Mastectomy with immediate breast reconstruction: Results of a mono-centric 4-years cohort

Introduction Oncological safety, quality of life and cosmetic outcomes seems to be similar between breast conserving surgery (BCS) and mastectomy with immediate breast reconstruction (IBR). We report our experience of IBR for consecutive mastectomies realized in a recent period of four years in order to determined immediate surgical results according to type of mastectomy and type of reconstruction, as mains objectives. Methods All mastectomies with IBR during years 2016–2019 were included. A retrospective analysis with prospective data collection was performed. Results We analyzed 748 IBR: 353 nipple-sparing mastectomies (NSM), 391 skin-sparing mastectomies (SSM) and 4 standard mastectomies, 551 with definitive implant or expanders and 196 with latissimus dorsi-flap (LDF). More NSM were performed during the 2 last years and more LDF were performed for high BMI, high breast cup-size, neo-adjuvant chemotherapy and radiotherapy and local recurrence. We realized 111 robotic NSM and 125 robotic LDF. Longer duration of surgery was significantly associated with the robotic procedures. The overall complications crude rate was 31.4% with 9.9% of re-operations and 5.8% of implant loss. Grade 2–3 complications were significantly associated with smoking. Breast complications occurred in 32.9% of mastectomies with principally skin or nipple-areola-complex suffering or necrosis, hematomas and infections. A predictive score was determined to evaluate risk of complications before surgery. Conclusion Mastectomy with IBR seems to be a safe technique with an acceptable complication rate which is increased by tobacco use, high breast cup-size and IBR-type.


Introduction
Breast-conserving surgery (BCS) for breast cancer (BC) has increase since numerous years and recently with development of oncoplasty and re-operation only for non in-sano resection. However total mastectomies for BC were still required in 12%-30% of patients [1][2][3]. Mastectomies can be required for extended ductal carcinoma in-situ (DCIS), multifocal disease, large BC according to breast size without indication of neo-adjuvant chemotherapy (NAC), prophylactic mastectomies, ipsilateral BC local recurrence (ILBCLR), non in-sano initial resection and patient's wishes. Secondary mastectomy for non in-sano BCS was realized in 40.8%-58.4% [4].
In France, immediate breast reconstruction (IBR) rate was lower than others European countries but has been increasing for several years [5]. Until now, IBR indications were: extended or multifocal DCIS, ILBCLR and prophylactic mastectomy [6] but was discussed for BC requiring adjuvant chemotherapy or radiotherapy [7]. In a recent French prospective study, satisfaction with the cosmetic outcome strongly influenced quality of life and an unsatisfactory outcome after IBR was still considered a better condition than simple mastectomy [8]. In the US, variable rates of breast reconstruction were reported, depending a great deal on where patients lived, what kind of health insurance they had and her race/ethnicity [9].
Several publications proved the benefit of risk reducing nipplesparing-mastectomy (NSM) in high risk patients [18][19][20], with a 90% reducing in BC development [18]. NSM studies reported better esthetic results than skin-sparing-mastectomy (SSM) and better quality of life [21,22]. Otherwise, quality of life and cosmetic outcomes seems to be similar between BCS and IBR [23]. NSM with IBR is considered as a valid procedure for prophylactic mastectomy and an acceptable option for BC [24][25][26][27]. Consequently, the demand of NSM by patients and the propositions of NSM by surgeons increased [28,29]. However few prospective studies were reported to evaluate complication rates and oncological outcomes of NSM [29].
The main technics of IBR are definitive implant or tissue expanders and LDF. In a French study, IBR was performed in 404 patients (67.9%), with implants in 46.5% and LDF in 46.9% [8]. Complications rates ranged between 5 and 61% are difficult to compare between studies due to great disparities of IBR types, type of complications recorded, indications of mastectomy and time of survey.
We report our experience of IBR for consecutive mastectomies realized in a recent period of four years in order to determined immediate surgical results according to type of mastectomy and type of reconstruction, as mains objectives.

Cohort study design
Among all consecutive mastectomies performed during years 2016-2019, we select patients with IBR from breast institutional database. A retrospective analysis with prospective data collection was performed in order to determined immediate surgical results according to type of mastectomy and reconstruction. Institutional committee approved this study (ClinicalTrial.gov n • NCT03461172 Database of Data Collection (BDD-G3S), Paoli Calmettes Institute, Marseille, France).
The work has been reported in line with the STROCSS [30].

Patients and outcomes
We analyzed patient's characteristics such as age, body mass index (BMI), breast cup-size, ASA status (American Society of Anesthesiology score), diabetes and tobacco use. Tumor characteristics or prophylactic treatment, previous treatment received (neo-adjuvant chemotherapy, radiotherapy), surgical procedures of mastectomy and IBR, complications have also been listed.
Data were collected regarding patient and tumor characteristics, treatment received and years of treatment, surgical procedures of mastectomy and IBR, complications during post-operative 90-days.
Analyses were performed separately for all complications, breast complications, LDF complications and for endoscopic surgical procedures. Technics of endoscopic NSM and robotic LDF were reported previously [15][16][17]. Complication rate was analyzed with Clavien-Dindo grading [31]: Grade 3 corresponded to any complication which required re-operation and Grade 4 corresponded to severe general infection. Grade 1 or 2 complications corresponded to infection or dehiscence or hematoma or bleeding or skin necrosis, without re-operation.
The duration of surgery was recorded from skin incision to the end of skin suture. The number of post-operative hospitalization days was reported from day of surgery to discharge. Interval-time between surgery and adjuvant chemotherapy (AC) or post-mastectomy radiotherapy (PMRT) were analyzed.

Procedures
Several techniques of IBR have been used for both NSM and SSM: sub-pectoral implant, tissue expanders or LDF; traditional open technique or robotic technic have been listed. The surgeon according to his habits chose incision. Patients underwent mastectomy with NAC conservation when distance between tumor and NAC was at least 2 cm on the preoperative imagery and a retro-mammary biopsy was performed.

Statistics
Quantitative criteria were analyzed with median, mean, CI95% and range. Comparisons were determined using Chi2-test for qualitative criteria and t-test for quantitative criteria. Factors significantly associated with criteria analyzed were determined by binary logistic regression adjusted for all significant variables determined by univariate analysis. Using Odds Ratio derived from logistic regression, we calculated a score for prediction of complications. Performance of this score was analyzed with calculation of area under the ROC curve (AUC). Statistical significance was set as p ≤ 0.05. Analyses were performed with SPSS version 16.0 (SPSS Inc., Chicago, Illinois).
In univariate analysis, NSM versus SSM, was significantly associated with median age, breast cup-size, indication and histology, years of treatment, bilateral mastectomy and tobacco (

Type of reconstruction
IBR were performed in 551 mastectomies with implants (459 definitive implants and 92 expanders), in 196 with LDF (including 48 with concomitant definitive implant) and in 1 with exclusive secondary lipofilling. IBR were performed with implant in 72.1% of primary BC ( Table 2).
Type of reconstruction in 579 NSM or SSM, excluding 4 standard mastectomies, 113 prophylactic mastectomies (1 LDF-IBR) and 52 NAC-R (52 LDF-IBR): In univariate analysis, IBR with implant or with LDF ± implant, was significantly associated with indication, bilateral mastectomy, histology, years of treatment, breast cup-size, age, NSM or SSM and BMI. In multivariate analysis, IBR with LDF versus implant was associated with lobular BC, year 2019, BMI, age >49-years old, breast cup-size C and SSM ( Fig. 1).
Median interval time between surgery and first adjuvant treatment was 44 days: 43 and 60 days for AC and PMRT, respectively. Median interval time between surgery and first adjuvant treatment were 43 and 54 days for mastectomies without and with Grade 2-3 complications, respectively (p = 0.042). According to type of complication, median interval times were not significantly different (Supplementary Table 3).

Discussion
In our study with a large number of patients, the overall complications crude rate was 31.4% with 74 re-operations (9.9%) and 35 implant losses (5.8%). Grade 2-3 breast-complication rate was 10.96%, significantly associated with tobacco use: 10% for implant-IBR, 9.7% for LDF-IBR and 15.4% for LDF-implant-IBR. There was no significant difference of complications rates between R-LDF and traditional LDF. Using our simplified score we are able to evaluate risk of complications before surgery which can help the decision and type of IBR in agreement with patient's wishes.
Even if comparison of complications rates between studies is difficult due to a great disparity of IBR types, complications recorded, indications of mastectomy and time of survey, we reported an overall complication rate similar with others studies [32][33][34][35][36][37][38][39]. However, complications rates reported in recent studies for NSM-IBR, were lower (5.1-20%) and the average overall complication rate were 20.5% in a recent review of 3716 prophylactic-NSM [25].
We reported a 4.7% rate of implant loss for implant-IBR, mainly in relation with infectious complication, even with use of pre-operative antimicrobial therapy for patients with nasal-germs and per-operative antimicrobial-prophylaxis. This rate was lesser than rates reported by others [32,33,38]. Implant loss rate was higher for LDF with combined implant-IBR in our study. In literature, the more frequent complication was infection (0%-17.8%) with implant loss reported between 1.0% and 9.9%. Wound infection rate was 9.8% (230/2343) in Bennett et al. study [39] with a reconstructive failure rate of 7.1% (116/1637). Moreover, obesity was associated with higher risks of any complication in a recent study, in agreement with our results [40].
Major complication rate: Like others authors we observed higher breast complication rate Grade 2-3 with tobacco use (OR = 2.064): higher failure rate [41,42], higher flap necrosis rate [43][44][45] and higher infection rate [36,42,45]. Major complications rates, grade 3-4 with re-operation and/or re-hospitalization, reported in literature were comprised between 9 and 37% but with different IBR procedures, different criteria of complications recorded and different time of survey. In a multicenter prospective cohort study [39] reoperation rate was 19.3% (453/2343). In the large NMBRA-cohort with 3389 IBR, this rate was 15.8% [41]. In Srinivasa et al. study [40], obesity was significantly associated with higher risk of major complication in both implant reconstruction (OR = 1.71) and autologous reconstruction (OR = 2.72). It is interesting to note that complications Grade 2-3 had, in our study, a significant impact on interval time between surgery and adjuvant treatment with possible negative impact on prognosis. This topic was not analyzed in others studies.
LDF-IBR were performed in 67.1% (94/140) of our patients with previous radiotherapy. We think that LDF-reconstruction is a good choice after radiotherapy, because LDF protect and nourish skin flaps. A prospective multicenter study [23] shows that autologous reconstruction appears to yield a superior patient-reported satisfaction and lower risk of complications than implant placement among patients receiving PMRT. Sbitany et al. were specifically interested in pre-pectoral implant breast reconstruction in 175 patients compared to 236 sub-muscular reconstruction and have shown no significant differences in complication rates: 15.4% versus 19.3% [63].
Robotic surgery: Currently, only a few studies have looked at series of patients who underwent R-NSM. Sarfati et al. reported 63 prophylactic R-NSM with no mastectomy skin flap or NACx necrosis, 4.8% of infections and 1.6% implant loss [10]. For Toesca et al., with 94 R-NSM procedures, the rate of reoperation was 4.3%, flap or nipple necrosis at 1.1% and they did not highlight local recurrences [64]. Endoscopic procedure is an emerging technique that has not yet been fully validated. This allows a NSM with a unique axillary approach with endoscopic or robotic technic, which is now well determined [65] but contribution of these procedures in comparison with traditional-NSM must be confirmed by prospective studies with analysis of complication rates, aesthetics advantages and cost efficiency. All recent studies about R-NSM showed that this technic could be performed with a brief learning curve [14][15][16][17][65][66][67].
In our study we reported 236 endoscopic procedures: 111 R-NSM and 125 R-LDF. The complication rate was not higher for R-LDF than conventional-LDF, but longer duration of surgery for NSM-implant-IBR was significantly associated with the robotic procedures. A recent mono-centric study, on 91 Endoscopic-NSM and 40 R-NSM showed that R-NSM is associated with higher satisfaction but at the price of longer operation and higher medical cost [66] and two studies showed that endoscopic surgery were associated with a better esthetic outcome [68,69]. Robotic-LDF appears as a safe, reproducible and contributive procedure when skin paddle is not required with any dorsal scar and less pain without significant longer procedure [15,16]. This can be explained by the enhanced surgical exposure resulting in the minimization of tissue traction and the resultant tissue trauma and skin necrosis. Clemens et al. published similar results and concluded that R-LDF harvesting is an efficient technique with low complication rate (16.7% among 12 R-LDF versus 37.5% among 64 Traditional-LDF) [70].
Robotic surgery is associated with many advantages when compared to traditional surgery such as a smaller incision, better surgical exposure, decreased tissue trauma and an enhanced viability of the LDF. Acquiring a good experience in robotic surgery (pelvic or breast) is considered crucial: this can be accomplished while assisting more experienced surgeons especially with a dual robot console.
Radiotherapy: In a recent review, Ho et al. [71] wondered if IBR and PMRT combination were possible while minimizing the frequency of complications without compromising oncological or cosmetic outcomes. It seemed like IBR and PMRT were compatible. Otherwise autologous reconstructions tolerate radiotherapy better compared with implants. However, implants remain the predominant type of reconstruction because it preserve the option of delayed autologous reconstruction [71]. In our study PMRT was realized for 107 patients with implant-IBR (72.9%). Reverberi et al. have shown that the type of reconstruction does not influence late toxicity rate: 25.3% among 91 IBR with PMRT [72]. Regarding oncological safety of IBR with PMRT, Bjohle et al. [73] in a matched cohort study with implant-IBR patients (n = 128) compared to patients without implant (n = 252) observed no difference in survival and recurrence [73].
Several limits of our study can be underlined: post-operative complications were recorded only during 90-days and we can't evaluate patient's satisfaction and quality of life.

Conclusion
In conclusion, IBR were performed in 37.7% of mastectomies and after RTH in 18.9%, with NSM in 47.2% and more NSM during the 2 last years. LDF-IBR was performed in 26.2% of all mastectomies with IBR. More LDF-IBR for high BMI and high breast cup-size were performed for primary BC and LDF-IBR were frequently performed for patients with NAC-R and local recurrence.
Mastectomy with IBR for local recurrence seems to be a safe technique with an acceptable complication rate, which is increased by tobacco use. This technique can be proposed after a strict selection of patient's characteristics and informed the patient of the risk of increasing the interval time for adjuvant treatments in the event of complications. Predictive score to evaluate the complication rate could be used to informed patients to help the decision with patient wishes. Otherwise, robotic surgery is associated with many advantages but needs complementary evaluation by a prospective study.

Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interest
The authors declare that there are no conflicts of interest regarding this study. Acknowledgement none.

Data statement
The database used and/or analyzed during the current study are not publicly available, but can be available from the corresponding author on reasonable request.

Provenance and peer review
Not commissioned, externally peer-reviewed.

Ethical approval
Institutional committee approved this study (Paoli Calmettes review board).

Research registration Unique Identifying number (UIN)
Name of the registry: Database of Data Collection in Senological Surgery.