Background:Early-stage breast cancer has the complex challenge of carrying a favorable prognosis with multiple treatment options, including breast-conserving surgery (BCS) or mastectomy. Social media is increasingly used as a source of information and as a decision tool for patients, and awareness of these conversations is important for patient counseling. Objective:The goal of this study was to compare sentiments and associated emotions in social media discussions surrounding BCS and mastectomy using natural language processing (NLP). Methods:Reddit posts and comments from the Reddit subreddit r/breastcancer and associated metadata were collected using pushshift.io. Overall, 105,231 paragraphs across 59,416 posts and comments from 2011 to 2021 were collected and analyzed. Paragraphs were processed through the Apache Clinical Text Analysis Knowledge Extraction System and identified as discussing BCS or mastectomy based on physician-defined Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) concepts. Paragraphs were analyzed with a VADER (Valence Aware Dictionary for Sentiment Reasoning) compound sentiment score (ranging from -1 to 1, corresponding to negativity or positivity) and GoEmotions scores (0-1) corresponding to the intensity of 27 different emotions and neutrality. Results:Of the 105,231 paragraphs, there were 7306 (6.94% of those analyzed) paragraphs mentioning BCS and mastectomy (2729 and 5476, respectively). Discussion of both increased over time, with BCS outpacing mastectomy. The median sentiment score for all discussions analyzed in aggregate became more positive over time. In specific analyses by topic, positive sentiments for discussions with mastectomy mentions increased over time; however, discussions with BCS-specific mentions did not show a similar trend and remained overall neutral. Compared to BCS, conversations about mastectomy tended to have more positive sentiments. The most commonly identified emotions included neutrality, gratitude, caring, approval, and optimism. Anger, annoyance, disappointment, disgust, and joy increased for BCS over time. Conclusions:Patients are increasingly participating in breast cancer therapy discussions with a web-based community. While discussions surrounding mastectomy became increasingly positive, BCS discussions did not show the same trend. This mirrors national clinical trends in the United States, with the increasing use of mastectomy over BCS in early-stage breast cancer. Recognizing sentiments and emotions surrounding the decision-making process can facilitate patient-centric and emotionally sensitive treatment recommendations.

Purpose/Objective(s) Patients with breast cancer who desire breast conservation often receive lumpectomy followed by adjuvant radiation therapy (RT). Hypofractionation and ultra-hypofractionation have necessitated greater interprofessional collaboration to optimize dose homogeneity and side effect profiles at higher doses per fraction. We hypothesized that the implementation of an interprofessional breast RT curriculum would increase learners’ knowledge of clinical care and comfort with interprofessional collaboration. Materials/Methods We developed a novel two-week breast RT curriculum consisting of integrated clinical and didactic components, which we piloted with 3 cohorts of interprofessional learners from 10/2022 to 3/2023. Role-specific learning objectives were provided for each profession. We conducted a mixed methods analysis of learners’ perceptions of curriculum impact. Pre- and post-curriculum surveys were administered with IRB approval, and two-tailed paired t-tests determined differences in scores on a 5-point Likert scale (1: Not at all comfortable to 5: Extremely comfortable). Listening sessions with each cohort of learners were analyzed qualitatively. Results Ten interprofessional learners, including physics residents (n = 3), radiation oncology residents (n = 2), breast surgery fellows (n = 2), a dosimetrist (n = 1), a nurse (n = 1), and a medical student (n = 1), completed the pre- and post-curriculum surveys (response rate 100%). Most (60%) had prior lectures on breast RT and associated toxicity management but not clinical experiences (20%). From pre- to post-curriculum, in role-specific domains, there were increases in self-rated comfort with performing breast exams (2.7 vs 3.6, p = 0.009), assessing and managing radiation dermatitis (1.6 vs 3.9, p < 0.001), assessing and managing lymphedema (2.0 vs 3.4, p = 0.004), counseling patients on skin toxicities (2.0 vs 4.1, p < 0.001), positioning patients at simulation (1.5 vs 3.5, p = 0.002), and assessing RT plans (2.1 vs 3.6, p = 0.002). Nearly all (90%) reported that the amount of time spent on lectures, contouring, and treatment planning were each “just right.” Thematic analysis highlighted that the curriculum increased understanding of patient experiences, departmental workflows, and specific collaborative care opportunities during breast RT. Conclusion An integrated clinical and didactic curriculum on breast RT positively impacted learners’ understanding of treatment planning, skin care, and interprofessional collaboration. Further studies are needed to assess the impact and sustainability of these skills across clinical environments.

Coronary reperfusion after acute ST-elevation myocardial infarction (STEMI) is standard therapy to salvage ischemic heart muscle. However, subsequent inflammatory responses within the infarct lead to further loss of viable myocardium. Transforming growth factor (TGF)-beta 1 is a potent anti-inflammatory cytokine released in response to tissue injury. The aim of this study was to investigate the protective effects of TGF-beta 1 after MI. In patients with STEMI, there was a significant correlation (P = 0.003) between higher circulating TGF-beta 1 levels at 24 hours after MI and a reduction in infarct size after 3 months, suggesting a protective role of early increase in circulating TGF-beta 1. A mouse model of cardiac ischemia reperfusion was used to demonstrate multiple benefits of exogenous TGF-beta 1 delivered in the acute phase. It led to a significantly smaller infarct size (30% reduction, P = 0.025), reduced inflammatory infiltrate (28% reduction, P = 0.015), lower intracardiac expression of inflammatory cytokines IL-1 beta and chemokine (C-C motif) ligand 2 (>50% reduction, P = 0.038 and 0.0004, respectively) at 24 hours, and reduced scar size at 4 weeks (21% reduction, P = 0.015) after reperfusion. Furthermore, a low-fibrogenic mimic of TGF-beta 1, secreted by the helminth parasite Heligmosomoides polygyrus, had an almost identical protective effect on injured mouse hearts. Finally, genetic studies indicated that this benefit was mediated by TGF-beta signaling in the vascular endothelium.

Purpose/Objective(s) The luminal B (LumB) breast cancer subtype is a prognostic and potentially predictive biomarker. LumB is inherently a cell subtype (as its name suggests) but has mostly been studied as a bulk tumor subtype, in large part because tumor profiling techniques have only recently begun to offer single-cell resolution. We sought to leverage single-cell proteomic data from two large cohorts with known long-term clinical outcomes to determine whether enrichment of the LumB cell subtype was associated with resistance to endocrine therapy in breast cancer. Materials/Methods Imaging mass cytometry data from a training cohort (METABRIC) and separate validation cohort were obtained and integrated. Patients with non-metastatic breast cancer who received surgery and adjuvant hormone therapy were included. Cell subtypes were defined using the Phenograph cell-clustering approach. Per-sample “cell fraction” of a given cell subtype was defined as cell count of that subtype divided by total number of cancer cells in the sample. The optimal cutpoint for defining LumB cell enrichment in the training cohort was determined using the maximally selected rank statistic approach, and the same cutpoint was used in the validation cohort. Distant metastasis free survival (DMFS) was the clinical endpoint for all univariate and multivariable (cause-specific proportional hazards) survival analyses. Resistance to endocrine therapy was defined at time of data collection as disease progression within 58 months of initiating endocrine therapy. Results Single-cell expression data for 1,335,512 cells from 929 breast cancer tumor biopsies comprising two cohorts were aggregated and harmonized. Single-cell clustering analysis revealed 34 distinct breast, stromal, and immune cell subtypes. Ten breast cancer cell subtypes demonstrated a co-expression pattern of hormone receptor positivity (HR+) and either Ki-67+ or HER2+, most consistent with a LumB or “LumB-like” expression profile. 353 patients in the training cohort and 161 patients in the validation cohort received adjuvant endocrine therapy and had long-term clinical follow-up. In the training cohort, patients with LumB-enriched tumors demonstrated shorter 10-year DMFS than those with LumB non-enriched tumors (70% vs. 82%, P<0.05). On multivariable analysis, LumB cell enrichment was prognostic of 10-year DMFS (HR 1.73; 95% CI, 1.04 to 2.87) independently of other known prognostic factors including tumor grade, T-stage, and lymph node positivity status. In the validation cohort, LumB cell enrichment was associated with resistance to endocrine therapy (33% vs. 18%, chi-square P<0.05). Conclusion Enrichment of LumB cells was associated with resistance to hormone therapy in two independent breast cancer cohorts. Our single-cell biomarker for LumB enrichment can be used to identify patients less likely to demonstrate durable response to hormone therapy and who may benefit from treatment intensification through other strategies.

IMPORTANCE Postmastectomy radiation therapy (PMRT) improves local-regional disease control and patient survival. Hypofractionation (HF) regimens have comparable efficacy and complication rates with improved quality of life compared with conventional fractionation (CF) schedules. However, the use of HF after mastectomy in patients undergoing breast reconstruction has not been prospectively examined. OBJECTIVE To compare HF and CF PMRT outcomes after implant-based reconstruction. DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial assessed patients 18 years or older undergoing mastectomy and immediate expander or implant reconstruction for breast cancer (Tis, TX, or T1-3) and unilateral PMRT from March 8, 2018, to November 3, 2021 (median [range] follow-up, 40.4 [15.4-63.0] months), at 16 US cancer centers or hospitals. Analyses were conducted between September and December 2023. INTERVENTIONS Patients were randomized 1:1 to HF or CF PMRT. Chest wall doses were 4256 cGy for 16 fractions for HF and 5000 cGy for 25 fractions for CF. Chest wall toxic effects were defined as a grade 3 or higher adverse event. MAIN OUTCOMES AND MEASURES The primary outcome was the change in physical well-being (PWB) domain of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality-of-life assessment tool at 6 months after starting PMRT, controlling for age. Secondary outcomes included toxic effects and cancer recurrence. RESULTS Of 400 women (201 in the CF arm and 199 in the HF arm; median [range] age, 47 [23-79] years), 330 patients had PWB scores at baseline and at 6 months. There was no difference in the change in PWB between the study arms (estimate, 0.13; 95% CI, -0.86 to 1.11; P = .80), but there was a significant interaction between age group and study arm (P = .03 for interaction). Patients younger than 45 years had higher 6-month absolute PWB scores if treated with HF rather than CF regimens (23.6 [95% CI, 22.7-24.6] vs 22.0 [95% CI, 20.7-23.3]; P = .047) and reported being less bothered by adverse effects (mean [SD], 3.0 [0.9] in the HF arm and 2.6 [1.2] in the CF arm; P = .02) or nausea (mean [SD], 3.8 [0.4] in the HF arm and 3.6 [0.8] in the CF arm; P = .04). In the as-treated cohort, there were 23 distant (11 in the HF arm and 12 in the CF arm) and 2 local-regional (1 in the HF arm and 1 in the CF arm) recurrences. Chest wall toxic effects occurred in 39 patients (20 in the HF arm and 19 in the CF arm) at a median (IQR) of 7.2 (1.8-12.9) months. Fractionation was not associated with chest wall toxic effects on multivariate analysis (HF arm: hazard ratio, 1.02; 95% CI, 0.52-2.00; P = .95). Fewer patients undergoing HF vs CF regimens had a treatment break (5 [2.7%] vs 15 [7.7%]; P = .03) or required unpaid time off from work (17 [8.5%] vs 34 [16.9%]; P = .02). CONCLUSIONS AND RELEVANCE In this randomized clinical trial, the HF regimen did not significantly improve change in PWB compared with the CF regimen. These data add to the increasing experience with HF PMRT in patients with implant-based reconstruction.

MOV file - 868K, Supplementary Movie 4. Inhibitory Anti-Beta1 Integrin mAb OS2966 Disrupts BRG3 Adhesion, Spreading, And Migration. Related to Figure 2. Timelapse phase-contrast imaging of BRG3 bevacizumab-resistant cells on fibronectin demonstrates mesenchymal migration of control (10 μg/ml IgG, left) cells into the wound in a scratch wound healing assay. In contrast, BRG3 cells in the treatment condition (10μg/ml OS2966, right) rapidly lose adhesive contacts to the substrate (within 20-30 mins) and are unable to migrate into the wound. Movie images captured with a 40x objective representing approximately 10 hours of imaging, 35 minutes between each frame.

Rationale Successful and timely coronary reperfusion following acute ST-elevation myocardial infarction (STEMI) is standard therapy to salvage transiently ischaemic heart muscle. However, the subsequent inflammatory response within the infarct can lead to further loss of viable myocardium. Robust interventions are required in the acute MI setting to minimise cardiac injury and reduce risk of further detrimental progression. Objective TGFβ1 is an anti-inflammatory cytokine released endogenously in response to infection or tissue injury. The goal of this study was to investigate its protective effects when given exogenously following myocardial infarction. Methods and Results TGFβ1 is found at increased levels in the blood of STEMI patients immediately following myocardial infarction. We observe a significant correlation (p=0.003) between higher circulating TGFβ1 levels at 24h post MI and a reduction in infarct size over the following 3 months, suggesting that an early increase in circulating TGFβ1 is protective in these patients. Using a mouse model of cardiac ischaemia-reperfusion we demonstrate that additional exogenous TGFβ1 delivered in the acute setting has multiple beneficial outcomes. At 24 hours post-reperfusion It leads to a significantly smaller infarct size (30% reduction, p=0.025), reduced inflammatory infiltrate (28% reduction, p=0.015), lower intra-cardiac expression of inflammatory cytokines IL1β and CCL2 (>50 % reduction, p=0.038 and 0.0004, respectively) and reduced scar size at 4 weeks (21% reduction, p=0.015). Furthermore exogenous delivery of an equivalent dose of HpTGM, a recently described low-fibrogenic mimic of TGFβ1, secreted by a helminth parasite to evade immune rejection, has an almost identical protective effect on injured mouse hearts. Furthermore using a genetic approach we show the benefit is mediated by the vascular endothelium. Conclusions This work reveals the potential of exogenous TGFβ1 and HpTGM delivered in the acute MI setting to provide protective anti-inflammatory effects and reduce infarct size, leading to a smaller scar and reduced detrimental progression.

MOV file - 1367K, Supplementary Movie 2. Beta1 Integrin Knockdown Impairs BRG Migration. Related to Figure 2. Timelapse phase-contrast imaging of BRG3 bevacizumab-resistant cells on fibronectin demonstrates mesenchymal migration of control (shCTRL, left) cells into the wound in a scratch wound assay. In contrast, migration of beta1 knockdown cells (shB1-c6, right) is significantly attenuated . As in Supplementary Movie 1, knockdown cells demonstrate impaired ability to spread upon the fibronectin substrate (rounded, phasebright cells). Movie images captured with a 40x objective representing approximately 16 hours of imaging, 35 minutes between each frame.

Supplementary Methods, Figure Legends 1-3 from Breast Cancer Cells in Three-dimensional Culture Display an Enhanced Radioresponse after Coordinate Targeting of Integrin α5β1 and Fibronectin

MOV file - 1285K, Supplementary Movie 3. Epithelial Migration Of Bevacizumab-Na�ve Glioma Cells. Related to Figure 2. Timelapse phase-contrast imaging of N1 bevacizumab-na�ve (left) and BRG3 bevacizumab-resistant (right) cells on fibronectin. N1 cells demonstrated classic epithelial migration with broad lamellipodial extensions and slow rearward translocation with an overall polygonal morphology. In contrast, BRG3 cells display rapid, saltatory migration with spindle-like morphology. Movie images captured with a 40x objective representing approximately 14 hours of imaging, 35 minutes between each frame.

<p>PDF File - 1444K, Interactions of �1-integrin with NF-�B p65 and �5-integrin were oppositely regulated in 3D lrECM in S1 and T4-2 cells after radiation.</p>

Supplementary Figure 1 from β₁ Integrin Inhibitory Antibody Induces Apoptosis of Breast Cancer Cells, Inhibits Growth, and Distinguishes Malignant from Normal Phenotype in Three Dimensional Cultures and <i>In vivo</i>

Supplementary Figure 2 from Breast Cancer Cells in Three-dimensional Culture Display an Enhanced Radioresponse after Coordinate Targeting of Integrin α5β1 and Fibronectin

<p>PDF File - 1455K, Radiation-induced phospho and total �1-integrin and focal adhesion kinase (FAK) expressions were downregulated by NF-�B inhibitor.</p>

Purpose:The aim of this work was two-fold: a) to assess two treatment planning strategies for accounting CT artifacts introduced by temporary tissue-expanders (TTEs); b) to evaluate the dosimetric impact of two commercially available and one novel TTE.Methods:The CT artifacts were managed using two strategies. 1) Identifying the metal in the RayStation treatment planning software (TPS) using image window-level adjustments, delineate a contour enclosing the artifact, and setting the density of the surrounding voxels to unity (RS1). 2) Registering a geometry template with dimensions and materials from the TTEs (RS2). Both strategies were compared for DermaSpan, AlloX2, and AlloX2-Pro TTEs using Collapsed Cone Convolution (CCC) in RayStation TPS, Monte Carlo simulations (MC) using TOPAS, and film measurements. Wax slab phantoms with metallic ports and breast phantoms with TTEs balloons were made and irradiated with a 6 MV AP beam and partial arc, respectively. Dose values along the AP direction calculated with CCC (RS2) and TOPAS (RS1 and RS2) were compared with film measurements. The impact in dose distributions was evaluated with RS2 by comparing TOPAS simulations with and without the metal port.Results:For the wax slab phantoms, the dose differences between RS1 and RS2 were 0.5% for DermaSpan and AlloX2 but 3% for AlloX2-Pro. From TOPAS simulations of RS2, the impact in dose distributions caused by the magnet attenuation was (6.4 ± 0.4) %, (4.9 ± 0.7)%, and (2.0 ± 0.9)% for DermaSpan, AlloX2, and AlloX2-Pro, respectively. With breast phantoms, maximum differences in DVH parameters between RS1 and RS2 were as follows. For AlloX2 at the posterior region: (2.1 ± 1.0)%, (1.9 ± 1.0)% and (1.4 ± 1.0)% for D1, D10, and average dose, respectively. For AlloX2-Pro at the anterior region (-1.0 ± 1.0)%, (-0.6 ± 1.0)% and (-0.6 ± 1.0)% for D1, D10 and average dose, respectively. The impact in D10 caused by the magnet was at most (5.5 ± 1.0)% and (-0.8 ± 1.0)% for AlloX2 and AlloX2-Pro, respectively.Conclusion:Two strategies for accounting for CT artifacts from three breast TTEs were assessed using CCC, MC, and film measurements. This study showed that the highest differences with respect to measurements occurred with RS1 and can be mitigated if a template with the actual port geometry and materials is used.

Purpose/Objective(s) This randomized trial of fractionation after breast reconstruction (FABREC) sought to compare quality-of-life (QOL) and clinical outcomes of hypofractionated (HF) vs. conventionally-fractionated (CF) postmastectomy radiation therapy (PMRT) in the setting of immediate prosthetic reconstruction. Materials/Methods Between 3/2018 and 11/2021, 400 patients at 18 centers with Stage 0-III breast cancer and immediate placement of tissue expander (TE) or implant (I) after mastectomy were randomized 1:1 to HF or CF photon PMRT. Respective doses in the two arms were 42.56 Gy/16 fractions to the chest wall (CW), with or without axillary/supraclavicular lymph node (LN) radiation (39.9 Gy/15 fractions) and 50 Gy in 25 fractions to CW (46-50 Gy to axillary LNs). A boost was not permitted; bolus was used at physician discretion. CW toxicity was defined as any grade ≥3 adverse event (CTCAE) after PMRT initiation. Patients were censored at study withdrawal or at diagnosis of distant recurrence. Participants completed QOL instruments (FACT-B, BREAST-Q, Lymph-ICF) at baseline, 6, 12 and 18-months from PMRT initiation. Questions regarding financial burden were included with the 6-month survey. Primary endpoint of the study was improvement in the Physical Well-Being (PWB) domain of FACT-B at 6 months with pre-specified stratification by age (younger than 45 vs. 45 years or older). QOL scores were compared using Student's t-test. Results Median follow-up for the 385 patients analyzed was 31.8 months (range, 6.9-54.4); median age was 47.0 years (range, 23-79). Preoperative chemotherapy was used in 67.8% and preoperative endocrine therapy (ET) in 21.5% of the cohort. There were 16 distant (8 in each arm), and 2 local-regional (1 in each arm) recurrences. CW toxicity occurred in 35 patients (19 HF, 16 CF, p=0.58) at medians of 3.4 and 4.8 months after RT initiation in the HF and CF arms, respectively (p=0.82). Post-operative infection before RT (HR=3.31, p=0.03), irradiation of TE vs I (HR=7.74, p=0.046), preoperative endocrine therapy (HR=3.45, p=0.0007) and number of LNs removed (HR=1.06/node, p=0.02) were significant for developing CW toxicity on multivariate analysis, while fractionation was not (HF HR=1.19, p=0.63). There was no significant difference in overall change in PWB scores at 6 months between the two treatment arms (p=0.71) or separately in younger (p=0.15) and older cohorts (p=0.27). However, HF patients younger than 45 were less bothered by side-effects of treatment (p=0.045) and nausea (p=0.02) vs. CF patients younger than 45. Among patients who took unpaid time off from work during treatment (n=51), those receiving HF required fewer hours off than those receiving CF (73.7 vs. 125.8, p=0.046). Conclusion Physical well-being and overall toxicity profile of HF PMRT were comparable between HF and CF PMRT. HF was associated with better 6-month QOL in some domains among younger patients. Our early results support the use of HF PMRT in the setting of TE- or implant-based breast reconstruction. This randomized trial of fractionation after breast reconstruction (FABREC) sought to compare quality-of-life (QOL) and clinical outcomes of hypofractionated (HF) vs. conventionally-fractionated (CF) postmastectomy radiation therapy (PMRT) in the setting of immediate prosthetic reconstruction. Between 3/2018 and 11/2021, 400 patients at 18 centers with Stage 0-III breast cancer and immediate placement of tissue expander (TE) or implant (I) after mastectomy were randomized 1:1 to HF or CF photon PMRT. Respective doses in the two arms were 42.56 Gy/16 fractions to the chest wall (CW), with or without axillary/supraclavicular lymph node (LN) radiation (39.9 Gy/15 fractions) and 50 Gy in 25 fractions to CW (46-50 Gy to axillary LNs). A boost was not permitted; bolus was used at physician discretion. CW toxicity was defined as any grade ≥3 adverse event (CTCAE) after PMRT initiation. Patients were censored at study withdrawal or at diagnosis of distant recurrence. Participants completed QOL instruments (FACT-B, BREAST-Q, Lymph-ICF) at baseline, 6, 12 and 18-months from PMRT initiation. Questions regarding financial burden were included with the 6-month survey. Primary endpoint of the study was improvement in the Physical Well-Being (PWB) domain of FACT-B at 6 months with pre-specified stratification by age (younger than 45 vs. 45 years or older). QOL scores were compared using Student's t-test. Median follow-up for the 385 patients analyzed was 31.8 months (range, 6.9-54.4); median age was 47.0 years (range, 23-79). Preoperative chemotherapy was used in 67.8% and preoperative endocrine therapy (ET) in 21.5% of the cohort. There were 16 distant (8 in each arm), and 2 local-regional (1 in each arm) recurrences. CW toxicity occurred in 35 patients (19 HF, 16 CF, p=0.58) at medians of 3.4 and 4.8 months after RT initiation in the HF and CF arms, respectively (p=0.82). Post-operative infection before RT (HR=3.31, p=0.03), irradiation of TE vs I (HR=7.74, p=0.046), preoperative endocrine therapy (HR=3.45, p=0.0007) and number of LNs removed (HR=1.06/node, p=0.02) were significant for developing CW toxicity on multivariate analysis, while fractionation was not (HF HR=1.19, p=0.63). There was no significant difference in overall change in PWB scores at 6 months between the two treatment arms (p=0.71) or separately in younger (p=0.15) and older cohorts (p=0.27). However, HF patients younger than 45 were less bothered by side-effects of treatment (p=0.045) and nausea (p=0.02) vs. CF patients younger than 45. Among patients who took unpaid time off from work during treatment (n=51), those receiving HF required fewer hours off than those receiving CF (73.7 vs. 125.8, p=0.046). Physical well-being and overall toxicity profile of HF PMRT were comparable between HF and CF PMRT. HF was associated with better 6-month QOL in some domains among younger patients. Our early results support the use of HF PMRT in the setting of TE- or implant-based breast reconstruction.

PDF File - 768K, The binding of the NF-B subunit, p65, to its target region of 1-integrin promoter was significantly increased by IR.

<p>PDF File - 1455K, Radiation-induced phospho and total �1-integrin and focal adhesion kinase (FAK) expressions were downregulated by NF-�B inhibitor.</p>

BACKGROUND:Intensity-modulated radiation therapy and other modifiable radiation factors have been associated with decreased radiation toxicity. These factors could allow for improved reconstructive outcomes in patients requiring postmastectomy radiation therapy (PMRT). However, they have not yet been well studied in implant-based breast reconstruction. METHODS:The authors performed a retrospective chart review of patients who underwent mastectomy with immediate tissue expander placement followed by PMRT. Radiation characteristics were collected, including radiation technique, bolus regimen, x-ray energy, fractionation, maximum radiation hot spot, and tissue volume receiving more than 105% or more than 107% of the prescription dose. Reconstructive complications occurring after initiation of PMRT were analyzed with respect to these radiation characteristics. RESULTS:Sixty-eight patients (70 breasts) were included in this study. The overall complication rate was 28.6%, with infection being the most common complication (24.3%), requiring removal of the tissue expander or implant in greater than half of infections (15.7%). Maximum radiation hot spot was greater in patients who required explantation after PMRT, and this approached statistical significance (114.5% ± 7.2% versus 111.4% ± 4.4%; P = 0.059). Tissue volume receiving more than 105% and 107% were also greater in patients who required explantation after PMRT (42.1% ± 17.1% versus 33.0% ± 20.9% and 16.4% ± 14.5% versus 11.3% ± 14.6%, respectively); however, this was not statistically significant ( P = 0.176 and P = 0.313, respectively). There were no significant differences in complication rates between patients with respect to radiation technique or other radiation characteristics studied. CONCLUSION:Minimizing the radiation hot spots and volumes of tissue receiving greater than the prescription dose of radiation may improve reconstructive outcomes in patients undergoing implant-based breast reconstruction followed by PMRT. CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, III.