Abstract
Introduction:
Contralateral prophylactic mastectomy (CPM) is often recommended for risk reduction in BRCA mutation carriers while in non-carriers bilateral mastectomy is driven by patient choice. To determine if psychosocial consequences vary among these groups, we characterized differences in satisfaction and well-being in BRCA carriers and non-carriers after CPM using the validated BREAST-Q patient reported outcome metric.
Methods:
We analyzed BREAST-Q data obtained preoperatively and postoperatively at 6-months, 1 year, 2 years, and 3 years from breast cancer patients who underwent bilateral mastectomy with immediate reconstruction at a single institution from 2016 to 2022. Associations between BRCA status and satisfaction with breasts, psychosocial well-being, and sexual well-being (all scored from 0-100) were assessed, adjusting for preoperative scores and relevant confounders using general estimating equations with a Bonferroni correction.
Results:
149 BRCA carriers and 842 non-carriers were included. Response rates were 56%, 78%, 51%, 52%, and 59% at preoperative, 6-months, 1-year, 2-year, and 3-year timepoints. BRCA carriers were younger (p<0.01) and more frequently received neoadjuvant chemotherapy (p<0.01) than non-carriers. Non-carriers had a higher proportion of hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) tumors (p<0.01) and more frequently received endocrine therapy (p<0.01). BRCA carriers differed in median baseline score for satisfaction with breasts (70 [53 82] vs. 58 [48 70] non-carriers; p<0.01) but not for psychosocial (p=0.14) and sexual well-being (p=0.20). Compared to non-carriers, BRCA carriers had a greater decrease from baseline to 6 months postoperatively for satisfaction (p=0.04) and psychological well-being (p=0.05). but not sexual well-being (p=0.38). Incorporating all timepoints, BRCA status did not influence satisfaction with breasts, sexual well-being, and psychosocial well-being on univariate or multivariable analyses.
Conclusions:
Overall, bilateral mastectomy resulted in comparable satisfaction and well-being between BRCA carriers and non-carriers despite differences in primary indication for CPM. Relative to non-carriers, BRCA carriers experience a greater decline in satisfaction with breasts and psychological well-being at 6 months after CPM.
Keywords: BRCA, breast cancer, patient reported outcomes
INTRODUCTION
Patient-reported outcome measures (PROMs) provide a validated means of assessing quality of life (QOL), which is a primary focus in the delivery of value-based healthcare.1 Various professional organizations including the American College of Surgeons and the International Consortium of Health Outcome Measures have called for the systematic incorporation of PROMs to facilitate shared therapeutic decision-making between patients and their providers. For women with unilateral breast cancer, managing the risk of developing a second primary breast cancer involves choosing between diligent surveillance after oncologic resection of the index malignancy or contralateral prophylactic mastectomy (CPM).2 While the latter may mitigate general3 and cancer-related distress,4 body image and well-being may be negatively affected.5,6
An increasing number of women undergo CPM,7,8 with up to 30% of women who are at average risk of developing a future contralateral breast cancer choosing this treatment strategy.9 In contrast to these women, in whom contralateral breast cancer risk is 0.5% annually,10 women harboring germline BRCA1/2 mutations have an estimated 2% annual risk.11 Consequently, CPM is recommended as an effective risk-reducing strategy in BRCA1/2 carriers. 12 Although women may consider multiple factors, family history and harboring a genetic mutation strongly impact the decision for CPM.13 While the high level of risk in BRCA mutation carriers has led guidelines to endorse CPM for these women, in those with sporadic cancer, the decision is usually based upon patient preference.14,15
It is unclear whether these differences influence postoperative QOL. Here, we aim to address this knowledge gap by comparing satisfaction and well-being in BRCA carriers and non-carriers after CPM using the validated BREAST-Q PROM.
METHODS
Women who underwent bilateral mastectomy with immediate reconstruction at Memorial Sloan Kettering Cancer Center between 2016 and 2022 were identified from a prospectively maintained database of breast cancer patients. Patients with Stage 1-3 cancer who had either autologous or implant-based reconstruction and had genetic testing for BRCA1 and BRCA2 germline mutations were included. Patients who had non-BRCA mutations or variants of uncertain significance were excluded.
PROs were assessed using the BREAST-Q, a validated survey instrument that assesses several QOL domains. Serial data was collected electronically through a web-based platform preoperatively and at 6-month, 1, 2, and 3-year postoperative visits. BREAST-Q subscale summary scores ranging from 0-100 were generated for each QOL domain via Q-Score software.16 Previous investigations have established standardized reference ranges and the minimal clinically important difference for satisfaction with breasts, psychosocial well-being, and sexual well-being has been shown to be 4.17 Our primary objective was to assess the association of BRCA carrier status with QOL scores measured in the following domains over time: 1) satisfaction with breasts, 2) psychosocial well-being, and 3) sexual well-being. Additional clinical and demographic data was abstracted from patients’ electronic medical record and included age, body mass index (BMI), history of tobacco use, history of anxiety or depression, clinical T (cT) and N stage, race, ethnicity, marital status, tumor subtype, neoadjuvant and adjuvant chemotherapy use, endocrine therapy, and receipt of postmastectomy radiation (PMRT). Descriptive statistics are presented using medians and interquartile ranges (IQR) for continuous variables and counts and percentages for categorical variables. Wilcoxon rank sum test and Pearson’s Chi-square test were used to assess differences in clinicopathologic features by BRCA carrier status. Univariate analysis (UVA) was conducted to study the association between QOL scores from the three domains and the factors mentioned above. Factors that were significant on the UVA were then included in the multivariable analysis (MVA). Both UVA and MVA were done in the generalized estimating equations framework to account for correlation between repeated QOL measures. Multiple comparison correction was implemented using Bonferroni procedure for MVA. All statistical analysis was conducted using R 4.2. A p-value of 0.016 was considered the threshold for statistical significance in the MVA.
RESULTS
149 BRCA carriers and 842 non-carriers were included. Response rates were 56%, 78%, 51%, 52%, and 59% at preoperative, 6-months, 1-year, 2-year, and 3-year timepoints. Table 1 presents clinicopathologic features by BRCA mutation status. BRCA carriers were younger (p<0.01) and more frequently received neoadjuvant chemotherapy (p<0.01) than non-carriers. Non-carriers had a higher proportion of hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) tumors (p<0.01) and more frequently received endocrine therapy (p<0.01).
Table 1.
Clinicopathologic features by BRCA carrier status
| Characteristic | Overall N=991 |
BRCA-carrier N=149 |
Non-carrier N=842 |
p-value |
|---|---|---|---|---|
| Age, median (IQR) | 47 (41, 53) | 43 (36, 52) | 47 (41, 53) | <0.001 |
| BMI, median (IQR) | 25.3 (22.1, 29.3) | 24.8 (21.8, 28.7) | 25.4 (22.2, 29.5) | 0.4 |
| Smoking status, n (%) | 0.12 | |||
| Non-smoker | 625 (73%) | 101 (79%) | 524 (72%) | |
| Smoker | 228 (27%) | 27 (21%) | 201 (28%) | |
| Unknown | 138 | 21 | 117 | |
| Clinical T stage, n (%) | 0.2 | |||
| T1 | 480 (53%) | 69 (49%) | 411 (53%) | |
| T2 | 365 (40%) | 56 (40%) | 309 (40%) | |
| T3 | 69 (7%) | 16 (11%) | 53 (7%) | |
| Unknown | 77 | 8 | 69 | |
| Race, n (%) | 0.4 | |||
| White | 761 (80%) | 120 (83%) | 641 (79%) | |
| Black | 81 (8.%) | 9 (6.2%) | 72 (8.9%) | |
| Asian-American, Far East | 64 (6.7%) | 6 (4.2%) | 58 (7.1%) | |
| Other | 51 (5.3%) | 9 (6.2%) | 42 (5.2%) | |
| Unknown | 34 | 5 | 29 | |
| Ethnicity, n (%) | >0.9 | |||
| Hispanic | 80 (8.2%) | 12 (8.1%) | 68 (8.2%) | |
| Not Hispanic | 894 (92%) | 136 (92%) | 758 (92%) | |
| Unknown | 17 | 1 | 16 | |
| Marital status, n (%) | 0.3 | |||
| Married/domestic partner | 738 (75%) | 108 (73%) | 630 (75%) | |
| Divorced/separated/widowed | 79 (8%) | 9 (6.1%) | 70 (8.4%) | |
| Single | 167 (17%) | 31 (21%) | 136 (16%) | |
| Unknown | 7 | 1 | 6 | |
| Tumor molecular profile, n (%) | <0.001 | |||
| HR+/HER2− | 475 (61%) | 54 (43%) | 421 (64%) | |
| HR−/HER2+ | 63 (8%) | 6 (4.8%) | 57 (8.6%) | |
| HR+/HER2+ | 111 (14%) | 5 (4%) | 106 (16%) | |
| TNBC | 135 (17%) | 60 (48%) | 75 (11%) | |
| Unknown | 207 | 24 | 183 | |
| Neoadjuvant chemotherapy, n (%) | 285 (29%) | 63 (42%) | 222 (26%) | <0.001 |
| Adjuvant chemotherapy, n (%) | 402 (41%) | 70 (47%) | 332 (39%) | 0.084 |
| Post-mastectomy radiation, n (%) | 291 (29%) | 38 (26%) | 253 (30%) | 0.3 |
| Endocrine therapy, n (%) | 741 (75%) | 86 (58%) | 655 (78%) | <0.001 |
| Reconstruction, n (%) | 0.3 | |||
| Autologous | 175 (18%) | 22 (15%) | 153 (18%) | |
| Implant-based | 816 (82%) | 127 (85%) | 689 (82%) | |
| Anxiety and/or depression, n (%) | 103 (10%) | 17 (11%) | 86 (10%) | 0.7 |
Statistical significance analyzed by Wilcoxon rank sum, Pearson’s Chi-squared, or Fisher’s exact tests
Abbreviations: IQR, interquartile range; BMI, body mass index, HR, hormone receptor; HER2, human epidermal growth factor receptor 2; TNBC, triple-negative breast cancer.
BRCA carriers differed in median baseline score for satisfaction with breasts (70 [53 82] vs. 58 [48 70] non-carriers; p<0.01) but not for psychosocial (p=0.14) and sexual well-being (p=0.20; Table 2). Incorporating all timepoints, BRCA status did not influence satisfaction with breasts, sexual well-being, and psychosocial well-being on univariate or multivariable analyses (Figure 1). In exploratory analyses, compared to non-carriers, BRCA carriers had a greater decrease from baseline to 6 months postoperatively for satisfaction (p=0.04) and psychological well-being (borderline significant at p=0.05) but not sexual well-being (p=0.38) (Figure 2).
Table 2.
Median BREAST-Q scores at each time point stratified by BRCA status
| BREAST-Q Subscale | Overall N=991 |
BRCA-carrier N=149 |
Non-carrier N=842 |
p-value |
|---|---|---|---|---|
| Satisfaction with breasts, median (IQR) | ||||
| Baseline | 58 (48, 71) | 70 (53, 82) | 58 (48, 70) | 0.006 |
| 6 months | 61 (53, 73) | 58 (52, 66) | 62 (53, 73) | 0.5 |
| 1 year | 64 (53, 75) | 53 (54, 75) | 64 (53, 75) | 0.8 |
| 2 years | 62 (52, 73) | 61 (51, 71) | 62 (52, 73) | 0.9 |
| 3 years | 62 (52, 73) | 65 (57, 75) | 62 (52, 73) | 0.2 |
| Sexual well-being, median (IQR) | ||||
| Baseline | 57 (46, 67) | 63 (48, 77) | 57 (45, 67) | 0.14 |
| 6 months | 48 (39, 63) | 50 (37, 66) | 48 (39, 62) | 0.5 |
| 1 year | 50 (37, 66) | 53 (39, 66) | 50 (36, 65) | 0.5 |
| 2 years | 50 (36, 66) | 50 (36, 66) | 50 (36, 66) | 0.7 |
| 3 years | 50 (36, 66) | 53 (38, 79) | 48 (36, 66) | 0.15 |
| Psychosocial well-being, median (IQR) | ||||
| Baseline | 64 (56, 82) | 70 (57, 92) | 64 (55, 80) | 0.2 |
| 6 months | 64 (50, 82) | 70 (50, 83) | 64 (50, 82) | 0.7 |
| 1 year | 66 (55, 85) | 69 (58, 84) | 66 (55, 84) | 0.7 |
| 2 years | 66 (56, 83) | 70 (56, 87) | 66 (56, 83) | 0.6 |
| 3 years | 64 (55, 83) | 69 (54, 90) | 54 (55, 83) | 0.7 |
Statistical significance analyzed by Wilcoxon rank sum
Abbreviations: IQR, interquartile range.
Figure 1.
Responses to BREAST-Q domains over time
Figure 2.
Comparison in change from preoperative to 6-month BREAST-Q domains
Several significant associations were apparent on univariate analysis (Table 3). PMRT and endocrine therapy were associated with lower satisfaction scores (p<0.001). Relative to autologous reconstruction, implant-based reconstruction was associated with lower satisfaction (p=0.001). These variables were not significant in the multivariable model (Table 4).
Table 3:
Univariate analysis
| Characteristic | Satisfaction with breasts Coeff. (95% CI) |
p-value | Sexual well-being Coeff. (95% CI) |
p-value | Psychological well-being Coeff. (95% CI); |
p-value |
|---|---|---|---|---|---|---|
| Non-carrier | −0.29 (−3.7, 3.1) | 0.9 | −2.4 (−6.9, 2.1) | 0.3 | −0.94 (−5.0, 3.1) | 0.6 |
| Age | −0.05 (−0.18, 0.08) | 0.5 | −0.06 (−0.23, 0.10) | 0.5 | 0.09 (−0.06, 0.24) | 0.3 |
| Race | 0.8 | 0.2 | ||||
| White | -- | 0.026 | -- | -- | ||
| Black | 1.5 (−3.8, 6.8) | 1.9 (−4.2, 7.9) | 1.1 (−4.7, 7.0) | |||
| Asian | −1.5 (−6.5, 3.4) | −1.2 (−6.5, 4.2) | −1.2 (−7.1, 4.7) | |||
| Other | −8.5 (−14, 2.8) | −2.6 (−9.7, 4.6) | −6.6 (−13, −0.17) | |||
| BMI | −0.22 (−0.47, 0.03) | 0.088 | −0.34 (−0.65, −0.02) | 0.039 | −0.40 (−0.67, −0.12) | 0.006 |
| Marital status | 0.3 | 0.061 | 0.025 | |||
| Married/Domestic partner | -- | -- | -- | |||
| Divorce/separated/widowed | −1.5 (−5.3, 2.4) | −6.2 (−12, −0.80) | −4.0 (−8.8, 0.87) | |||
| Single | −2.7 (−6.0, 0.67) | −2.3 (−6.8, 2.2) | −4.8 (−8.8, −0.88) | |||
| Clinical T stage | 0.080 | 0.3 | 0.2 | |||
| T1 | -- | -- | -- | |||
| T2 | −2.6 (−5.2, 0.10) | −1.9 (−5.3, 1.4) | −2.3 (−5.3, 0.74) | |||
| T3 | −4.2 (−9.3, 1.0) | −4.1 (−9.8, 1.6) | −3.4 (−9.4, 2.7) | |||
| Smoking status | 0.2 | 0.5 | 0.5 | |||
| Non-smoker | -- | −1.2 (−5.1, 2.7) | -- | |||
| Smoker | −2.0 (−5.1, 1.2) | -- | −1.3 (−4.8, 2.3) | |||
| Depression/anxiety | −3.8 (−7.9. 0.31) | 0.070 | −1.5 (−6.1, 3.0) | 0.5 | −8.8 (−14, −4.0) | <0.001 |
| Adjuvant chemotherapy | −1.3 (−3.8, 1.3) | 0.3 | −1.6 (−4.8, 1.6) | 0.3 | −1.6 (−4.5, 1.3) | 0.3 |
| Neoadjuvant chemotherapy | −1.4 (−4.3, 1.4) | 0.3 | −2.4 (−5.9, 1.1) | 0.2 | −1.8 (−4.9, 1.3) | 0.2 |
| PMRT | −8.9 (−12, −6.3) | <0.001 | −6.7 (−10.0, −3.4) | <0.001 | −6.4 (−9.5, −3.4) | <0.001 |
| Endocrine therapy | −5.3 (−8.3, −2.2) | <0.001 | −6.6 (−11, −2.7) | 0.001 | −3.5 (−6.9, −0.07) | 0.045 |
| Reconstruction | 0.001 | 0.2 | 0.2 | |||
| Autologous | -- | -- | -- | |||
| Implant-based | −5.4 (−8.7, −2.2) | −2.6 (−6.7, 1.5) | −2.7 (−6.5, 1.0) |
Statistical significance analyzed by general estimating equations. Variables are considered significant in the UVA if p <0.05.
Abbreviations: 95% CI, 95% confidence interval; IQR, interquartile range; BMI, body mass index; PMRT, post-mastectomy radiation therapy
Table 4:
Multivariable analysis for quality of life domains (p value considered significant if <0.016)
| Characteristic | Satisfaction with breasts Coeff. (95% CI) |
p-value | Sexual well-being Coeff. (95% CI) |
p-value | Psychological well-being Coeff. (95% CI) |
p-value |
|---|---|---|---|---|---|---|
| Non-carrier | 1.3 (−6.9, 9.4) | 0.8 | −0.34 (−7.7, 7.0) | >0.9 | 3.5 (−2.4, 9.5) | 0.2 |
| Race | 0.7 | |||||
| White | -- | − | ||||
| Black | 2.3 (−9.0, 14) | |||||
| Asian | −1.7 (−4.2, 7.7) | − | ||||
| Other | −6.3 (−18, 5.7) | |||||
| BMI | −0.16 (−0.64, 0.32) | 0.5 | −0.01 (−0.45, 0.44) | >0.9 | ||
| Marital status | 0.3 | |||||
| Married/Domestic partner | − | − | − | |||
| Divorce/separated/widowed | −1.9 (−10, 6.3) | |||||
| Single | −5.1 (−11, 1.2) | |||||
| Subtype | 0.5 | 0.3 | >0.9 | |||
| HR+ HER2− | ||||||
| HR− HER2+ | 6.7 (−2.2, 16) | 9.1 (−3.0, 21) | 3.5 (−6.2, 13) | |||
| HR+ HER2+ | 0.03 (−6.7, 6.8) | −1.9 (−8.8, 5.0) | 0.76 (−6.1, 7.6) | |||
| HR− HER2− | 1.0 (−7.2, 9.2) | −0.74 (−11, 9.0) | 1.2 (−7.0, 9.4) | |||
| Anxiety/depression | −3.4 (−9.1, 2.2) | 0.2 | ||||
| PMRT | −1.8 (−9.0, 13) | 0.7 | −8.0 (−12, −3.6) | <0.001 | −5.2 (−9.5, −0.92) | 0.017 |
| Endocrine therapy | 0.07 (−7.2, 7.3) | >0.9 | −7.3 (−17, 2.4) | 0.14 | −3.3 (−11, 4.4) | 0.4 |
| Implant-based reconstruction | −3.4 (8.6, 1.8) | 0.2 |
Higher BMI was associated with worse sexual well-being (p=0.039). Both PMRT and endocrine therapy were associated with lower sexual well-being scores (p<0.001 and p=0.001, respectively) on univariate analysis. After adjusting for potential confounders in the MVA, PMRT continued to be inversely associated with sexual well-being.
Several variables were negatively associated with psychological well-being; higher BMI, PMRT, endocrine therapy, history of depression and/or anxiety, and not being married were associated with worse psychological well-being (p=0.006, p<0.001, p=0.045, p<0.001, respectively). Of these, only PMRT remained significantly and negatively associated with psychological well-being on multivariable analysis (p=0.017).
DISCUSSION
The decision to pursue risk-reducing CPM differs in patients who have a hereditary predisposition to breast cancer compared to those with sporadic breast cancers. Patients and providers must weigh the degree to which risk of developing a second primary breast cancer is reduced by CPM against changes in postoperative QOL. This decision making can be significantly informed by PROMs. In this study, BRCA-carrier status was not associated with differences in QOL after bilateral mastectomy with immediate reconstruction in women with unilateral invasive breast cancer. After adjusting for clinically relevant variables, PMRT was the only factor that independently and negatively influenced sexual and psychological well-being.
The National Comprehensive Cancer Network (NCCN) recommends considering risk-reducing surgery or increased breast cancer surveillance in individuals with a deleterious BRCA mutation.18 Although the decision to pursue CPM is multifactorial, knowledge of mutational status has been shown to affect surgical decision-making. Chiba et al. found that after a diagnosis of breast cancer, 83% of women who were aware of their BRCA1/2 mutation chose CPM in comparison to 29% of women who did not know they had a mutation at the time of their initial breast cancer surgery.19 These data suggest that a subset of women with hereditary predisposition to breast cancer may have preferred unilateral mastectomy or breast-conserving surgery prior to identifying their genetic mutation. For these women, it is important to understand the psychosocial consequences and postoperative QOL after bilateral mastectomy.
Existing data has demonstrated that BRCA1/2 carriers who undergo CPM with immediate reconstruction have statistically similar satisfaction with breasts, psychosocial well-being, and sexual well-being at 1-year postoperatively relative to women who opt for surveillance.2 However, counseling BRCA carriers about QOL after CPM also requires insight into how satisfaction and well-being domains stabilize over time. To our knowledge, this is the first study that compares longitudinal trends in QOL domains after risk-reducing surgery for women with BRCA-associated breast cancer versus sporadic disease. Although BRCA carriers had a more pronounced initial decline in satisfaction with their breasts and psychosocial well-being compared to noncarriers, over time QOL was similar between cohorts. As a higher proportion of BRCA-associated disease was triple negative, this finding may reflect differences in tumor subtype and adjuvant treatment regimens between cohort which would have impacted the immediate postoperative period.
Baseline differences in QOL between BRCA carriers and noncarriers may have contributed to differences in the magnitude of decline in the first 6 months after surgery. The only significant difference between demographic and social factors that may potentially impact preoperative satisfaction was age. As women with genetic predisposition were younger at the time of their cancer diagnosis, it is possible that baseline satisfaction with breasts might reflect age-related differences. There is little data concerning factors that influence preoperative satisfaction scores or how age affects QOL after CPM. Nevertheless, earlier age at diagnosis among patients with BRCA mutations underscores the importance of long-term treatment sequela that continue into survivorship. Although patient age was not significantly associated with postoperative QOL domains in this study, it is an important parameter to consider when assessing risk for contralateral breast cancer and may shift risk-benefit assessment. Women who are diagnosed with BRCA-associated breast cancer before age 40 have the highest risk of developing contralateral disease.20,21,22 Understanding age-related variation in risk and possible survival benefit may change patient’s preferences for CPM, especially when acknowledging that even among those with a hereditary predisposition, CPM does not provide a survival benefit over surveillance.23
Several factors have been shown to negatively impact post-mastectomy quality of life including implant-based reconstruction (vs. autologous),24 PMRT,25 higher BMI,26 and single relationship status.27 In addition to these, we found that adjuvant endocrine therapy also was associated with lower satisfaction with breasts, psychosocial well-being, and sexual well-being on univariate analysis. After adjusting for relevant clinical variables, only PMRT was independently associated with diminished sexual and psychosocial well-being. This observation is consistent with work from others that PMRT is negatively associated with multiple quality of life domains.25 As existing data by us and others indicates that PMRT strongly affects QOL, patients who require it should be counseled accordingly during discussions regarding CPM.
We acknowledge several limitations of this study. The generalizability and applicability of the findings are affected by response rate variability and bias attributed to the retrospective single-institution nature of our data. Additionally, lack of granularity with respect to chemotherapy regimen, endocrine therapy and duration, and radiation treatments, which likely influenced patients’ experiences perioperatively, restrict our understanding of how oncologic resection and immediate reconstruction shape QOL. The comparison represented in this manuscript is of CPM among patients with and without hereditary predisposition for malignancy. Understanding how QOL differs between those at high risk for contralateral breast cancer who undergo CPM for risk-reduction and those at average risk who do not undergo CPM would be helpful in elucidating how much QOL gain and/or anxiety relief is achieved by CPM. Additional insight might come from understanding whether there are clinically meaningful differences that may not be statistically significant among BRCA1/2 carriers and noncarriers that choose CPM. Finally, we did not take into account other non-BRCA genetic mutations or use a validated risk model on non-carriers.
CONCLUSION
BRCA-carriers and noncarriers who undergo CPM and immediate reconstruction for unilateral breast cancer have comparable satisfaction and well-being despite differences in primary indication for CPM. These data may be particularly useful in counseling women regarding risk-reducing surgery who had preferred less aggressive surgical intervention prior to identifying their genetic mutation.
Acknowledgements
We would like to acknowledge the significant contribution of the Department of Plastic Surgery research project manager.
Footnotes
Conflicts of Interest
The authors have no relevant disclosures or conflicts of interest to disclose
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