Reconstructing Failure: Assessing Surgical and Patient Reported Outcomes Following Loss of Initial Breast Reconstruction.

BACKGROUND: Breast reconstruction failure, defined as the removal of a prosthetic device or flap without immediate replacement, can be traumatic for patients. We aim to describe the progression of patients who experience tissue expander (TE), implant, or autologous breast reconstructive failure and assess the patient reported outcomes (PROs) among patients who undergo additional reconstruction. METHOD: Patients undergoing TE, implant, or autologous breast reconstruction between 2017 and 2022 were included, and patients with reconstructive failures were identified. Outcomes of interests included (1) receipt of additional reconstruction and (2) BREAST-Q scores 1-year after reconstructive failure. We also performed a propensity-matched analysis between patients who undergo secondary reconstruction and patients who had an uncomplicated reconstruction. RESULTS: 4,258 TE, 4,420 implant, and 1,545 autologous breast reconstruction patients were included. Of patients who experienced reconstructive failures, 49.5% of TE, 4.8% of implant, and 53.8% of autologous patients underwent secondary reconstruction. Age, psychiatric diagnosis, chemotherapy, radiation, and mastectomy type were associated with increased likelihood of secondary reconstruction. Between patients with and without additional reconstruction, higher Psychosocial Well-being trended towards the former cohort (61 [Interquartile Range: 56, 80] vs 50 [46, 65], p=0.085). Propensity-matched analysis demonstrated comparable PROs at 1-year after definite reconstruction. CONCLUSION: Less than half of reconstructive failure patients undergo an additional reconstruction. Patients with secondary reconstruction may have improved Psychosocial Well-being than those who do not and comparable PROs to those who had uncomplicated initial reconstruction. Surgeons should counsel patients with reconstructive failures that although traumatizing, secondary reconstruction may be beneficial.

Breast cancer-related lymphedema: A comprehensive analysis of risk factors.

BACKGROUND: Breast cancer-related lymphedema is a devastating condition that negatively affects the quality of life of breast cancer survivors. We sought to identify risk factors that predicted the timing and development of lymphedema. METHODS: Women with breast cancer that underwent sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) at our institution between 2007 and 2022 were identified and sociodemographic and clinical information was extracted. We used logistic regression analysis to identify risk factors for lymphedema and performed cox-regression analysis to predict the timing of lymphedema presentation after surgery. RESULTS: We identified 1,223 patients, of which 161 (13.2%) developed lymphedema within 1.8 (mean, SD = 2.5) years postoperatively. Patients with SLNB had significantly lower odds for lymphedema development (vs. ALND, OR = 0.29 [0.14-0.57]). Patients between 40 and 49 years of age, and 50-59 (vs. <40 years, OR = 2.14 [1.00-4.60]; OR = 2.42, [1.13-5.16] respectively), African American patients (vs. Caucasian, OR = 1.86 [1.12-3.09]), patients with stage II, III, and IV disease (vs. stage 0, OR = 3.75 [1.36-10.33]; OR = 6.62 [2.14-20.51]; OR = 9.36 [2.94-29.81]), and patients with Medicaid (vs. private insurance, OR = 3.56 [1.73-7.28]) had higher rates of lymphedema. Cox-regression analysis showed that African American (HR = 1.71 [1.08-2.70]), higher BMI (HR = 1.03 [1.00-1.06]), higher stage (stage II, HR = 2.22 [1.05-7.09]; stage III, HR = 5.26 [1.86-14.88]; stage IV, HR = 6.13 [2.12-17.75]), and Medicaid patients (HR = 2.15 [1.12-3.80]) had higher hazards for lymphedema. Patients with SLNB had lower hazards for lymphedema (HR = 0.43 [0.87-2.11]). CONCLUSION: Lymphedema has identifiable risk factors that can reliably be used to predict the chances of lymphedema development and enable clinicians to educate patients better and formulate treatment plans accordingly. LEVEL OF EVIDENCE: III (Retrospective study).

Predicting Postoperative Satisfaction with Breasts: How Important is the Preoperative BREAST-Q Score?

BACKGROUND: The role that preoperative Satisfaction with Breast plays in a patient's postoperative course after postmastectomy breast reconstruction (PMBR) is not understood. The aim of this study is to understand the impact of the preoperative score on postoperative outcome as an independent variable. METHODS: We examined patients who underwent PMBR between 2017 and 2021 and who completed the BREAST-Q Satisfaction with Breasts at 1 year postoperatively. Two multiple linear regression models (Model 1 with the preoperative Satisfaction with Breasts score and Model 2 without the preoperative score), likelihood ratio tests, simple t-statistics, and sample patient dataset to predict the 1 year score were performed. Multiple imputation was used to account for missing preoperative scores. RESULTS: Overall, 2324 patients were included. Model 1 showed that the preoperative score is significantly associated with the postoperative score (ß = 0.09, 95% confidence interval 0.04-0.14; p < 0.001). Comparing Model 1 and Model 2 demonstrated that including preoperative Satisfaction with Breasts in a regression significantly improves model fit (test statistic = 10.04; p = 0.0021). Using the absolute value of the t-statistics as a measure of variable importance in linear regression, the importance of the preoperative score was quantified as 3.39-more important than neoadjuvant radiation, mastectomy weight, body mass index, bilateral prophylactic mastectomy, and race, but less than adjuvant radiation, reconstruction type, and psychiatric diagnoses. CONCLUSION: Preoperative Satisfaction with Breasts scores are an important independent predictor of postoperative satisfaction after PMBR. Just as vital sign and work-up are carefully documented before surgery, preoperative scores should be collected to pre-emptively gauge patients' satisfaction and optimize postoperative outcomes.

Breast-Conserving Therapy Versus Postmastectomy Breast Reconstruction: Propensity Score-Matched Analysis.

BACKGROUND: Although studies have compared patient-reported outcomes (PROs) after breast conserving-therapy (BCT) and postmastectomy breast reconstruction (PMBR), they often have been confounded by treatment or other factors that complicate a direct comparison. This study aimed to compare PROs after BCT and PMBR by using propensity score-matching analysis. METHODS: Patients who underwent BCT or PMBR between 2010 and 2022 and completed the BREAST-Q were identified. Each BCT patient was matched to a PMBR patient using nearest-neighbor 1:1 matching with replacement for each BREAST-Q time point. Outcomes included all prospectively collected BREAST-Q domains preoperatively, at 6 months, and at 1, 2, and 3 years postoperatively. A 4-point difference was considered clinically meaningful. RESULTS: For this study, 6215 patients (2501 BCT [40.2%] and 3714 PMBR [59.8%] patients) were eligible, and 2616 unique patients were matched. Preoperatively, 463 BCT and 463 PMBR patients were matched for analysis (6 months [443 matched pairs], 1 year [639 matched pairs], 2 years [421 matched pairs], 3 years [254 matched pairs]). At 6 months postoperatively, the BCT patients scored higher on all BREAST-Q domains than the PMBR patients (p < 0.05; differences > 4 points). At 1, 2, and 3 years, the patients who underwent BCT consistently had superior Satisfaction With Breasts, Psychosocial Well-Being, and Sexual Well-Being (p < 0.05), and the differences were clinically meaningful. CONCLUSION: In this statistically powered study, the BCT patients reported higher quality of life than the PMBR patients in early assessment and also through 3 years of follow-up evaluation. Given the equivalency in survival and recurrence outcomes between BCT and PMBR, patients eligible for either surgery should be counseled regarding the superiority of BCT in terms of PROs.

Impact of Mastectomy Flap Necrosis on Patient-Reported Quality-of-Life Measures After Nipple-Sparing Mastectomy: A Preliminary Analysis.

BACKGROUND: Mastectomy skin flap necrosis (SFN) is common following nipple-sparing mastectomy (NSM), but studies on its quality-of-life (QOL) impact are limited. We examined patient-reported QOL and satisfaction after NSM with/without SFN utilizing the BREAST-Q patient-reported outcome measure (PROM) survey. PATIENTS AND METHODS: Patients undergoing NSM between April 2018 and July 2021 at our institution were examined; the BREAST-Q PROM was administered preoperatively, and at 6 months and 1 year postoperatively. SFN extent/severity was documented at 2-3 weeks postoperatively; QOL and satisfaction domains were compared between patients with/without SFN. RESULTS: A total of 573 NSMs in 333 patients were included, and 135 breasts in 82 patients developed SFN (24% superficial, 56% partial thickness, 16% full thickness). Patients with SFN reported significantly lower scores in the satisfaction with breasts (p = 0.032) and psychosocial QOL domains (p = 0.009) at 6 months versus those without SFN, with scores returning to baseline at 1 year in both domains. In the "physical well-being-of-the-chest" domain, there was an overall decline in scores among all patients; however, there were no significant differences at any time point between patients with or without SFN. Sexual well-being scores declined for patients with SFN compared with those without at 6 months and also at 1 year, but this did not reach significance (p = 0.13, p = 0.2, respectively). CONCLUSIONS: Patients undergoing NSM who developed SFN reported significantly lower satisfaction and psychosocial well-being scores at 6 months, which returned to baseline by 1 year. Physical well-being of the chest significantly declines after NSM regardless of SFN. Future studies with larger sample sizes and longer follow-up are needed to determine SFN's impact on long-term QOL.

Langerhans cells regulate immunity in adulthood by regulating postnatal dermal lymphatic development.

The communication between skin and draining lymph nodes is crucial for well-regulated immune responses to skin insults. The skin sends antigen and other signals via lymphatic vessels to regulate lymph node activity, and regulating dermal lymphatic function is another means to control immunity. Here, we show that Langerhans cells (LCs), epidermis-derived antigen-presenting cells, mediate dermal lymphatic expansion and phenotype acquisition postnatally, a function is independent of LC entry into lymphatic vessels. This postnatal LC-lymphatic axis serves in part to control inflammatory systemic T cell responses in adulthood. Our data provide a tissue-based mechanism by which LCs regulate T cells remotely across time and space and raise the possibility that immune diseases in adulthood could reflect compromise of the LC-lymphatic axis in childhood.

Breast Conserving Therapy Preserves Sexual Well-Being More Than Postmastectomy Breast Reconstruction: Trends, Factors, and Interventions.

BACKGROUND: Up to 85% of breast cancer patients report sexual health concerns, but their concerns are not adequately addressed by providers. Sexual dysfunction among breast cancer patients remains understudied. We aimed to investigate the impact of breast-conserving therapy (BCT) and postmastectomy breast reconstruction (PMBR) on the sexual health of breast cancer patients and frequency of sexual medicine consultation in postoperative care. METHODS: We conducted a retrospective analysis of patients who underwent BCT or PMBR and completed the Sexual Well-being of the BREAST-Q BCT and Reconstruction modules from January 2010 to October 2022. We compared Sexual Well-being scores between BCT and PMBR patients overtime up to 5-years postoperatively, delineated associated demographic and clinical factors with Sexual Well-being, and evaluated the frequency of sexual medicine consultations. RESULTS: Of 15,857 patients, 8,510 (53.7%) underwent BCT and 7,347 (46.3%) underwent PMBR. PMBR patients had significantly lower Sexual Well-being scores than BCT patients from preoperative to 5-year postoperative. Regression analyses showed that PMBR patients scored 7.6 points lower at 1-year than BCT patients. Separated marital status, higher body mass index, cardiovascular disease, hyperlipidemia, psychiatric diagnosis, and neoadjuvant chemotherapy were associated with significantly lower Sexual Well-being. 299 (3.5%) of BCT and 400 (5.4%) of PMBR patients received sexual medicine consultations. CONCLUSION: Sexual health concerns must be considered in breast cancer care, particularly among patients who undergo PMBR. Although many patients experience sexual dysfunction, most do not receive a sexual medicine consultation, suggesting an opportunity for providers to improve breast cancer patients' sexual health.

Analysis of the microsurgery fellowship match: 2019-2022 update.

BACKGROUND: A recent analysis of microsurgery fellowship match data published in 2019 demonstrated increased competition for available positions. With growing opportunities in the field, the authors hypothesize that the landscape for both applicants and programs has become more competitive. The aim of this study is to compare two periods of match data to inform residents and programs in microsurgery. METHODS: Microsurgery fellowship match data was obtained from the San Francisco Match with approval by the American Society for Reconstructive Microsurgery for the years 2014-2022. Data were stratified into the categories of 2016-2018 and 2019-2022. Parameters assessed included: program and position fill rates, match rates, and in-service examination percentiles. Data were analyzed using Pearson's Chi-square tests and unpaired t-tests. RESULTS: The median number of participating programs and positions increased to 29 and 47 in 2019-2022, compared with 23 and 40 in 2016-2018. This coincided with a decrease in the number of applicants per position (1.3 [52-40] vs. 1.1 [50-47], p = .45). There was a significant increase in the match rate between groups (67.8% vs. 80.2%, p = .007). Recently, 2022 saw the lowest position fill rate on record, at 75.4% (40 of 53 positions filled), down from 85.3% (35 of 41) in 2018 (p = .35) and 95.6% (43 of 45) in 2019 (p = .006). Mean in-service examination percentiles for successfully matched applicants did not differ between (2016-2018) and (2019-2022) applicants. CONCLUSION: Recent years have seen a rise in the number of microsurgery fellowship training programs with a decline in the number of applicants. Accordingly, there has been an increased match rate for prospective applicants. Despite this, a pool of unmatched applicants and unfilled positions with training opportunities still remain. The reasons for which are likely multifactorial.

Iterative qualitative approach to establishing content validation of a patient-reported outcome measure for arm lymphedema: the LYMPH-Q Upper Extremity Module.

BACKGROUND: Breast cancer-related lymphedema (BRCL) is one of the most common causes of upper extremity (UE) lymphedema in developed nations and substantially impacts health-related quality of life. To advance our understanding of the epidemiology and treatment of BRCL, rigorously developed and validated patient-reported outcome measures (PROMs) are needed. This study aimed to demonstrate the iterative content validity of a modular UE lymphedema-specific PROM called the LYMPH-Q UE module. METHODS: A multi-step iterative qualitative approach was used. Semi-structured interview data from in-depth qualitative interviews with adult women (18 years and older) with BCRL were used to develop the first set of the LYMPH-Q UE scales. The content validity of these scales was demonstrated with patient and clinician feedback. Over the course of cognitive debriefing interviews, additional concepts of lymphedema worry and impact on work were identified as missing from the LYMPH-Q UE module. Subsequently, two new qualitative studies (a focus group and in-depth concept elicitation interviews with patients) were conducted, and two new scales were developed to measure lymphedema worry and impact on work life and their content validity was demonstrated. RESULTS: Qualitative data from in-depth and cognitive interviews with 15 (age 40-74 years) and 16 (age 38-74 years) women with BRCL, respectively, and feedback from 12 clinical experts, were used to develop and demonstrate the content validity of six LYMPH-Q UE scales measuring symptoms, function, appearance, psychological, information, and arm sleeve. Additionally, data from in-depth interviews with 12 (age 35-72 years) women with UE lymphedema and four focus groups (n = 16 women; age 35-74 years) was used to develop and assess the content validity of two new LYMPH-Q UE scales measuring lymphedema worry and impact on work life. The content validity of the previously established six scales was also demonstrated in these subsequent qualitative studies. CONCLUSION: The LYMPH-Q UE is a modular PROM developed using international guidelines for PROM development and can be used in clinical practice, research, and quality improvement to enhance patient-centered shared decision-making. This study's innovative and iterative approach to content validation demonstrates that the LYMPH-Q UE is a comprehensive measure that includes important concepts relevant to patients with UE lymphedema.

Breast Cancer-Related Lymphedema Results in Impaired Epidermal Differentiation and Tight Junction Dysfunction.

Breast cancer-related lymphedema (BCRL) is characterized by skin changes, swelling, fibrosis, and recurrent skin infections. Clinical studies have suggested that lymphedema results in skin barrier defects; however, the underlying cellular mechanisms and the effects of bacterial contamination on skin barrier function remain unknown. In matched biopsies from patients with unilateral BCRL, we observed decreased expression of FLG and the tight junction protein ZO-1 in skin affected by moderate lymphedema or by subclinical lymphedema in which dermal backflow of lymph was identified by indocyanine green lymphography, relative to those in the controls (areas without backflow and from the unaffected arm). In vitro stimulation of keratinocytes with lymph fluid obtained from patients undergoing lymphedema surgery led to the same changes as well as increased expression of keratin 14, a marker of immature keratinocytes. Finally, using mouse models of lymphedema, we showed that similar to the clinical scenario, the expression of skin barrier proteins was decreased relative to that in normal skin and that colonization with Staphylococcus epidermidis bacteria amplified this effect as well as lymphedema severity. Taken together, our findings suggest that lymphatic fluid stasis contributes to skin barrier dysfunction in lymphedema.

Satisfaction with Breasts Following Autologous Reconstruction: Assessing Associated Factors and the Impact of Revisions.

BACKGROUND: Autologous breast reconstruction (ABR) may confer higher patient reported outcomes than implant breast reconstruction, but an in-depth examination of factors associated with satisfaction after ABR is lacking. We aimed to determine independent predictors of 1-year Satisfaction with Breasts after ABR and assess the importance of elective procedures on satisfaction. METHODS: A retrospective analysis of patients who underwent abdominal-based ABR between 2010 and 2021 and completed the BREAST-Q Satisfaction with Breasts module at 1-year was performed. Elective procedures comprised of breast revision and nipple areolar complex (NAC) reconstruction. RESULTS: 959 patients were included. Satisfaction with Breasts score improved from 53 (IQR: 44 to 64) preoperatively to 64 (53 to 78) at 1-year postoperatively (p<0.001). Factors significantly associated with decreased postoperative score included lower preoperative scores (ß=0.19 [95% CI: 0.08, 0.31], p=0.001), older age (ß=-0.17 [-0.34, -0.01], p=0.042), Asian race (versus White, ß=-6.7 [-12, -1.7], p=0.008), and a history of psychiatric diagnoses (ß=-3.4 [-6.2, -0.66], p=0.015). Patients who received radiation (ß=-5.6 [-9.0, -2.3], p=0.001) or had mastectomy skin flap/nipple necrosis (ß=-3.8 [-7.6, -0.06], p=0.046) also had significantly decreased scores. Satisfaction with Breasts significantly improved after breast revision procedures (54 [42 to 65] to 65 [54 to 78], p<0.001) and NAC reconstruction (58 [47 to 71] to 67 [57 to 82], p<0.001). CONCLUSION: Multiple independent patient and treatment level factors are associated with lower 1-year Satisfaction with Breasts following ABR. Elective procedures have the potential to improve satisfaction. Understanding these findings is imperative for optimizing clinical decision making and managing expectations.

TRPV4-Expressing Tissue-Resident Macrophages Regulate the Function of Collecting Lymphatic Vessels via Thromboxane A2 Receptors in Lymphatic Muscle Cells.

Rationale: TRPV4 channels are critical regulators of blood vascular function and have been shown to be dysregulated in many disease conditions in association with inflammation and tissue fibrosis. These are key features in the pathophysiology of lymphatic system diseases, including lymphedema and lipedema; however, the role of TRPV4 channels in the lymphatic system remains largely unexplored. TRPV4 channels are calcium permeable, non-selective cation channels that are activated by diverse stimuli, including shear stress, stretch, temperature, and cell metabolites, which may regulate lymphatic contractile function. Objective: To characterize the expression of TRPV4 channels in collecting lymphatic vessels and to determine the extent to which these channels regulate the contractile function of lymphatics. Methods and Results: Pressure myography on intact, isolated, and cannulated lymphatic vessels showed that pharmacological activation of TRPV4 channels with GSK1016790A (GSK101) led to contractile dysregulation. The response to GSK101 was multiphasic and included, 1) initial robust constriction that was sustained for ≥1 minute and in some instances remained for ≥4 minutes; and 2) subsequent vasodilation and partial or complete inhibition of lymphatic contractions associated with release of nitric oxide. The functional response to activation of TRPV4 channels displayed differences across lymphatics from four anatomical regions, but these differences were consistent across different species (mouse, rat, and non-human primate). Importantly, similar responses were observed following activation of TRPV4 channels in arterioles. The initial and sustained constriction was prevented with the COX inhibitor, indomethacin. We generated a controlled and spatially defined single-cell RNA sequencing (scRNAseq) dataset from intact and microdissected collecting lymphatic vessels. Our data uncovered a subset of macrophages displaying the highest expression of Trpv4 compared to other cell types within and surrounding the lymphatic vessel wall. These macrophages displayed a transcriptomic profile consistent with that of tissue-resident macrophages (TRMs), including differential expression of Lyve1 , Cd163 , Folr2 , Mrc1 , Ccl8 , Apoe , Cd209f , Cd209d , and Cd209g ; and at least half of these macrophages also expressed Timd4. This subset of macrophages also highly expressed Txa2s , which encodes the thromboxane A2 (TXA2) synthase. Inhibition of TXA2 receptors (TXA2Rs) prevented TRPV4-mediated contractile dysregulation. TXA2R activation on LMCs caused an increase in mobilization of calcium from intracellular stores through Ip3 receptors which promoted store operated calcium entry and vasoconstriction. Conclusions: Clinical studies have linked cancer-related lymphedema with an increased infiltration of macrophages. While these macrophages have known anti-inflammatory and pro-lymphangiogenic roles, as well as promote tissue repair, our results point to detrimental effects to the pumping capacity of collecting lymphatic vessels mediated by activation of TRPV4 channels in macrophages. Pharmacological targeting of TRPV4 channels in LYVE1-expressing macrophages or pharmacological targeting of TXA2Rs may offer novel therapeutic strategies to improve lymphatic pumping function and lymph transport in lymphedema.

Age Impacts Clinical and Patient Reported Outcomes following Post Mastectomy Breast Reconstruction.

BACKGROUND: While the current literature indicates that age should not be a deterring factor in postmastectomy breast reconstruction (PMBR), the true impact of increasing age on postoperative outcomes remains unknown. The purpose of this study is to understand the impact of age on complications and patient-reported outcomes (PROs) using BREAST-Q longitudinally 5-years after PMBR. METHODS: We conducted a retrospective analysis of patients who underwent autologous (ABR) or implant-based reconstruction (IBR). Age was studied as both a categorical and continuous variable. Outcome measures included complications and BREAST-Q scores at preoperative, 6-months, and 1-5 years postoperative. RESULTS: 4,730 patients were included, of which 1,536 (32.5%) underwent ABR while 3,194 (67.5%) had IBR. Older age was significantly associated with increased risk of developing mastectomy skin flap/nipple necrosis, infection, and seroma. Older age was negatively correlated with Satisfaction with Breasts (ß=-0.06 [-0.12, -0.01]; p=0.033) and positively correlated with Psychosocial Well-being (ß=0.14 [0.09, 0.20]; p<0.001). Older age was not correlated with Physical Well-being of the Chest (ß=-0.03 [-0.08, 0.02], p=0.2) and Sexual Well-being (ß=-0.04 [-0.12, 0.02]; p=0.2). Subgroup analyses of ABR and IBR patients demonstrated different complications and PRO profiles. CONCLUSIONS: Our analysis of the impact of age on surgical outcomes and PROs suggests that complication rates increase with age and older age is negatively correlated with Satisfaction with Breasts but positively correlated with Psychosocial Well-being. Overall, older patients should be informed about the potential associated risks and anticipated patient reported outcomes.

A Phase II Study Evaluating the Effect of Intensity Modulated Postmastectomy Radiation Therapy on Implant Failure Rates in Breast Cancer Patients With Immediate, 2-Stage Implant Reconstruction With an MRI Imaging Correlative Substudy.

PURPOSE: Postmastectomy radiation therapy is a mainstay in the adjuvant treatment of node-positive breast cancer, but it poses risks for women with breast reconstruction. Multibeam intensity-modulated radiation therapy improves dose conformality and homogeneity, potentially reducing complications in breast cancer patients with implant-based reconstruction. To investigate this hypothesis, we conducted a single-arm phase 2 clinical trial of breast cancer patients who underwent mastectomy/axillary dissection and prosthesis-based reconstruction. METHODS AND MATERIALS: The primary endpoint was the rate of implant failure (IF) within 24 months of permanent implant placement, which would be considered an improvement over historical controls if below 16%. IF was defined as removal leading to a flat chest wall or replacement with another reconstruction. Patients were analyzed in 2 cohorts. Cohort 1 (RT-PI) received radiation therapy to the permanent implant. Cohort 2 (RT-TE) received radiation therapy to the TE. IF rates, adverse events, and quality of life were analyzed. Follow-up/postradiation therapy assessments were compared with the baseline/preradiation therapy assessments at 3 to 10 weeks after exchange surgery. A subgroup underwent serial magnetic resonance imaging (MRI) sessions to explore the association between MRI-detected changes and capsular contracture, a known adverse effect of radiation therapy. RESULTS: Between June 2014 and March 2017, 119 women were enrolled. Cohort 1 included 45 patients, and cohort 2 had 74 patients. Among 100 evaluable participants, 25 experienced IF during the study period. IF occurred in 8/42 (19%) and 17/58 (29%) in cohorts 1 and 2, respectively. Among the IFs, the majority were due to capsular contracture (13), infection (7), exposure (3), and other reasons (2). Morphologic shape features observed in longitudinal MRI images were associated with the development of Baker grade 3 to 4 contractures. CONCLUSIONS: The rate of IF in reconstructed breast cancer patients treated with intensity-modulated radiation therapy was similar to, but not improved over, that observed with conventional, 3-dimensional-conformal methods. MRI features show promise for predicting capsular contracture but require validation in larger studies.