Association Between Soft Tissue Measures From Computed Tomography and Upper Airway Collapsibility on Drug-Induced Sleep Endoscopy.

OBJECTIVE: Positive airway pressure (PAP) titration during drug-induced sleep endoscopy (DISE) provides objective measures of upper airway collapsibility. While skeletal measurements relate to collapsibility measures on DISE, the influence of soft tissue dimensions on upper airway collapsibility is not known. We analyzed the relationship of measures of upper airway soft tissue volumes, specifically soft palate, pharyngeal lateral walls, and tongue, with metrics of collapsibility. STUDY DESIGN: Cross-sectional analysis from a prospective cohort. SETTING: Academic medical center. METHODS: Patients seeking PAP alternative therapies for obstructive sleep apnea (OSA) underwent standardized supine computed tomography (CT) acquisition and DISE protocols. The CT analysis primarily focused on soft tissue volumes and, secondarily, on airway and skeletal volumetric measures. DISE with PAP administration (DISE-PAP) enabled the determination of the pressure at which inspiratory airflow first commenced (pharyngeal critical pressure, PcritA) and the pressure at which inspiratory flow limitation was abolished (pharyngeal opening pressure, PhOP). Both unadjusted and adjusted correlation analyses were performed to understand the relationship between upper airway anatomy and either PcritA or PhOP. RESULTS: One hundred thirty-nine subjects completed both CT and DISE-PAP. On average, patients were male (70.5%), white (84.2%), middle-aged (56.6 ± 13.5 years), and overweight (29.6 ± 4.7 kg/m2), with moderate-severe apnea-hypopnea index (29.7 ± 21.3 events/h). Adjusted for age, sex, body mass index, and skeletal volumes, soft palate, and lateral pharyngeal wall volumes were not associated with PhOP or PcritA, but a larger tongue was associated with more positive PhOP (⍴ = 0.20, P = .02), and more positive PcritA (⍴ = 0.16, P = .07). Exploratory analyses revealed smaller minimum cross-sectional retropalatal area and intramandibular volume were also associated with increased collapsibility measures. CONCLUSION: After controlling for clinical factors and skeletal volume, greater tongue volume was associated with more severe collapsibility during DISE. These results, in concert with previous work, suggest that greater tongue volume in a smaller skeletal dimensions contribute to the severity of airway collapsibility, a key driver of OSA pathogenesis.

Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial.

BACKGROUND: Weight reduction is a standard recommendation for obstructive sleep apnea (OSA) treatment in people with obesity or overweight; however, weight loss can be challenging to achieve and maintain without bariatric surgery. Currently, no approved anti-obesity medication has demonstrated effectiveness in OSA management. This study is evaluating the efficacy and safety of tirzepatide for treatment of moderate to severe OSA in people with obesity. METHODS: SURMOUNT-OSA, a randomized, placebo -controlled, 52-week phase 3 trial, is investigating the efficacy and safety of tirzepatide for treatment of moderate to severe OSA (apnea hypopnea- index ≥15 events/h) in participants with obesity (body mass index ≥30 kg/m2) and an established OSA diagnosis. SURMOUNT-OSA is made of 2 intervention-specific appendices (ISAs): ISA-1 includes participants with no current OSA treatment, and ISA-2 includes participants using positive airway pressure therapy. Overall, 469 participants have been randomized 1:1 to receive tirzepatide or placebo across the master protocol (ISA-1, n = 234; ISA-2, n = 235). All participants are also receiving lifestyle intervention for weight reduction. RESULTS: The primary endpoint for the individual ISAs is the difference in apnea hypopnea- index response, as measured by polysomnography, between tirzepatide and placebo arms at week 52. Secondary endpoints include sleep apnea-specific hypoxic burden, functional outcomes, and cardiometabolic biomarkers. The trial employs digital wearables, including home sleep testing to capture time to improvement and accelerometry for daily physical activity assessment, to evaluate exploratory outcomes. CONCLUSION: SURMOUNT-OSA brings a novel design to investigate if tirzepatide provides clinically meaningful improvement in obesity-related OSA by targeting the underlying etiology. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05412004.

A phase 1b study of zilovertamab in combination with paclitaxel for locally advanced/unresectable or metastatic Her2-negative breast cancer.

BACKGROUND: Zilovertamab is a humanized monoclonal antibody targeting ROR1, an onco-embryonic antigen expressed by malignant cells of a variety of solid tumors, including breast cancer. A prior phase 1 study showed that zilovertamab was well tolerated and effective in inhibiting ROR1-signaling, which leads to activation of ERK1/2, NF-κB, and NRF2 target genes. This phase 1b study evaluated the safety and tolerability of zilovertamab with paclitaxel in patients with advanced breast cancer. PATIENTS AND METHODS: Eligible patients had locally advanced, unresectable, or metastatic HER2- breast cancer with Eastern Cooperative Group performance status of 0-2 and without prior taxane therapy in the advanced setting. Study treatment included 600 mg of zilovertamab administered intravenously (IV) on Days 1 and 15 of Cycle 1 and then Day 1 of each 28-day cycle along with paclitaxel weekly at 80 mg/m2 IV. RESULTS: Study patients had received a median of 4 prior therapies (endocrine therapy + chemotherapy) for locally advanced, unresectable, or metastatic disease. No patient discontinued therapy due to toxicity ascribed to zilovertamab. Adverse events were consistent with the known safety profile of paclitaxel. Of 16 patients, 6 (38%) had a partial response, and 6/16 (38%) patients had stable disease as best tumor response. CONCLUSION: The combination of zilovertamab and paclitaxel was safe and well tolerated in heavily pre-treated advanced breast cancer patients. Further evaluation of ROR1 targeting in breast cancer patients with zilovertamab is warranted. TRIAL REGISTRATION: NCT02776917. Registered on ClinicalTrials.gov on 05/17/2016.

Association of baseline ROR1 and ROR2 gene expression with clinical outcomes in the I-SPY2 neoadjuvant breast cancer trial.

PURPOSE: ROR1 and ROR2 are Type 1 tyrosine kinase-like orphan receptors for Wnt5a that are associated with breast cancer progression. Experimental agents targeting ROR1 and ROR2 are in clinical trials. This study evaluated whether expression levels of ROR1 or ROR2 correlated with one another or with clinical outcomes. METHODS: We interrogated the clinical significance of high-level gene expression of ROR1 and/or ROR2 in the annotated transcriptome dataset from 989 patients with high-risk early breast cancer enrolled in one of nine completed/graduated/experimental and control arms in the neoadjuvant I-SPY2 clinical trial (NCT01042379). RESULTS: High ROR1 or high ROR2 was associated with breast cancer subtypes. High ROR1 was more prevalent among hormone receptor-negative and human epidermal growth factor receptor 2-negative (HR-HER2-) tumors and high ROR2 was less prevalent in this subtype. Although not associated with pathologic complete response, high ROR1 or high ROR2 each was associated with event-free survival (EFS) in distinct subtypes. High ROR1 associated with a worse EFS in HR + HER2- patients with high post-treatment residual cancer burden (RCB-II/III) (HR 1.41, 95% CI = 1.11-1.80) but not in patients with minimal post-treatment disease (RCB-0/I) (HR 1.85, 95% CI = 0.74-4.61). High ROR2 associated with an increased risk of relapse in patients with HER2 + disease and RCB-0/I (HR 3.46, 95% CI = 1.33-9.020) but not RCB-II/III (HR 1.07, 95% CI = 0.69-1.64). CONCLUSION: High ROR1 or high ROR2 distinctly identified subsets of breast cancer patients with adverse outcomes. Further studies are warranted to determine if high ROR1 or high ROR2 may identify high-risk populations for studies of targeted therapies.

GLORIA: phase III, open-label study of adagloxad simolenin/OBI-821 in patients with high-risk triple-negative breast cancer.

Triple-negative breast cancer (TNBC) has the highest rate of distant metastasis and poorest overall survival among breast cancer subtypes. In a phase II study, adagloxad simolenin (AdaSim), a synthetic Globo H conjugate vaccine administered with adjuvant OBI-821, was shown to induce IgM and IgG anti-Globo H humoral responses in patients with metastatic breast cancer overexpressing the glycosphingolipid Globo H. GLORIA is an ongoing phase III, randomized, open-label clinical trial to evaluate the safety and efficacy of AdaSim and the quality of life (QoL) of patients receiving AdaSim plus standard of care (SOC) versus SOC alone in high-risk, early-stage TNBC. The primary end point is invasive progression-free survival; secondary end points include overall survival, QoL, breast cancer-free interval, distant disease-free survival, safety, and tolerability.

Patients with triple-negative breast cancer generally do very poorly with the current available therapies. A vaccine with a totally different mechanism of action is being investigated in these patients to see how they do with this new therapy. This trial is a very early investigation and is currently ongoing. Clinical Trial Registration: NCT03562637 (ClinicalTrials.gov).

Cancer-cell-secreted extracellular vesicles suppress insulin secretion through miR-122 to impair systemic glucose homeostasis and contribute to tumour growth.

Epidemiological studies demonstrate an association between breast cancer (BC) and systemic dysregulation of glucose metabolism. However, how BC influences glucose homeostasis remains unknown. We show that BC-derived extracellular vesicles (EVs) suppress pancreatic insulin secretion to impair glucose homeostasis. EV-encapsulated miR-122 targets PKM in ß-cells to suppress glycolysis and ATP-dependent insulin exocytosis. Mice receiving high-miR-122 EVs or bearing BC tumours exhibit suppressed insulin secretion, enhanced endogenous glucose production, impaired glucose tolerance and fasting hyperglycaemia. These effects contribute to tumour growth and are abolished by inhibiting EV secretion or miR-122, restoring PKM in ß-cells or supplementing insulin. Compared with non-cancer controls, patients with BC have higher levels of circulating EV-encapsulated miR-122 and fasting glucose concentrations but lower fasting insulin; miR-122 levels are positively associated with glucose and negatively associated with insulin. Therefore, EV-mediated impairment of whole-body glycaemic control may contribute to tumour progression and incidence of type 2 diabetes in some patients with BC.

Real-World Data From a Molecular Tumor Board: Improved Outcomes in Breast and Gynecologic Cancers Patients With Precision Medicine.

PURPOSE: Next-generation sequencing is increasingly used in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide matched therapy; however, outcome data are limited. We evaluate the effect of the degree of matching of tumors to treatment as well as compliance to MTB recommendations on outcomes. METHODS: Overall, 164 patients with consecutive gynecologic and breast cancers presented at MTB were assessed for clinicopathologic data, next-generation sequencing results, MTB recommendations, therapy received, and outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment over total pathogenic alterations, and compliance to MTB recommendations were analyzed in context of oncologic outcomes. RESULTS: Altogether, 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS ≥ 40% had higher overall response rate (30.8% v 7.1%; P = .001), progression-free survival (PFS; hazard ratio [HR] 0.51; 95% CI, 0.31 to 0.85; P = .002), and a trend toward improved overall survival (HR 0.64; 95% CI, 0.34 to 1.25; P = .082) in univariate analysis. The PFS advantage remained significant in multivariate analysis (HR 0.5; 95% CI, 0.3 to 0.8; P = .006). Higher MTB recommendation compliance was significantly associated with improved median PFS (9.0 months for complete; 6.0 months for partial; 4.0 months for no compliance; P = .004) and overall survival (17.1 months complete; 17.8 months partial; 10.8 months none; P = .046). Completely MTB-compliant patients had higher MS (P < .001). In multivariate analysis comparing all versus none MTB compliance, overall response (HR 9.5; 95% CI, 2.6 to 35.0; P = .001) and clinical benefit (HR 8.8; 95% CI, 2.4 to 33.2; P = .001) rates were significantly improved with higher compliance. CONCLUSION: Compliance to MTB recommendations resulted in higher degrees of matched therapy and correlates with improved outcomes in patients with gynecologic and breast cancers.

Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2+ breast cancer in the adaptively randomized I-SPY2 trial.

HER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two HER2-targeted combinations in the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab and pertuzumab (THP). Eligible women have >2.5 cm clinical stage II/III HER2+ breast cancer, adaptively randomized to T-DM1/P, THP, or a common control arm of paclitaxel/trastuzumab (TH), followed by doxorubicin/cyclophosphamide, then surgery. Both T-DM1/P and THP arms 'graduate' in all subtypes: predicted pCR rates are 63%, 72% and 33% for T-DM1/P (n = 52), THP (n = 45) and TH (n = 31) respectively. Toxicity burden is similar between arms. Degree of HER2 pathway signaling and phosphorylation in pretreatment biopsy specimens are associated with response to both T-DM1/P and THP and can further identify highly responsive HER2+ tumors to HER2-directed therapy. This may help identify patients who can safely de-escalate cytotoxic chemotherapy without compromising excellent outcome.

Personalized First-Line Treatment of Metastatic Pancreatic Neuroendocrine Carcinoma Facilitated by Liquid Biopsy and Computational Decision Support.

BACKGROUND: We present the case of a 50-year-old female whose metastatic pancreatic neuroendocrine tumor (pNET) diagnosis was delayed by the COVID-19 pandemic. The patient was in critical condition at the time of diagnosis due to the extensive tumor burden and failing liver functions. The clinical dilemma was to choose between two registered first-line molecularly-targeted agents (MTAs), sunitinib or everolimus, or to use chemotherapy to quickly reduce tumor burden. METHODS: Cell-free DNA (cfDNA) from liquid biopsy was analyzed by next generation sequencing (NGS) using a comprehensive 591-gene panel. Next, a computational method, digital drug-assignment (DDA) was deployed for rapid clinical decision support. RESULTS: NGS analysis identified 38 genetic alterations. DDA identified 6 potential drivers, 24 targets, and 79 MTAs. Everolimus was chosen for first-line therapy based on supporting molecular evidence and the highest DDA ranking among therapies registered in this tumor type. The patient's general condition and liver functions rapidly improved, and CT control revealed partial response in the lymph nodes and stable disease elsewhere. CONCLUSION: Deployment of precision oncology using liquid biopsy, comprehensive molecular profiling, and DDA make personalized first-line therapy of advanced pNET feasible in clinical settings.

A computational method for prioritizing targeted therapies in precision oncology: performance analysis in the SHIVA01 trial.

Precision oncology is currently based on pairing molecularly targeted agents (MTA) to predefined single driver genes or biomarkers. Each tumor harbors a combination of a large number of potential genetic alterations of multiple driver genes in a complex system that limits the potential of this approach. We have developed an artificial intelligence (AI)-assisted computational method, the digital drug-assignment (DDA) system, to prioritize potential MTAs for each cancer patient based on the complex individual molecular profile of their tumor. We analyzed the clinical benefit of the DDA system on the molecular and clinical outcome data of patients treated in the SHIVA01 precision oncology clinical trial with MTAs matched to individual genetic alterations or biomarkers of their tumor. We found that the DDA score assigned to MTAs was significantly higher in patients experiencing disease control than in patients with progressive disease (1523 versus 580, P = 0.037). The median PFS was also significantly longer in patients receiving MTAs with high (1000+ <) than with low (<0) DDA scores (3.95 versus 1.95 months, P = 0.044). Our results indicate that AI-based systems, like DDA, are promising new tools for oncologists to improve the clinical benefit of precision oncology.

Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial.

The combination of PD-L1 inhibitor durvalumab and PARP inhibitor olaparib added to standard paclitaxel neoadjuvant chemotherapy (durvalumab/olaparib/paclitaxel [DOP]) was investigated in the phase II I-SPY2 trial of stage II/III HER2-negative breast cancer. Seventy-three participants were randomized to DOP and 299 to standard of care (paclitaxel) control. DOP increased pathologic complete response (pCR) rates in all HER2-negative (20%-37%), hormone receptor (HR)-positive/HER2-negative (14%-28%), and triple-negative breast cancer (TNBC) (27%-47%). In HR-positive/HER2-negative cancers, MammaPrint ultra-high (MP2) cases benefited selectively from DOP (pCR 64% versus 22%), no benefit was seen in MP1 cancers (pCR 9% versus 10%). Overall, 12.3% of patients in the DOP arm experienced immune-related grade 3 adverse events versus 1.3% in control. Gene expression signatures associated with immune response were positively associated with pCR in both arms, while a mast cell signature was associated with non-pCR. DOP has superior efficacy over standard neoadjuvant chemotherapy in HER2-negative breast cancer, particularly in a highly sensitive subset of high-risk HR-positive/HER2-negative patients.

Clinical Radiographic Predictors of Response to Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea.

OBJECTIVE: To determine if clinically acquired cephalometric measurements, specifically soft palate size, can predict hypoglossal nerve stimulation outcomes. STUDY DESIGN: Combined prospective cohort study and retrospective review. SETTING: US sleep otolaryngology training program. METHODS: Adults with obstructive sleep apnea and apneahypopnea index greater than 15 events/h who underwent hypoglossal nerve stimulation. Eligible subjects had diagnostic preoperative sleep studies and full-night efficacy postoperative studies for analysis. Lateral neck x-rays were obtained as part of routine clinical care and measured for key cephalometric variables by trained head and neck radiologists. Continuous variables were compared using the Student t test, while χ2 testing was used for categorical variables. RESULTS: Fifty-one patients met all study criteria. On average, patients were white, middle aged, and overweight. Following hypoglossal nerve stimulation, the overall cohort achieved a significant apnea-hypopnea index reduction from 36.7 events/h to 20.6 events/h (P < .01) and a response rate of 47% (defined as apnea-hypopnea index reduction >50% and apnea-hypopnea index <20 events/h). On average, therapy responders had significantly thinner soft palates than nonresponders (13.4 ± 3.8 mm vs 16.0 ± 3.4 mm, P = .045). CONCLUSIONS: Patient-specific anatomic factors, specifically soft palate thickness, may help identify optimal candidates for hypoglossal nerve stimulation. A larger, prospective study including both anatomic and physiologic variables is required to validate these findings.

Real-world data from a molecular tumor board demonstrates improved outcomes with a precision N-of-One strategy.

Next-generation sequencing (NGS) can identify novel cancer targets. However, interpreting the molecular findings and accessing drugs/clinical trials is challenging. Furthermore, many tumors show resistance to monotherapies. To implement a precision strategy, we initiated a multidisciplinary (basic/translational/clinical investigators, bioinformaticians, geneticists, and physicians from multiple specialties) molecular tumor board (MTB), which included a project manager to facilitate obtaining clinical-grade biomarkers (blood/tissue NGS, specific immunohistochemistry/RNA expression including for immune-biomarkers, per physician discretion) and medication-acquisition specialists/clinical trial coordinators/navigators to assist with medication access. The MTB comprehensively reviewed patient characteristics to develop N-of-One treatments implemented by the treating physician's direction under the auspices of a master protocol. Overall, 265/429 therapy-evaluable patients (62%) were matched to ≥1 recommended drug. Eighty-six patients (20%) matched to all drugs recommended by MTB, including combinatorial approaches, while 38% received physician's choice regimen, generally with unmatched approach/low degree of matching. Our results show that patients who receive MTB-recommended regimens (versus physician choice) have significantly longer progression-free (PFS) and overall survival (OS), and are better matched to therapy. High (≥50%) versus low (<50%) Matching Score therapy (roughly reflecting therapy matched to ≥50% versus <50% of alterations) independently correlates with longer PFS (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.50-0.80; P < 0.001) and OS (HR, 0.67; 95% CI, 0.50-0.90; P = 0.007) and higher stable disease ≥6 months/partial/complete remission rate (52.1% versus 30.4% P < 0.001) (all multivariate). In conclusion, patients who receive MTB-based therapy are better matched to their genomic alterations, and the degree of matching is an independent predictor of improved oncologic outcomes including survival.

Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study.

PURPOSE: This randomized, double-blind, placebo-controlled, parallel-group, phase II trial assessed the efficacy and safety of adagloxad simolenin (OBI-822; a Globo H epitope covalently linked to keyhole limpet hemocyanin (KLH)) with adjuvant OBI-821 in metastatic breast cancer (MBC). METHODS: At 40 sites in Taiwan, USA, Korea, India, and Hong Kong, patients with MBC of any molecular subtype and ≤2 prior progressive disease events with stable/responding disease after the last anticancer regimen were randomized (2:1) to adagloxad simolenin (AS/OBI-821) or placebo, subcutaneously for nine doses with low-dose cyclophosphamide. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, correlation of clinical outcome with humoral immune response and Globo H expression, and safety. RESULTS: Of 349 patients randomized, 348 received study drug. Patients with the following breast cancer subtypes were included: hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) (70.4%), triple negative (12.9%), and HER2+ (16.7%), similarly distributed between treatment arms. Median PFS was 7.6 months (95% CI: 6.5-10.9) with AS/OBI-821 (n=224) and 9.2 months (95% CI: 7.3-11.3) with placebo (n=124) (HR=0.96; 95% CI: 0.74-1.25; p=0.77), with no difference by breast cancer subtype. AS/OBI-821 recipients with anti-Globo H IgG titer ≥1:160 had significantly longer median PFS (11.1 months (95% CI: 9.3-17.6)) versus those with titers <1:160 (5.5 months (95% CI: 3.7-5.6); HR=0.52; p<0.0001) and placebo recipients (HR=0.71; p=0.03). Anti-KLH immune responses were similar at week 40 between AS/OBI-821 recipients with anti-Globo IgG titer ≥1:160 and those with anti-Globo IgG titer <1:160. The most common adverse events with AS/OBI-821 were grade 1 or 2 injection site reactions (56.7%; placebo, 8.9%) and fever (20.1%; placebo, 6.5%). CONCLUSION: AS/OBI-821 did not improve PFS in patients with previously treated MBC. However, humoral immune response to Globo H correlated with improved PFS in AS/OBI-821 recipients, leading the way to further marker-driven studies. Treatment was well tolerated.NCT01516307.

Healthcare use and costs in adult cancer patients with anxiety and depression.

OBJECTIVE: Anxiety and depression are common in individuals with cancer and may impact healthcare service use and costs in this population. This study examined the effects of anxiety alone, depression alone, and comorbid anxiety and depressive disorder on healthcare use and costs among patients with cancer. METHOD: This was a retrospective cohort analysis of administrative data of patients aged 18 or older with an International Classification of Diseases, Ninth Revision diagnosis of cancer. Key outcomes were any visit to emergency department (ED), any inpatient hospitalization, length of hospital stays, and annual healthcare costs 1 year from cancer diagnosis. RESULTS: A total of 13,426 patients were included. Relative to patients with neither anxiety nor depression, those with anxiety alone, depression alone, or comorbid anxiety and depression were more likely to experience an ED visit and be hospitalized. Length of hospital stays were also longer and annual healthcare costs were significantly higher in all three clinical groups. CONCLUSIONS: Cancer patients with anxiety and depression were at greater risk for ED visits and hospitalizations, experienced longer hospital stays, and accrued higher healthcare costs. Future researchers should determine whether screening and treating comorbid anxiety and depression may decrease healthcare utilization and improve turnover wellbeing among cancer patients.

Age-related differences in breast cancer mortality according to race/ethnicity, insurance, and socioeconomic status.

BACKGROUND: We assessed breast cancer mortality in older versus younger women according to race/ethnicity, neighborhood socioeconomic status (nSES), and health insurance status. METHODS: The study included female breast cancer cases 18 years of age and older, diagnosed between 2005 and 2015 in the California Cancer Registry. Multivariable Cox proportional hazards modeling was used to generate hazard ratios (HR) of breast cancer specific deaths and 95% confidence intervals (CI) for older (60+ years) versus younger (< 60 years) patients separately by race/ethnicity, nSES, and health insurance status. RESULTS: Risk of dying from breast cancer was higher in older than younger patients after multivariable adjustment, which varied in magnitude by race/ethnicity (P-interaction< 0.0001). Comparing older to younger patients, higher mortality differences were shown for non-Hispanic White (HR = 1.43; 95% CI, 1.36-1.51) and Hispanic women (HR = 1.37; 95% CI, 1.26-1.50) and lower differences for non-Hispanic Blacks (HR = 1.17; 95% CI, 1.04-1.31) and Asians/Pacific Islanders (HR = 1.15; 95% CI, 1.02-1.31). HRs comparing older to younger patients varied by insurance status (P-interaction< 0.0001), with largest mortality differences observed for privately insured women (HR = 1.51; 95% CI, 1.43-1.59) and lowest in Medicaid/military/other public insurance (HR = 1.18; 95% CI, 1.10-1.26). No age differences were shown for uninsured women. HRs comparing older to younger patients were similar across nSES strata. CONCLUSION: Our results provide evidence for the continued disparity in Black-White breast cancer mortality, which is magnified in younger women. Moreover, insurance status continues to play a role in breast cancer mortality, with uninsured women having the highest risk for breast cancer death, regardless of age.