1. Introduction

Since the 1990s, there has been a steady increase in breast-conserving surgeries associated with the development of oncoplasty. Nevertheless, total mastectomies for breast cancer (BC) are still indicated for 12 to 30% of patients and up to 40% [1-4]. It was 12.2% in a large French cohort of invasive BC [5]. The complication rates varies between 5% and 61% in the literature [6]. However, it is difficult to compare results between the different studies because of the large disparities in immediate breast reconstruction (IBR) rates and techniques, the complications reported, the indications for mastectomies and the monitoring time. However, increased body mass index (BMI) and smoking were reported factors to increase the risk of complications as well as previous radiotherapy and operative time [7]. IBR rate increase during the last years [8] in order to improve quality of life [9] and implant-based reconstruction was the most commonly performed procedure [10-12]. Several new procedures are been developed, as robotic procedures [13-16], pre-pectoral implant-IBR with or without mesh [7, 17-20]. Moreover, in recent year’s nipple sparing mastectomy (NSM) increase for prophylactic mastectomies [21], for local recurrence [22] and for primary BC [23, 24]. Generally, the NSM studies reported better aesthetic results than skin sparing mastectomy (SSM) and better quality of life [25-27]. NSM with IBR is consider today as a valid procedure for prophylactic mastectomy [21, 28-31] and an acceptable option for breast cancer (BC) therapeutic mastectomy [32-34]. The time to delivery adjuvant therapy after mastectomy is a key point to optimized oncologic treatments and has been few analyzed specifically for mastectomies with or without IBR [35]. In this study, we report our experience at the Paoli Calmettes Institute, by analyzing the data collected over 55 months from 2016 to 2020 to assess IBR rate, complication rate, interval-time to adjuvant therapy and to establish a predictive score for postoperative complications.

2. Materials and Methods

We included all mastectomies performed from January 2016 to July 2020, with or without IBR from institutional database (study: MAST-C-IPC 2021-024). A retrospective analysis with a prospective data collection was perform in order to determine the immediate surgical results and interval-time to adjuvant treatments.

2.1 Patients

Data were collected regarding patients: age, BMI, ASA (American Society of Anesthesiologists) status, diabetes, tobacco use, treatments received (neo-adjuvant or adjuvant chemotherapy, radiotherapy, endocrine therapy), year of treatment, type of mastectomy (nipple-sparing mastectomy (NSM), skin-sparing mastectomy (SSM), or classic if no reconstruction), modalities of IBR, and complications appeared in 90 days following the operation. Thirteen surgeons performed mastectomies.

Complications were analyzed according to the Clavien-Dindo classification [36]. The operative time was recorded from skin incision to skin closure collected on the anesthetic data. The length of postoperative stay was reported from the surgery day to the discharge day from hospital. A loco regional anesthesia with pectoralis block was systematically perform. Interval-times between surgery and adjuvant chemotherapy (AC) or post-mastectomy radiotherapy (PMRT) were analyze.

2.2 Statistics

Quantitative criteria were analyze with median, mean, 95% CI. Comparisons were determined using the Chi-2 test for qualitative criteria and t-test for quantitative criteria. Factors significantly associated with criteria analyzed were determine by a binary logistic regression adjusted for all significant variables identified by the univariate analysis. We calculated a predictive score for complications using the odds ratio derived from logistic regression. The performance of this score was analyze by calculating the AUC (Area under the Curve) value. Statistical significance was set as p ≤ 0.05. Analyses were perform with SPSS version 16.0 (SPSS Inc., Chicago, Illinois).

3. Results

3.1 Population

During a period of 55 months, 2,112 mastectomies were perform for 1,983 patients: 1,748 mastectomies for primary BC, 219 for local recurrence and 145 for prophylactic mastectomies. Mastectomies were realized after ipsilateral surgery for first non-in-sano conservative surgery in 430 patients (430/1748: 25%). Bilateral mastectomies (258 mastectomies) were perform for 129 patients (12.2%): for primary BC in 56.6%, for local recurrence in 8.9% and for prophylactic mastectomy in 34.5%.

Previous radiotherapy was perform for 287 mastectomies (13.6%): 219 for local recurrences after conservative treatment, 57 for reversals therapeutic sequence (neo-adjuvant chemotherapy [NAC] and neo-adjuvant radiotherapy [N-RTH]) and 11 for a history of irradiation as treatment of Hodgkin's disease. For patients with IBR, a high rate of NSM was achieved (399/851: 46.9%).

3.2 IBR

The IBR rate was 40.5%: 35.4% (618/1,748) for primary BC, 47.9% (105/219) for local recurrences and 91% (132/145) for prophylactic mastectomies. The annual IBR rates according to years of surgery were not significantly different. Number of mastectomies with or without IBR for each surgeon is report in Supplementary Figure 1. Characteristics of patients according to IBR status are report in Table 1. In univariate analysis, several criteria were significantly associated with or without IBR (Tables 1, 2). Tobacco use did not appear as a significant factor to perform an IBR.

Supplementary Figure 1: Number of mastectomies with or without IBR for each surgeon.

Legend: IBR: immediate breast reconstruction

Legend: IBR: immediate breast reconstruction, ASA: American Society of Anesthesiologists, BMI: Body mass index, POHLS: Post-operative hospitalization length, NAC: neo-adjuvant chemotherapy, N-RTH: neo-adjuvant radiotherapy, DCIS: ductal carcinoma in-situ, NST: non-specific invasive carcinoma, BC: breast cancer, SLNB: sentinel lymph node biopsy, ALND: axillary lymph node dissection.

Table 1: Characteristics of all patients and according to immediate breast reconstruction (IBR) or no-IBR.

Legend: IBR: immediate breast reconstruction, BMI: Body mass index, POHLS: Post-operative hospitalization length.

Table 2: Results (median, mean and 95% confidence interval) of quantitative variables.

Legend: IBR: immediate breast reconstruction, ASA: American Society of Anesthesiologists status, NAC: neo-adjuvant chemotherapy, RTH: radiotherapy.

Table 3: Binary logistic regression analysis: Factors associated with immediate breast reconstruction (IBR) in comparison with patients with no-IBR.

In binary logistic regression, IBR were significantly associated with age (less IBR for patients >50 years), ASA status (less IBR for ASA 2-3 versus ASA 1), diabetes (less IBR for diabetic patients), BMI (less IBR for BMI >25), mastectomy weight (less IBR for weight >300gr), neo-adjuvant treatment (less IBR for neo-adjuvant treatment), histological status (more IBR for preoperative diagnosis of in situ carcinomas and prophylaxis, and less IBR for local recurrence), and history of radiotherapy (Table 3).

3.3 Complications

The complication rate was 31.90% (n=675): 29.9% for IBR group and 33.3% for no-IBR group, including 23.2% of grade 3 complications requiring revision surgery. The different grades of 599 breast complications were distributed as 59.6% grade 1 (n=357), 11.0% grade 2 (n=66), 29.2% grade 3 (n=175) and 0.0017% grade 4 (n=1). Others complications were in relation with dorsal complication for latissimus dorsi-flap reconstruction.

Criteria significantly associated with complications in univariate analysis are reported in Table 4, with a significantly higher rate of grade 2 and 3 complications for ASA score ≥2, BMI>= 30, mastectomy weight >300g. In binary logistic regression, complications were significantly associated with year of treatment (fewer complications during the last 2 years), smokers (more complications for smoker patients), age (more complications for patients >50 years), radiotherapy (more complications for patients with a previous radiotherapy), axillary lymph-node dissection associated with mastectomy +/- IBR (more complications than SLNB or no axillary surgery) and mastectomy weight (more complications for weight >300g) (Table 5). In binary logistic regression, grade 2 and 3 complications were significantly more frequent only for a BMI >30 (OR=1.8, p=0.002). When adjusting the regression analysis for IBR or no IBR, there was no significant difference between IBR group and no-IBR group.

Legend: IBR: immediate breast reconstruction, ASA: American Society of Anesthesiologists, BMI: Body mass index, NSM: Nipple-sparing mastectomy, SSM: Skin-sparing mastectomy, BC: breast cancer, DCIS: ductal carcinoma in-situ, NST: non-specific invasive carcinoma NAC: neo-adjuvant chemotherapy, N-RTH: neo-adjuvant radiotherapy, SLNB: sentinel lymph node biopsy, ALND: axillary lymph node dissection.

Table 4: Significant criteria associated with complications in univariate analysis.

Legend: ASA: American Society of Anesthesiologists, BMI: Body mass index, POHLS: Post-operative hospitalization length, RTH: radiotherapy.

Table 5: Factors associated to complications and grade 2-3 breast complications in binary logistic regression.

Legend: IBR: immediate breast reconstruction.

Table 6: Breast complications according to grading for all patients and for patients with or without IBR.

Breast complications according to grading is report in Table 6: Seroma was the most frequent complication with 86.9% of grade 1, while there was 66.7% of grade 3 hematomas. There were 68.8% of grade 1 cutaneous complications. Cutaneous complications and infections were more frequent for IBR-patients and seromas were more frequent for no-IBR patients. Implant loss rate was 7.2% (44/609): 6.1% (34/560) for implant-based IBR and 20.4% (10/49) for latissimus dorsi-flap (LDF) IBR with implant (p <0.001).

Legend: 543 patients score 0 (25.7%), 621 score 1 (29.4%), 914 score 2 (43.3%) and 34 score 3 (1.6%).

For example, for a simplified C-score G1-2-3 value of 3, the postoperative complication rate was 64.7% with 26.5% of grade 2-3 complications versus 20.8% of complications for a simplified score of 0 with only 8.1% of grade 2 and 3 complications.

Figure 1: Complication rate and grade 2-3 complications according to the simplified score (C-score G1-2-3).

3.4 Complication score

The following equation to calculate a complication risk score was: smoker + age + previous radiotherapy + axillary surgery + mastectomy weight. Odds ratios described above were used to determine the value of each criterion: smoker (0 or 2), age (0 for age ≤50 years, 1.5 for age between 61 and 74, 2 for age ≥75 years), previous radiotherapy (0 or 2), axillary surgery (0 for SLNB or no axillary surgery and 1 for axillary lymph-node dissection), mastectomy weight (0 if ≤ 300g or 1.5 if > 300g). A simplified score (C-score-G1-2-3) was determined according to the result of the equation: 0 for values ≤ 1.5, 1 for values between 2 and 3, 2 for values between 3.5 and 6 and 3 for values ≥6.5. A significantly increasing rate of complications (p<0.0001) and grade 2-3 complications was observe for higher values of this simplified score (Figure 1) with 0.603 AUC value (95% CI: 0.577-0.628) for all complications.

A simplified score for Grade 2-3 breast complications (C-score-G2-3) was determined [simplified C-score-G1-2-3 value (0 to 3) + BMI (>=30=2, <30=0)]. A significant increase of Grade 2-3 breast complications rates was observed (p<0.0001) with 0.591 AUC value (95%CI: 0.552-0.630) (Figure 2).

Figure 2: Grade 2-3 complications rates according to the simplified score.

Legend: 519 patients score 0 (24.6%), 510 score 1 (24.1%), 771 score 2 (36.5%), 137 score 3 (6.5%), 167 score 4 (7.9%) and 8 score 5 (0.4%).

3.5 IBR types

Implant-based IBR were performed on 649 patients (76%), excluding one patient with exclusive lipofilling IBR. LDF-IBR was performing for 205 patients (24%) and was associated with an implant-based for 52 patients (22.2%). Factors significantly associated with IBR-LDF in univariate analysis are report in Supplementary Table 1. In binary logistic regression, higher rate of IBR by LDF was significantly associated with BMI ≥25, neo-adjuvant treatments, diabetes, radiotherapy, lobular histology, age between 51-74 years old, and lesser rate was significantly associated with SSM, bilateral mastectomies and prophylactic mastectomies (Supplementary Table 2).

Legend: IBR: immediate breast reconstruction, LDF: latissimus dorsi-flap, ASA: American Society of Anesthesiologists, BMI: Body mass index, RTH: radiotherapy, NSM: Nipple-sparing mastectomy, SSM: Skin-sparing mastectomy, BC: breast cancer, DCIS: ductal carcinoma in-situ, NST: non-specific invasive carcinoma NAC: neo-adjuvant chemotherapy, N-RTH: neo-adjuvant radiotherapy, SLNB: sentinel lymph node biopsy, ALND: axillary lymph node dissection.

Supplementary Table 1: Factors associated with LDF-IBR versus implant-IBR.

Legend: IBR: immediate breast reconstruction, LDF: latissimus dorsi-flap, ASA: American Society of Anesthesiologists, BMI: Body mass index, NAC: neo-adjuvant chemotherapy, NSM: Nipple-sparing mastectomy, SSM: Skin-sparing mastectomy, DCIS: ductal carcinoma in-situ, NST: non-specific invasive carcinoma NAC: neo-adjuvant chemotherapy.

Supplementary Table 2: Factors associated with LDF-IBR versus implant IBR in binary logistic regression.

3.6 Post-operative hospitalization length (POHL)

The median POHL was 1 day (mean 1.87): 1 day without IBR and 2 days with IBR (Table 2) and 247 patients (11.7%) were hospitalize more than 3 days. The POHL was ≤1 day for 54.3% of mastectomies (1,146/2,112): 73.5% (924/1,257) in the no-IBR group and 25.96% (222/855) in the IBR-group (222/650: 34.2% of IBR-implants).

The POHL rate ≤1 day has increased over the past 2 years compared to 2016-2018 for patients without IBR (69.9% vs. 78.8%) and for patients with IBR (19.8% vs. 37.6%). In univariate analysis, factors significantly associated with a POHL >3 days were the year of treatment, age, type of mastectomy, indication for mastectomy, histology, bilateral mastectomy, IBR or no-IBR, axillary surgery, previous ipsilateral surgery, previous ipsilateral radiotherapy and the surgeon (Table 7). In binary logistic regression, POHL >3 days was significantly increased by NST or lobular histological status, bilateral mastectomies, IBR, previous radiotherapy, and decreased during the last 2 years of treatment, and by age between 41-50 years (Table 8).

Legend: POHL: postoperative hospitalization length, IBR: immediate breast reconstruction, ASA: American Society of Anesthesiologists, BMI: Body mass index, NAC: neo-adjuvant chemotherapy, N-RTH: neo-adjuvant radiotherapy, NSM: Nipple-sparing mastectomy, SSM: Skin-sparing mastectomy, BC: breast cancer, DCIS: ductal carcinoma in situ, NST: non-specific tumor (invasive ductal carcinoma), SLNB: sentinel lymph node biopsy, ALND: axillary lymph node dissection.

Table 7: Factors associated with a POHL >3 days in univariate analysis.

Legend: POHL: postoperative hospitalization length, IBR: immediate breast reconstruction, RTH: radiotherapy, NSM: Nipple-sparing mastectomy, SSM: Skin-sparing mastectomy, DCIS: ductal carcinoma in situ, NST: non-specific tumor (invasive ductal carcinoma), SLNB: sentinel lymph node biopsy, ALND: axillary lymph node dissection.

Table 8: Factors associated with a POHL >3 days in binary logistic regression

3.7 Operative time and anesthesia time

The median operative time was 92 minutes (mean 115.8). The median duration of anesthesia was 142 minutes (mean 169.1) with a significant longer duration for IBR versus no-IBR (Table 2).

3.8 Adjuvant treatments

AC was administered in 28.6% of mastectomies (603/2112): 35.5% (463/1306) for primary invasive BC without neo-adjuvant chemotherapy (NAC) [25.6% (127/497) and 41.5% (336/809) for mastectomies with and without IBR, respectively] and 17.0% (31/182) of patients for invasive ipsilateral breast local recurrence [14.6% (15/103) and 20.3% (16/79) for mastectomies with and without IBR, respectively]. NAC was administered in 482 patients (22.8%: 482/2112): 21.5% (95/442) for primary invasive BC [15.7% (19/121) and 23.7% (76/321) for mastectomies with and without IBR, respectively] and 24.3% (9/37) of patients for invasive ipsilateral breast local recurrence (2 patients with IBR and 35 without IBR). PMRT was delivered in 38.2% of mastectomies (806/2112): 48.3% (802/1661) for primary invasive BC without previous radiotherapy: 21.7% (120/553) and 61.6% (682/1108) for mastectomies with and without IBR, respectively.

Endocrine therapy was delivered in 76.9% (1166/1517) of mastectomies for primary invasive BC [79.7% (372/467) and 75.6% (794/1050) for mastectomies with and without IBR, respectively] and 70.9% (127/179) of patients with invasive ipsilateral breast local recurrence [76.3% (58/76) and 67% (69/103) for mastectomies with and without IBR, respectively]. Median interval-time between surgery and adjuvant therapy was 46 days: 42 days for AC and 51 days for PMRT (Table 9). Median interval-times between surgery and adjuvant therapy were not significantly different for mastectomies with and without IBR (p=0.536), for mastectomies with and without complications (p=0.057) and significant (50 and 45 days) for mastectomies with and without Grade 2-3 complications (p<0.0001), and for patients 51-74 years old (p=0.048) and >=75 years old (p=0.033). Interval-times were >60-days in 20.5% of patients (184/896) (712 patients <= 60-days): in 16.1% for AC and 26.8% for PMRT (p<0.0001). Results were non-significant according to IBR or no-IBR (p=0.294), according to complications or not (p=0.138). Higher rates of interval-times >60-days were observed for mastectomies with Grade 2-3 complications (p=0.026) and according to age groups (p<0.0001).

Legend: IBR: immediate breast reconstruction, AC: adjuvant chemotherapy, PMRT: post-mastectomy radiotherapy.

Table 9: Interval time between surgery and adjuvant therapy.

In binary logistic regression, significant factor associated with interval-time >60-days for AC was age >=75-years old (OR=3.718, p=0.008, CI95%=1.42-9.74) in comparison with patients <=40-years old. Others age groups (41-50 and 51-74), grade 2-3 complications and IBR versus no IBR were non-significant. Significant factors associated with interval-time >60-days for PMRT were age >=75-years old (OR=4.146, p=0.002, CI95%=1.66-10.34) in comparison with patients <=40-years old, Grade 2-3 complications (OR=2.059, p=0.040, CI95%=1.03-4.10) in comparison with no-Grade 2-3 complications and IBR (OR=3.000, p=0.002, CI95%=1.49-6.02) versus no-IBR. Others age groups (41-50 and 51-74) were non-significant.

4. Discussion

We reported a large cohort of patients treated by mastectomy in recent years with a high rate of IBR. IBR was significantly associated with several factors in multivariate analysis corresponding to a selection of patients in whom an IBR was perform. Consequently, complication rate was analyze in regression analysis adjusted on confounding factors and there was no significant impact of IBR or no-IBR. High BMI (> 30) was the only independent factor associated with Grade 2-3 complications. A predictive score of complication risk was calculate in order to evaluate for each patient the level of complication rate for all grades and grade 2-3. Performing IBR was not significantly associated with higher rate of interval time >60-days for AC but interval time >60-days rate for PMRT was increased by IBR and complications Grade 2-3.

4.1 IBR

IBR rate from 2016 to 2020 was estimate at 40.5%, which is relatively high and much higher than reported in the literature. It also marks a significant increase compared to 2014. Indeed, Negre et al. [5] carried out an observational study in France using the database of the Information Systems Medicalization Program (PMSI) between 2008 and 2014 making it possible to identify 140,904 women who had undergone a total mastectomy for BC. The IBR rate in France was therefore assess at 16.1%. In England, the number or implant-IBR have increased since 2009: 10.0% until 2005 and 23.3% by 2013-2014 [10]. In Chinese, IBR rate was 9.6% (1,554/16,187) in year 2018, with implant or expander in 76.6% of these IBR [12]. However, the average rate of reconstruction in the United States in 2010 was 45%, surging to 54% in 2015 [37].

There is a great disparity in IBR rates among surgeons in the same center, linked to surgical habits, their training, and the average age of their patient. However, some of the surgeons not performing IBR either referred their patients to other surgeons on the team, or performed the procedure in collaboration with another surgeon on the team. In the UK multicenter prospective cohort study [7], 2108 patients had 2655 mastectomies with implant-IBR in 81 units during 28 months: 11 patients’ per-year per unit in comparison with 144 implant-IBR patients per-year in our unit. We reported a high rate of NSM, 46.9% among patients with IBR. NSM rate was 17.7% (287/1625) for implant reconstructions in the MROC study [6] and 23% (486/2108) in the UK multicenter prospective cohort study [7].

4.2 Complications

There was no significant difference of complication rate between the IBR group and the no-IBR group: 29.9% for the IBR group vs. 33.3% for the no-IBR group. The surgical revision rate was 23.2%. However, we have shown patient’s selection for IBR in comparison with no-IBR in regression analysis. Consequently, factors associated with complications were analyze with adjustment on these confounding factors and IBR was not associated with complications or Grade 2-3 complications. Only BMI >=30 was significantly associated with more Grade 2-3 complications (OR=1.836).

In a prospective multicenter American study, the surgical revision rate was 19.3% (453/2343) [38] and in the NMBRA cohort, which included 3,389 patients with IBR, this rate was 15.8%. [39]. Although the comparison of complication rates between different studies is difficult due to a large disparity of IBR types, reported complications, indications for mastectomies, and monitoring time, we reported a complication rate similar to those reported in other studies [6, 40-45]. However, complications rates reported in recent studies of NSM were lower (5.1% to 20%) with 20.5% average overall complication rate in a recent review of 3716 NSM-IBR only for prophylactic indications [34].

We reported a 6.1% rate of implant loss for 560 implant-based IBR, which is lesser than rates reported by others [6, 40, 41], mainly in relation with infectious and cutaneous complications, but with use of pre-operative antimicrobial therapy for patients with nasal germs and per-operative antimicrobial prophylaxis that is not performed systematically by others. However, implant loss rate was higher for LDF-IBR associated with breast implant, 20.4% in our study, frequently realized for patients with previous ipsilateral radiotherapy.

Different types of complications were observe for patients with IBR in comparison with patients without IBR in our study: a small difference of infection rate (30/855: 3.5%) was observe for IBR in comparison with patients without IBR (38/1257: 3.0%) and higher cutaneous complication rate was observe after IBR (96/855: 11.2%) in comparison with patients without IBR (61/1257: 4.9%). In literature studies, the more frequent complication for mastectomy with implant-IBR was infection, 0% to 17.8%, and obesity was associated with more complications [7, 46] as we reported. In contrast, hematomas and seromas were more frequent for patients without IBR: 90/1257: 7.2% versus 42/855: 4.9% hematomas, 174/1257: 13.8% versus 1/855: 0.1% seromas for no-IBR-group versus IBR-group, respectively. However, hematomas were more severe complications for IBR versus no-IBR, 78.6% (33/42) grade 3 for IBR and 61.1% (55/90) for no-IBR. The most frequent complication that we reported was seromas (29.2%), with 87.4% (152/174) of grade 1 seromas and then, cutaneous complications (26.2%), with 18.5% of grade 3 as extensive necrosis requiring surgical revision. The 3^rd most frequent complication is hematoma (22%), of which 67% were grade 3.

We reported an implant loss rate of 7.2%, concordant with literature rates from 1 to 9.9%. Potter et al [7] reported an implant loss rate of 8.75% (182/2081: 95%CI=8-10), infection rate of 25% (522 patients, 95%CI=23-27) and 370 patients (18%, 95%CI=16-20) required return to theatre for complications within 3 months of their initial surgery. Bennet et al. reported a skin infection rate of 9.8% and a reconstruction failure rate of 7.1% [38]. In addition, as our results show, obesity is significantly associated with a high complication risk rate, as reported in a recent study by Srinivasa et al. with an increased high-grade complication rate for implant-IBR: (OR 1.71) and for autologous flap (OR 2.72) in the BMI > 30 group [46]. This significant BMI impact was also reported by Potter et al [7] for implant loss, infection and reoperation. The Simplified Predictive Complication Score is a decision aid to inform patients of complications risk, especially for high scores. It can be use very simply during the preoperative consultation, the main goal being to avoid delaying adjuvant treatments and to more precisely identify patients eligible for IBR, and the risk of failure. Moreover, this Score can help to compare complications rates between several studies, several techniques of IBR and several periods of treatment. For example, implant-IBR with or without meshes, and pre-pectoral or retro-pectoral implant-IBR. Predictive score of complication include several factors known before surgery but also mastectomy weight that is not known before surgery. Breast cup size was not recorded in our database for patients without IBR. However, a strong correlation is well established between mastectomy weight >300 gr and breast cup size >=C. An external validation of this score is necessary with, if possible, optimized accuracy.

4.3 NSM

We reported 46.4% NSM that is particularly high. In the MROC study, the NSM rate was 17.7% (287/1,625) for IBR by implants [6]. The limits to performing NSM were the risk of local recurrence linked to a retro-areolar glandular residue [24] or, conversely, the management of the skin casing (and therefore the risk of nipple areola complex (NACx) necrosis) [47]. Nevertheless, in the literature, there are many data contradicting, since the reported local recurrence rate on NAC is very low and the rate of NAC necrosis was less than 11% [21, 24, 48, 49, 50]. NSM can therefore be proposed safely and after information on the risk of NACx necrosis when it’s indicated. The remaining question, which still generates considerable questioning and requires validating prospective series, is regarding the limits of the therapeutic indication of NSM, particularly tumor-nipple distance of 2 centimeters or 1 centimeter [51].

4.4 Treatment

Regarding radiotherapy, a recent review by Ho et al [52] evaluated the possibility of IBR in combination with radiotherapy without increasing the risk of complications, and without compromising the oncological or esthetic outcome. It seems that PMRT and IBR are compatible, but PMRT may adversely affect patient-reported outcome [53].

4.5 POHL

54.3% of mastectomies had a POHL ≤1 day. The mean POHL was 1.8 days with a median of 1 day for mastectomies without IBR, and 2 days for mastectomies with IBR. Ambulatory or semi-ambulatory hospitalization is tending to increase, since studies have shown that it allows, on the one hand, reducing postoperative complications and, on the other hand, to help socio-professional reintegration. In addition, in a study carried out by the American College of Surgeons [54] including 40,000 patients, 8,365 (20.6%) were operated in ambulatory surgery, 23,252 (57.2%) spent one night in hospital and 8,958 (22.2%) stayed more than one night in hospital. Patients operated in ambulatory had a morbidity of 2.4% vs. 3.9% after 1 night hospitalization vs. 8.8% for prolonged hospitalization (p <0.0001).

This is the largest study on the safety of ambulatory surgery for breast cancer, showing a significantly higher complication rate in hospitalized patients. These data suggest that mastectomy for breast cancer can be perform safely as ambulatory surgery with patients who have been well informed.

4.6 Interval time between mastectomy and adjuvant treatment

Interval time >60-days between mastectomy and AC was not impacted by IBR and complications. However, interval time >60-days between mastectomy and PMRT was significantly impacted by IBR and complications Grade 2-3. Age >=75-years was also significantly associated with interval time >60-days between mastectomy and AC or PMRT. These results suggest that IBR is not a contra-indication in order to start adequately AC. However, O’Connell et al reported that major complications were significantly associated with treatment delays [35].

4.7 Bilateral mastectomies

A study of the American College of Surgeons [55] between 2007 and 2010 compared the morbidity of unilateral (n=3,722) versus bilateral mastectomies (n=497).

The surgical complication rate was significantly higher in the bilateral versus unilateral group: 5.8% versus 2.9% [unadjusted odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3–3.3, p <0.01]. The data observed in our series differ from those observed by the American College of Surgeons. Indeed, we have observed a complication rate similar in the bilateral mastectomies group and the unilateral mastectomies group: 31% vs 32% with p = 0.143.

5. Limitations

The main limitation is the retrospective design of this study but with a prospective data collection.

6. Conclusion

Treatment by mastectomy with or without IBR is a technique with an acceptable overall complication rate. Performing IBR was not significantly associated with complications and higher rate of interval time >60-days for AC but rate of interval time >60-days for PMRT was increased by IBR and complications Grade 2-3. The preoperative complication predictive score can be a tool to orient the therapeutic strategy by informing patients at risks of complications. The aim of this score is also to not delay adjuvant treatments and to compared results with others studies and or with more recent techniques like pre-pectoral implant-IBR with or without use of acellular or synthetic matrices and tumescent or non-tumescent techniques.

Acknowledgements

Not applicable.

Conflict of Interest Statement

The authors have no conflict of interest to declare.

Funding Sources

No funding

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