Key Points
Question
Is the quality of life in patients who have undergone mastectomy greater after receiving total breast reconstruction with autologous fat transfer (AFT) compared with reconstruction with implants?
Findings
This randomized clinical trial including 193 patients from 7 hospitals in the Netherlands (91 patients in the AFT group and 80 patients in the implant-based reconstruction group) found that quality of life scores on the BREAST-Q questionnaire were higher following AFT for all 5 BREAST-Q domains, and scores were significantly higher for 3 of 5 domains (satisfaction with breasts, physical well-being: chest, and satisfaction with outcome). Fewer complications were found in the AFT group as well.
Meaning
The findings of this study indicate that AFT offers patients with breast cancer an effective and safe option breast reconstruction that uses their own tissue and is minimally invasive.
This randomized clinical trial of patients in the Netherlands who have undergone mastectomy compares self-reported quality of life among those receiving total breast reconstruction using autologous fat transfer with that among those receiving implant-based reconstruction.
Abstract
Importance
There is a need for a new, less invasive breast reconstruction option for patients who undergo mastectomy in their breast cancer treatment.
Objective
To investigate quality of life (QoL) among patients undergoing a new breast reconstruction technique, autologous fat transfer (AFT), compared with that among patients undergoing implant-based reconstruction (IBR).
Design, Setting, and Participants
The BREAST trial was a randomized clinical trial conducted between November 2, 2015, and October 31, 2021, performed in 7 hospitals across the Netherlands. Follow-up was 12 months. Referrals could be obtained from general practitioners and all departments from participating or nonparticipating hospitals. The patients with breast cancer who had undergone mastectomy and were seeking breast reconstruction were screened for eligibility (radiotherapy history and physique) by participating plastic surgeons. Patients receiving postmastectomy radiotherapy were excluded.
Interventions
Breast reconstruction with AFT plus expansion or 2-phased IBR. Randomization was done in a 1:1 ratio.
Main Outcomes and Measures
The statistical analysis was performed per protocol. The predefined primary outcome was QoL at 12 months after final surgery. This was measured by the BREAST-Q questionnaire, a validated breast reconstruction surgery questionnaire. Questions on the BREAST-Q questionnaire are scored from 0 to 100, with a higher score indicating greater satisfaction or better QoL (depending on the scale). Secondary outcomes were breast volume and the safety and efficacy of the techniques.
Results
A total of 193 female patients (mean [SD] age, 49.2 [10.6] years) 18 years or older who desired breast reconstruction were included, of whom 91 patients in the AFT group (mean [SD] age, 49.3 [10.3] years) and 80 in the IBR group (mean age, 49.1 [11.0] years) received the allocated intervention. In total, 64 women in the AFT group and 68 women in the IBR group completed follow-up. In the IBR group, 18 patients dropped out mainly due to their aversion to implant use while in the AFT group 6 patients ended their treatment prematurely because of the burden (that is, the treatment being too heavy or tiring). The BREAST-Q scores were higher in the AFT group in all 5 domains and significantly higher in 3: satisfaction with breasts (difference, 9.9; P = .002), physical well-being: chest (difference; 7.6; P = .007), and satisfaction with outcome (difference, 7.6; P = .04). Linear mixed-effects regression analysis showed that QoL change over time was dependent on the treatment group in favor of AFT. The mean (SD) breast volume achieved differed between the groups (AFT: 300.3 [111.4] mL; IBR: 384.1 [86.6] mL). No differences in oncological serious adverse events were found.
Conclusions and Relevance
This randomized clinical trial found higher QoL and an increase in QoL scores over time in the AFT group compared with the IBR group. No evidence was found that AFT was unsafe. This is encouraging news since it provides a third, less invasive reconstruction option for patients with breast cancer.
Trial Registration
ClinicalTrials.gov Identifier: NCT02339779
Introduction
Breast cancer has a high prevalence among women worldwide. In the US, the incidence of any invasive form of breast cancer is about 1 in 8 women (13.0%).1 Potential treatments are a combination of surgery, neoadjuvant or adjuvant chemotherapy, radiotherapy, immunotherapy, or hormone therapy. When mastectomy is indicated, women may experience negative effects on both physical and emotional well-being.2,3 To alleviate symptoms caused by mastectomy, these women may opt to have their breasts reconstructed to reduce pain; restore self-esteem; and improve vitality, femininity, and sexuality.4,5,6,7 Breast reconstruction has been found to have positive influence on patients’ quality of life (QoL).7
The currently available techniques for breast reconstruction can be subdivided into 2 main categories: implant-based reconstruction (IBR) and autologous flap reconstruction (AFR). In AFR, tissue is transferred to the breast in the form of a flap, such as the deep inferior epigastric artery perforator flap, which is the gold standard in breast reconstruction using AFR. These techniques have proven to be effective in improving QoL in patients with breast cancer.6,8,9,10 Nevertheless, possible disadvantages cannot be ignored. Adverse effects of IBR include infection, hematoma, capsular contracture, device failure, and extrusion of the implant.11 For this reason, once an implant is inserted, a patient should consider reintervention in the future. In turn, AFR is not suitable for all patients who have undergone mastectomy because it entails a more complex procedure, possibly leading to complications such as blood loss, prolonged surgery and recovery time, necrosis, and donor area complications with extensive scars.4 Moreover, not every patient has an adequate donor site for transplantation. Thus, both of these techniques carry generally known risks with complication rates of up to 32.9% and may not be applicable to all women.12
An ideal breast reconstruction method entails low risks and high satisfaction rates. This study investigates a third technique that fits this request by combining the use of autologous tissue with a less invasive approach, autologous fat transfer (AFT).
Breast augmentation using fat injection was described as early as 1987.13 Results of various studies14,15 researching AFT for total breast reconstruction suggest that it is feasible and safe. As the evidence grade of published studies16,17 is low, controversy surrounding the safety and efficacy of this technique remains. Important limitations of literature on AFT are a lack of control groups and random allocation to support procedural standardization and address concerns about oncological safety.
The aim of the BREAST trial was to compare QoL among patients who received breast reconstruction using an external expansion device with that among patients who received IBR. We also compared breast volume and the safety and efficacy of the techniques.
Methods
The study followed the Consolidated Standards of Reporting Trials (CONSORT) guideline. Ethical approval was obtained from the medical ethics committee of Maastricht University Medical Centre/Maastricht University. Data on race and ethnicity were not collected for this study; however, only Dutch women were included. Data were not collected because at the time of writing the protocol, no differences in outcomes were suspected. In addition, to obtain an adequate sample of the Dutch population no distinction was made. Even if there were different race and ethnicity categories (most women in the Netherlands are White), these categories would have too few women each to include in the analysis. The informed consent form, as approved by the ethical committee, was signed by all participants before randomization was performed. The trial protocol is provided in Supplement 1.
Study Design
The BREAST trial is a multicenter, randomized clinical trial with an active control including a 1:1 allocation ratio. Randomization took place from November 2, 2015, to September 30, 2019; the 12-month follow-up appointments took place between February 1, 2017 and October 31, 2021. In July 2017, an amendment to the study was proposed to the medical ethics committee to reduce the period when patients were not allowed to smoke prior to reconstruction from 3 months to 4 weeks. This change to the methods after trial commencement was done to expand the group of eligible patients.
Participants
This trial was performed in 7 hospitals in the Netherlands. Patients were recruited internally from the participating centers or through external referrals from other hospitals or general practitioners. Patients with breast cancer or desiring preventive mastectomy who met the inclusion and exclusion criteria were considered eligible for participation. Inclusion criteria included female sex, age of 18 years or older, and history of or candidacy for mastectomy. Exclusion criteria included history of smoking within 4 weeks before surgery; current substance misuse; and history of radiotherapy in the breast area, including as oncological treatment after mastectomy. Complete inclusion and exclusion criteria are presented in the eMethods in Supplement 2. The patient flow diagram is provided in Figure 1.
Figure 1. Patient Flow Diagram.
Interventions
Patients randomized to the intervention group underwent breast reconstruction achieved by serial AFT. The initial AFT procedure took place during the mastectomy procedure or later. After mastectomy, AFT was performed in the sub- and intrapectoral areas before closing the mastectomy wound. This created an initial volume in the deep muscular planes. The AFT sessions were accompanied by preexpansion and postexpansion periods using a commercially available device (EveBra Nonsurgical Natural Breast Enlargement; Lipocosm) to increase fat graft survival.18,19,20 The EveBra uses negative pressure to prepare the recipient for grafting by creating subdermal edema, which leads to increased skin elasticity. The AFT was preceded by a period of 4 weeks in which patients wore the EveBra device on an intermittent schedule and was followed by 2 weeks in which they wore it on a low continuous suction schedule. Additionally, a pressure compression garment was worn over the donor sites for 2 to 4 weeks. Patients returned for regular clinical follow-up 2 and 6 weeks after every AFT session. There was a minimum of 10 weeks between AFT sessions.
Patients in the control group underwent a 2-stage breast reconstruction with implants. Patients received a tissue expander in the same surgical session as the mastectomy. The breast pocket was prepared for placement of the final implant by tissue expansion at intervals of at least 2 weeks. Patients returned for regular clinical follow-up 2 weeks and 6 weeks after the tissue expander’s placement and after the placement of the definite implant.
Autologous Fat Transfer
The technique for harvesting fat cells and lipofilling was applied as described by Coleman and Saboeiro.21 An illustration of the AFT procedure is provided in Figure 2. Harvesting was performed via 2-mm to 3-mm incisions. A solution of saline and lidocaine with adrenaline was infiltrated in the fat grafting area. The fat was harvested through a 3-hole blunt cannula using a 60-mL syringe. The fat was processed using the PureGraft 250 System for unilateral cases and PureGraft 850 System for bilateral cases to collect and purify the lipoaspirate. Contaminants were washed out, and the semiliquid lipoaspirate was transferred to 10-mL syringes. The fat was then injected in microdroplets and aliquots, fanning the fat graft in different pectoral planes and into the breast’s deep and superficial subdermal layers. Patients returned for regular clinical follow-up 2 weeks and 6 weeks after AFT.
Figure 2. Autologous Fat Transfer Procedure, Including Use of the EveBra Device.
Copyright, Ava Krueger, medical and scientific illustrator. Published with permission.
Primary Outcomes
The primary outcome was the difference in QoL at 12 months. The BREAST-Q, version 1.0,22 which was used for measuring QoL, has several domains, 5 of which we used: psychosocial well-being, sexual well-being, physical well-being: chest, satisfaction with breasts, and satisfaction with outcome. Questions on the BREAST-Q questionnaire are scored from 0 to 100 (worst to best, with a higher score indicating greater satisfaction or better QoL, depending on the scale. The questionnaire was administered at the time of study inclusion; at 6 months; and at the primary end point, 12 months after the last reconstruction procedure.
Secondary Outcomes
VECTRA XT 3-dimensional imaging (Canfield Scientific Inc) was used to assess breast volumes at the same time as the QoL measurements.23 Reporting of complications was divided into adverse events (AEs) and serious adverse events (SAEs), which were further categorized as oncological and nononcological. Oncological SAEs included incomplete tumor resection requiring reexcision, new primary tumor in the contralateral breast, metastasis, and recurrence tumor requiring reoperation. There was a prespecified list of complications made for the surgeons.24
Sample Size
The sample size was calculated using G*Power, version 3.1.25 To be able to detect a clinically relevant change, defined as a standardized effect size expressed as Cohen d of 0.50, using a 2-tailed significance level α of 0.05, a group size of 172, requiring 86 patients per study group for 90% power. A dropout rate of 15% was expected, requiring at least 101 patients per study group.
Randomization
Once patients were included by the local researchers, they were allocated to a treatment group by the coordinating investigators (S.S.J.S. and T.K.K.) who used the ALEA randomization system (ALEA Clinical). Randomization was stratified by medical center. Patients were informed about their treatment before the first surgical procedure.
Statistical Analysis
IBM SPSS, version 25 (IBM Corp), was used for statistical analyses. This was a per-protocol analysis. The independent samples 2-tailed t test was used to test for differences in QoL between the intervention (AFT) and control (IBR) groups at 6 months and 12 months after the last surgical procedure. To explore whether the change of QoL scores over time differed between the treatment groups, a linear mixed-effects regression analysis was performed with the QoL score as a dependent variable. Participant identification was specified as a random effect to account for clustering of multiple measures within patients, and time and treatment group as fixed effects. The fully conditional specification method of multiple imputation was used for imputing missing scores, with m = 20. A 2-tailed P < .05 was considered significant.
Results
Patient Characteristics
From November 2, 2015, to September 30, 2019, a total of 193 patients (mean [SD] age, 49.2 [10.6] years) were randomized at 7 centers; 93 patients to the AFT group and 98 patients to the control (IBR) group. The mean (SD) age was 49.3 (10.3) years in the AFT group and 49.1 (11.0) years in the IBR group. The final follow-up sessions took place between February 1, 2017, and October 31, 2021. The ongoing COVID-19 pandemic resulted in downsizing of nonacute health care in the Netherlands. As a result, 12 patients in the AFT group were unable to complete their treatment and follow-up by October 2021. In the IBR group, 18 patients dropped out mainly due to their aversion to implant use, and in the AFT group 6 patients ended their treatment prematurely because of the burden of the treatment being too heavy or tiring. Funding for this study was extended twice. Due to continued uncertainty of elective health care during the pandemic, the research group was compelled to terminate the study after approval by the ethical committee.26,27 Overall, indications for reconstruction and baseline characteristics (Table 1) did not differ to any clinically meaningful extent between the groups.
Table 1. Indications for Reconstructive Treatment and Baseline Characteristics of Patients in the BREAST Trial.
| Indication or characteristic | Participants, No. (%) | |
|---|---|---|
| Autologous fat transfer (n = 91) | Implant-based reconstruction (n = 80) | |
| Indication | ||
| Wish for immediate reconstruction (planned mastectomy for breast cancer) | 33 (36.3) | 33 (41.3) |
| Wish for immediate reconstruction (planned preventive mastectomy) | 6 (6.6) | 9 (11.3) |
| Carrier of tissue expander (after recent mastectomy with tissue expander placement) | 8 (8.8) | 11 (13.8) |
| Indication for a change of implant (after a mastectomy for a previous breast cancer or preventive mastectomy) | 10 (11.0) | 5 (6.3) |
| Wish for late reconstruction (after mastectomy in the past) | 34 (37.4) | 22 (27.5) |
| Characteristic | ||
| Age, mean (SD), y | 49.3 (10.3) | 49.1 (11.0) |
| BMI, mean (SD) | 23.8 (2.6) | 23.2 (2.4) |
| Cup size | ||
| AA | 2 (2.2) | 1 (1.3) |
| A | 7 (7.7) | 10 (12.5) |
| B | 34 (37.4) | 35 (43.8) |
| C | 34 (37.4) | 21 (26.3) |
| D | 7 (7.7) | 9 (11.3) |
| E | 0 | 2 (2.5) |
| F | 2 (2.2) | 0 |
| G | 1 (1.1) | 0 |
| Missing | 4 (4.4) | 2 (2.5) |
| Bra circumference, mean (SD), m | 0.8 (0.1) | 0.8 (0.1) |
| Bilateral | 23 (29.5) | 19 (26.8) |
| Pathological breast cancer staginga | ||
| In situ | 22 (24.4) | 14 (17.5) |
| Ia | 12 (13.2) | 9 (11.3) |
| Ib | 1 (1.1) | 3 (3.8) |
| IIa | 8 (8.8) | 6 (7.5) |
| IIb | 8 (8.8) | 4 (5.0) |
| IIIa | 0 | 1 (1.3) |
| Preventive | 16 (17.6) | 13 (16.3) |
| Missing | 24 (26.4) | 30 (37.5) |
Abbreviation: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared).
For pathological breast cancer staging of primary tumor, the American Joint Committee on Cancer staging manual, 7th edition, was used.
The primary outcome assessment was performed with 132 patients, of whom 64 were in the AFT group and 68 were in the IBR group. Reasons for dropout or loss to follow-up are shown in the Figure 1.
A mean (SD) of 4.2 (1.2) surgical procedures were performed in the AFT group (ranging from 2-7 sessions), whereas a mean (SD) of 1.7 (0.5) procedures were performed in the IBR group (ranging from 1-3 procedures). The mean (SD) injected volume per session per breast was 217.8 (74.6) mL for the AFT group. The mean (SD) duration of treatment was 13.4 (6.9) months in the AFT group compared with 5.1 (4.0) months in the IBR group.
Primary Outcome
Table 2 shows the outcomes for the different BREAST-Q domains, stratified by treatment group and time of measurement. At 12 months postoperatively, the AFT group scored higher on all BREAST-Q domains, of which the difference among 3 domains was statistically significant and clinically relevant: satisfaction with breast (difference, 9.9; P = .002), physical well-being: chest (difference, 7.6; P = .007), and satisfaction with outcome (difference, 7.6; P = .04).28
Table 2. BREAST-Q Scores per Domain, Reported at Inclusion, and at 6 and 12 Months Postoperatively.
| BREAST-Q domain | BREAST-Q score, mean (SD)a | Effect size (95% CI) | Differencec | ||
|---|---|---|---|---|---|
| AFT group | IBR group | P valueb | |||
| Study inclusion | |||||
| No. of patients | 80 | 76 | |||
| Satisfaction with breasts | 60.0 (23.4) | 61.8 (22.9) | NA | NA | NA |
| Psychosocial well-being | 62.5 (17.5) | 65.8 (16.0) | NA | NA | NA |
| Physical well-being: chest | 77.4 (14.3) | 79.2 (14.3) | NA | NA | NA |
| Sexual well-being | 54.4 (16.8) | 61.1 (16.6) | NA | NA | NA |
| 6 mo | |||||
| No. of patients | 63 | 55 | |||
| Satisfaction with breasts | 66.3 (16.6) | 62.4 (16.7) | .21 | 0.23 (−0.13 to 0.60) | 3.9 |
| Psychosocial well-being | 65.6 (16.0) | 69.1 (18.1) | .27 | −0.21 (−0.57 to 0.16) | –3.5 |
| Physical well-being: chest | 79.1 (14.6) | 73.7 (15.9) | .06 | 0.35 (−0.01 to 0.72) | 5.4 |
| Sexual well-being | 57.3 (18.7) | 58.1 (19.0) | .81 | −0.04 (−0.41 to 0.32) | –0.8 |
| Satisfaction with outcome | 70.1 (20.1) | 73.2 (20.4) | .52 | −0.12 (−0.48 to 0.25) | 2.4 |
| 12 mo | |||||
| No. of patients | 64 | 68 | |||
| Satisfaction with breasts | 70.3 (17.8) | 60.4 (17.2) | .002 | 0.56 (022 to 0.91) | 9.9 |
| Psychosocial well-being | 69.6 (17.4) | 68.3 (17.9) | .66 | 0.08 (−0.27 to 0.42) | 1.4 |
| Physical well-being: chest | 79.9 (14.7) | 72.3 (17.0) | .007 | 0.48 (0.13 to 0.82) | 7.6 |
| Sexual well-being | 61.5 (18.6) | 58.6 (18.7) | .37 | 0.16 (−0.19 to 0.50) | 2.9 |
| Satisfaction with outcome | 73.9 (22.4) | 66.3 (19.8) | .04 | 0.36 (0.02 to 0.70) | 7.6 |
Abbreviations: AFT, autologous fat transfer; IBR, implant-based reconstruction; NA, not applicable.
Questions on the BREAST-Q questionnaire are scored from 0 to 100 (worst to best), with a higher score indicating greater satisfaction or better quality of life (depending on the scale).
P < .05 was considered significant.
Clinically relevant difference in BREAST-Q scores defined as 4 or higher, except for physical well-being (≥3).28
Linear mixed-effects regression analysis demonstrated that the change in QoL over time also differed between the groups in favor of the AFT group for the domains satisfaction with breasts (difference, 6.2; P = .005), physical well-being: chest (difference, 4.6; P = .001), and sexual well-being (difference, 5.2; P = .003) (eTable 1 in Supplement 2).
Secondary Outcomes
The mean (SD) breast volume achieved at 12 months was 300.3 (111.4) mL in the AFT group vs 384.1 (86.6) mL in the IBR group. With a mean difference in the final breast volume between the groups of only −83.8 (95% CI, −116.2 to −51.3) mL at 12 months after the last AFT session, the results show that considerable breast volume can be achieved. For AFT, no postoperative differences in mean volumes were found between 6 and 12 months. Examples of the final breast reconstruction with AFT and IBR are shown in Figure 3.
Figure 3. Examples of Final Results of Breast Reconstruction for Both Techniques .
A and B, Autologous fat transfer. C and D, Implant-based reconstruction.
A total of 26 SAEs, of which 9 oncological SAEs (4 in the AFT group and 5 in the IBR group) were reported during this short follow-up. Finally, 43 AEs were reported across 331 AFT sessions, while 25 AEs were reported across 124 IBR procedures. A detailed overview of all AEs and SAEs in the 2 groups is presented in eTables 2 to 4 in Supplement 2.
Discussion
To our knowledge, the BREAST trial is the first multicenter randomized clinical trial to compare AFT for total breast reconstruction with IBR. Quality of life scores at 12 months after the last reconstructive procedure were considerably higher in the intervention group. Furthermore, the AFT group showed favorable change of QoL over time compared with the IBR group. Breasts were slightly smaller in the intervention group (mean [SD], 300.3 [111.4] mL vs 384.1 [86.6]), and 12-month safety data showed no increased oncological risk for patients in the intervention group. This study provides level 1 evidence and shows that serial lipofilling with preexpansion is a new successful breast reconstruction method and should be offered to suitable patients seeking breast reconstruction.
With the continuing debate on implant safety,29 results of this study are a pivotal milestone in female health. This new autologous technique will be especially welcomed by the growing number of patients who are diagnosed with breast cancer, are not eligible for AFR, or do not wish to receive breast implants due to possible foreign body consequences.30,31 A higher QoL score for AFT is in line with previous studies8,9 of other autologous techniques, showing a greater QoL in women who underwent AFR compared with women who received IBR. A possible explanation for differences between the AFT and IBR groups over time could be the ability of an autologous reconstructed breast to naturally age and undergo ptosis and follow weight fluctuations, thereby maintaining a better symmetry with the contralateral breast.32 Another important advantage of AFT is that unlike for IBR, no infections occurred in the AFT group.
Of note, although scores were higher for all domains at 12 months, for 2 of 5 domains, psychosocial well-being and sexual well-being, the differences between the treatment groups were not significant. One reason could be the effects of measures that were taken to control spread of the COVID-19 pandemic on mental health.33,34,35 This may have attenuated between-group differences on the psychosocial well-being domain of the BREAST-Q in particular, given that this domain focuses on emotional stability. The AFT treatment period is longer than that of IBR. This led to a majority of patients in the AFT group completing the 12-month questionnaire after the first nationwide lockdown starting March 2020, possibly causing lower reported scores. Additionally, the BREAST-Q version 1.0 was used instead of version 2.0. In version 1.0, patients are able to answer “not applicable” for questions in the domain sexual well-being. As approximately 20% chose to do so for this domain, data of only 80% of the total sample were available for analysis, resulting in a low power to detect differences in sexual well-being. Last, a reason for lower scores and indifference for these domains could be due to the reduced sensation of the breast and/or fear for potential recurrence regardless of reconstruction method.
Another concern about AFT is the future detection of breast cancer, specifically that AFT could lead to the formation of calcifications, necrotic fat, and cysts that could not be distinguished from cancer on a mammogram.16 However, studies21,36,37 have shown that benign lesions were not perceived as a nuisance in breast imaging and that benign findings could be easily distinguished from malignant lesions. A recent meta-analysis by Krastev et al38 showed there is no increased oncological risk in patients receiving AFT and that AFT can therefore be performed safely in patients with breast cancer. Our results support these findings, as no differences in oncological SAEs were found between the groups. Moreover, consistent with the literature,17 we found no increased risk for any serious complications in the AFT group associated with the procedure.
However, we still emphasize that this study used a short follow-up, and definitive conclusions should be based on studies with a longer follow-up and adequate sample size. As most oncological studies on AFT have been performed with smaller grafting volumes, results of our ongoing 5-year oncological follow-up are essential to assess oncological safety of larger fat volumes grafted for total breast reconstruction.
Finally, some surgeons are concerned regarding the vitality of the injected fat cells.39,40 With a mean difference in the final breast volume between the groups of only −83.8 (95% CI, −116.2 to −51.3) mL at 12 months after the last AFT session, the results show that considerable breast volume can be achieved. Moreover, these volumes did not decrease over time between 6 and 12 months after surgery.
Limitations
This study has several limitations. The inclusion phase was slow because many patients had a clear preference for a certain method, mostly AFT, due to increasing media attention concerning the safety of breast implants and the association of foreign body material with general health.29 Although inclusion should have been for only patients without a clear preference for the AFT procedure, the dropout rate (Figure 1) in the implant group suggests that this could not be fully avoided. This could have altered the QoL scores of the women in the IBR group because IBR was not their preferred reconstruction method. Although distribution of patient indications for participation was equally divided over the groups, scores at the moment of inclusion are heterogeneous since some patients did not receive their mastectomy yet, while others already had an implant, as is also the case in the real-life situation. Due to the COVID-19 pandemic, which led to a downsizing of nonacute health care in the Netherlands, there were missing follow-ups.
As every reconstruction method has its disadvantages, the main disadvantages of AFT are the length of treatment and the number of procedures needed. Thus, it is not suitable for every patient. Specifically, AFT is thought to be considerably less effective in patients with previous radiotherapy in the chest area. Therefore, this group of patients was excluded. Future studies should be warranted especially in this group of patients.
An interesting study would be an RCT comparing AFT with another autologous reconstruction, although the feasibility of such a study is questionable, since most women eligible for AFT do not have adequate donor sites for other available autologous options.
Conclusions
Results of this RCT showed 3 of 5 BREAST-Q domains were scored higher for the AFT group compared with the IBR group at 12 months postoperatively. Furthermore, there was an increase over time for all 5 domains in the AFT group. This correlates to a higher QoL for AFT patients with an increase of QoL over time. At 12 months postoperatively, no evidence was found to indicate that AFT is unsafe. These results are encouraging for all eligible women who have undergone mastectomy and are seeking a less invasive and autologous option for breast reconstruction. A larger population is recommended to further explore effect sizes, and a longer follow-up duration is advised to investigate the QoL transition over time. Safety will be further investigated during the ongoing 5-year oncological follow-up of the BREAST trial.
Trial Protocol
eMethods. Inclusion and Exclusion Criteria for the BREAST Trial
eTable 1. Linear Mixed-Effects Regression Analysis of Fixed Effects Group*Time
eTable 2. Oncological Serious Adverse Events (SAE), Shown per Treatment Type
eTable 3. Non-Oncological Serious Adverse Events (SAE), Shown per Treatment Type
eTable 4. Adverse Events, Shown per Treatment Type
Nonauthor Contributors. The BREAST Trial Investigators
Data Sharing Statement
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Trial Protocol
eMethods. Inclusion and Exclusion Criteria for the BREAST Trial
eTable 1. Linear Mixed-Effects Regression Analysis of Fixed Effects Group*Time
eTable 2. Oncological Serious Adverse Events (SAE), Shown per Treatment Type
eTable 3. Non-Oncological Serious Adverse Events (SAE), Shown per Treatment Type
eTable 4. Adverse Events, Shown per Treatment Type
Nonauthor Contributors. The BREAST Trial Investigators
Data Sharing Statement