St. John Medical Center

The immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix®, GlaxoSmithKline Biologicals) administered according to its licensed vaccination schedule (3-dose, 3D) and formulation (20 μg of each HPV antigen; 20/20F) has previously been demonstrated. This partially-blind, controlled, randomized trial (NCT00541970) evaluated 2-dose (2D) schedules using the licensed 20/20F or an alternative formulation containing 40 μg of each antigen (40/40F), compared with the licensed 3D schedule. Healthy females stratified by age (9-14, 15-19, 20-25 y) were randomized to receive 2 doses of 20/20F at Months (M) 0,6 (n=240), 40/40F at M0,6 (n=241) or 40/40F at M0,2 (n=240), or 3 doses of 20/20F at M0,1,6 (licensed schedule/formulation, n=239). One month after the last dose, the 3D schedule was not immunologically superior to 2D schedules except in the 40/40F M0,2 group for HPV-16 (lower limit of 95% CI geometric mean antibody titer (GMT) ratio [2D/3D] < 0.5). For both HPV-16 and HPV-18, the 2D schedules in girls 9-14 y were immunologically non-inferior to the 3D schedule in women 15-25 y (the age group in which efficacy has been demonstrated) (upper limit of 95% CI for GMT ratio [3D/2D] < 2) one month after the last dose. At Month 24, non-inferiority was maintained for the 2D M0,6 schedules in girls 9-14 y versus the 3D schedule in women 15-25 y. All formulations had acceptable reactogenicity and safety profiles. These results indicate that the HPV-16/18 vaccine on a 2D M0,6 schedule is immunogenic and generally well tolerated in girls 9-14 y and that the 2D schedule is likely adequate for younger females.

Oritavancin is a lipoglycopeptide antibiotic that has been shown to be effective for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). This antibiotic has multiple mechanisms of action including inhibiting peptidoglycan cell wall synthesis and disrupting bacterial cell membrane, leading to cell death. Oritavancin is highly active against common gram-positive pathogens including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate S. aureus, vancomycin-resistant S. aureus, and vancomycin-resistant enterococci. The drug is administered as a single intravenous dose of 1200 mg over 3 hours in adult patients, and because of its terminal half-life of 393 hours, repeat dosing is not required in the treatment of ABSSIs. There is a very slow elimination from tissue sites, and no dosing adjustments are required for renal or hepatic insufficiency. Two clinical trials have demonstrated noninferiority compared with vancomycin in the treatment of ABSSSIs. Other than liver enzyme elevation and the occurrence of osteomyelitis, oritavancin has been associated with adverse events similar to those of vancomycin in follow-up for up to 60 days. Patients should be monitored for osteomyelitis and alternate therapy given in the case of confirmed or suspected osteomyelitis. Although oritavancin is an attractive antibiotic to consider in the outpatient area, its efficacy and safety in the treatment of other sites of infection are yet to be established.

PURPOSE: Hormone receptor-positive (HR+) tumors have heterogeneous biology and present a challenge for determining optimal treatment. In the Neoadjuvant Breast Registry Symphony Trial (NBRST) patients were classified according to MammaPrint/BluePrint subtyping to provide insight into the response to neoadjuvant endocrine therapy (NET) or neoadjuvant chemotherapy (NCT). OBJECTIVE: The purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional 'clinical' immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in 'clinical luminal' [HR+/human epidermal growth factor receptor 2-negative (HER2-)] breast cancer patients to predict treatment sensitivity. METHODS: NBRST IHC/FISH HR+/HER2- breast cancer patients (n = 474) were classified into four molecular subgroups by MammaPrint/BluePrint subtyping: Luminal A, Luminal B, HER2, and Basal type. Pathological complete response (pCR) rates were compared with conventional IHC/FISH subtype. RESULTS: The overall pCR rate for 'clinical luminal' patients to NCT was 11 %; however, 87 of these 474 patients were reclassified as Basal type by BluePrint, with a high pCR rate of 32 %. The MammaPrint index was highly associated with the likelihood of pCR (p < 0.001). Fifty-three patients with BluePrint Luminal tumors received NET with an aromatase inhibitor and 36 (68 %) had a clinical response. CONCLUSIONS: With BluePrint subtyping, 18 % of clinical 'luminal' patients are classified in a different subgroup, compared with conventional assessment, and these patients have a significantly higher response rate to NCT compared with BluePrint Luminal patients. MammaPrint/BluePrint subtyping can help allocate effective treatment to appropriate patients. In addition, accurate identification of subtype biology is important in the interpretation of neoadjuvant treatment response since lack of pCR in luminal patients does not portend the worse prognosis associated with residual disease in Basal and HER2 subtypes.

Persistent Staphylococcus aureus bacteremia (SAB-P) is well known but poorly delineated due to unclear definition. We retrospectively studied 78 patients with SAB-P using a stringent definition (bacteremia for > or = 7 d), in a single teaching hospital, during 1 January 2002 to 30 June 2003 and 1 November 2005 to 31 December 2006 to determine whether the frequency, risk factors and outcome changed over time. SAB was encountered in 354 and 259 instances during the 2 periods, respectively. Patients' characteristics changed with increasing organ dysfunction score (2.9+/-1.7 vs 3.4+/-1.4; p <0.001), patients with invasive devices (27.7% vs 41.3%; p=0.001), hemodialysis dependence (19.2% vs 27.8%; p=0.04), MRSA (50.8% vs 64.5%; p=0.001), and vancomycin treatment (57.9% vs 67.2%; p=0.02). SAB-P frequency increased slightly (11.0% vs 15.1%). Risk (associated) factors for SAB-P (identified by logistic regression) were metastatic infection (OR=5.60; 95% CI 3.00 - 10.47), vancomycin treatment (OR=4.17; 95% CI 2.14 - 8.11), endovascular sources (OR=3.35; 95% CI 1.92 - 5.85) and diabetes (OR=2.14; 95% CI 1.26 - 3.64). SAB- and SAB-P-associated case-fatality did not change (23.2% vs 18.5% and 25.6 vs 30.8%, respectively). All survivors ultimately achieved clearance. These findings suggest that patients with SAB are changing over time. Additionally, SAB-P frequency is higher than previously reported. SAB-P rise is probably due to increasing SAB, MRSA, and patients at risk for complications. Innovative approaches should target novel treatment modalities and risk reduction.

Wiedemann-Rautenstrauch syndrome, also known as neonatal progeroid syndrome, is a rare condition with fewer than 40 patients reported in the literature. Characteristic physical findings include neonatal progeroid appearance, sparse scalp hair, prominent scalp veins, and lipoatrophy; in addition, neonatal teeth are often a distinctive finding. The inheritance pattern of this disorder has been postulated to be autosomal recessive, although a specific gene has not been identified. Here we report an infant with the characteristic phenotypic features of Wiedemann-Rautenstrauch syndrome in whom exome sequencing identified two pathogenic variants in POLR3A: c.1909+18G>A; p.(Y637Cfs*23) and c.2617C>T; p.(R873*). Mutations in POLR3A (OMIM #614258) are associated with 4H leukodystrophy syndrome characterized by the triad of hypomyelination, hypodontia, and hypogonadotrophic hypogonadism. The present patient's genotype implies a broader phenotypic range for POLR3A mutations and might expand the clinical spectrum. This proband is notable because she had two null pathogenic variants. Replication in other patients clinically diagnosed with Wiedemann-Rautenstrauch syndrome is needed to further demonstrate this gene-disease association. © 2016 Wiley Periodicals, Inc.

Candidemia rate and species distribution vary according to the type of patients, country of origin and antifungal prophylaxis use. To present current candidemia epidemiological trends. A retrospective examination of candidemia in adults (≥18 years-old) hospitalised from 2007 to 2015. Cases were identified through the microbiology laboratory. Candida species were distinguished based on colony morphology and VITEK-2 YBC cards, (bioMerieux, Durham, NC, USA). Patient characteristics, species distribution, source and outcome were assessed. We encountered 275 patients (294 episodes) with candidemia. The rate of candidemia dropped in 2010 (P = 0.003) without further decline. Nearly all cases (97.5%) were healthcare-associated. C. albicans (n = 118) and C. glabrata (n = 77) proportions varied without a discernable trend. C. glabrata was more common in diabetics [52.9% vs. 32.0% (non-diabetics); P = 0.004] and abdominal sources [53.3% vs. 35.5% (other sources); P = 0.03], especially gastric/duodenal foci [88.9% vs. 44.1% (other abdominal foci); P = 0.02]. All-cause 30-day mortality rate was 43.3% without changes over time or differences between C. albicans and C. glabrata. In conclusion, the candidemia rate remains stable after a decline in 2010. C. albicans remains the most common species but C. glabrata predominates in diabetics and abdominal sources. These findings suggest possible species-related differences in colonisation dynamics or pathogenicity.

We assessed the role of Panton-Valentine leukocidin (PVL) and SCCmec type in community associated (CA) and healthcare associated (HC) Staphylococcus aureus (SA) skin/soft-tissue infections (STI). We prospectively monitored microbiology results (11 January 2005 to 6 January 2006), screened inpatients with SA in tissue samples or blood, and selected adults with STI. We recorded clinical/microbiological characteristics, and tested saved isolates for PVL genes (real time PCR) and SCCmec type (conventional multiplex PCR). We encountered 204 patients. MRSA strains that accounted for 70.5% CA and 66.0% HC cases, caused more abscesses (55.7% vs 29.7%; p =0.001) and were often PVL-positive (68.9% vs 4.8%; p <0.001). PVL-positive isolates caused more abscesses (72.9% vs 26.5%; p <0.001) but similar bacteremia (7.3% vs 7.1%). SCCmec IVa made up 95.8% of PVL-positive strains and accounted for 69.8% of the abscesses. SCCmec II caused higher mortality (14.8% vs 0-3.1%; p = 0.02). PVL was a predictor of abscesses (p <0.001). Predictors of bacteremia were age > or = 65 y (p =0.004), necrotizing infection (p =0.014), and head/neck location (p =0.05). These findings suggest that SCCmec type and PVL status influence STI manifestations and contribute to MRSA-MSSA differences. PVL is implicated in abscess formation but not bacteremia. Bacteremia is likely related to host condition and/or other virulence factors that were not studied.

The effect of hydroxyethyl starch (HES) on granulocyte and platelet functions was assessed. No alteration of granulocyte viability, morphology, phagocytic ability, or bactericidal capacity was detected after incubation with 6 per cent HES at 25 C for two hours. Platelet morphology, size distribution, aggregation, nucleotide and serotonin release, and platelet factor‐3 availability were also unchanged after exposure to HES. It is concluded that HES has no adverse effect on cell function and appears to be a suitable adjuvant agent for blood cell component collection.

Established guidelines and standardized protocols exist to assist clinicians in effectively addressing disease-related malnutrition in hospitalized adults. The goals of this treatment vary according to the disease state and the severity of the malnutrition. In starvation-related malnutrition, the goal of nutrition therapy is to restore healthy levels of lean body mass and body fat. For chronic disease-related malnutrition, the goals of treatment are to maintain and improve lean body mass and body fat. In acute-disease-related malnutrition, the goals of nutrition therapy are to support vital organ function and preserve the host response through the acute episode. The success of addressing malnutrition in hospitalized patients depends not just on the nutrition therapy selected, but also on the timely and appropriate application of guidelines and protocols by the clinicians dedicated to caring for malnourished patients. Coordination of nutrition care among providers is highly desirable, and usually includes a multidisciplinary team of clinicians typically comprising a physician, nurse, dietitian, and pharmacist. For greatest success, this attention to recognizing and addressing malnutrition begins at admission and continues beyond discharge to the community. When addressing malnutrition in hospitalized patients, oral feeding through diet enrichment or oral nutrition supplementation (ONS) is the first line of defense. ONS has consistently been demonstrated to provide nutrition, clinical, functional, and economic benefits to malnourished patients in both individual trials and meta-analyses. In an era when the cost of healthcare is rising as the population ages, addressing malnutrition in hospitalized patients is an important priority.

BACKGROUND: The benefit of extended-duration thromboprophylaxis in patients hospitalised for acute medical illness beyond hospital stay remains controversial. AIMS: To perform a meta-analysis of randomised controlled trials (RCT) in order to examine the efficacy and safety of extended-duration anticoagulation for venous-thromboembolism (VTE) prophylaxis in this high-risk population. METHODS: An electronic database search was conducted to include all RCT comparing between extended-duration versus short-duration prophylactic anticoagulation in medically ill patients. The primary efficacy outcome was the composite events of asymptomatic deep vein thrombosis (DVT), symptomatic VTE and death from VTE-related causes. RESULTS: Five RCT were included totalling 40 124 patients, with a mean age of 71 years and 51% were male. In comparison to standard-duration therapy, extended-duration thromboprophylaxis was associated with a significant reduction in the primary efficacy outcome (risk ratio (RR) 0.75; 95% confidence interval (CI) 0.67-0.85; P < 0.01), symptomatic VTE (RR 0.53; 95% CI 0.33-0.84; P < 0.01) and asymptomatic DVT (RR 0.81; 95% CI 0.71-0.94; P < 0.01). However, there were no significant differences between both groups with regard to VTE-related death (RR 0.81; 95% CI 0.60-1.10; P = 0.18) or all-cause death (RR 0.97; 95% CI 0.88-1.08; P = 0.64). In contrast, extended-duration thromboprophylaxis was associated with an increased risk of major bleeding (RR 2.04; 95% CI 1.42-2.91; P < 0.01) and non-major clinically relevant bleeding (RR 1.81; 95% CI 1.29-2.53; P < 0.01). CONCLUSIONS: Among hospitalised medically ill patients, prolonging venous thromboprophylaxis was associated with a decreased risk of composite events of the primary efficacy outcome and increased risk of bleeding with no significant difference in VTE-related death.

Solid organ transplant recipients (SOTR) are at increased risk for a wide variety of typical and atypical infections as a consequence of impaired cell mediated and humoral immunity. We report a case of meningoencephalitis in a renal transplant recipient caused by lymphocytic choriomeningitis virus (LCMV) acquired by exposure to mice excreta. The clinical course was complicated by the development of hydrocephalus, requiring a ventriculoperitoneal shunt. To our knowledge, this is the first reported case of LCMV infection in a SOTR that was not organ donor derived.

PURPOSE: The purpose was to understand how African American children with asthma and their families living in underserved urban areas experience and perceive asthma. DESIGN AND METHODS: A narrative inquiry design with metaphorical analysis was used in this study with 20 African American children and their 10 families. RESULTS: Participants metaphorically viewed the family system as a functioning healthcare facility. Children didn't find their asthma abnormal but did use asthma symptoms to their advantage. Caregivers were viewed as first-line medical responders but often made errors in delivering medical treatment. Lack of knowledge relating to appropriate asthma interventions led to insufficient asthma care. PRACTICE IMPLICATIONS: Results provide evidence to improve patient-nurse interactions for this vulnerable patient group.

OBJECTIVES: This study aimed to evaluate the efficacy and safety of genotype- and phenotype-guided intensified antiplatelet therapy compared with conventional therapy in patients undergoing stent implantation. BACKGROUND: receptor inhibitors are recommended for percutaneous coronary intervention (PCI)-treated acute coronary syndrome, their usage is limited by a high bleeding risk. Therefore, personalized antiplatelet therapy could provide a valuable foundation for selection of antiplatelet therapy in this population. METHODS: We conducted a Bayesian network meta-analysis for all randomized clinical trials (RCTs) that evaluated genotype- and/or phenotype-guided therapy in PCI-treated coronary artery disease. RESULTS: Thirteen RCTs were included with a total of 6,845 patients. The results showed no significant differences in major adverse cardiovascular events (MACE) between the treatment options ((genotype guided vs. standard of care; OR 0.64; 95% CI: 0.38-1.05) and (phenotype vs. standard of care; OR 0.93; 95% CI: 0.54-1.37)). In addition, no significant differences were demonstrated in bleeding events ((genotype guided vs. standard of care; OR 0.73; 95% CI: 0.45-1.25) and (phenotype vs. standard of care; OR 0.90; 95% CI: 0.62-1.39)). CONCLUSIONS: In this mixed treatment meta-analysis of RCTs, neither genotype- nor phenotype-guided antiplatelet therapy in patients with PCI-treated coronary artery disease was superior to conventional therapy.

The incidence and mortality data for patients with breast cancer in the United States are important to healthcare administrators for planning healthcare measures such as screening mammograms. In this study, we examined breast cancer incidence and incidence-based mortality in the United States from 2004-2018 using the Surveillance, Epidemiology, and End Results (SEER) database. We reviewed 915,417 cases of breast cancer diagnosed between 2004 and 2018. Overall, the data showed an increased incidence rate of breast cancer among all races and a decreased mortality rate among all races. Breast cancer incidence rates increased by 0.3% (95% CI, 0.1, 0.4, p<0.001) per year over the study period. Breast cancer incidence rates increased for all age, race, and stage groups except for stage regional, which showed a statistically significant decrease in the incidence of -0.9% (95% CI, -1.1, -0.7, p<0.001). The highest decrease in mortality was observed among white patients, with an overall statistically significant decrease in rates by -14.3% (95% CI, -18.1, -10.4, p <0.001). The highest decrease in rates was observed between 2016 and 2018: -48.6 (95% CI, -52.6, -44.3, p <0.001). In black/African American patients, the overall incidence-based mortality decreased by -11.6% (95% CI -15.9, -7.1 p <.001), with the highest decrease in rates observed between 2016 and 2018 with a decrease of -51.3% (95% CI -56.6, -45.3, p <0.001). In Hispanic Americans, the overall incidence-based mortality decreased by -12.3% (95% CI -16.9, -7.4, p <.001), which is lower than in white Americans.

Approximately 3 million patients with symptoms suggestive of obstructive coronary artery disease (CAD) present to primary care offices in the United States annually, resulting in approximately $6.7 billion in cardiac workup costs. Despite wide application of existing diagnostic technologies, yield of obstructive CAD at invasive coronary angiography (ICA) is low. This study used a decision analysis model to assess the economic utility of a novel gene expression score (GES) for the diagnosis of obstructive CAD. Within a representative commercial health plan's adult membership, current practice for obstructive CAD diagnosis (usual care) was compared to a strategy that incorporates the GES test (GES-directed care). The model projected the number of diagnostic tests and procedures performed, the number of patients receiving medical therapy, type I and type II errors for each strategy of obstructive CAD diagnosis, and the associated costs over a 1-year time horizon. Results demonstrate that GES-directed care to exclude the diagnosis of obstructive CAD prior to myocardial perfusion imaging may yield savings to health plans relative to usual care by reducing utilization of noninvasive and invasive cardiac imaging procedures and increasing diagnostic yield at ICA. At a 50% capture rate of eligible patients in GES-directed care, it is projected that a commercial health plan will realize savings of $0.77 per member per month; savings increase proportionally to the GES capture rate. These findings illustrate the potential value of this new blood-based, molecular diagnostic test for health plans and patients in an age of greater emphasis on personalized medicine.

Hereditary angioedema (HAE) is a rare autosomal-dominant disorder; most cases are characterized by low plasma levels of C1 esterase inhibitor (C1-INH). Clinical manifestations of HAE due to C1-INH deficiency include unpredictable, acute, recurrent episodes of nonpruritic swelling that can affect the face, trunk, limbs, and the respiratory, gastrointestinal, and genitourinary tracts. Attacks can be disfiguring, disabling, painful, and even life-threatening if laryngeal swelling occurs. Symptoms of HAE generally manifest in childhood. Effective medications are available and approved to treat HAE in children. However, evidence informing use of these medications in pediatric clinical practice is limited. Hereditary angioedema management plans are critical to optimize outcomes and should address on-demand treatment for acute attacks and plans to prevent potentially fatal laryngeal attacks. The plan should also comprise a holistic approach to address nonclinical aspects of HAE, including quality of life (QoL) and psychological issues. This article provides an overview of HAE management principles that health care providers can apply to treat pediatric patients to improve their QoL.

BACKGROUND: Symptoms of hereditary angioedema (HAE) typically first present during childhood, but the frequency/severity of attacks often increases at puberty. Real-world data on long-term HAE prophylaxis in adolescents are limited. We report pooled data from adolescent patients enrolled in two Phase 4 studies (EMPOWER, ENABLE) evaluating the effectiveness/safety of lanadelumab (monoclonal antibody directed against plasma kallikrein) for the prevention of HAE attacks. METHODS: Adolescent patients (aged 12 to <18 years) with HAE-C1INH enrolled in EMPOWER and ENABLE received open-label lanadelumab 300 mg once every 2 weeks. Effectiveness outcomes were based on patient-reported assessments of on-treatment HAE attacks. Safety was assessed through the recording of treatment-emergent adverse events (TEAEs) and serious adverse events. This analysis categorized patients as "new" or "established" lanadelumab patients. RESULTS: Thirteen new and seven established patients on lanadelumab were included. The observed monthly attack rate in new patients fell from 3.8 (mean) and 2.8 (median) during the pre-enrollment period to 0.65 (mean) and 0.21 (median) during the cumulative study period after lanadelumab initiation (84.2% and 92.9% reductions, respectively). In established patients, mean (SD) HAE attack rate (as treated) during the overall study period was 0.04 (0.03) attacks/month. Most HAE attacks were of mild/moderate severity. Nine new patients reported 42 TEAEs, mostly mild/moderate in severity, with 3 TEAEs reported as serious. Seven established patients reported 12 TEAEs (all mild/moderate and non-serious). No TEAEs were related to lanadelumab. CONCLUSION: These data support lanadelumab's effectiveness/safety in adolescents with HAE, consistent with results from Phase 3 lanadelumab studies in mixed adult/adolescent populations. CLINICAL TRIAL IDENTIFIERS: NCT03845400 (EMPOWER) and NCT04130191 (ENABLE).

Machine translation supported by artificial intelligence (AI) may enhance linguistically-concordant care for patients speaking languages other than English. This assessment of free-text inpatient discharge instructions in Arabic, Armenian, Bengali, simplified Chinese, Somali, and Spanish compared linguist, clinician, and family caregiver evaluations of translations generated by (1) ChatGPT-4o, (2) professional linguists, and (3) human-in-the-loop (AI-generated, professional linguist post-edited). Likert scales (1-5; higher is better) evaluated linguistic and clinical characteristics of each translation. ChatGPT-4o exhibited variable performance relative to professional translations, with poorest ratings for digitally underrepresented languages (Armenian and Somali). Conversely, human-in-the-loop translations achieved comparable, often better, outcomes to professional translations for all languages, (e.g., Armenian mean overall quality: 3.9 [95% CI 3.7-4.2] vs. professional 3.6 [3.4-3.9], p = 0.01), were most frequently preferred (46.5% vs. 28.4%) and had shorter mean translation time (7.1 [5.4-8.8] vs. 16.8 [13.7-19.9] min, p < 0.001). Human-in-the-loop strategies may enable safe, efficient, equitable machine translation application in clinical practice.

Stroke is the second-leading cause of death and the third-leading cause of disability worldwide. Low- and middle-income countries continue to experience an increase in stroke incidence despite scientific advances to prevent strokes. In this topical review, we provide an overview of primordial and primary prevention strategies and present actionable practices that may improve access to stroke prevention including policies and population-wide strategies, such as task-shifting and sharing and health system reengineering. Most strokes can be prevented through primordial prevention defined as the avoidance of the emergence of risk factors and primary prevention defined as effective management of risk factors. Primordial and primary stroke prevention strategies are predominantly behavioral (eg, smoking and recreational drug avoidance or cessation, physical activity, healthy diet) and pharmacological (eg, medications that control risk factors such as diabetes, hypertension, or cholesterol). However, access to primordial and primary stroke prevention is variable and affected by multiple social and commercial determinants of the health of individuals as well as the environments in which they live, cultural considerations, and the policies that govern these environments. In light of emerging novel risk factors such as mental stressors, air pollutants, diet types, and risk factors specific to women, additional societal, individual, health care professionals, funders, and health system efforts should be mobilized for equitable and effective implementation of stroke prevention.

Abstract Background: MammaPrint (MP) is used to identify breast cancer (BC) patients who can safely forego adjuvant chemotherapy. MP combined with the BluePrint (BP) molecular subtyping signature identifies BC subtypes with distinct therapeutic response rates and survival outcomes. In the Neoadjuvant Breast Symphony Trial (NBRST), MP and BP (MP/BP) predicted rates of pathologic complete response to neoadjuvant chemotherapy (NCT) and partial response to neoadjuvant endocrine therapy (NET). Here, we report 5-year overall survival (OS) and distant metastasis-free survival (DMFS) in patients from the NBRST registry according to MP/BP molecular classification. Methods: The NBRST trial (NCT01479101) prospectively enrolled 1072 patients from 2011 to 2014, who received MP and BP testing. Patients were assigned to receive NCT or NET according to NCCN guidelines and consented to 5 years post-surgery follow-up (FU). Clinical outcomes were available for 913 patients from 67 US institutions. Median FU for OS and DMFS was 5 and 4.6 years, respectively. Tumors classified by MP as High Risk (HR) or Low Risk (LR) were further stratified into four molecular subtypes by BP: Luminal A, Luminal B, HER2, and Basal. Differences in OS and DMFS at 3 and 5 years were assessed by Kaplan Meier analysis and log-rank test. Results: MP results from neoadjuvant patients (N=913) classified 16% of tumors as MP LR and 84% as MP HR. MP and BP classified 15.7% (143/913) of tumors as Luminal A, 32.5% (297/913) as Luminal B, 17.1% (156/913) as HER2, and 34.7% (317/913) as Basal. The 5-year OS and DMFS probabilities were significantly lower in HR compared to LR patients (p &amp;lt; 0.001 for OS and DMFS), and lowest in Basal and Luminal B compared to Luminal A and HER2 subtypes (p &amp;lt; 0.001 for OS and DMFS). Most DMFS events in BP Basal tumors occurred within the first 3 years. Of 841 patients that received NCT with or without HER2-targeted therapy, 12.2% (103/841) were LR and 87.8% (738/841) were HR. MP and BP classified 11.9% (100/841) of these patients as Luminal A, 32.6% (274/841) as Luminal B, 8.3% (154/841) as HER2 subtype, and 37.2% (313/841) as Basal. The 5-year OS and DMFS probabilities were lowest in HR, Basal or Luminal B patients (p &amp;lt; 0.001). In 59 patients who received NET alone, 5-year OS and DMFS were significantly worse in HR patients that had Luminal B or HER2 tumors compared to LR Luminal A patients. In the 39 patients with Luminal A tumors, response to NET at the time of surgery was: 46.2% partial response, 41.0% stable disease, 5.1% progressive disease, 2.6% not reported. Five year DMFS in patients with Luminal A tumors treated with NCT or NET was not significantly different (p=0.67).Conclusions: MammaPrint remained prognostic in BC patients undergoing neoadjuvant therapy. Long -term prognosis was excellent in LR groups who received NCT or NET alone. MP and BP can accurately classify patients into specific subtypes with distinct OS and DMFS outcomes at five years, with BP Basals having the worst outcomes, followed by Luminal B, HER2, and Luminal A subtypes. BP Basal patients had the highest frequency of events within the first 3 years post-surgery, suggesting a genomic risk timeline distinct from other BP subtypes and a potential benefit from a secondary therapeutic immediately post-surgery. Additionally, Luminal A patients had a very low risk of progressive disease while on NET alone prior to surgery, with similar DMFS outcomes to Luminal A-types who received NCT. Number of patientsObserved events% at 5 year (95% CI)p-valueAll patients - MammaPrint Risk GroupOS913134p&amp;lt;0.001Low Risk146794.7 (88.4-97.6)High Risk76712781.1 (77.7-84.0)DMFS913182p&amp;lt;0.001Low Risk1461191.2 (84.2-95.2)High Risk76717175.5 (71.9-78.7)All patients - MammaPrint + BluePrint SubtypeOS913134p&amp;lt;0.001Luminal A143794.6 (88.3-97.6)Luminal B2974484.5 (80.0-88.7)Basal3177472.2 (66.2-77.3)HER2156993.4 (87.1-96.7)DMFS913182p&amp;lt;0.001Luminal A1431191.1 (82.1-94.3)Luminal B2976975.2 (68.0-80.4)Basal3178570.4 (64.6-75.5)HER21561787.2 (79.7-92.0)NCT patients - MammaPrint Risk GroupOS841121p&amp;lt;0.001Low Risk103397.4 (90.1-99.4)High Risk73811881.7 (78.3-84.7)DMFS841167p&amp;lt;0.001Low Risk103792.6 (84.1-96.6)High Risk73816076.2 (72.5-79.4)NCT patients - MammaPrint + BluePrint SubtypeOS841121p&amp;lt;0.001Luminal A100395.5 (86.2-98.6)Luminal B2743978.9 (71.7-84.5)Basal3137168.7 (57.9-77.2)HER2154892.8 (85.9-96.4)DMFS841167p&amp;lt;0.001Luminal A100792.4 (83.8-96.5)Luminal B2746375.7 (65.6-76.5)Basal3138171.4 (65.6-76.5)HER21541687.7 (80.2-92.5)NET alone patients - MammaPrintOS597p=0.01Low Risk39293.0 (74.6-98.2)High Risk20580.0 (55.1-92.0)DMFS598p=0.003Low Risk39293.0 (74.6-98.2)High Risk20674.7 (49.4-88.6)NET alone patients - MammaPrint +BluePrint SubtypeOS597p=0.008Luminal A39293.0 (74.6-98.2)Luminal B18483.3 (56.8-94.3)Basal00N/AHER221N/ADMFS598p=0.005Luminal A39293.0 (74.6-98.2)Luminal B18577.4 (50.3-90.9)Basal00N/AHER221N/A Citation Format: Pat Whitworth, James V Pellicane, Jr., Paul Baron, Peter Beitsch, Laura Lee, Michael Rotkis, Angela Mislowsky, Carrie Dul, Charles Nash, Bichlien Nguyen, Mary Murray, Paul Richards, Mark Gittleman, Stephanie Akbari, Shiyu Wang, Erin B Yoder, Andrea Menicucci, Lisa Blumencranz, William Audeh, NBRST Investigators Group. 5-year outcomes in the NBRST trial: Preoperative MammaPrint and BluePrint breast cancer subtype is associated with neoadjuvant treatment response and survival [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD9-01.