BACKGROUND:The use of 3D imaging with navigation bronchoscopy has increased with the introduction of mobile cone-beam CT (mCBCT). Shape-sensing robotic-assisted bronchoscopy (ssRAB) integrated with mCBCT has been introduced to correct for CT to body divergence (CT-BD) during the biopsy of peripheral pulmonary nodules (PPNs). METHODS:Prospective observational multicentre study, enrolling patients with a PPN of ≤20 mm suspicious for malignancy, assessing tool-in-lesion (TIL), diagnostic yield, sensitivity for malignancy and incidence of pneumothorax or airway bleeding. Non-malignant index biopsies were followed for 12 months. Descriptive statistics are reported for all variables along with 95% CI for primary endpoints. RESULTS:155 consecutive patients were enrolled at six centres. Median nodule size was 14.0 mm (IQR 11.0-17.0), with 54.8% of nodules (85/155) in the upper lobes, 25.8% (40/155) with CT bronchus sign present and median distance to the nearest pleural surface of 8.2 mm (IQR 1.8-20.0). TIL was achieved in 154/155 (99.4%, 95% CI 96.5 to 100.0) procedures. A median of two (IQR 1-3) mCBCT spins were performed, with median dose area product of 25.7 Gy · cm2 (IQR 11.0-46.7). Diagnostic yield per the American Thoracic Society/American College of Chest Physicians (ATC/ACCP) definition was 89.0% (n=138/155; 95% CI 83.0 to 93.5) and sensitivity for malignancy was 91.5% (95% CI 86.4 to 96.5). No pneumothorax (0%, 95% CI 0.0 to 2.4) and two Nashville Grade three bleeding events were reported (1.3%, 95% CI 0.2 to 4.6). INTERPRETATION:The first prospective multicentre study of integrated ssRAB and mCBCT for small peripheral nodules resulted in diagnostic outcomes similar to those reported for transthoracic biopsy with a more favourable safety profile. TRIAL REGISTRATION NUMBER:ClinicalTrials.gov ID: NCT05562895.

Lung cancer in never-smokers has a distinct genomic profile characterized by lower tumor mutational burden, more tumor-promoting mutations, and fewer somatic copy number variations (CNVs) compared to smokers. While CNVs are linked to poor outcomes in advanced-stage cancer, their role in early-stage lung adenocarcinoma remains unclear. In a cohort of 210 treatment-naive never-smokers with early-stage lung adenocarcinoma, hierarchical clustering of CNVs identified three distinct groups: CNV low (n = 86 [41%]), CNV moderate (n = 75 [36%]), and CNV high (n = 49 [23%]). CNV low tumors had minimal CNV burden, CNV moderate tumors exhibited loss of heterozygosity in chromosomes 3, 9, 13, 15, and 18, and CNV high tumors showed genome-wide amplifications and whole-genome doubling. Recurrence occurred in 42 patients (20%), with a significantly lower 5-year cumulative incidence in the CNV low group (14% [95% CI, 7%-25%]) compared to the CNV moderate (31% [95% CI, 18%-44%]) and CNV high group (48% [95% CI, 27%-66%]) (p = .004). Adjusted hazard ratios for recurrence were 2.30 (p = .074) and 2.65 (p = .037) for CNV moderate and CNV high, respectively. These findings suggest CNV status is an independent predictor of recurrence, with CNV low tumors being associated with the most favorable prognosis.

BACKGROUND Micropapillary and solid subtypes of lung adenocarcinoma are associated with high rates of recurrence in early-stage non-small cell lung cancer and may help guide the extent of resection if known preoperatively. We examined the accuracy of CT-guided core needle biopsy in determining high-risk subtypes in small (≤2 cm) tumors. METHODS A retrospective review was performed to identify patients with clinical T1a-T1bN0M0 (≤2 cm) lung adenocarcinoma who underwent CT-guided core needle biopsy before surgical resection from 2010 to 2024. The accuracy, sensitivity, and specificity of preoperative biopsy were determined for each histologic subtype. Multivariable logistic regression identified preoperatively known clinicopathologic risk factors for micropapillary/solid subtypes on surgical pathology. RESULTS We identified 658 patients with early-stage lung adenocarcinoma who underwent preoperative biopsy, with 372 (57%) patients undergoing core-needle biopsy resulting in a pathology specimen with histologic subtype reported. Preoperative biopsy was highly specific (96.9%) but not sensitive (37.1%) for the presence of solid or micropapillary subtypes. Of the 288 patients without a high-risk subtype identified on preoperative biopsy, 134 (47%) had a high-risk subtype identified on surgical pathology. Multivariable analysis identified male sex, current/former smoking history, tumor maximum standardized uptake value (SUVmax), and solid tumor CT texture as independently associated with greater risk of having micropaillary/solid features on surgical pathology. CONCLUSIONS Preoperative biopsy is effective at ruling in, but not ruling out, high-risk lung adenocarcinoma subtypes. The presence of high-risk features on biopsy may be helpful in treatment planning.

Chimeric antigen receptor (CAR) T cells have transformed hematologic cancer therapy but remain limited in solid tumors by antigen heterogeneity and a suppressive, pro-fibrotic microenvironment. We previously identified the urokinase plasminogen activator receptor (uPAR) as upregulated in senescent, pro-fibrotic cells and showed that uPAR-directed CAR T cells could safely reverse fibrosis in mice. Integrative analyses now reveal that uPAR is broadly expressed in solid tumors enriched for TP53 and RAS pathway mutations. These tumors adopt a progenitor-like state supported by a niche of uPAR-positive stromal cells with senescence features. Human uPAR CAR T cells eliminate tumor cells and their stromal support, induce durable regressions across diverse models, eradicate systemic metastases, and are potentiated by senescence-inducing therapies. Importantly, these cells achieve robust antitumor activity without sustained myelosuppression in mice reconstituted with human immune systems. Together, these findings establish uPAR as a broadly applicable CAR T target capable of overcoming major barriers in solid tumor therapy.

BACKGROUND:Mediastinal sampling of the subaortic - station 5 - and paraaortic - station 6 - lymph nodes and mediastinal lesions traditionally requires surgical access. Image-guided shape-sensing robotic-assisted bronchoscopy (ssRAB) extends endoscopic reach and may offer an alternative sampling approach. We evaluated the feasibility, diagnostic yield, and safety of ssRAB-guided sampling of these anatomically challenging lesions. METHODS:All ssRAB procedures performed from October 2019 to September 2025 were reviewed retrospectively. Procedures in which a subaortic or paraaortic mediastinal lesion was targeted were included in the final analysis. Abstracted variables included patient data, pre-operative imaging, procedural details, peri-operative complications, and sampling results. The primary endpoint was conservative diagnostic yield, defined as the rate of procedures establishing a specific diagnosis. RESULTS:A total of 16 procedures targeting a subaortic or paraaortic mediastinal lesion were identified for the final analysis. The conservative diagnostic yield rate was 69 %. After elimination in one case in which sampling was planned but not pursued, the lenient diagnostic yield rate was 73 %. The conservative diagnostic yield rate was 75 % and 62 % for the subaortic and paraaortic samplings, respectively. One instance of grade 1 pneumothorax was documented. No additional complications were observed. CONCLUSION:This single-center retrospective case series demonstrated that image-guided ssRAB may represent a feasible, safe, and minimally invasive approach for sampling subaortic and paraaortic mediastinal lymph nodes and lesions, potentially obviating the need for surgical procedures.

Objective:We evaluated the feasibility and long-term outcomes of minimally invasive surgery (MIS) after neoadjuvant immunotherapy in patients with resectable non-small cell lung cancer (NSCLC). Methods:Patients with stage IB-IIIB NSCLC who underwent induction immunotherapy followed by surgery (2015-2022) were included. Overall and event-free survival were estimated using the Kaplan-Meier approach. Cox regression was used to quantify associations between clinical and pathologic variables and survival outcomes. Results:In total, 69 patients met the inclusion criteria (MIS, n = 38; open surgery, n = 31). Patients who underwent open surgery had larger tumors (P < .001), more-frequent extended resection (P = .007), more major complications (P = .03), and longer in-hospital stay (P = .002), compared with patients who underwent MIS. The rate of conversion to open surgery in the MIS group was 16% (6/38). Histologic subtype (P = .057), completeness of resection (P > .9), response to treatment (P > .9), and stage (P = .6) were not statistically different between groups. Five-year event-free and overall survival in the MIS patients were 72% and 80%, respectively. Among all patients, pathologic N2 disease (hazard ratio [HR], 3.04; 95% CI, 1.1-8.38; P = .031) and upstaging (HR, 2.57; 95% CI, 1.05-6.34; P = .04) were associated with a greater risk of recurrence. Major pathologic response was associated with longer event-free survival (HR, 0.22; 95% CI, 0.05-0.93; P = .039). Programmed death-ligand 1 level (HR, 1.02; 95% CI, 1.01-1.04; P = .007) and tumor dimensional reduction after treatment (HR, 0.96; 95% CI, 0.93-0.99; P = .016) were associated with major pathologic response. Conclusions:MIS after induction immunotherapy is feasible and does not compromise long-term oncologic outcomes.

Background Guidelines recommend invasive mediastinal nodal staging (IMNS) for patients with synchronous primary lung cancer (SPLC) who are candidates for curative resection. We investigated the prevalence of occult nodal disease and selective use of IMNS in patients with SPLC. Methods Patients with SPLC suspected on preoperative imaging who underwent resection from 2000 to 2022 were included. Exclusion criteria included metachronous and recurrent lung cancer, cStage III-IV, carcinoid histology, absence of preoperative PET/CT, and receipt of neoadjuvant therapy. Univariable analysis identified clinicopathologic risk factors for occult nodal disease. Proposed criteria for identifying a patient at low risk for occult nodal disease were as follows: all primary tumors are peripheral, subsolid, ≤3 cm on preoperative CT, and have a maximum standardized uptake value (SUVmax) < 3.6, and lymph nodes must be PET negative. Results Of 484 eligible patients, only 19% (n = 90) underwent IMNS. After excluding patients with clinical nodal disease on IMNS and/or imaging, 472 patients remained, of which 14% (68/472) had occult nodal disease, with 5.9% (28/472) having occult N2 disease. Patients with occult nodal disease had dominant tumors with a higher SUVmax (median, 6.0 vs. 3.2; p < 0.001), central location (31% vs. 17%; p = 0.009) and solid appearance (76% vs. 46%; p < 0.001). Our proposed criteria categorized 21% of patients with complete data (96/449)as low risk for occult nodal disease(sensitivity = 24.4%, specificity = 96.9%, positive predictive value = 97.9%, negative predictive value = 17.6%). Conclusions The decision to pursue IMNS in patients with SPLC should be individualized using imaging characteristics including central location, solid-appearance, tumor size, and SUVmax.

Fibrotic remodeling of tissues and tumors establishes immune-suppressive microenvironments that drive organ dysfunction and, in cancer, limit responses to immunotherapy. Cells exhibiting features of cellular senescence are conserved drivers of fibrotic remodeling and thus represent therapeutic targets, yet senescent states are heterogeneous and can exert both beneficial and pathogenic effects, complicating therapeutic intervention. Here, we show that P-selectin is selectively expressed by subsets of senescent-like cells in fibrotic tissues and fibrotic tumor microenvironments. Leveraging fucoidan-based nanoparticles that bind P-selectin, we develop senescence-modulating nanoparticles (SMNPs) to selectively target these disease-associated cell states. SMNPs exhibit potent antifibrotic and immunomodulatory activity while markedly improving therapeutic index. Mechanistically, we identify a pathogenic, immune-suppressive macrophage population as a principal functional target of SMNPs in vivo. In fibrotic tumors, niche remodeling restores immune infiltration and sensitizes tumors to immune checkpoint-based therapies. More broadly, SMNPs establish a generalizable nanotherapeutic strategy for selectively targeting pathogenic senescent cell subsets across fibrotic disease and cancer.

Objective: To evaluate the feasibility of sentinel lymph node (SLN) identification in distal esophageal and esophagogastric junction (EGJ) adenocarcinoma and determine whether the SLN concept applies to this disease. Methods: Patients undergoing esophagectomy for clinical stage I-IVA esophageal and EGJ adenocarcinoma underwent SLN mapping by near-infrared detection of indocyanine green (ICG) injected via endoscopy before esophagectomy. Lymphatic drainage patterns were recorded, and the first identified nodes (SLNs) were harvested. Standard esophagectomy and lymphadenectomy were performed. SLN status was compared with overall nodal status. Results: Of 90 included patients, 77 received ICG; SLN mapping was successful in 64 (83%). Ten patients had two SLN stations identified; the remainder had one. The most common SLN location was along the left gastric artery (36/74 [48%]), followed by the paracardial (17/74 [23%]) and periesophageal (15/74 [20%]) stations. Seven patients had SLNs positive for metastasis (in one, the SLN was the only positive node; in the rest, metastatic nodes were identified in the same or other stations). Of the 57 patients with negative SLNs, 11 (19%) had ≥1 positive node in the same or different nodal station. The false-negative rate was 61.1%. Conclusions: SLN mapping with ICG is feasible in patients with distal esophageal and EGJ adenocarcinoma, with a high rate of successful node identification. Occult nodal metastasis in patients with negative SLNs limits the reliability of SLN assessment as a determinant for selective lymphadenectomy.

PURPOSE:We sought to characterize the genomic landscape of gastroesophageal adenocarcinoma (GEA) using next-generation sequencing (NGS) of circulating cell-free DNA (cfDNA), compare the genomic profile to tissue NGS, and determine the association of circulating tumor DNA (ctDNA) detection with clinical outcomes. METHODS:In this prospective biospecimen-collection study (2017-2022), cfDNA was analyzed using a clinically validated 129-gene tumor-informed NGS assay Memorial Sloan Kettering-Analysis of Circulating cfDNA to Evaluate Somatic Status (MSK-ACCESS); tissue-NGS was performed using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets. RESULTS:In total, 169 patients with GEA underwent baseline molecular profiling of cfDNA; 93 had localized disease, 55 had untreated metastatic disease, and 21 had progressive metastatic disease. The frequency of the most common alterations was similar between platforms, although copy-number alterations were detected less frequently in plasma than in tissue (10% v 40%; P < .001). Matched-tumor NGS was conducted in 154 patients (91%). Baseline ctDNA detection and on-treatment clearance were associated with improved overall survival and recurrence-free survival in patients with localized disease and progression-free survival in patients with metastatic disease. Baseline ctDNA detection was a stronger predictor of overall survival than American Joint Committee on Cancer (AJCC) clinical stage and positively predicted lymph node metastasis in 87% of cases. Trends in variant allele fractions correlated with pathologic responses to neoadjuvant therapy more closely than fluorodeoxyglucose-positron emission tomography standard uptake values. Persistence or resurgence of ctDNA was associated with worse survival and forecasted recurrent disease a median of 7 months sooner than imaging. CONCLUSION:cfDNA analysis using MSK-ACCESS in patients with GEA is a valuable adjunctive clinical tool that enhances molecular profiling, prognostication, treatment response assessment, and detection of recurrent disease in conjunction with tissue NGS, imaging, and AJCC clinical staging criteria.

Reprogramming of aged donor tissue cells into induced pluripotent stem cells (A-iPSC) preserved the epigenetic memory of aged-donor tissue, defined as genomic instability and poor tissue differentiation in our previous study. The unbalanced expression of RNA exosome subunits affects the RNA degradation complex function and is associated with geriatric diseases including premature aging and cancer progression. We hypothesized that the age-dependent progressive subtle dysregulation of EXOSC2 (exosome component 2) causes the aging traits (abnormal cell cycle and poor tissue differentiation). We used embryonic stem cells as a tool to study EXOSC2 function as the aging trait epigenetic memory determined in A-iPSC because these aging traits could not be studied in senesced aged cells or immortalized cancer cells. We found that the regulatory subunit of PP2A phosphatase, PPP2R5E, is a key target of EXOSC2 and this regulation is preserved in stem cells and cancer.

Background:Surgical management of gastroesophageal junction adenocarcinoma extending into both the esophagus and the stomach often requires distal esophagectomy and total gastrectomy (extended total gastrectomy). Roux-en-Y jejunal conduits are commonly used for reconstruction; however, concerns exist regarding the ability to obtain adequate length for a supradiaphragmatic anastomosis. Methods:This retrospective study included patients with esophagogastric adenocarcinoma who underwent extended total gastrectomy at our institution between 2016 and 2023. Clinicopathologic characteristics were analyzed descriptively. Quality of life was assessed using a Likert scale survey. The Roux-en-Y jejunal conduit was constructed by dividing the second and occasionally third jejunal arterial branches to obtain sufficient length. Disease-free survival (DFS) was defined as the time from surgery to recurrence or death from any cause. Results:Overall, 29 patients were included. The median patient age was 64 years, and 83% of the patients received neoadjuvant therapy. Five patients (17%) had an anastomotic leak, and 9 (31%) had grade 3-4 complications. The median DFS was 4.5 years; 72% of patients had resumed a regular diet by 3 months. Compared with standard esophagectomy patients at our institution, gastrectomy patients had a longer median length of stay (11 days vs 9 days; P = .048) but similar complication rates. With the exception of diarrhea at 2 weeks (worse for gastrectomy patients; mean score, 2.8 vs 1.4; P ≤ .001), quality of life was not statistically different between gastrectomy patients and standard esophagectomy patients. Conclusions:Supradiaphragmatic Roux-en-Y jejunal reconstruction after extended total gastrectomy for gastroesophageal junction adenocarcinoma is a feasible approach, associated with low complication rates and adequate recovery of quality of life.

Objective: Minimally invasive surgery (MIS) (video-assisted thoracoscopic surgery and robot-assisted thoracoscopic surgery) for pulmonary resection is standard in early-stage non-small cell lung cancer because it is associated with better perioperative outcomes than thoracotomy. MIS for resection of more advanced non-small cell lung cancer (Stages IB-IIIB) treated with neoadjuvant therapy has been utilized. However, the determinants of success are not well defined. Methods: A single institution retrospective review of a prospectively maintained database was conducted, querying for patients with clinical Stage IB through IIIB non-small cell lung cancer who had resection after neoadjuvant systemic therapy without radiation from 2013 to 2022. Patients were grouped by surgical approach; that is, open versus MIS. Successful MIS was defined by no conversion, R0 resection, and no major (grade 3 or greater) morbidity. Analyses by intent-to-treat assessed outcomes by Wilcoxon rank-sum test and Fisher exact test. (Multivariable regression analysis identified variables that contributed to successful MIS resection.) Results: Of 627 eligible patients, 360 (57%) had open and 267 (43%) had MIS procedures. Most patients (79.1%) received neoadjuvant platinum-based chemotherapy, and 21.9% were treated with immunotherapy or targeted therapy alone or combined with chemotherapy. Among MIS resections, 179 (67%) were performed by video-assisted thoracoscopic surgery and 88 (33%) by robot-assisted thoracoscopic surgery. The conversion rate was 16% (n 1/4 43). Successful MIS resection was achieved in 77% of patients. Multivariable regression analysis showed that pretreatment clinical N stage was a significant determinant of success, but not pretreatment clinical T stage or type of neoadjuvant therapy. Conclusions: Following neoadjuvant systemic therapy for clinical stage IB or IIIB non-small cell lung cancer, MIS resection can be successfully accomplished and should be considered in appropriate patients. Presence of pretreatment nodal disease is associated with higher odds of conversion, major morbidity, and incomplete resection.

Objective: Shape-sensing robotic-assisted bronchoscopy is an emerging technology for the sampling of pulmonary lesions. We seek to characterize the shape-sensing robotic-assisted bronchoscopy learning curve at an academic center. Methods: Shape-sensing robotic-assisted bronchoscopy procedures performed by 9 proceduralists at a single institution were analyzed. Cumulative sum analyses were performed to examine diagnostic sampling and procedure time over each operator's first 50 cases, with the acceptable yield threshold set to 73%. Results: During the study period, 442 patients underwent sampling of 551 lesions. Each operator sampled 61 lesions (interquartile range, 60-63 lesions). Lesion size was 1.90 cm (interquartile range, 1.33-2.80 cm). The median procedure time for single-target cases decreased from 62 minutes during the first 10 cases to 39 minutes after case 40 (P < .001). The overall diagnostic yield was 72% (range, 58%-83%). Six of 9 operators achieved proficiency over the study period. An aggregated cumulative sum analysis of those who achieved competency demonstrated a steep improvement between lesions 1 and 21 and crossing of the competency threshold by lesion 25. Temporal analysis of yield-related lesion characteristics demonstrated that at approximately lesion 20, more challenging lesions were increasingly targeted, as evidenced by smaller target size, higher rates of unfavorable radial endobronchial ultrasound views, and a negative bronchus sign. Conclusions: Skills acquisition in shape-sensing robotic-assisted bronchoscopy is variable. Approximately half of proceduralists become facile with the technology within 25 lesions. After the initial learning phase, operators increasingly target lesions with more challenging features. Overall, these findings can inform certification and competency standards and provide new users with expectations related to performance over time.

OBJECTIVE:To investigate disease-free survival (DFS) of sublobar resection versus lobectomy for stage IA non-small cell lung cancer (NSCLC) with preoperative high-risk features. METHODS:Data were abstracted from a prospective database to identify patients with clinical T1a-T1bN0M0 NSCLC (≤2 cm) who underwent lobectomy or sublobar resection (wedge resection or segmentectomy). 1:1 propensity matching was used to balance the dataset for forced expiratory volume in 1 second ≥60% and high-risk features: cT1b versus cT1a, standard uptake value of the primary tumor on positron emission tomography, solid versus subsolid tumor texture on computed tomography, and micropapillary/solid histology. The primary outcome was DFS. RESULTS:In total, 825 patients met inclusion criteria: 52% (n = 426) patients underwent lobectomy and 48% (n = 399) of patients underwent sublobar resection (45% segmentectomy, 55% wedge resection). Lobectomy was associated with more preoperative high-risk features: cT1b (P < .001), greater standard uptake value (P < .001), solid tumor texture on computed tomography (P < .001), and micropapillary/solid histology (P < .001). In total, 660 patients were included in the matched analysis with all high-risk features balanced. Nodal upstaging (N1) was greater in patients who underwent lobectomy (9.1% vs 3.4%, P = .004). Five-year DFS (85% vs 74%, P = .12) was equivalent in the matched cohort. Lobectomy was protective for recurrence in the presence of 2 or greater high-risk features: sublobar resection patients with 2 high-risk features (hazard ratio, 1.77; 95% confidence interval, 1.13-2.76, P = .012) or 3-4 high-risk features (hazard ratio, 1.97; 95% confidence interval, 1.25-3.10, P = .004) had worse DFS. CONCLUSIONS:Lobectomy should be considered over sublobar resection for stage IA NSCLC ≤2 cm in the presence of multiple high-risk features.

BACKGROUND:The identification of high-grade patterns and mucinous features of invasive primary lung adenocarcinoma on biopsy specimens can have implications on therapeutic decisions across all stages of disease. Shape sensing robotic-assisted bronchoscopy (ssRAB) is an emerging modality for the concomitant diagnosis and staging of lung cancer. We evaluated the performance of ssRAB for adenocarcinoma pattern identification, and particularly high-grade patterns, as well as the histopathologic concordance between biopsy and surgical resection specimens. METHODS:Patients with lung adenocarcinoma diagnosed via ssRAB forceps or cryobiopsy specimens between October 2019 and December 2023 were included in the analysis. Biopsy specimens were evaluated for the identification of histopathologic patterns and mucinous features. A generalized linear mixed model quantified the association between pre- and intra-operative factors and successful pattern identification on biopsy. The concordance between high-grade patterns and mucinous features on ssRAB-acquired biopsy and poorly differentiated grade and mucinous features on subsequent surgical resection was determined. RESULTS:A total of 242 ssRAB-acquired specimens were included in the final analysis. The biopsy specimen was sufficient to identify adenocarcinoma histopathologic patterns in 71 %. In a multivariable analysis, sampling by cryobiopsy was positively associated with pattern identification (OR 3.54, CI: 1.02-12.30; P = 0.04), as compared with forceps biopsy. A corresponding surgical resection specimen was available in 66 cases. The sensitivity, specificity, positive, and negative predictive values of biopsy were 63, 72, 61, and 74 %, respectively for the presurgical detection of poorly differentiated adenocarcinoma, and 87, 100, 100, and 96 %, respectively for the presurgical detection of mucinous features. CONCLUSION:This study is the first to report the performance of ssRAB-acquired biopsy for identification of adenocarcinoma patterns and its concordance with surgical resection. Our findings align with those previously reported for percutaneous lung biopsy. ssRAB emerges as a viable tool for the identification of adenocarcinoma patterns. Future studies are needed to confirm these findings in larger patient cohorts.

Objective We sought to determine perioperative characteristics, rates of recurrence, and survival among patients who underwent chest wall resection for breast cancer. Methods We identified patients who underwent chest wall resection for breast cancer at our institution from 2000 to 2024. Progression-free survival and overall survival were estimated using the Kaplan-Meier approach. Cumulative incidence of local recurrence was calculated, and its association with disease-free interval was analyzed using Gray's test. Cox models quantified the association between patient characteristics and survival outcomes. Results Sixty-three patients were included. Chest wall resection was performed for recurrent breast cancer in 81% of patients (51/63). Most patients underwent rib resection (55/63; 87%) and partial or complete sternal resection (37/63; 59%). Fifty-five patients (87%) had a prosthesis placed for reconstruction; 55 patients (87%) received myocutaneous flaps. R0 resection was performed in 52 patients (83%). Eight patients (13%) had grade 3 or greater complications, nearly all of which (n = 7) were flap infection or necrosis. No patients died within 30 days; 3 patients (5%) died within 90 days. Median follow-up was 10 years (interquartile range, 5-17 years). At 5 years, cumulative incidence of local recurrence was 32%, progression-free survival was 13%, and overall survival was 31%. Conclusions Among patients with locally advanced or recurrent breast cancer, chest wall resection can provide local control and has acceptable morbidity and mortality. Given the known effect of chest wall disease on quality of life, chest wall resection should be considered in the multimodal management of patients with locally aggressive breast cancer.