal carcinoma in situ: A 10-year follow-up study. Breast J. 2018;24 (03):298-303. Doi: 10.1111/tbj.12947
https://doi.org/10.1111/tbj.12947...
2018, and Wu et al.,1212 Wu ZY, Kim HJ, Lee J, Chung IY, Kim JS, Lee SB, et al. Recurrence outcomes after nipple-sparing mastectomy and immediate breast reconstruction in patients with pure ductal carcinoma in situ. Ann Surg Oncol. 2020;27(05):1627-1635. Doi: 10.1245/s10434-019-08184-z
https://doi.org/10.1245/s10434-019-08184...
2020. In the long-term follow-up, Lago et al.1111 Lago V, Maisto V, Gimenez-Climent J, Vila J, Vazquez C, Estevan R. Nipple-sparingmastectomy as treatment for patients with ductal carcinoma in situ: A 10-year follow-up study. Breast J. 2018;24 (03):298-303. Doi: 10.1111/tbj.12947
https://doi.org/10.1111/tbj.12947...
and Wu et al.1212 Wu ZY, Kim HJ, Lee J, Chung IY, Kim JS, Lee SB, et al. Recurrence outcomes after nipple-sparing mastectomy and immediate breast reconstruction in patients with pure ductal carcinoma in situ. Ann Surg Oncol. 2020;27(05):1627-1635. Doi: 10.1245/s10434-019-08184-z
https://doi.org/10.1245/s10434-019-08184...
indicated overall survival (OS) rates of 98.6% and 98.5% respectively in patients diagnosed with DCIS who underwent NSM. Despite the expanded NSM indications applied in the present study, such as patients with compromised margins after a previous surgery, large and high-grade tumors, and no cutoff for distance between the tumor and the nipple-areola complex, the relapses did not interfere with patient survival in 60 months of follow-up.

The present study has several limitation,s such as the retrospective design of the analysis, the small sample size, and the short follow-up. External validation is needed to confirm our results.

Conclusion

At a mean follow-up of 60 months, we demonstrated low complication rates and good survival in 67 patients who underwent NSM for pure DCIS with immediate implant-based reconstruction. The local recurrence rate was high, and characteristics such as young age, multifocal tumors, and no criteria for the distance between the lesion and the skin or the nipple-areola complex might have influenced the relapses found in the present study. We observed that the multifocality of the tumor might be a risk factor for local relapse; however further studies are needed to confirm this correlation. The present study supports that expanding the indication for NSM with immediate implant-based breast reconstruction to treat patients diagnosed with pure DCIS is acceptable when BCS is not an option and the patient wishes to preserve the nipple-areola complex.

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Publication Dates

  • Publication in this collection
    27 June 2022
  • Date of issue
    Apr 2022

History

  • Received
    28 Apr 2021
  • Accepted
    03 Nov 2021
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