Breast Reconstruction: Necessity for Further Standardization of the Current Surgical Techniques Attempting to Facilitate Scientific Evaluation and Select Tailored Individualized Procedures Optimizing Patient Satisfaction

Abstract

Background

Various breast cancer reconstruction methods and novel surgical techniques include autologous or allogenic procedures, which can increase patient's quality of life and provide options when dealing with patients seen as challenging clinical scenarios.

Summary

Our aim was to review the current literature and present published evidence on innovative standards in whole breast reconstruction. Advances in flap monitoring or newly published data regarding neurotization in breast reconstruction, arm lymphedema management, breast implant-associated anaplastic large cell lymphoma reconstruction treatment, and robotic surgery with regard to radiotherapy define innovative standards in the breast reconstruction setting. The role of meshes/acellular dermal matrix and fat grafting as well as optimal sequencing of postmastectomy radiotherapy in autologous and alloplastic breast reconstruction appear highly debatable also in expert panel meetings rendering further clinical research including RCTs imperative.

Key Messages

There is an abundance of novel available techniques, which mandate further standardization, facilitating scientific evaluation in an attempt to help surgeons select tailored procedures for each patient with the goal to promote informed decision-making in breast reconstruction.

Introduction

Selection of the best option regarding autologous or alloplastic breast reconstruction is always based on taking into consideration a variety of criteria, while differences between reconstructive modalities can influence the patient decision-making process. Single-stage direct-to-implant reconstruction and autologous tissue reconstruction can be performed in a single operation. In contrast, a two-stage tissue expander/implant reconstruction demands at least two operations [1, 2].

Evolution regarding microsurgical expertise has given space to the rise of various surgical techniques regarding free autologous tissue transfer, with the abdominally based free flaps remaining the gold standard and the most popular option in breast reconstruction. Innovation and improved imaging techniques have enabled to map out perforators and harvest flaps from every part of the human body. However, objective comparisons of esthetic outcomes are challenging and require long-term follow-up [2, 3, 4, 5].

Unfortunately, studies presented in the literature so far present a significant selection bias due to nonstandard methods of assessing complications and presentation of inadequate data on radiotherapy timing and technique. Robust evidence and standardization of the various novel surgical techniques is lacking, while benefits of other adjunctive surgical techniques, such as fat grafting attempting to correct contour deformities after radiotherapy are debatable and still unknown [2, 3, 4, 5, 6].

Notably, the Oncoplastic Breast Consortium (OBC) conference on nipple-sparing mastectomy (NSM) and immediate reconstruction has already highlighted the need for standardization of various aspects of NSM and immediate reconstruction, given the lack of a uniform definition of OPS nomenclature and the presented heterogeneity in breast reconstruction practice. Consensus recommendations of the expert panel on controversial topics attempted to achieve standardization of surgical techniques, type and timing of reconstruction in the setting of adjuvant radiotherapy and radiological follow-up, empowering scientific comparability and clinical applicability [7].

Moreover, the OPBC initiative has already identified important knowledge gaps in the field of oncoplastic breast-conserving surgery, aiming to further suggest appropriate research strategies. Interestingly, among the matters discussed, the optimal type and timing of reconstruction after nipple-sparing or skin-sparing mastectomy with planned radiotherapy should be addressed by further prospective cohort studies at an international level, whereas the role of adjunctive mesh and the implant positioning during breast reconstruction should preferably be further researched via randomized controlled trials of pragmatic design [8].

The aim of this article is to review the current literature and present published evidence on current standards in whole breast reconstruction in an attempt to help promote further evaluation of the techniques used, outcomes, and overall safety.

Basic and Alternative Flap Options for Autologous Breast Reconstruction

Abdominally based flaps continue to be the gold standard for autologous breast reconstruction as tissue from the abdominal donor site resembles breast tissue the most. Transverse rectus abdominis myocutaneous (TRAM) and deep inferior epigastric artery perforator (DIEP) flaps are the most popular abdominally based flaps in breast reconstruction procedures [1, 2, 3, 9, 10, 11].

Notably, two types of autologous breast reconstruction techniques can be described. Firstly, the vascularized pedicled skin/muscle flaps with examples including the latissimus dorsi flap, the TRAM flap, and secondly the free flaps with examples including the DIEP flap, the superficial inferior epigastric artery flap, the gluteal artery perforator flaps, and the profunda artery perforator (PAP) flap [2, 11].

A systematic review and meta-analysis comparing complications and quality of life for all major abdominally based breast reconstruction techniques evaluating the impact of preoperative risk factors has not yet been performed. Regarding patient-reported outcomes following TRAM and DIEP flap reconstructions, patients with pedicled TRAMs (pTRAMs) reported decreased general satisfaction and physical well-being measured by the BREAST-Q and increased energy and emotional well-being measured by the SF-36. Interestingly, patients reported higher BREAST-Q abdominal physical well-being scores with DIEP flaps compared with free TRAM (fTRAM) flaps [12].

Based on the current published evidence, there exists a need to re-examine flap selection criteria in an attempt to create flap-specific guidelines for improving patient safety, as the lack of standardization in flap harvest techniques is another definite source of bias, due to surgeon-specific preferences in techniques, thereby confounding the results. A further comparison of complications and patient-reported outcomes following pTRAM, fTRAM, muscle sparing MS fTRAM, and DIEP flaps to guide flap selection is vital, particularly as novel variations in muscle-sparing flap harvest techniques are developed, so as to consult a uniform classification system, providing accurate outcomes according to patient characteristics [9, 10, 12].

There is a significantly greater risk of abdominal bulge/hernia following fTRAMs compared to DIEPs and MS fTRAMs due to an increased tension on the weakened abdominal fascia. Notably, when comparing nonobese to obese patients, the latter experience an augmented risk of abdominal bulge/hernia with fTRAMs compared with DIEP flaps, which subsequently should be preferably performed in this patient population. Conventional recommendations however suggest that TRAM flaps should be raised for obese patients [9]. pTRAMs highly risk abdominal bulge/hernia compared with DIEPs, indicating that muscle loss weakens the abdominal fascia. Vascular complications, including flap loss and fat necrosis are also more linked to pTRAMs, especially in low-volume hospitals. However, they can still be the preferred alternative when microsurgery equipment is not available. Compared with DIEP flaps, pTRAM flaps were associated with lower general satisfaction but comparable emotional well-being [10, 12, 13, 14].

Muscle conservation increases the flap loss relative risk, with DIEPs presenting a higher risk of flap loss due to robust vascular supply and fewer perforators included compared with MS fTRAM flaps and lastly the least with fTRAM flaps. fTRAM flaps demonstrated higher chances of abdominal morbidity compared with DIEP flaps, whereas muscle-sparing flaps had a higher risk of flap loss than fTRAM flaps did [1, 2, 3, 13, 14].

In order to prevent vascular complications such as flap loss, planned DIEPs and MS fTRAMs should be converted to fTRAM flaps. Evolutionary, the utilization of stacked and conjoined flaps or bi-pedicled DIEP flaps can maximize volume in the reconstructed breast, with the donor vessels anastomosed to the antegrade and retrograde internal mammary vessels or the thoracodorsal vessels for a more laterally placed flap [1, 2, 3, 14, 15].

Preserving the latissimus dorsi flap for salvage reconstruction is a popular choice in the breast reconstruction setting and provides a good alternative for women with small breasts often combined with the use of fat grafting. However, it has been reported that patients can experience long-term shoulder dysfunction, although standardized assessment of follow-up periods within the literature are inexistent, and findings are conflicting [16, 17].

Alternative flap options include thigh-based flaps also used as stacked flaps, such as the posterior thigh-based PAP flap, the inner thigh-based transverse upper gracilis (TUG) flap, or the newly described TUGPAP, all presented as reliable with low morbidity and satisfactory cosmesis additionally to the first described tensor fasciae latae myocutaneous free flap [2, 18, 19]. In a recent systematic review of breast reconstruction with PAP, TUG, or TUGPAP flaps, TUG flaps had a significantly higher recipient and donor complication rate compared with both PAP and TUGPAP flaps, concluding that the TUGPAP flap is a safe and effective alternative. Salibian et al. [20] highlighted the safety of stacked and conjoined flap breast reconstruction presenting low complication rates, regardless of donor site, and lower rates of fat necrosis. Interestingly, in their analysis half of the flaps were anastomosed to anterograde/retrograde internal mammary vessels, whereas the rest used internal mammary/intraflap anastomoses. Notably, age, body mass index, flap weight, flap donor site, and recipient vessels were not linked to a higher flap complication risk [2, 18, 19, 20].

A question raised is which is the better secondary option for autologous breast reconstruction, as patient-reported satisfaction has not been presented as an outcome in the studies. In a systematic review comparing the TUG and profunda femoris artery perforator flaps, the PAP flap had longer pedicle length and higher flap weight, while regarding donor morbidity the PAP flap group presented less wound dehiscence and fewer sensory disturbance rates [18].

Myocutaneous gracilis free flaps have been well described and presented in the literature, comparing variations of the upper gracilis flap [21]. Thigh-based flaps are considered a secondary alternative. Flap choice is based on the patient's fat distribution and skin laxity, perforator location, and donor/recipient scar location. In order to minimize donor-site morbidity, lymphatics in the femoral triangle and along the greater saphenous vein should be avoided in an attempt to reduce wound healing complications and distal ischemia [22].

The TUG flap is suitable for patients with small to moderately sized breasts as it provides a relatively short pedicle length (6–8 cm) harvested with a perforator arising from the medial circumflex femoral artery. It is an anatomically consistent flap and is technically easy and rapid to harvest, facilitating central flap positioning. Notably, it is correlated with worst donor site morbidity, wound dehiscence, sensory deficit, and lymphedema. TUG flap-reconstructed breasts often require additional and more lipofilling procedures [18, 21, 23].

The PAP flap, oriented longitudinally or transversely, is supplied by perforators from the profunda femoris artery offering a longer and larger pedicle measuring 10–12 cm and an artery of 2 mm, due to larger perforasomes. It is presumably correlated with less donor site morbidity, potentially presenting lower transient lymphedema rates due to its posterior location. Bilateral PAP flaps provide more volume for shaping with lower fat necrosis risks. Most of the stacked PAP flap cases utilize retrograde internal mammary vessels even when the flap is stacked with large DIEP flaps. However, the PAP flap has a greater technical difficulty in flap harvest compared to the TUG flap, while both flaps pose a partial flap loss risk at the apices [18, 22, 24].

Tissue from the gluteal region as a donor site is based on perforators arising from the superior or inferior gluteal artery and is preferred as a secondary option due to shorter pedicle and smaller caliber vessels, although providing very good outcomes. Interestingly, laterally based perforators offer a maximal pedicle length, while through coning of the flap a better projection can be demonstrated. This flap is available for patients with a low BMI, while the donor site has to supply enough tissue to achieve symmetry without leaving a contour deformity [2, 25].

A novel alternative consists of the lumbar artery perforator flap suitable for patients who have more fat in the flanks. The perforators arise at the level of the third or fourth lumbar vertebrae. However, the flap offers a short pedicle length and caliber [2].

Neurotization in Breast Reconstruction

Neurotization of autologous flaps for restoration of breast sensation represents a significant progress with a reported increasing number of patients already being evaluated for neurotization especially during DIEP flap procedures [26]. Notably, an actively recruiting randomized interventional breast reconstruction clinical trial (NCT04533373) recruiting patients undergoing DIEP flap breast reconstruction evaluates breast sensation using a graft material made by processing donated human nerves [27]. Without the nerve graft, a separate donor nerve may be required to join the two nerves, with possible complications including loss of sensation, infection, or neuroma formation.

Sensory loss following microvascular reconstruction has been an ongoing issue affecting quality of life in breast reconstruction. The question raised is which autologous reconstructive flap type affords the greatest sensory recovery. Moreover, spontaneous reinnervation patterns are less well defined and head-to-head comparative analyses of neurotized versus nonneurotized patients are nonexistent. Weisler et al. [26] recently reported that neurotized DIEPs provided the highest degree of sensation compared with both nonneurotized DIEPs and TRAMs, while although not presented as statistically significant nonneurotized DIEPs were more sensate than nonneurotized TRAMs. Given the above, it is presented as a highlighted gap in the literature to further investigate the influence of flap type on sensory restoration and further standardize the way in which breast sensation is qualitatively measured. Indeed, the above is reinforced by the notion that the BREAST-Q, which is used as the gold standard for reconstructive outcomes, partly addresses breast sensation, in addition to the lack of presented sensation studies that incorporate the BREAST-Q as a qualitative tool [26, 28].

Indocyanine Green Laser-Assisted Fluorescence Angiography in Autologous Breast Reconstruction

Apart from the traditional clinical assessment using capillary refill, temperature, color, turgor, and bleeding that can miss more than half of the cases of mastectomy skin flap ischemia, indocyanine green laser-assisted fluorescence angiography can empower the evaluation of perfusion zones enabling for an immediate, more accurate, real-time assessment of tissue perfusion to help decrease ischemia-related complications intraoperatively and further complications, such as fat necrosis, partial flap loss, and the need for future operations. The application may help in flap elevation by effectively identifying individual perforators better perfusing the flap and areas of hypoperfusion requiring further measures such as debridement. However, there has not been a large multicenter study to date that specifically addresses this issue. The only systematic review published so far regarding indocyanine green angiography during free flap breast reconstruction showed an effective identification of perfusion deficit areas reporting a statistically significant reduction in flap fat necrosis in the follow-up period, highlighting that further assessment will necessitate standardization of measurements for fat necrosis [29, 30, 31].

Autologous versus Alloplastic Breast Reconstruction (Prepectoral vs. Subpectoral Approach) − Complications

Recently, breast implants have been frequently placed in the subcutaneous pocket, in other words via the prepectoral approach. A significant question raised is which breast reconstruction technique improves more individual quality of life and achieves satisfaction as measured with a patient-reported outcome. Eltahir et al. [32, 33] recently reported that autologous breast reconstruction had superior outcomes compared with alloplastic breast reconstruction as measured by the BREAST-Q, despite the lack of RCTs presented. As expected, patients undergoing autologous breast reconstruction scored higher on almost all BREAST-Q scales compared with alloplastic breast reconstruction, while interestingly the greatest difference was observed in satisfaction with breasts [32, 33].

Taking into account the optimal plane in prosthetic placement procedures, various techniques have been presented and used to enhance cosmesis and minimize morbidity. More specifically, while prepectoral implant placement is a promising technique, appropriate patient selection is crucial. Evolution in NSM techniques, emphasis on intraoperative skin flap assessment, assessment of patients' skin flap thickness and vascularity, have led to improved skin flap viability, which has reintroduced the prepectoral prosthetic breast reconstruction approach [33, 34, 35, 36].

Abbate et al. [37] recently showed that rippling of the skin over the implant especially in the superior pole was the most frequently observed postoperative complication, followed by seroma and mastectomy skin flap necrosis in the prepectoral plane breast reconstruction setting. In their analysis, patients receiving prepectoral reconstruction were more likely to undergo direct-to-implant reconstruction than tissue expander placement, demonstrating a statistically significant decrease in chances of skin flap necrosis and capsular contracture in the prepectoral setting compared to the subpectoral one.

Indications for the use of prepectoral versus subpectoral IBBR have already been identified as a knowledge gap in the OPBC meeting which led to a further recommendation of a pragmatic superiority RCT to address the question of whether patients undergoing prepectoral versus subpectoral IBBR are more satisfied evaluated by the breast satisfaction scale scores measured by the BREAST-Q [8].

Complications assessment in a 1-year follow-up using the Mastectomy Reconstruction Outcomes Consortium (MROC) data linked autologous reconstruction to elevated complications rates but low flap failure rates. Additionally, patients receiving pTRAMs and DIEP flaps had greater chances of experiencing complications versus those receiving implants, although the last experienced an elevated risk in infections, capsular contracture, and rupture in implant-based procedures. Although abdominally based autologous reconstruction patients had higher revision rates, they underwent fewer total procedures, while tissue expander/implant reconstructions have undergone the greatest total number of procedures. Interestingly, time to adjuvant therapy was significantly increased in patients with wound complications undergoing immediate breast reconstruction (IBR). Longitudinal studies capable of measuring long-term, implant-related complications will help ease informed decision-making [38, 39, 40, 41].

Salibian et al. [42] recently evaluated reconstructions concluding that the published pooled short-term complication rates regarding subcutaneous implant-based breast reconstructions with acellular dermal matrix (ADM) versus mesh are few. Notably, capsular contracture rates appear higher in no-mesh cohorts, whereas seroma rates were higher in contemporary no-mesh cohorts. Limited data exist to understand the benefits of surgical mesh devices in prepectoral breast reconstruction. Level I studies with an appropriate control group are required [42].

Utilizing ADM and developed synthetic mesh products address better the infra-mammary fold and the lower pole shape and projection, while seemingly decreases capsular contracture rates, implant exposure, and implant loss, possibly contributing to decreased ischemic complications according to the authors [42, 43, 44]. Notably, localized inflammation or erythema is also known as red breast syndrome and was thought to be a delayed hypersensitivity reaction to ADMs [44, 45]. Overall, data on synthetic meshes are considered insufficient to be included in further analyses.

The role of adjunctive mesh and the positioning of implants in relation to the pectoral muscle during IBBR has already been identified as a knowledge gap from the OPBC [8]. A limitation is that there is no consensus on how complications should be defined, diagnosed, included, and evaluated, subsequently increasing the risk of bias. There are no data on risk of recurrence of cancer, delay of adjuvant treatment and health related quality of life (HRQoL). Moreover, we know little about the long-term effects of ADM, meaning in situ maintenance for more that 10 years. Ideally RCTs of pragmatic design will further enlighten us on the matter [42, 43, 44, 45].

Breast Reconstruction following Breast Implant-Associated Anaplastic Large Cell Lymphoma

As breast implant-associated anaplastic large cell lymphoma starts in the capsule, surgical options may include partial or total capsulectomy. Conversion from implant to autologous reconstruction has been linked to improved patient-reported outcomes. The reported risk of flap loss is low in the literature, but perioperative complications are typically higher than flap loss [46, 47, 48].

The authors reported that, also supported by the NCCN consensus guidelines, en bloc surgical resection of the surrounding capsule and removal of the implant demonstrated long-term, disease-free survival highlighting that there is a distinction between complete capsulectomy and en bloc resection, the latter aiming to achieve clear margins. Patients may undergo immediate or delayed (occurring between 6 and 12 months) breast reconstruction depending on their disease severity with alternatives such as implant replacement with smooth, round silicone implants, autologous tissue transfer, mastopexy, or fat grafting. NCCN guidelines for breast reconstruction after breast implant-associated anaplastic large cell lymphoma are currently nonexistent, which must be highlighted as a significant knowledge gap demonstrating a lack in best evidence-based practices [46, 47, 48].

Arm Lymphedema Development in the Breast Reconstruction Setting

Risk factors for breast cancer-related lymphedema include increased BMI, having a mastectomy, higher number of lymph nodes dissected, infection, seroma, radiotherapy, sedentary lifestyles, etc. Siotos et al. [49] recently reported that breast reconstruction was notably linked to lower odds of lymphedema compared to mastectomy only or breast-conserving surgery. Lymphedema rates were not statistically significantly different in implant-based or autologous BR. Notably, no consensus agreement exists on how to clinically diagnose lymphedema nor a standardized method to assess its severity.

Surgical treatment options include liposuction or Charles operation for patients who have a nonfunctioning lymphatic system, or procedures focusing on restoring the lymphatic circulation. The surgical treatment of lymphedema can be performed alone or in combination with microsurgical autologous breast reconstruction. Forte et al. [50] reported that lymphedema improved significantly after vascularized lymph node transfer combined with a DIEP or ms-TRAM flap.

Robotic Surgery: A Novel Approach in Breast Reconstruction

Donelly et al. [51, 52] recently reported that the robotic system has so far harvested the latissimus dorsi muscle for utilization as a tissue flap presenting a total harvest time of 92 min and has already performed NSM with immediate breast reconstruction demonstrating a total operation time of 85 min. As a latest application, the robotic system has been used successfully to harvest a deep inferior epigastric perforator flap via an intra-abdominal approach [51, 52].

Notably, the robotic system can minimize scarring prevalence better than traditional laparoscopic techniques, as it offers precision through enhanced 3-dimensional visualization, tremor elimination, high resolution, freedom of motion and guidance, better results regarding aesthetic outcomes and decreased complications rates when offered as a preferred alternative even in the radiotherapy setting. Limitations on the other hand include lack of an official approval, high cost of the da Vinci system, and specialized skills required. Vourtsis et al. [53] reported 32 cases of robotically assisted harvesting of pedicled latissimus dorsi muscle flaps for implant-based breast reconstruction, successfully conducted without converting them in open harvesting procedures [51, 52, 53].

Radiotherapy in the Setting of Breast Reconstruction: Types, Techniques, and Timing

Conflicting evidence questions clinical decision-making with regard to breast reconstruction in the radiotherapy setting [6, 54].

Several questions arise given that in locally advanced breast cancer, patients with node-positive disease, particularly those patients presenting with clinical stage II breast cancer, receive postmastectomy radiotherapy (PMRT) with decreasing local recurrence rates and benefit regarding survival rates. Those questions address matters regarding the type of reconstruction (alloplastic vs. autologous) used with PMRT, optimal timing of reconstruction (immediate vs. delayed vs. hybrid delayed–immediate) with regards to PMRT, whether radiotherapy treatment should target the tissue expander or the implant, the optimal timing of expander-to-implant exchange related to timing of radiotherapy, and the optimal time to exchange or proceed with delayed reconstruction following PMRT [6, 54, 55, 56, 57].

As already mentioned, current data regarding optimal beginning of reconstruction after radiation therapy are conflicting, while variation in radiation regimens among different teams may contribute to further bias disabling further assessment. Treatment plans need to be assessed [58], especially during the first 3 months after radiation when complication rates are significantly increased, while superior reconstruction outcomes appear in patients who traditionally wait more than 6 or 12 months after radiation. Patients who present with an unknown nodal status before surgery with the need for PMRT are treated with a delayed-immediate reconstruction as a preferred alternative [6, 58].

Optimal type of reconstruction in the setting of planned adjuvant radiotherapy was presented by the OPBC as a knowledge gap that should be addressed through a prospective cohort study with propensity score matching and patient-reported satisfaction evaluated by the BREAST-Q questionnaire at 2 years, as the primary outcome [8].

Autologous Microsurgical Breast Reconstruction, Complications and Timing of Adjuvant Radiation Therapy

Although autologous free flap reconstruction appears to be more resistant in the setting of radiation than alloplastic reconstruction, effects of PMRT are controversial regarding cosmetic appearance, quality of life, and surgical complications [59, 60].

Autologous breast reconstruction occurring several months after radiation therapy sequencing can pose risks and difficulties for microsurgical based breast reconstructions, subsequently leading to potential higher thrombosis rates and ultimate flap loss. Complications of autologous reconstruction following PMRT include poor wound healing, fibrosis, fat necrosis, and flap shrinkage, with a subsequent decreased patient satisfaction and worse aesthetic outcomes compared with nonirradiated flaps [58, 59, 60, 61, 62, 63, 64].

Complete and partial flap loss rates have been reported to be significantly elevated in the delayed reconstruction setting as well as vascular complications and unplanned reoperations, while surgical site infections and wound-healing complication rates appear higher in the immediate reconstruction setting. A comparison of cosmetic outcomes based on timing of PMRT has been difficult among the studies presented due to a lack of standardization in reporting aesthetic outcomes, while late effects of radiation, up to more than a latency period of 5 years has not yet been assessed. Notably, inclusion of patient satisfaction scores and aesthetic results appear contradictory in the literature [58, 59, 60].

A Mastectomy Reconstruction Outcomes Consortium prospective, multicohort study (MROC) [57] analyzing postoperative complications in women receiving immediate or delayed autologous reconstruction with PMRT demonstrated similar complication rates after 1 year between groups. Although patients having delayed reconstruction reported lower reconstruction scores in the BREAST-Q regarding satisfaction with their breasts, psychosocial well-being, and sexual well-being than patients with immediate reconstruction, both groups presented close satisfaction levels at 1–2 years after reconstruction. The authors concluded that immediate abdominal-based reconstructions tolerate radiotherapy better showing minimal morbidity [57, 65].

Optimal Sequencing of PMRT and Two Stages of Prosthetic Reconstruction

Several randomized controlled trials have demonstrated that sequencing differently chemotherapy and radiotherapy may not affect the oncologic outcomes, given that the adjuvant radiotherapy starts within 7 months after mastectomy. PMRT can target the tissue expander in situ or after the exchange of the implant, usually occurring 3 months after the initial placement [66, 67].

To date, there is no consensus on the proper timing of PMRT related to the two stages of the breast reconstruction procedure. Lee and Mun [68] reported that delivering PMRT decreases the risk of severe capsular contracture in tissue expanders compared to implants, without however further enlightening us regarding optimal sequence of mastectomy, adjuvant radiotherapy, and the two stages of the prosthetic reconstruction. Overall, reports show lower rates of complications using polyurethane implants compared to silicone implants after radiotherapy [68]. Frasier et al. [69, 70] reported a PMRT association with increased reconstruction failure rates, capsular contracture, and overall complications. Moreover, they reported that the effectiveness of PMRT could be affected by study design and quality, mean age, stage of IBR and duration of follow-up. Hong et al. [69, 70] reported similar conclusions regarding PMRT for patients undergoing immediate implant-based breast reconstruction, which has been linked to decreased patient satisfaction and inferior aesthetic results.

The above-mentioned uncertainties and grey zones regarding treatment recommendations for patients having breast reconstruction in the radiotherapy setting led to the International Oncoplastic Breast Surgery Meeting in Milan in 2017 [71]. Among the fruitful topics of discussion without however reaching expert panel consensus was the role of neoadjuvant radiotherapy (NART) in the reconstructive setting, the role of new techniques and devices (ADM, prepectoral breast reconstruction) in improving outcomes with regard to radiation treatment and the role of fat grafting.

Using NART in women undergoing mastectomy and IBR could minimize delays in adjuvant radiotherapy, providing cosmetic superiority and possible advances regarding loco-regional control and pathological complete response.

Notably, there is a lack of high-quality evidence in favor of NART as an alternative to PMRT in immediate or delayed autologous procedures, obstructing a further establishment of evidence-based optimal timings for radiotherapy and BRR to guide contemporary management. Interestingly, the expert panel inclined to a delayed-immediate implant-based approach, however without reaching a consensus regarding preferring to irradiate the expander-implant versus the permanent implant [71, 72].

Use of Autologous Fat Grafting in Breast Reconstruction with and without ADM after Radiotherapy

Empirically from the data, the use of autologous fat grafting after radiotherapy does not augment complication rates or the risk of tumor recurrence, although reports from basic research present that adipocytes are highly vascularized enabling angiogenesis promotion. However, adipose stem cells and mesenchymal stem cells in fat tissue can potentially improve wound healing, tissue repair and symptoms after radiotherapy. Notably, in vitro fat grafting might promote the growth and migration of breast cancer cells and increase tumor recurrence. Chung et al. [73] acknowledged an urgent need to present prospective clinical data on outcomes and follow-up from different anatomical locations of the implants (subpectoral or prepectoral) in mesh-assisted implant reconstructions in the radiotherapy setting.

Subsequently, a question raised is how safe and effective autologous fat grafting is after breast radiotherapy and if an optimal timing exists for the procedure after therapy completion. Chen and Li [74] reported that autologous fat grafting after radiotherapy does not seem to increase complications or tumor recurrence. Clinical evidence indicating that AFT is associated with increased risk for cancer relapse is still lacking, as the so far published studies have been limited by a short follow-up in the context of evaluating oncologic outcomes. Published case series have been presented reporting on better outcomes using fat grafting before the second stage of an implant-based reconstruction. To date, no panel consensus has been reached regarding the efficacy of fat grafting in the context of radiotherapy [74, 75, 76].

Conclusion

There is an abundance of available techniques, which mandate further standardization, facilitating scientific evaluation in the future, and help surgeons select a tailored procedure for each patient with the goal to optimize patient satisfaction by improving esthetic outcomes after whole breast reconstruction, promoting informed decision-making in breast reconstruction.

Conflict of Interest Statement

The authors have no conflict of interest to declare.

Funding Sources

The authors received no funding for this paper.

Author Contributions

Conceptualization, E.C.T.; investigation, E.C.T.; data curation, E.C.T., A.T.; writing − original draft preparation, E.C.T.; writing − review and editing, E.C.T., A.T.; supervision, E.C.T., A.T.