Duchenne muscular dystrophy: promising early-stage clinical trials to watch.

INTRODUCTION: Current therapies are unable to cure Duchenne muscular dystrophy (DMD), a severe and common form of muscular dystrophy, and instead aim to delay disease progression. Several treatments currently in phase I trials could increase the number of therapeutic options available to patients. AREAS COVERED: This review aims to provide an overview of current treatments undergoing or having recently undergone early-stage trials. Several exon-skipping and gene therapy approaches are currently being investigated at the clinical stage to address an unmet need for DMD treatments. This article also covers Phase I trials from the last 5 years that involve inhibitors, small molecules, a purified synthetic flavanol, a cell-based therapy, and repurposed cardiac or tumor medications. EXPERT OPINION: With antisense oligonucleotide (AON) treatments making up the majority of conditionally approved DMD therapies, most of the clinical trials occurring within the last 5 years have also evaluated exon-skipping AONs. The approval of Elevidys, a micro-dystrophin therapy, is reflected in a recent trend toward gene transfer therapies in phase I DMD clinical trials, but their safety and efficacy are being established in this phase of development. Other Phase I clinical-stage approaches are diverse, but have a range in efficacy, safety, and endpoint measures.

Intraoperative Radiation Therapy: A Large Integrated Health Care System's Approach and Outcomes.

Introduction Intraoperative radiation therapy (IORT) may not be as effective in the community compared with clinical trials. Methods The authors reviewed data from the electronic health records of patients who received IORT between February 2014 and February 2020 at a single center within a large integrated health care system. The primary outcome was ipsilateral breast tumor recurrence. Results Of 5731 potentially eligible patients, 245 (4.3%) underwent IORT (mean age: 65.4 ± 0.4 years; median follow-up time: 3.5 years ± 2.2 months). According to the American Society for Radiation Oncology's accelerated partial breast irradiation guidelines based on final pathology, 51% of patients were suitable candidates for IORT, 38.4% were cautionary, and 10.6% were unsuitable. For adjuvant therapy, 6.5% had consolidative whole breast irradiation, and 66.4% received endocrine treatment. At the median follow-up time of 3.5 years, overall ipsilateral breast tumor recurrence was 3.7%. Recurrences tended to be more frequent in patients who refused or did not complete endocrine treatment than in those who received it (7.4% vs 1.9%, p = 0.07). The complication rate was 14.7%, with seroma being the most common (8.2%). Discussion The IORT ipsilateral breast tumor recurrence rate of 3.7% confirms a higher-than-expected rate compared to randomized clinical trials, possibly due to less compliance with endocrine therapy. Conclusion The authors subsequently revised their IORT protocol to require endocrine treatment as a part of the IORT treatment plan and to strongly recommend adjuvant whole breast irradiation for all patients deemed cautionary or unsuitable for IORT according to the American Society for Radiation Oncology's accelerated partial breast irradiation guidelines.

Gender-Affirming Mastectomy Trends and Surgical Outcomes in Adolescents.

Background: There are over 150,000 transgender adolescents in the United States, yet research on outcomes following gender-affirming mastectomy in this age group is limited. We evaluated gender-affirming mastectomy incidence, as well as postoperative complications, including regret, in adolescents within our integrated health care system. Methods: Gender-affirming mastectomies performed from January 1, 2013 - July 31, 2020 in adolescents 12-17 years of age at the time of referral were identified. The incidence of gender-affirming mastectomy was calculated by dividing the number of patients undergoing these procedures by the number of adolescents assigned female at birth ages 12-17 within our system at the beginning of each year and amount of follow-up time within that year. Demographic information, clinical characteristics (comorbidities, mental health history, testosterone use), surgical technique, and complications, including mention of regret, of patients who underwent surgery were summarized. Patients with and without complications were compared to evaluate for differences in demographic or clinical characteristics using chi-squared tests. Results: The incidence of gender-affirming mastectomy increased 13-fold (3.7 to 47.7 per 100,000 person-years) during the study period. Of the 209 patients who underwent surgery, the median age at referral was 16 years (range 12-17) and the most common technique was double-incision (85%). For patients with greater than 1-year follow-up (n=137, 65.6%), at least one complication was found in 7.3% (n=10), which included hematoma (3.6%), infection (2.9%), hypertrophic scars requiring steroid injection (2.9%), seroma (0.7%), and suture granuloma (0.7%); 10.9 % underwent revision (n=15). There were no statistically significant differences in patient demographics and clinical characteristics between those with and without complications (p>0.05). Two patients (0.95%) had documented postoperative regret but neither underwent reversal surgery at follow-up of 3 and 7 years postoperatively. Conclusion: Between 2013-2020, we observed a marked increase in gender-affirming mastectomies in adolescents. The prevalence of surgical complications was low and of over 200 adolescents who underwent surgery, only two expressed regret, neither of which underwent a reversal operation. Our study provides useful and positive guidance for adolescent patients, their families, and providers regarding favorable outcomes with gender-affirming mastectomy.

Telehealth for Preoperative Evaluation of Patients With Breast Cancer During the COVID-19 Pandemic.

Introduction The COVID-19 pandemic drove rapid, widespread adoption of telehealth (TH). We evaluated surgical telehealth utilization and outcomes for newly diagnosed breast cancer patients during the initial pandemic period. Methods We identified patients with breast cancer diagnosed March 17, 2020 through May 17, 2020 who underwent surgery as the initial treatment. Clinicodemographic characteristics were collected. Initial consultation types (office, telephone, or video) were categorized. Outcomes included time to consultation, surgeon touchpoints, time to surgery, surgery types, and reexcision rates. Continuous variables were compared using Mann-Whitney tests or t-tests, and categorical variables were compared using χ2 or Fisher's exact tests. Results Of 158 patients, 56% had initial telehealth consultations (21% telephone, 35% video) and 42% did not have a preoperative physical examination. Age, race/ethnicity, and stage distributions were similar between initial visit types. Median time to consultation was lower in the initial telehealth group than the office group (6 days vs 9 days, p = 0.01). Other outcomes (surgeon touchpoints, time to surgery, surgery type, reconstruction) were similar between visit types. We observed higher reexcision rates in patients with initial telehealth visits (20% telehealth vs 4% office, p = 0.01), but evaluation was limited by small numbers. The reexcision rate was 13% for patients with telehealth visits and no preoperative physical exam. Discussion During the initial pandemic period, the majority of new breast cancer patients had an initial telehealth surgical consultation. Office and telehealth consultation visits had comparable numbers of postconsultation surgeon touchpoints and most outcomes. Our findings suggest that telehealth consultations may be feasible for preoperative breast cancer consultations.

Economic Impact of Reducing Reexcision Rates after Breast-Conserving Surgery in a Large, Integrated Health System.

BACKGROUND: Reexcision after breast-conserving surgery (BCS) is costly for patients, but few studies have captured the economic burden to a healthcare system. We quantified operating room (OR) charges as well as OR time and then modeled expected savings of a reexcision reduction initiative. METHODS: We performed a retrospective cohort review of all breast cancer patients with BCS between January 1, 2016 and December 31, 2020. Operating room charges of disposable supplies and implants as well as operative time were calculated. RESULTS: During the 5-year period, the 8804 patients who underwent BCS, 1628 (18.5%) required reexcision. The reexcision cohort was younger (61 vs. 64 years, p < 0.001), more likely to have ductal carcinoma in situ (DCIS) (23.7% vs. 15.2%, p < 0.001), and had larger tumors (T1+T2 73.2% vs. 83.1%, p < 0.001). Reexcision costs represented 39% of total costs, the cost per patient for surgery was fourfold higher for reexcision patients. Reexcision operations comprised 14% of total operating room (OR) time (1848 of 13,030 hours). The reexcision rate for 54 surgeons varied from 7.2-39.0% with 46% (n = 25) having a reexcision rate >20%. A model simulating reducing reexcision rates to 20% or below for all surgeons reduced the reexcision rate to 16.2% overall. Using per procedure data, the model predicted a decrease in reexcision operations by 18% (327 operations), OR costs by 14% ($287,534), and OR time by 11% (204 hours). CONCLUSIONS: Reexcision after BCS represents 39% of direct OR costs and 14% of OR time in our healthcare system. Modest improvements in surgeon reexcision rates may lead to significant economic and OR time savings.

Care in the time of COVID-19: impact on the diagnosis and treatment of breast cancer in a large, integrated health care system.

PURPOSES: To delineate operational changes in Kaiser Permanente Northern California breast care and evaluate the impact of these changes during the initial COVID-19 Shelter-in-Place period (SiP, 3/17/20-5/17/20). METHODS: By extracting data from institutional databases and reviewing electronic medical charts, we compared clinical and treatment characteristics of breast cancer patients diagnosed 3/17/20-5/17/20 to those diagnosed 3/17/19-5/17/2019. Outcomes included time from biopsy to consultation and treatment. Comparisons were made using Chi-square or Wilcoxon rank-sum tests. RESULTS: Fewer new breast cancers were diagnosed in 2020 during the SiP period than during a similar period in 2019 (n = 247 vs n = 703). A higher percentage presented with symptomatic disease in 2020 than 2019 (78% vs 37%, p < 0.001). Higher percentages of 2020 patients presented with grade 3 (37% vs 25%, p = 0.004) and triple-negative tumors (16% vs 10%, p = 0.04). A smaller percentage underwent surgery first in 2020 (71% vs 83%, p < 0.001) and a larger percentage had neoadjuvant chemotherapy (16% vs 11%, p < 0.001). Telehealth utilization increased from 0.8% in 2019 to 70.0% in 2020. Times to surgery and neoadjuvant chemotherapy were shorter in 2020 than 2019 (19 vs 26 days, p < 0.001, and 23 vs 28 days, p = 0.03, respectively). CONCLUSIONS: During SiP, fewer breast cancers were diagnosed than during a similar period in 2019, and a higher proportion presented with symptomatic disease. Early-stage breast cancer diagnoses decreased, while metastatic cancer diagnoses remained similar. Telehealth increased significantly, and times to treatment were shorter in 2020 than 2019. Our system continued to provide timely breast cancer treatment despite significant pandemic-driven disruption.

Factors delaying chemotherapy in patients with breast cancer at a safety-net hospital.

BACKGROUND: Despite advances in healthcare and improved chemotherapy, disparities in breast cancer outcomes continue to persist. Our aim was to evaluate socioeconomic factors that may impact timing of treatment for patients receiving chemotherapy in underserved communities. METHODS: A review of patients with breast cancer who received neoadjuvant or adjuvant chemotherapy from 2015-2019 was conducted at a safety-net hospital. The primary outcomes were times from diagnosis to chemotherapy and surgery. Clinicodemographic factors including race, age, clinical stage, primary language, comorbidities, and median income by zip code were collected. Multivariable regression analysis was performed to evaluate for factors associated with the primary outcomes. RESULTS: One hundred patients were identified. For the neoadjuvant group, median time from diagnosis to chemotherapy and surgery was 52 ± 34 days and 256 ± 59 days, respectively. For the adjuvant group, median time from diagnosis to surgery and chemotherapy was 24.5 ± 18 days and 94.5 ± 53 days, respectively. Non-English language and older age were associated with increased time to chemotherapy in the adjuvant group (p < 0.05). Language and age were not associated with increased time to surgery in both groups. Race, age, comorbidities, and income were not associated with delay in treatment in either groups. CONCLUSIONS: Older age and non-English language were associated with prolonged time from surgery to adjuvant chemotherapy. Targeted interventions directed at patient education and decreasing language barriers especially post-operatively may decrease delays in treatment and subsequently reduce disparities seen in the breast cancer population.

Observational management of penetrating occult pneumothoraces: Outcomes and risk factors for interval tube thoracostomy placement.

BACKGROUND: Guidelines for penetrating occult pneumothoraces (OPTXs) are based on blunt injury. Further understanding of penetrating OPTX pathophysiology is needed. In observational management of penetrating OPTX, we hypothesized that specific clinical and radiographic features may be associated with interval tube thoracostomy (TT) placement. Our aims were to (1) describe OPTX occurrence in penetrating chest injury, (2) determine the rate of interval TT placement in observational management and clinical outcomes compared with immediate TT placement, and (3) describe risk factors associated with failure of observational management. METHODS: Penetrating OPTX patients presenting to our level 1 trauma center from 2004 to 2019 were reviewed. Occult pneumothorax was defined as a pneumothorax on chest computed tomography but not on chest radiograph. Patient groups included immediate TT placement versus observation. Clinical outcomes compared were TT duration and complications, need for additional thoracic procedures, length of stay (LOS), and disposition. Clinical and radiographic factors associated with interval TT placement were determined by multivariable regression. RESULTS: Of 629 penetrating pneumothorax patients, 103 (16%) presented with OPTX. Thirty-eight patients underwent immediate TT placement, and 65 were observed. Twelve observed patients (18%) needed interval TT placement. Regardless of initial management strategy, TT placement was associated with longer LOS and more chest radiographs. Chest injury complications and outcomes were similar. Factors associated with increased odds of interval TT placement included Chest Abbreviated Injury Scale score of ≥4 (adjusted odds ratio [aOR], 7.38 [95% confidence interval, 1.43-37.95), positive pressure ventilation (aOR, 7.74 [1.07-56.06]), concurrent hemothorax (aOR, 6.17 [1.08-35.24]), and retained bullet fragment (aOR, 11.62 [1.40-96.62]) (all p < 0.05). CONCLUSION: The majority of patients with penetrating OPTX can be successfully observed with improved clinical outcomes (LOS, avoidance of TT complications, reduced radiation). Interval TT intervention was not associated with risk for adverse outcomes. In patients undergoing observation, specific clinical factors (chest injury severity, ventilation) and imaging features (hemothorax, retained bullet) are associated with increased odds for interval TT placement, suggesting need for heightened awareness in these patients. LEVEL OF EVIDENCE: Prognostic, level IV.

An Epidemic Within the Pandemic: The Rising Tide of Trauma During COVID-19.

BACKGROUND: In the age of COVID-19 and enforced social distancing, changes in patterns of trauma were observed but poorly understood. Our aim was to characterize traumatic injury mechanisms and acuities in 2020 and compare them with previous years at our level I trauma center. MATERIAL AND METHODS: Patients with trauma triaged in 2016 through 2020 from January to May were reviewed. Patient demographics, level of activation (1 versus 2), injury severity score, and mechanism of injury were collected. Data from 2016 through 2019 were combined, averaged by month, and compared with data from 2020 using chi-squared analysis. RESULTS: During the months of interest, 992 patients with trauma were triaged in 2020 and 4311 in 2016-2019. The numbers of penetrating and level I trauma activations in January-March of 2020 were similar to average numbers for the same months during 2016 through 2019. In April 2020, there was a significant increase in the incidence of penetrating trauma compared with the prior 4-year average (27% versus 16%, P < 0.002). Level I trauma activations in April 2020 also increased, rising from 17% in 2016 through 2019 to 32% in 2020 (P < 0.003). These findings persisted through May 2020 with similarly significant increases in penetrating and high-level trauma. CONCLUSIONS: In the months after the initial spread of COVID-19, there was a perceptible shift in patterns of trauma. The significant increase in penetrating and high-acuity trauma may implicate a change in population dynamics, demanding a need for thoughtful resource allocation at trauma centers nationwide in the context of a global pandemic.

High Compliance With Choosing Wisely Breast Surgical Guidelines at a Safety-Net Hospital.

BACKGROUND: Professional organizations recently set guidelines for avoiding surgeries of low utility and overutilization for the Choosing Wisely campaign. These include re-excision for invasive cancer close to margins, double mastectomy in patients with unilateral breast cancer, axillary lymph node dissection in patients with limited nodal disease, and sentinel lymph node biopsy (SLNB) in patients ≥70 years with early-stage breast cancer. Variable adherence to these recommendations led us to evaluate implementation rates of low-value surgical guidelines at a safety-net hospital. METHODS: We retrospectively analyzed breast cancer patients who underwent surgery from 2015 to 2020. Each patient was assessed for eligibility for omission of the listed surgeries. Trends were evaluated by cohorts before and after a fellowship-trained breast surgeon joined the faculty in 2018. Outcomes were compared using Fisher's exact test. RESULTS: Among 195 patients, none underwent re-excision for close margins of invasive cancer. Only 6.7% of patients (3/45) received contralateral mastectomy and 1.8% of eligible patients (3/169) received axillary lymph node dissection. Overall, 60% of patients ≥ 70 years with stage 1 hormone-positive breast cancer (9/15) received SLNB. There was a downward trend from 71% of eligible patients receiving SLNB in 2015-2018 to 50% in 2019-2020. CONCLUSIONS: De-implementation of traditional surgical practices, deemed as low-value care, toward newer guidelines is achievable even at community hospitals serving a low socioeconomic community. By avoiding overtreatment, hospitals can achieve effective resource allocation which allow for social distributive justice among patients with breast cancer and ensure strategic use of scarce health economic resources while preserving patient outcomes.

A practical methodology to improve the dosimetric accuracy of MR-based radiotherapy simulation for brain tumors.

PURPOSE: To investigate the dosimetric accuracy of synthetic computed tomography (sCT) images generated by a clinically-ready voxel-based MRI simulation package, and to develop a simple and feasible method to improve the accuracy. METHODS: 20 patients with brain tumor were selected to undergo CT and MRI simulation. sCT images were generated by a clinical MRI simulation package. The discrepancy between planning CT and sCT in CT number and body contour were evaluated. To resolve the discrepancies, an sCT specific CT-relative electron density (RED) calibration curve was used, and a layer of pseudo-skin was created on the sCT. The dosimetric impact of these discrepancies, and the improvement brought about by the modifications, were evaluated by a planning study. Volumetric modulated arc therapy (VMAT) treatment plans for each patient were created and optimized on the planning CT, which were then transferred to the original sCT and the modified-sCT for dose re-calculation. Dosimetric comparisons and gamma analysis between the calculated doses in different images were performed. RESULTS: The average gamma passing rate with 1%/1 mm criteria was only 70.8% for the comparison of dose distribution between planning CT and original sCT. The mean dose difference between the planning CT and the original sCT were -1.2% for PTV D95 and -1.7% for PTV Dmax, while the mean dose difference was within 0.7 Gy for all relevant OARs. After applying the modifications on the sCT, the average gamma passing rate was increased to 92.2%. Mean dose difference in PTV D95 and Dmax were reduced to -0.1% and -0.3% respectively. The mean dose difference was within 0.2 Gy for all OAR structures and no statistically significant difference were found. CONCLUSIONS: The modified-sCT demonstrated improved dosimetric agreement with the planning CT. These results indicated the overall dosimetric accuracy and practicality of this improved MR-based treatment planning method.

Implementation of Intraoperative Ultrasound Localization for Breast-Conserving Surgery in a Large, Integrated Health Care System is Feasible and Effective.

BACKGROUND: Intraoperative ultrasound (IUS) localization for breast cancer is a noninvasive localization technique. In 2015, an IUS program for breast-conserving surgery (BCS) was initiated in a large, integrated health care system. This study evaluated the clinical results of IUS implementation. METHODS: The study identified breast cancer patients with BCS from 1 January to 31 October 2015 and from 1 January to 31 October 2019. Clinicopathologic characteristics were collected, and localization types were categorized. Clinical outcomes were analyzed, including localization use, surgeon adoption of IUS, day-of-surgery intervals, and re-excision rates. Multivariate logistic regression analysis was performed to evaluate predictors of re-excision. RESULTS: The number of BCS procedures increased 23%, from 1815 procedures in 2015 to 2226 procedures in 2019. The IUS rate increased from 4% of lumpectomies (n = 79) in 2015 to 28% of lumpectomies (n = 632) in 2019 (p < 0.001). Surgeons using IUS increased from 6% (5 of 88 surgeons) in 2015 to 70% (42 of 60 surgeons) in 2019. In 2019, 76% of IUS surgeons performed at least 25% of lumpectomies with IUS. The mean time from admission to incision was shorter with IUS or seed localization than with wire localization (202 min with IUS, 201 with seed localization, 262 with wire localization in 2019; p < 0.001). The IUS re-excision rates were lower than for other localization techniques (13.6%, vs 19.6% for seed localization and 24.7% for wire localization in 2019; p = 0.006), and IUS predicted lower re-excision rates in a multivariable model (odds ratio [OR], 0.59). CONCLUSIONS: In a high-volume integrated health system, IUS was adopted for BCS by a majority of surgeons. The use of IUS decreased the time from admission to incision compared with wire localization, and decreased re-excision rates compared with other localization techniques.

Health Equity Within Inequity: Timing of Diagnostic Breast Cancer Care in an Underserved Medical Population.

BACKGROUND/AIM: We evaluated timeliness of care at a safety-net hospital after implementation of a multidisciplinary breast program. PATIENTS AND METHODS: A prospective database of patients with breast cancer was created after multidisciplinary breast program initiation in 2018. Patients were tracked to obtain time to completion of diagnostic imaging, biopsy, and treatment initiation. Patients with breast cancer diagnosed from 2015-2017 were reviewed for comparison. RESULTS: A total of 102 patients were identified. There was no statistical difference in time to completion of imaging, biopsy, and initial treatment between the 2018 and the 2015-2017 cohorts (p>0.05). No statistical difference was observed in time to completion of imaging, biopsy, and initial treatment between different races (p>0.05). CONCLUSION: Within the same socioeconomic status, there was no differential delivery of screening, work-up, and treatment by race. Despite protocol implementations, efficiency of care remained limited in a safety-net hospital with lack of financial resources.

Relationship between body mass index and malignancy rates of MRI-guided breast biopsies: impact of clinicodemographic factors.

PURPOSE: To determine the positive predictive value (PPV) of magnetic resonance imaging (MRI)-guided breast biopsy stratified by body mass index (BMI). Secondary endpoints include evaluation of indications for breast MRI and identification of factors associated with malignant biopsy. METHODS: We retrospectively analyzed results of MRI-guided breast biopsies in a consecutive cohort of women at a single institution between 2014 and 2019. The PPV was compared between BMI subgroups and the overall group by the one-sample z-test. Factors associated with malignant biopsy were analyzed using multivariate regression analysis. RESULTS: Among 427 MRI-guided breast biopsies, the PPV was significantly higher in patients with a BMI ≥ 35 compared to BMI < 35 (38.6% versus 24.5%, p = 0.043). This remained true in the 180 biopsies from high-risk screening studies, but there was no difference in PPV by BMI in the 205 biopsies performed to evaluate extent of known disease. Among this cohort who underwent MRI-guided breast biopsy, the underlying indication for MRI was less likely to be high-risk screening in those with a higher BMI or Black or Hispanic race (p = 0.015 and p < 0.001, respectively). For high-risk screening studies, only BMI ≥ 35 was associated with malignant biopsies (OR 37.5, p = 0.003). For evaluation of extent of disease studies, only increased lesion size was a significant predictor of malignant result (OR 1.01, p = 0.04). CONCLUSIONS: Among women who underwent MRI-guided breast biopsy, elevated BMI was associated with increased PPV and malignant biopsies. Patients with a higher BMI or Black or Hispanic race who had MRI-guided biopsy were less likely to be undergoing high-risk screening and more likely to have breast MRI to evaluate extent of known disease.

Patients Older 65 Years With Early Breast Cancer Prefer Intraoperative Radiation as a Locoregional Treatment Choice.

BACKGROUND: Patients 65 years old or older with early endocrine-responsive breast cancer have many treatment options, including no radiation. This study aimed to evaluate treatment preference when intraoperative radiation therapy (IORT) is offered in this population. METHODS: The study reviewed patients 65 years old or older with a diagnosis of early-stage endocrine-responsive breast cancer in 2016-2019 at a single hospital in a large integrated health care system. Electronic medical records of multidisciplinary breast tumor board discussion, treatment options documented by the treatment team, and final treatment offered were reviewed. Variables including age at biopsy, language, endocrine treatment, and comorbidities were collected. Regression analysis was used to evaluate for variables associated with patients' choice regarding radiation treatment. RESULTS: The institutional IORT guidelines were met by 63 patients in the described age group who had a documented offer of all radiation treatment options. The median age of the patients was 70 years (interquartile range 63-77 years). Overall, 74.6% of the patients chose IORT, and 14.3% opted for whole-breast irradiation. Only 4.8% chose to omit radiation after breast-conserving surgery, and 6.3% chose mastectomy. The patients who chose IORT were more likely to receive endocrine treatment (odds ratio 3.70; p = 0.03). Age, race, language, and comorbidities were not associated with preference for IORT (p < 0.05). CONCLUSIONS: Patients 65 years old or older with early-stage endocrine-responsive breast cancer preferred to have IORT despite counsel about the lack of survival benefit. This study suggests that local cancer control with the convenient radiation delivery method is important to the described patient population.

Gender-Affirming Mastectomy in Transmasculine Patients: Does Obesity Increase Complications or Revisions?

BACKGROUND: Obesity can often be a barrier to gender-affirming top surgery in transmasculine patients because of concern for increased surgical site complications. STUDY DESIGN: All adult patients (N = 948) within an integrated health care system who underwent gender-affirming mastectomy from 2013 to 2018 were retrospectively reviewed to evaluate the relationship between obesity and surgical site complications or revisions. RESULTS: One third of patients (n = 295) had obese body mass index (BMI), and those patients were further stratified into obesity class I (BMI of 30-34.9 kg/m2, 9.4%), class II (BMI of 35-39.9 kg/m2, 8.9%), and class III (BMI of ≥40 kg/m2, 2.9%). A majority of patients across BMI categories underwent double incision surgery. There were no significant differences in complications or revisions between patients with obesity versus those with normal BMI, when BMI was treated as a categorical or continuous variable and when evaluating only patients who underwent double incision surgery. CONCLUSIONS: Obesity alone should not be considered a contraindication for gender-affirming mastectomy. Attention should be given to several modifiable risk factors identified in this study, including lesser incision surgical techniques, tobacco use, and testosterone use. Further research is needed to understand risks associated with the highest BMI (≥40 kg/m2) patients and to assess patient satisfaction with surgical outcome.