Multivariate Cox Proportional Hazards Model Research Articles

Safety of Janus kinase inhibitors compared to biological DMARDs in patients with rheumatoid arthritis and renal impairment: the ANSWER cohort study

Data on the safety of Janus kinase inhibitors (JAKis) in patients with renal impairment are lacking. This study aimed to investigate the safety of JAKis compared to biological (b) DMARDs in patients with rheumatoid arthritis (RA) and renal impairment. We used a multi-centre observational registry of patients with RA in Japan (the ANSWER cohort). We assessed the drug retention rates of b/targeted synthetic DMARDs with different modes of action (tumour necrosis factor inhibitors (TNFis), immunoglobulins fused with cytotoxic T-lymphocyte antigen (CTLA-4-Ig), interleukin-6 receptor inhibitors (IL-6Ris), and JAKis) in patients with RA stratified by pre-treatment estimated glomerular filtration rate (eGFR) levels. The time to discontinuation of bDMARDs or JAKis was analysed using a multivariate Cox proportional hazards model This study included 3775 patients, who were classified into three groups (the normal group (eGFR ≥ 60 mL/min/1.73 m2): 2893 patients; CKDa group (eGFR 45–60 mL/min/1.73 m2): 551; and CKDb group (eGFR < 45 mL/min/1.73 m2): 331). In the CKDb group, the 12-month drug retention rate due to adverse events (AE) was the lowest in patients treated with JAKi (TNFi: 93.1%; IL-6Ri: 94.1%; CTLA-4-Ig: 92.3%; JAKi: 75.1%). In the normal and CKDa groups, drug retention rates due to AE were similar among patients treated with bDMARDs and JAKi. In contrast, drug retention rates due to inefficacy were similar between bDMARDs and JAKis in all groups. In the Cox-proportional model, in the CKDb group, TNFi, IL-6Ri, and CTLA-4-Ig showed lower incidence of drug discontinuation due to AE than JAKis (TNFi: hazard ratio = 0.23 (95% confidence interval 0.09–0.61), IL-6Ri: 0.34 (0.14–0.81), CTLA-4-Ig: 0.36 (0.15–0.89)). JAKis showed the lowest drug retention due to AE in patients with moderate-to-severe and severe renal impairment (eGFR < 45 mL/min/1.73 m2). Physicians should pay more attention to renal function when using JAKis than when using bDMARDs.

Psychotropic medication use and mortality in patients with acute myocardial infarction complicated by cardiogenic shock

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation the Research Foundation of Odense University Hospital &amp; Rigshospitalet. Background The impact of pre-existing mental illness on mortality in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains unclear. Purpose This study aims to assess the relation between pharmacologically treated mental disorders at the time of AMICS admission with patient characteristics and mortality. A surrogate marker for mental illness was defined as having at least one reimbursed prescription for psychotropic medication (Anatomical Therapeutic Chemical (ATC) group and subgroups N05, N06) within one year prior to admission with AMICS. Patients were divided into three therapy categories: None, one ATC subgroup, or two or more ATC subgroups. One-year survivors were further stratified by therapy status one year before admission and one year after discharge. Mortality was assessed at 30 days (5 years for one-year survivors). Kaplan-Meier estimates and univariable and multivariable Cox proportional hazards models were used to assess mortality rates stratified by treatment group. Results Of the cohort, 425 patients (25%) received therapy with psychotropic medication within the previous year at the time of presentation with AMICS. Polypharmacy (two or more ATC N05, N06 subgroups) was identified in 132 patients (8%). In these patients, there was a higher prevalence of comorbidities and a greater proportion of females (42% vs. 21%, p&amp;lt;0.001), compared to no treatment. More patients in the polypharmacy group presented with chest pain (60% vs. 52%, p=0.031), they were less often triaged directly to an invasive center (55% vs. 70%, p&amp;lt;0.001), and 30-day mortality was higher (73% vs. 51%, p&amp;lt;0.001). Among the 712 one-year survivors, 121 (17%) were treated with one or more drugs within one year before and after their AMICS admission. 149 (21%) began receiving therapy in the year following their AMICS admission. 422 (59%) never received psychotropic medication. In an unadjusted Cox model, therapy with two or more drugs, compared to no therapy, was associated with higher 30-day mortality (hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.43-2.19, p&amp;lt;0.001). This association remained significant in multivariable analysis (HR 1.66, 95%CI 1.22-2.26, p=0.001). Among one-year survivors, therapy with one or more drugs before and after AMICS was tied to an almost two-fold increase in five-year mortality (adjusted HR 1.95, 95%CI 1.23-3.10, p=0.004). Conclusions AMICS patients with pharmacologically treated mental illnesses were associated with higher mortality rates, as well as less favorable clinical profiles and treatment patterns. This increased risk remains evident among one-year survivors.

CD163+ macrophages in the triple-negative breast tumor microenvironment are associated with improved survival in the Women’s Circle of Health Study and the Women’s Circle of Health Follow-Up Study

BackgroundTumor-associated macrophages (TAMs) are a prominent immune subpopulation in the tumor microenvironment that could potentially serve as therapeutic targets for breast cancer. Thus, it is important to characterize this cell population across different tumor subtypes including patterns of association with demographic and prognostic factors, and breast cancer outcomes.MethodsWe investigated CD163+ macrophages in relation to clinicopathologic variables and breast cancer outcomes in the Women’s Circle of Health Study and Women’s Circle of Health Follow-up Study populations of predominantly Black women with breast cancer. We evaluated 611 invasive breast tumor samples (507 from Black women, 104 from White women) with immunohistochemical staining of tissue microarray slides followed by digital image analysis. Multivariable Cox proportional hazards models were used to estimate hazard ratios for overall survival (OS) and breast cancer-specific survival (BCSS) for 546 cases with available survival data (median follow-up time 9.68 years (IQR: 7.43–12.33).ResultsWomen with triple-negative breast cancer showed significantly improved OS in relation to increased levels of tumor-infiltrating CD163+ macrophages in age-adjusted (Q3 vs. Q1: HR = 0.36; 95% CI 0.16–0.83) and fully adjusted models (Q3 vs. Q1: HR = 0.30; 95% CI 0.12–0.73). A similar, but non-statistically significant, association was observed for BCSS. Macrophage infiltration in luminal and HER2+ tumors was not associated with OS or BCSS. In a multivariate regression model that adjusted for age, subtype, grade, and tumor size, there was no significant difference in CD163+ macrophage density between Black and White women (RR = 0.88; 95% CI 0.71–1.10).ConclusionsIn contrast to previous studies, we observed that higher densities of CD163+ macrophages are independently associated with improved OS and BCSS in women with invasive triple-negative breast cancer.Trial registrationNot applicable.

A retrospective study of clinical outcomes for patients with esophageal cancer who were treated with radiotherapy alone

Introduction: Patients with esophageal cancer who are in a poor general condition receive radiotherapy alone, but outcomes are often unsatisfactory. The aim of this study was to clarify recent outcomes of radiotherapy alone for esophageal cancer. Methods: Patients who underwent 50 Gy or more of radiotherapy without chemotherapy were retrospectively reviewed. Endpoints were overall survival (OS), disease-specific survival (DSS), local control (LC), and progression-free survival (PFS). Survival curves were drawn using the Kaplan-Meier method and predictors were analyzed using the Cox proportional hazards model. Results: Sixty-nine patients were included. The median follow-up period was 17.9 months. The 5-year OS, DSS, LC, and PFS rates were 33.2%, 49.8%, 46.2%, and 16.8%, respectively. In the multivariate Cox proportional hazard model, clinical stage was a significant predictor for OS (hazard ratio [HR]: 4.42, 95% confidence interval [CI]: 1.80 – 11.17, p = 0.001), DSS (HR: 2.08, 95% CI: 1.43 – 3.12, p = 0.0001), LC (HR: 1.86, 95% CI: 1.28 – 2.74, p = 0.001), and PFS (HR: 1.65, 95% CI: 1.25 – 2.18, p = 0.0004). Radiation dose was a significant predictor for LC (HR: 0.87, 95% CI: 0.78 – 0.97, p = 0.018) and tumor location was a significant predictor for PFS (HR: 1.55, 95% CI: 1.10 – 2.19, p = 0.018). In subgroup analysis, the 5-year OS, DSS, LC, and PFS rates for stage I were 60.0%, 80.0%, 71.9%, and 46.1%, respectively. Conclusions: Stage, radiation dose and tumor location are significant predictors for outcomes. Patients with stage I esophageal cancer can be cured by radiotherapy alone.

Prediction of Subsequent Vertebral Fracture After Acute Osteoporotic Fractures from Clinical and Paraspinal Muscle Features.

To construct a nomogram based on clinical factors and paraspinal muscle features to predict vertebral fractures occurring after acute osteoporotic vertebral compression fracture (OVCF). We retrospectively enrolled 307 patients with acute OVCF between January 2013 and August 2022, and performed magnetic resonance imaging of the L3/4 and L4/5 intervertebral discs (IVDs) to estimate the cross-sectional area (CSA)and degree of fatty infiltration (FI) of the paraspinal muscles. We also collected clinical and radiographic data. We used univariable and multivariable Cox proportional hazards models to identify factors that should be included in the predictive nomogram. Post-OVCF vertebral fracture occurred within 3, 12, and 24months in 33, 69, and 98 out of the 307 patients (10.8%, 22.5%, and 31.9%, respectively). Multivariate analysis revealed that this event was associated with percutaneous vertebroplasty treatment, higher FI at the L3/4 IVD levelsof the psoas muscle, and lowerrelative CSA of functional muscle at the L4/5 IVD levelsof the multifidus muscle. Area under the curve values for subsequent vertebral fracture at 3, 12, and 24months were 0.711, 0.724, and 0.737, respectively, indicating remarkable accuracy of the nomogram. We developed a model for predicting post-OVCF vertebral fracture from diagnostic information aboutprescribed treatment, FI at the L3/4 IVD levels of the psoas muscle, and relative CSA of functional muscle at the L4/5 IVD levels of the multifidus muscle. This model could facilitate personalized predictions and preventive strategies.

Statin use and risks of breast cancer recurrence and mortality.

Preclinical evidence suggests improved breast cancer survival associated with statin use, but findings from observational studies are conflicting and remain inconclusive. The objective of this study was to assess the association between statin use after cancer diagnosis and cancer outcomes among breast cancer patients. In this retrospective cohort study, 38,858 women aged ≥66 years who were diagnosed with localized and regional stage breast cancer from 2008 through 2017 were identified from the linked Surveillance, Epidemiology, and End Results Medicare database. Statin use was ascertained from Medicare Part D pharmacy claims data. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post-diagnosis statin use and risks of breast cancer recurrence and breast cancer-specific mortality. Over a median follow-up of 2.9 years for recurrence and 3.7 years for mortality, 1446 women experienced a recurrence, and 2215 died from breast cancer. The mean duration of post-diagnosis statin use was 2.2 years. Statin use post-diagnosis was not associated with recurrence risk (HR, 1.05; 95% CI, 0.91-1.21), but was associated with a reduced risk of cancer-specific mortality (HR, 0.85; 95% CI, 0.75-0.96). The reduction was more pronounced in women with hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer (HR, 0.71; 95% CI, 0.57-0.88). These findings suggest that post-diagnosis statin use is associated with improved cancer-specific survival in women with breast cancer and should be confirmed in randomized trials of statin therapy in breast cancer patients.

Multisite Study of the Management of Musculoskeletal Infection after Trauma – The MMUSKIT Study

Multisite Study of the Management of Musculoskeletal Infection after Trauma – The MMUSKIT Study

Use of deep learning to evaluate tumor microenvironmental features for prediction of colon cancer recurrence.

Deep learning may detect biologically important signals embedded in tumor morphologic features that confer distinct prognoses. Tumor morphological features were quantified to enhance patient risk stratification within DNA mismatch repair (MMR) groups using deep learning. Using a quantitative segmentation algorithm (QuantCRC) that identifies 15 distinct morphological features, we analyzed 402 resected stage III colon carcinomas (191 d-MMR; 189 p-MMR) from participants in a phase III trial of FOLFOX-based adjuvant chemotherapy. Results were validated in an independent cohort (176 d-MMR; 1094 p-MMR). Association of morphological features with clinicopathologic variables, MMR, KRAS, BRAFV600E, and time-to-recurrence (TTR) was determined. Multivariable Cox proportional hazard models were developed to predict TTR. Tumor morphological features differed significantly by MMR status. Cancers with p-MMR had more immature desmoplastic stroma. Tumors with d-MMR had increased inflammatory stroma, epithelial tumor-infiltrating lymphocytes (TILs), high grade histology, mucin, and signet ring cells. Stromal subtype did not differ by BRAFV600E or KRAS status. In p-MMR tumors, multivariable analysis identified tumor-stroma ratio (TSR) as the strongest feature associated with TTR [HRadj 2.02; 95% CI,1.14-3.57; P=0.018; 3-year recurrence: 40.2% vs 20.4%; Q1 vs Q2-4]. Among d-MMR tumors, extent of inflammatory stroma [continuous HRadj 0.98; 95% CI,0.96-0.99; P=0.028; 3-year recurrence: 13.3% vs 33.4%, Q4 vs Q1] and N stage were the most robust prognostically. Association of TSR with TTR was independently validated. In conclusion, QuantCRC can quantify morphological differences within MMR groups in routine tumor sections to determine their relative contributions to patient prognosis, and may elucidate relevant pathophysiologic mechanisms driving prognosis.

Comparative long-term outcomes of airway resection and functional reconstruction for papillary thyroid cancer

IntroductionThe surgical management of patients diagnosed with papillary thyroid carcinoma (PTC) and tracheal invasion has been a subject of ongoing discussion, particularly regarding the approach to tracheal functional reconstruction. The objective of this study was to examine the surgical technique and prognosis of PTC patients with tracheal invasion. Materials and methodsThis study employed both univariate and multivariate Cox proportional hazard models to determine predictive factors that affect the progression-free survival (PFS) of PTC patients with tracheal invasion. Cox regression analysis was conducted by using R software version 4.3.1. ResultsIn our study, we included 247 patients with T4a PTC. Among them, 146 patients (59.1 %) were classified as Shin I, 57 patients (23.1 %) as Shin II-III, and 44 patients (17.8 %) as Shin IV. Patients in the Shin I group underwent shaving of the tumours in the airway. The preferred surgical methods in the Shin II, III and IV groups were window resection (66.7 %), sleeve resection (34.8 %) and partial tracheal resection and skin fistula (61.8 %), respectively. Multivariate analysis demonstrated that neither tracheal surgery nor reconstruction procedures had an impact on PFS in T4a PTC patients with tracheal invasion. The 5-year DSS rate for patients receiving radioiodine (RAI) therapy was 87.3 % (p = 0.033). ConclusionThis study confirmed that tracheal surgery and reconstruction methods had no impact on PFS in T4a PTC patients with tracheal invasion in different Shin groups. Furthermore, RAI therapy has the potential to increase the survival rate of patients with preoperative distant metastasis of T4a PTC.

Lipocalin-2 as a prognostic marker in patients with acute exacerbation of idiopathic pulmonary fibrosis

BackgroundLipocalin-2 (LCN2) is a secretory glycoprotein upregulated by oxidative stress; moreover, patients with idiopathic pulmonary fibrosis (IPF) have shown increased LCN2 levels in bronchoalveolar lavage fluid (BALF). This study aimed to determine whether circulatory LCN2 could be a systemic biomarker in patients with IPF and to investigate the role of LCN2 in a bleomycin-induced lung injury mouse model.MethodsWe measured serum LCN2 levels in 99 patients with stable IPF, 27 patients with acute exacerbation (AE) of IPF, 51 patients with chronic hypersensitivity pneumonitis, and 67 healthy controls. Further, LCN2 expression in lung tissue was evaluated in a bleomycin-induced lung injury mouse model, and the role of LCN2 was investigated using LCN2-knockout (LCN2 -/-) mice.ResultsSerum levels of LCN2 were significantly higher in patients with AE-IPF than in the other groups. The multivariate Cox proportional hazards model showed that elevated serum LCN2 level was an independent predictor of poor survival in patients with AE-IPF. In the bleomycin-induced lung injury mouse model, a higher dose of bleomycin resulted in higher LCN2 levels and shorter survival. Bleomycin-treated LCN2 -/- mice exhibited increased BALF cell and protein levels as well as hydroxyproline content. Moreover, compared with wild-type mice, LCN2-/- mice showed higher levels of circulatory 8-isoprostane as well as lower Nrf-2, GCLC, and NQO1 expression levels in lung tissue following bleomycin administration.ConclusionsOur findings demonstrate that serum LCN2 might be a potential prognostic marker of AE-IPF. Moreover, LCN2 expression levels may reflect the severity of lung injury, and LCN2 may be a protective factor against bleomycin-induced acute lung injury and oxidative stress.

Positive impact of obesity on the prognosis of liver cirrhosis.

The study aims to determine the prognostic impact of obesity, sarcopenic obesity, and dynapenic obesity in patients with chronic liver disease. This retrospective observational study enrolled patients with chronic hepatitis (n=746) and liver cirrhosis (n=434) without hepatocellular carcinoma at entry. The patients were evaluated for sarcopenia and obesity between April 2016 and April 2022. Obesity was defined as a body mass index of ≥25kg/m2. Sarcopenic obesity was defined as low skeletal muscle mass (pre-sarcopenia) with obesity and dynapenic obesity was defined as low muscle strength (dynapenia) with obesity. The effects of obesity on survival were evaluated retrospectively. The mean observation period was 2.5years. Obesity, sarcopenic obesity, and dynapenic obesity were found in 271 (45.5%), 17 (2.9%), and 21 (3.5%) men, and 261 (44.7%), 59 (10.1%), and 53 (9.1%) women, respectively. A multivariate Cox proportional hazards model revealed that Child-Pugh class, dynapenia (hazard ratio [HR] 3.89), elderly (≥65years old) (HR 2.11), and obesity (HR 0.58) were independently associated with overall survival (OS). However, neither sarcopenic nor dynapenic obesity were associated with OS. In patients with cirrhosis, the OS of the obese group was significantly higher than that of the non-obese group. The effect of obesity on OS was significant in elderly patients, but not in younger patients. Sarcopenic and dynapenic obesity seem unrelated to the prognosis of patients with chronic liver disease. Obesity has a positive effect on the prognosis of elderly patients with cirrhosis.

Associations between low- and high-fat dairy intake and recurrence risk in people with stage I-III colorectal cancer differ by sex and primary tumour location.

We previously demonstrated that intake of low-fat dairy, but not high-fat dairy, was associated with a decreased colorectal cancer (CRC) recurrence risk. These risks, however, may differ by sex, primary tumour location, and disease stage. Combining data from two similar prospective cohort studies of people with stage I-III CRC enabled these subgroup analyses. Participants completed a food frequency questionnaire at diagnosis (n = 2283). We examined associations between low- and high-fat dairy intake and recurrence risk using multivariable Cox proportional hazard models, stratified by sex, and primary tumour location (colon and rectum), and disease stage (I/II and III). Upper quartiles were compared to lower quartiles of intake, and recurrence was defined as a locoregional recurrence and/or metastasis. During a median follow-up of 5.0 years, 331 recurrences were detected. A higher intake of low-fat dairy was associated with a reduced risk of recurrence (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.43-0.83), which seemed more pronounced in men (HR: 0.51, 95% CI: 0.34-0.77) than in women (HR: 0.84, 95% CI: 0.47-1.49). A higher intake of high-fat dairy was associated with an increased risk of recurrence in participants with colon cancer (HR: 1.60, 95% CI: 1.03-2.50), but not rectal cancer (HR: 0.88, 95% CI: 0.54-1.45). No differences in associations were observed between strata of disease stage. Concluding, our findings imply that dietary advice regarding low-fat dairy intake may be especially important for men with CRC, and that dietary advice regarding high-fat dairy intake may be specifically important in people with colon cancer.

Estimates and Predictors of Mortality, Stroke Recurrence, and Functional Dependency 1-Year after Ischemic Stroke: A Prospective Multicenter Longitudinal Cohort Study in Central Norway

Background. Stroke incidence and mortality have drastically decreased in high-income countries in the past twenty years. In this study, we provide updated estimates on mortality, recurrent stroke, and functional dependency among patients with first-ever ischemic stroke and assess predictors associated with poor outcomes with a focus on age, vascular factors, stroke severity, function, and comorbidity burden. Methods. MIDNOR STROKE is a multicenter prospective longitudinal study including patients with first-ever ischemic stroke admitted to stroke units in Central Norway during 2015-2017. Data on survival, stroke recurrence, and functional dependency were collected during hospital stay and follow-up. Multivariable Cox proportional hazard models and logistic regression models were used to analyze predictors of mortality, stroke recurrence, and functional dependency. Results. A total of 794 participants were included in the study. After a year, 7.6% of the participants had died, 5.8% had a recurrent stroke, and 13.6% experienced functional deterioration to dependency. Multivariable analysis revealed that age (HR: 1.07, 96% CI: 1.03, 1.10), stroke severity (HR: 1.10, 95% CI: 1.07, 1.13), comorbidity burden (low: HR: 4.05, 95% CI: 1.48, 11.10; moderate: HR: 5.44, 95% CI: 2.06, 14.40; and high: 7.72, 95% CI: 2.85, 21.00), and coronary artery disease (HR: 2.40, 95% CI: 1.32, 4.38) predicted all-cause death. Statin therapy predicted improved survival (HR: 0.39, 95% CI: 0.21, 0.75). High age (HR: 1.09, 95% CI: 1.05, 1.14) and increased stroke severity (OR: 1.26, 95% CI: 1.17, 1.38) predicted elevated risk of functional dependency at one year. Conclusions. In this study, we have demonstrated that 1-year survival following first-ever ischemic stroke was high compared to previous reports and that statin therapy predicted improved survival. The risk of recurrent stroke after one year was found to be low compared to previous studies. Approximately 14% of stroke survivors who were initially functionally independent experienced deterioration to functional dependency. In addition to older age and stroke severity, increased comorbidity burden and a history of coronary artery disease predicted poor stroke prognosis. Interventions aimed at reducing stroke severity may improve patient outcomes. Furthermore, prevention efforts targeting conditions such as CAD and reducing overall comorbidity burden in stroke patients may favorably improve survival. This trial is registered with NCT03962127.

Prospects of CSF shunt independence among chronically shunted patients.

CSF shunt placement for hydrocephalus and other etiologies has arguably been the most life-saving intervention in pediatric neurosurgery in the past 6 decades. Yet, chronic shunting remains a source of morbidity for patients of all ages. Neuroendoscopic surgery has made shunt independence possible for newly diagnosed hydrocephalic patients. In this study, we examine the prospects of shunt independence with or without endoscopic third ventriculostomy (ETV) in chronically shunted patients. After IRB approval, a retrospective analysis was completed on patients whose shunt was ligated or removed to achieve shunt independence, with or without ETV. Clinical and imaging data were collected. Eighty-eight patients with CSF shunts had their shunt either ligated or removed, 57 of whom had a concomitant ETV. Original reasons for shunting included: congenital hydrocephalus 20 (23%), post-hemorrhagic hydrocephalus (PHH) of prematurity 14 (16%), aqueductal stenosis 10 (11%), intracranial cyst 8 (9%), tumor 8 (9%), infantile subdural hematomas 8 (9%), myelomeningocele 7 (8%), post-traumatic hydrocephalus 7 (8%) and post-infectious hydrocephalus 6 (7%). The decision to perform a simultaneous ETV was made based on etiology. Forty-nine (56%) patients became shunt independent. The success rate was 46% in the ETV group and 73% in the no ETV group. Using multivariate analysis and Cox Proportional Hazards models, age > 4 months at shunt placement (p = 0.032), no shunt revisions (p = 0.01), select etiologies (p = 0.043), and ETVSS > 70 (in the ETV group) (p = 0.017), were protective factors for shunt independence. Considering the long-term complications of shunting, achieving shunt independence may provide hope for improved quality of life. While this study is underpowered, it provides pilot data identifying factors that predict shunt independence in chronically shunted patients, namely age, absence of prior shunt revision, etiology, and in the ETV group, the ETVSS.

Abstract PO1-09-11: Racial Differences in Pathologic Complete Response Rate and Overall Survival Following Neoadjuvant Chemotherapy for Breast Cancer

Abstract Background: Neoadjuvant chemotherapy (NAC) is increasingly used in the treatment of breast cancer and has been utilized in multiple clinical trials assessing the efficacy of novel therapies. Pathologic complete response (pCR) following NAC is associated with improved survival outcomes in breast cancer and pCR is a commonly used endpoint in clinical trials. Despite improvements in breast cancer survival using modern treatment regimens, Black women continue to experience worse survival outcomes as compared to White women. The objective of this study was to evaluate the association between race and clinical outcomes, specifically pCR rate, recurrence free survival and overall survival, in patients undergoing neoadjuvant chemotherapy at our institution. Methods: We conducted a retrospective review of patients who completed at least 75% of the recommended cycles of neoadjuvant chemotherapy for breast cancer between 2010 and 2016 and underwent surgery. Receptor subtypes were defined as HR+/HER2-negative, HER2+ or triple-negative. The association between race and pCR, defined as ypT0/ypTis ypN0, and survival endpoints of overall survival and recurrence free survival were analyzed using multivariable logistic regression and Cox proportional hazard models. Results: A total of 532 women met the inclusion criteria, 323 (60.7%) were White, 188 (35.3%) were Black and 21 (3.9%) were other/unknown. Median follow-up was 65 months. The receptor subgroups consisted of 195 (36.7%) HR+/HER2-negative cancers, 193 (36.3%) HER2+ cancers and 144 (27.1%) triple-negative cancers. No significant association between race and receptor subtype (p=0.55) or pre-treatment clinical stage (p=0.96) was observed. The overall observed pCR rate was 19% for Black patients and 27% for White patients, demonstrating a significantly different pCR rate by race in multivariate analysis (odds ratio of pCR White vs Black of 1.75; p=0.02). The largest discrepancy in pCR rate between White and Black patients was within subjects with triple-negative disease (pCR rate 44% White patients vs 27% Black patients, p=0.03). There was no association between recurrence free survival and race in univariate analysis (p=0.15). A significant difference in overall survival by race was observed using multivariable Cox proportions hazard model (hazard ratio Black vs White 1.77; p=0.03). Conclusions: In this retrospective analysis of patients receiving neoadjuvant chemotherapy, Black patients experienced a significantly lower pCR rate compared to White patients, with the biggest gap identified within triple-negative breast cancers. During the study period, Black patients also experienced a lower overall survival rate compared to White patients. Differences in the ability to achieve a pCR may be a contributing factor to the worse survival outcomes of Black patients. Citation Format: Chad Livasy, Erin Donahue, Brittany Neelands, Lejla Hadzikadic-Gusic, Terry Sarantou, Mckenzie Needham, Alicia Patrick, Arielle Heeke, Antoinette Tan, Richard White. Racial Differences in Pathologic Complete Response Rate and Overall Survival Following Neoadjuvant Chemotherapy for Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-09-11.

Abstract PO4-23-04: Is breast-conserving surgery an optional local therapy for non-inflammatory skin involvement (T4b) breast cancer? A Propensity Score Matching and Inverse Probability Weighting Analysis of SEER Database Results

Abstract Introduction: Although breast-conserving surgery (BCS) usage has been widespread in breast cancer treatment, it is still controversial about its application in non-inflammatory skin involvement (T4b) breast cancer. We designed this study to compare the prognosis for BCS versus mastectomy in this population. Methods: This retrospective cohort study included patients from the SEER database diagnosed with tumor stage T4b breast cancer from 1998 to 2019. To create prognostic factors, balance between BCS+RT and Mastectomy+RT groups, we calculated propensity scores for each patient. The calculation was based on the advance assessment for factors affecting prognosis, with the use of univariable and multivariable Cox proportional hazards models. Based on it, two propensity score-based matchings were conducted, including propensity score matching (PSM) and inverse probability weighting (IPTW). After adjustment, we performed Kaplan-Meier curves and multivariable Cox proportional hazards models to estimate BCSS and OS. Results: Of 4,680 patients who met the criterion, 588 received BCS+RT, and 4092 received Mastectomy+RT. In the propensity score matching (PSM) cohort, BCS+RT was found to improve breast cancer cause-specific survival (HR, 0.67; 95% CI, 0.53 to 0.85; p=0.001) and overall survival (HR, 0.72; 95% CI, 0.59 to 0.88; p=0.001). Similar results in the analysis of the IPTW-matched cohort confirm this result (BCSS: HR, 0.672; OS: HR, 0.722). Subgroup analysis revealed that those less than 70 years old, grade I+II, 3cm or smaller tumor size, hormone receptor-positive, or received chemotherapy treatment were more likely to benefit from BCS+RT (all p&amp;lt; 0.05). Conclusions: Locally treatment with BCS usage presented a significantly better survival than with mastectomy for non-inflammatory skin involvement (T4b) breast cancer patients. This finding provided evidence of selection in the local treatment of these patients. Citation Format: Jingyi Lin, Shiping Luo, Jie Zhang, Chuangui Song. Is breast-conserving surgery an optional local therapy for non-inflammatory skin involvement (T4b) breast cancer? A Propensity Score Matching and Inverse Probability Weighting Analysis of SEER Database Results [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-23-04.

Abstract PO2-11-05: Pregnancy Trends Following Breast Cancer Treatment: Insights from a Large Single-Center Experience

Abstract Background The treatment of breast cancer (BC), particularly chemotherapy and long-term endocrine therapy (ETx), can have an impact on fertility which young women with BC have concerns about. This study was therefore conducted with the objective of providing comprehensive real-world data on pregnancy following BC treatment, aiming to shed light on this crucial aspect of survivorship and potentially guide clinical practice and patient counseling. Methods A retrospective analysis was conducted using medical records of women aged 18-40 years diagnosed with BC at a single tertiary medical center between December 2010 and September 2020. The pregnancy rate and timing in relation to characteristics and treatment were analyzed, along with the outcomes of discontinuing ETx for the purpose of pregnancy. Statistical analyses including Kaplan-Meier curves and Cox regression were performed. Results The study included 995 patients, with a mean age at diagnosis of 31.5 years. Of these, 115 (11.6%) patients became pregnant after BC treatment. Patients with a prior history of pregnancy had a lower likelihood of conception post-treatment (HR=0.39, 95% CI: 0.24-0.67, P&amp;lt; 0.001). Women with hormone receptor positive BC was also associated with lower pregnancy rates than with hormone receptor negative BC (HR=0.52, 95% CI: 0.36-0.77, P=0.001). Age at diagnosis and chemotherapy did not significantly impact pregnancy rates (P=0.251 and P=0.140, respectively). Among 662 women with hormone receptor positive BC, there were 76 (11.5%) women who discontinued ETx for the purpose of pregnancy and 69.7% (53 out of 76) achieved pregnancies. The median duration of medication before cessation among these women was 26.5 months and the duration of ETx did not significantly affect pregnancy rates (P=0.204). Recurrence after discontinuation of ETx for pregnancy was observed in 17% (13 out of 76) of cases. The median breast cancer-free interval among these cohort was 71 months. Late recurrence, occurring after 5 years of treatment, was observed in 77% (10 out of 13) of cases. Among the patients who experienced recurrence, 62% (8 out of 13) were loco-regional, while 38% (5 out of 13) were distant recurrences and the success rate of achieving pregnancy was 69% (9 out of 13), while 31% (4 out of 13) did not get pregnant. Conclusion This study provided real-world data regarding the influence and outcomes of ETx on pregnancy in young BC survivors. The discontinuation of ETx for the purpose of pregnancy appears to result in successful conception. Recurrence rates after therapy discontinuation for pregnancy were observed in a subset of cases, with late and loco-regional recurrences being more common. Results of uni- and multi-variable cox proportional hazards model evaluating time to pregnancy * The pregnancy rate was calculated using Kaplan-Meier (KM) estimates. Pregnancy rate according to ETx and its discontinuation Pregnancy rate according to duration of ETx prior to Discontinuation for pregnancy * The p-value was calculated using Chi-square analysis Citation Format: Young-jin Lee, Tae-Kyung Yoo, Sae Byul Lee, Jisun Kim, Il-Yong Chung, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Hee Jeong Kim, Jeonghee Ahn, Seonok Kim. Pregnancy Trends Following Breast Cancer Treatment: Insights from a Large Single-Center Experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-11-05.

Abstract PO1-17-01: Surgical Margins and prognosis of borderline and malignant phyllodes tumors of breast

Abstract Background. To determine the appropriate surgical margin and identify predictive factors for recurrence and prognosis of borderline and malignant phyllodes tumor (PT) of the breast. Methods. A retrospective review of patients with borderline and malignant PT treated from March 2011 to December 2022 at the First Affiliated Hospital of Chongqing Medical University were conducted. The main endpoints of this research were local recurrence-free survival (LRFS) and disease-free survival (DFS). Univariate and multivariate Cox proportional hazard models were used to examine the impacts of different variables on LRFS and DFS, and to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results. Of 155 patients with phyllodes tumors, 87 (56.1%) were classified as borderline while 68 (43.9%) were malignant. All patients included underwent operation, with a median age of 47 years (range,12-66 years) and a median tumor size of 60 mm (range,15-300 mm). Initial surgical margins &amp;lt; 1cm in 72 (46.5%) patients, of which 28 (38.9%) underwent reoperation, resulting in 45 (28.4%) patients with a margin &amp;lt; 1cm and 111 (71.6%) patients with a margin ≥1cm. At a median follow-up period of 66 months (range 3-146 months), local recurrence was observed in 36 patients (23.2%), and distant metastasis occurred in 10 patients (6.5%). In this cohort, the rates of 5-year LRFS was significantly higher in the surgical margin ≥1 cm group than in the surgical margin &amp;lt; 1 cm group (83.8% vs 50.4%, log-rank P&amp;lt; 0.001), both for the borderline (log-rank P=0.010) and the malignant PT (log-rank P&amp;lt; 0.001).Similarly, for both borderline (log-rank P=0.019) and malignant PT (log-rank P&amp;lt; 0.001), the rates of 5-year DFS was significantly higher in the surgical margin ≥1 cm group than in the surgical margin &amp;lt; 1 cm group (80.3% vs 47.5%, log-rank P=0.002). For 72 patients with the initial margin &amp;lt; 1 cm, 5-year DFS for undergoing reoperation to achieve a margin ≥1 cm and remaining with a margin &amp;lt; 1 cm were84.1% and 47.5%, respectively (P=0.008). In univariate analysis of the entire cohort, age, fibroadenoma surgery history, surgical methods, and surgical margins emerged as predictive factors for LRFS (P=0,003, 0.019, 0.026, and0.001, respectively), whereas age, reproductive history, fibroadenoma surgery history, tumor size and surgical margins were predictors of DFS (P= 0,011, 0.025, 0.039, 0.022, and0.002, respectively).In multivariate analysis, age&amp;lt; 45 years (HR=2.186, 95%CI:1.105-4.328, P=0.025)and surgical margins&amp;lt; 1cm (HR=2.181, 95%CI:1.021-4.659, P=0.044) were independent risk factors of LRFS. Independent risk factors for DFS included tumor size&amp;gt;5cm (HR=2.265, 95%CI:1.113-4.606, P=0.024) and surgical margins &amp;lt; 1cm (HR=2.689, 95%CI:1.438-5.027, P=0.002). Conclusion. For borderline and malignant PT, surgical margins of at least 1 cm should be achieved for a better prognosis. Patients aged &amp;lt; 45 years with a high risk of local recurrence and larger tumor patients with poor prognosis, multiple therapy modalities may be required for these high-risk patients. Survival curves for impact of variables on LRFS and DFS Table 1 Univariate and multivariate analysis of LRFS of PTs of the breast (n=155) Table 2 Univariate and multivariate analysis of DFS of PTs of the breast (n=155) Citation Format: lu Gan, Jialin Su. Surgical Margins and prognosis of borderline and malignant phyllodes tumors of breast [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-17-01.

Abstract PO5-18-02: A Population-Based Analysis of the Impact of Omission of Anthracyclines in the Neoadjuvant Setting on the Risk of Mortality

Abstract Background Most patients with high-risk non-metastatic breast cancer are treated with neoadjuvant chemotherapy (NAC), which includes the administration of anthracyclines. The omission of anthracyclines was shown to be associated with excellent outcomes in selected patients. However, the extent to which anthracyclines are omitted among a population of women treated with NAC and its impact on mortality remain unclear. Objective To investigate the extent to which anthracyclines are omitted among a population of patients with invasive breast cancer treated with NAC and to examine the impact of non-anthracycline NAC on risks of breast cancer-specific and all-cause mortality. Methods We performed a retrospective population-based cohort analysis using patient-level health administrative data. The cohort includes women aged ≥18 years with stage I – III invasive breast cancer diagnosed between January 2012 and December 2020, treated with NAC and surgery. Patients were excluded if they received &amp;lt; 50% of the planned chemotherapy regimen, had bilateral breast cancer and/or a previous malignancy. The exposure of interest was anthracycline versus non-anthracycline NAC regimen. The primary and secondary endpoints were breast cancer-specific mortality and overall (all-cause) mortality. Multivariable Cox proportional hazards models adjusted by propensity score, and clinical/pathologic variables including a measure of comorbidity was performed to examine impact of omission of anthracyclines on outcomes. Cumulative incidence curves were generated to calculate the 5-year cumulative incidence of breast cancer and all-cause mortality for the whole cohort and in subset analyses, stratified by stage and receptor subtype. Results The cohort includes 4,180 women. Median follow was 62 months (IQR 44-85) and median age was 51 years (IQR 43-60). Most patients had low co-morbidities (96.0%), Stage II (44.1%) or Stage III (47.7%) disease, underwent mastectomy (72.6%), had axillary node dissection (64.4%) and received post-operative radiotherapy (88.8%). 279 (6.7%) individuals were treated with a non-anthracycline NAC and 3,901 (93.3 %) received an anthracycline NAC. Women who received non-anthracycline NAC were older (median 62 years vs. 50 years; p&amp;lt; 0.001), more likely to have stage I-II disease (77.0% vs. 51.3%; p&amp;lt; 0.001), and more likely to have triple-negative breast cancer (TNBC) (14.0% vs. 24.4%; p&amp;lt; 0.001) than those who received anthracyclines.On propensity adjusted multivariable analysis, factors associated with an increased risk of BC mortality include Stage III (HR 9.3, 95%CI 4.5 - 19.2, p&amp;lt; 0.0001) or stage II at presentation (HR 2.57 95% CI 1.24, 5.34, p=.01) (ref: stage I) or triple negative subtype (HR 3.7 95% CI 3.03, 4.51, p&amp;lt; .0001) (ref: hormone positive/HER2-). There was no significant difference in the relative risks of BC death (HR 0.8, 95% CI 0.5-1.27) or all-cause mortality (HR 0.85, 95% CI 0.60-1.21) for patients selected for treatment without anthracyclines compared to those treated with anthracyclines.Overall, among individuals selected for treatment without or with anthracycline NAC there was no significant difference in the 5-year cumulative incidence of BC (15.4% vs 10.5%, P=.05) or all-cause mortality (16.4% vs 11.9%, P=.07). However, the 5-year cumulative incidence of BC specific death (31.8% vs 16.5%, p=.03) and 5-year cumulative incidence of all-cause death (31.8% vs. 18.2%, p=.06) was higher among 420 women with HER2+ Stage III breast cancer who received non-anthracycline versus anthracycline-based chemotherapy. No difference was observed for other subgroups. Conclusions The omission of anthracyclines in NAC for individuals with stage III HER2+ breast cancer was associated with higher cumulative risks of breast cancer and all-cause mortality but no difference was observed for other subgroups. Further research is warranted to better understand in whom anthracyclines can be safely omitted. Citation Format: Danilo Giffoni M. M. Mata, Rinku Sutradhar, Matthew Castelo, Lena Nguyen, Danielle Rodin, Ezra Hahn, Omolara Fatiregun, Cindy Fong, Sabina Trebinjac, Andrea Eisen, Lawrence Paszat, Katarzyna Jerzak, Eileen Rakovitch. A Population-Based Analysis of the Impact of Omission of Anthracyclines in the Neoadjuvant Setting on the Risk of Mortality [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-02.

Abstract PO1-03-02: Impact of Body Mass Index (BMI) on the efficacy of different adjuvant chemotherapy schedules in patients with breast cancer: analysis from the randomized phase III GIM2 trial

Abstract Background: The long-term results of the Italian randomized phase III GIM2 study showed that, in women with node-positive breast cancer (BC), dose-dense (DD) chemotherapy significantly improved both disease-free survival (DFS) and overall survival (OS) compared with standard-interval (SI) chemotherapy. Obesity has been identified as an independent poor prognostic factor in patients with BC, with a potential negative impact on the efficacy and toxicity of systemic therapies. Nevertheless, the specific influence of body mass index (BMI) on the efficacy of different adjuvant chemotherapy schedules (DD or SI) remains a subject of debate. This analysis aimed to investigate this hypothesis in patients enrolled in the GIM2 trial. Methods: GIM2 was a randomized multicentric phase III trial that compared different chemotherapy schedule (DD vs SI) and regimen (FEC-P vs EC-P) in 2091 node-positive early breast cancer patients. BMI (kg/m2) was categorized as follows: &amp;lt; 18.5 (underweight), 18.5 to &amp;lt; 25 (lean), 25 to &amp;lt; 30 (overweight), and ≥ 30 (obese). The primary endpoint was to assess association between BMI and DFS and OS. Survival estimates were compared using the Kaplan-Meier method and log-rank test. Univariate and multivariable Cox proportional hazard models, adjusted for relevant prognostic factors, were used. Results: A total of 1925 patients were included in the present analysis, of whom 31.6% (n=632) were overweight and 19.3% (n=386) obese. Median age was 52 years. Overweight-obesity condition was significantly associated with postmenopausal status, greater representation of T2-T4 tumors with N &amp;gt; 2 in both patients in the DD and SI arm. After a median follow-up of 15.0 years (IQR 8.4-16.3), compared to patients with normal BMI, those who were overweight or obese at diagnosis had a higher risk of experiencing a DFS event (Hazard Ratio [HR] 1.11 95% CI 0.94-1.31 and HR 1.37 95%CI 1.14-1.65, respectively, p=0.003) and OS event (HR 1.11 95% CI 0.89-1.38 and HR 1.59 95%CI 1.26-2.01, respectively, p=0.0003). No significant interaction was found between BMI and treatment schedule in terms of DFS (p for interaction=0.56) nor OS (p for interaction=0.19). At the multivariate analysis, in the DD arm, adjusted HR (aHR) for DFS and for OS were 1.01 (95% CI 0.75- 1.35) and 1.04 (95% CI 0.72-1.52) for obese vs. normal BMI groups, and 0.88 (95% CI 0.68- 1.15) and 0.77 (95%CI 0.54-1.10) for overweight vs. normal BMI groups, respectively. In the SI arm, aHRs for DFS and OS were 1.24 (95% CI 0.94- 1.63) and 1.35 (95%CI 0.96- 1.90) for obese vs. normal BMI groups, and 1.04 (95%CI 0.82- 1.33) and 1.01 (95% CI 0.74-1.40) for overweight vs. normal BMI groups, respectively. Similar results were observed when considering hormone receptor-positive and negative BC separately. Conclusion: In the GIM2 trial, BMI was prognostic but not predictive of different benefit to adjuvant chemotherapy. In high-risk patients, DD schedule should be considered the preferred schedule irrespective of BMI. Citation Format: Francesca Poggio, Eva Blondeaux, Marco Tagliamento, Marta Perachino, Simone Nardin, Benedetta Conte, Sabino De Placido, Mario Giuliano, Valeria Forestieri, Michelino De Laurentiis, Adriano Gravina, Giancarlo Bisagni, Anita Rimanti, Anna Turletti, Cecilia Nisticò, Angela Vaccaro, Francesco Cognetti, Alessandra Fabi, Simona Gasparro, Ornella Garrone, Ylenia Urracci, Maria Grazia Alicicco, Mauro Mansutti, Paola Poletti, Pierpaolo Correale, Claudia Bighin, Fabio Puglisi, Filippo Montemurro, Giuseppe Colantuoni, Luca Boni, Matteo Lambertini, Lucia Del Mastro. Impact of Body Mass Index (BMI) on the efficacy of different adjuvant chemotherapy schedules in patients with breast cancer: analysis from the randomized phase III GIM2 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-03-02.