Abstract
Background/Aim: The purpose was to analyze the impact of post-mastectomy radiation therapy (PMRT) on implant-based breast reconstruction (IBR) in self-identified Hispanic patients compared to non-Hispanic counterparts. Patients and Methods: We retrospectively reviewed patients who underwent IBR between January 1, 2017 and December 31, 2019 at a single hospital system. Patients were cisgender women, assigned female at birth, 18 years or older, and underwent mastectomy with immediate IBR +/− PMRT. We compared characteristics between Hispanic and non-Hispanic patients, assessing capsular contracture and implant loss rates. Multivariable analysis was performed to identify factors associated with complications. Results: A total of 317 patients underwent mastectomy and reconstruction. Of these patients, 302 underwent a total of 467 mastectomies with IBR, and these 467 procedures were included in the analysis of complications. Complications occurred in 175 breasts (37.5%), regardless of PMRT. Seventy-two of the 302 patients (24%) received PMRT to one breast. The overall rates of capsular contracture, implant loss, and overall complications did not vary significantly between Hispanic and non-Hispanic patients (p=0.866, 0.974, and 0.761, respectively). When comparing only irradiated patients, there was a trend towards increased implant loss and overall complication rates in Hispanic versus non-Hispanic patients (p=0.107 and 0.113, respectively). Following PMRT the rate of any complication was 71% in Hispanic women and 53% in non-Hispanic women. Conclusion: Our study illuminates a trend towards higher complication rates after PMRT in Hispanic versus non-Hispanic patients. Further studies are needed to understand why Hispanic patients may have more side effects from radiation therapy.
Breast cancer is the most common type of cancer as well as the leading cause of death in Hispanic women (1, 2). Studies in breast cancer have shown that Hispanic patients are more likely to present with overall later stage at diagnosis (3, 4) when compared to non-Hispanic white patients. Node positive disease increases the likelihood that patients undergoing surgery will be considered for post-mastectomy radiation therapy (PMRT) and be exposed to the potential side effects of radiation therapy. Those belonging to racial or ethnic minority groups are more likely to experience adverse health outcomes, making race and ethnicity important social determinants of health to control for when analyzing complications (5). Yet, race and ethnicity as predictive factors of complications have not been included in prior analyses assessing PMRT (5).
The primary role of PMRT is to eliminate occult disease, and it has been shown to reduce local recurrence and improve overall survival (OS) in appropriately selected patients (6). Generally, PMRT is reserved for locally advanced disease (T3N1, T4, N2-N3) and is not generally recommended for small, node negative tumors unless there are positive margins or other poor prognostic features. There is still debate regarding the use of PMRT for patients with intermediate risk disease (T1-2N1 disease or T3N0) (7), and decisions regarding PMRT are often individualized to balance the potential benefits with associated risks.
Approximately half of all patients who undergo mastectomy elect to have breast reconstruction (8). The discussion of the benefits versus complications of PMRT after breast reconstruction has become of greater interest as more clinical benefits of PMRT in high-risk patients are identified (9, 10). Prosthetic reconstruction is the most common type of breast reconstruction and includes insertion of either a permanent implant or a temporary tissue expander (TE) prior to implant placement (11). When prosthetic reconstruction is followed by radiation, there is an increased risk of complications, reoperation, and implant loss. The most commonly cited complications of PMRT after breast reconstruction are capsular contracture, pain, distortion, infection and need for reoperation (12). The rates of reconstruction failure vary by the type of prosthetic reconstruction, with higher rates in the setting of TE placement (13). Additionally, several factors have been shown to contribute to implant failure including poorly controlled diabetes, tobacco use, and elevated body mass index (BMI) (14). Nonetheless, it remains difficult to predict which patients will experience complications, and the decision regarding PMRT timing and breast reconstruction must involve shared decision making.
There is a paucity of data on skin toxicity for Hispanic patients receiving radiation therapy (15) though a population-based survey study showed that Latinos had higher self-reported toxicity severity (16). There has been more progress when discussing radiation-induced changes in African American patients with data suggesting worse radiation dermatitis in these patients (17-20). However, a more recent study which examined acute skin toxicity in a race and ethnically diverse breast cancer population including Hispanic white patients showed that while BMI predicted higher skin toxicity grade, race and ethnicity did not. This study did not focus on radiation outcomes in patients undergoing breast reconstruction (21). While studies like these demonstrate some progress in analyzing the effect of race on radiation complications, almost all compare non-Hispanic white and Black patients and mostly in the setting of breast conservation therapy. To our knowledge none have specifically addressed complications among Hispanic patients with implant-based reconstruction. We aimed to fill this knowledge gap by comparing differences in complication rates between Hispanic patients and non-Hispanic patients undergoing mastectomy with implant-based breast reconstruction (IBR) and the impact of PMRT on complication rates.
Patients and Methods
Study site and population. This retrospective cohort study was performed at the University of Miami Medical campus, comprised of the University of Miami Hospital, the Sylvester-Comprehensive Cancer Center, an NCI-designated Cancer Center, and the Jackson Health System, the associated partner safety-net hospital.
Patients who underwent mastectomy with reconstruction at University of Miami Medical campus between January 1, 2017, and December 31, 2019 were selected. Cisgender women assigned female at birth who were 18 years or older and underwent mastectomy with immediate IBR were included in the study. Patients who did not present to their follow-up visits were excluded. Patients who underwent autologous tissue reconstruction using a deep inferior epigastric perforator (DIEP) flap technique were included in demographic data but excluded from the statistical analysis of complications following IBR. Patient demographics, relevant clinical history, tumor information, treatment, and follow-up were abstracted from the medical records in accordance with an Institutional Review Board approved protocol and the Health Insurance Portability and Accountability Act (HIPAA). All patients were staged using the AJCC 7th edition staging system.
Outcome of interest. The primary objective of the study was to determine the difference in PMRT complications between Hispanic and non-Hispanic women. The secondary objective was to determine the overall complication rates between Hispanic and non-Hispanic patients in the setting of reconstruction, regardless of radiation status, and to identify additional variables that influence these complications. PMRT was considered adjuvant radiation to the reconstructed chest wall +/− the regional lymph nodes. The median dose was 50 Gy (range=42.56-60 Gy). A complication was defined as implant loss or Baker grade II or higher capsular contracture (22). For analysis of the entire patient population, implant losses were included if the patient had an emergent or unplanned surgery to remove or replace the implant due to infection (abscess formation, cellulitis), skin necrosis, high grade capsular contracture, or discomfort and cosmetic purposes. These implant losses were both acute related to surgery and long term. For patients who received PMRT, only implant loss and capsular contracture after the completion of PMRT were included.
Statistical analysis. Baseline differences and complication rates between Hispanic and non-Hispanic patients were assessed using Chi-square tests. A multivariable binary logistic regression was performed to determine predictors of developing any complications including receipt of PMRT, ethnicity, race, age (≤50 or >50), presence of obesity (defined as BMI ≥30), comorbid conditions, current smoking status, receipt of neoadjuvant chemotherapy (NAC), prior cosmetic breast surgery, and type of mastectomy and reconstruction performed.
Statistical analysis was performed using R version 4.2.1 (R Core Team, Vienna, Austria). All statistical tests were two-sided and deemed statistically significant at an alpha less than 0.05.
Results
Patient characteristics. A total of 351 patients underwent mastectomy with IBR during the time period. Of these, 34 patients were excluded for lack of follow up after surgery. The remaining 317 patients were included in the demographic analysis and 199 (62.0%) identified as Hispanic (Table I). Significant differences between the Hispanic and non-Hispanic patient cohorts included white race (95% of Hispanic patients vs. 71% of non-Hispanic patients, p<0.001), cancer stage at diagnosis of III or higher (7% of Hispanic patients vs. 16% of non-Hispanic patients, p=0.009), use of dermal matrix (70% of Hispanic patients vs. 82% of non-Hispanic patients, p=0.019), and use of skin sparing mastectomy (69% of Hispanic patients vs. 55% of non-Hispanic patients, p=0.035). The median age at time of mastectomy for all patients was 51 years old (range=19-83 years old). The median BMI was 26.5 (range=16.6-48.9), with 29% of patients with a BMI greater ≥30. Of the comorbidities analyzed, 5% of all patients were current tobacco users, 21% were former tobacco users, 6% had diabetes, and 2% had a known autoimmune disease, with no significant differences between the two groups.
The overall patient characteristics of our cohort.
Fifteen of the 317 patients underwent DIEP reconstruction and were excluded from further analysis of complications. Of the 302 remaining patients, 165 patients underwent bilateral mastectomy, and 137 patients underwent unilateral mastectomy, for a total of 467 breasts analyzed in our study. When analyzing the complications, each breast was considered a separate target of interest since each breast had independent risks for complications.
Analysis of complications. Complications occurred in 175 of 467 breasts (37.5%) that underwent IBR. Capsular contracture was observed in 19% of these breasts and implant loss in 23%. Multivariable analysis showed that PMRT (OR=4.39, 95%CI=2.10-9.59, p=0.0001) nipple-sparing mastectomy (NSM) (OR=1.80, 95%CI=1.13-2.87, p=0.0132), direct-to-implant (DTI) reconstruction (OR=1.92, 95%CI=1.23-3.00, p=0.0043), and NAC (OR=1.72, 95%CI=1.08-2.74, p=0.0229) were factors associated with an increased risk of complications (Table II) with PMRT having the most significant impact on complication rate.
The multivariable binomial logistic regression for overall complication rates.
Comparison of Hispanic and Non-Hispanic patients. The rates of capsular contracture, implant loss, and overall complications did not vary significantly between Hispanic and non-Hispanic patients (p=0.866, 0.974, and 0.761, respectively) (Table III). When comparing only irradiated patients, there was a trend towards increased implant loss and overall complication rates in Hispanic versus non-Hispanic patients (p=0.107 and 0.113, respectively) (Table IV) although this was not statistically significant. The rate of any complication in Hispanic patients following PMRT was 71%, while in non-Hispanic patients after PMRT the rate was 53%.
Comparison of the rates of complication in the breasts of all Hispanic and non-Hispanic patients, regardless of post-op radiation therapy.
Comparison of the rate of complications in the breasts of Hispanic and non-Hispanic patients who received post-mastectomy radiation therapy.
Comparison of patients with and without PMRT. Complication rates were significantly higher in patients who received PMRT compared to those who did not, regardless of ethnicity (Table V). However, a much stronger correlation was observed in Hispanic patients after PMRT compared to non-Hispanic patients. In the absence of PMRT, the rate of complications was about 30% in both groups. The rate of complications in Hispanic patients after PMRT increased significantly more than the rate of non-Hispanic patients. Hispanic patients who received PMRT were significantly more likely to develop a complication and have capsular contracture or implant loss compared to those who did not. For non-Hispanic patients there was only a significant difference in capsular contracture rates between those who did and did not receive PMRT but not overall complication rates or implant loss.
Comparison of the rate of complications in the breasts of patients who received and did not receive post-op radiation therapy (RT).
Discussion
The current rate of reconstruction failure or implant loss in patients with immediate IBR treated with PMRT ranges from 5% to 48% (14). While our study showed that NSM, DTI reconstruction, and NAC were associated with an increased risk of complications, PMRT (OR= 4.39) had the largest impact. This is consistent with previous studies, which analyzed factors associated with reconstructive failure and found that more adverse events could be attributed to PMRT than other patient characteristics and treatments (12, 14, 23).
When we examined the entire cohort of patients and compared complication rates between Hispanic and non-Hispanic patients who underwent mastectomy with IBR, there were no significant differences between the two groups, despite multiple differences in the patient characteristics of the two cohorts (race, stage at diagnosis, use of dermal matrix, and mastectomy type). Multivariable analysis showed that NSM, DTI reconstruction, NAC, and PMRT were associated with a statistically significant increase in risk of complications.
There are mixed reports in the literature regarding the impact of NSM, DTI reconstruction, and NAC on complication rates following mastectomy and IBR (24-33). Approximately 20% of patients undergoing NSM develop complications and the risk of skin necrosis is higher in patients undergoing NSM when compared to other mastectomy approaches (30, 33). Multiple studies show that DTI reconstruction is associated with higher complication rates and reconstruction loss (26-29, 31). A systematic review of one-stage DTI reconstruction compared to two-stage reconstruction showed that one-stage reconstruction was associated with a 2-fold higher risk of implant loss (OR=1.87, p=0.04) (27). In a systematic review and meta-analysis of complication rates following IBR after NAC, a statistically significant increase in implant/TE loss was observed after NAC, although overall complication rates were not increased (30). However, other analyses have not shown an increased rate of complications associated with NAC (25, 32). Of the 317 patients included in our study, 87 received NAC with 49/87 patients receiving PMRT. Due to the small sample size and significant impact of PMRT on implant loss, this could be a confounding factor.
The difference in complication rates between the two subgroups dramatically increased after PMRT from 38% to 62% for the entire cohort and to 71% and 53% in Hispanics and non-Hispanics, respectively. While it is well documented in the literature that PMRT increases the risk for capsular contracture, infection, and implant loss (12) there are no studies exploring complications among different races/ethnicities. We found that capsular contracture rates were similar between groups but implant loss rates were higher in Hispanic women after PMRT (44.7% vs. 26.5% for non-Hispanic patients), although this did not reach statistical significance. This may be due to the relatively small number of patients in the entire cohort who received PMRT. When comparing complication rates in Hispanic patients who did and did not receive PMRT, a significant increase in overall complication rates, capsular contracture and implant loss were observed. In non-Hispanic patients, there was only a significant increase in capsular contracture rates. This suggests that there may be differences in radiation toxicity in Hispanic patients compared to non-Hispanic patients.
While language barriers and other socioeconomic factors likely contribute to difference in care between ethnic groups, the effect of race and ethnicity itself has not been examined in most studies assessing radiation therapy toxicity. Toxicity studies often include race in their breakdown of patient characteristics, however, non-Hispanic white breast cancer patients are the most widely studied group (34). Although Hispanics are often grouped into the white category when selecting a race, Hispanics may have different genetic ancestry when compared to non-Hispanic whites and Black patients of African descent. There needs to be a stronger emphasis on including Hispanic ethnicity in studies as they are the second largest racial/ethnic group in the United States after non-Hispanic whites, with percentage only increasing (35).
To our knowledge, our study is the first study to address PMRT complications after IBR in Hispanic patients. However, there are several limitations to note including the fact that this is a single institution, retrospective study with a short follow-up period. Additionally, capsular contracture is a measurement based on a subjective grading scale and therefore assessment may vary by provider. This study also did not take into account the potential effects of adjuvant systemic therapy. Despite these factors, this study represents the first of its kind to assess Hispanic ethnicity as a factor contributing to PMRT complications after implant-based reconstruction.
Conclusion
Our study suggests a need to further explore complication rates of PMRT in the Hispanic population. While our data illuminates a trend towards increased complication rates in Hispanic patients after PMRT (71% in Hispanic compared to 53% in non-Hispanic), a larger patient cohort needs to be examined to determine the true significance of this difference. Additionally, further analysis needs to be performed to understand why Hispanic patients may have more side effects from PMRT than their non-Hispanic counterparts. Radiation sensitivity is a complex polygenic trait, but it is likely that there are differences between racial and ethnic groups in their risk of some radiation toxicities.
Footnotes
Authors’ Contributions
All Authors contributed to conceptualization, data curation, and review & editing. Original draft was written by Brianna Conte and Caroline Shermoen.
Conflicts of Interest
The Authors have no conflicts to interest to declare in relation to this study.
- Received September 5, 2023.
- Revision received October 4, 2023.
- Accepted October 5, 2023.
- Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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