(1) Background: Invasive micropapillary carcinoma (IMPC) is a rare, aggressive breast cancer subtype marked by high lymph node metastasis rates. While Oncotype DX recurrence score (RS) offers prognostic information for patients with hormone-receptor-positive (HR+) breast cancer, its utility in IMPC—a histology with distinct biologic behavior—remains unvalidated. This study evaluates whether Oncotype DX offers prognostic information with respect to overall survival (OS) in non-metastatic, early-stage patients with IMPC of the breast. (2) Methods: The National Cancer Database (2004–2020) was queried to select for women with ER+/HER2−, T1-T2N0-N1 IMPC who underwent Oncotype DX testing and received no neoadjuvant therapy. Patients were stratified by RS: low (≤11), intermediate (12–25), and high (>25). Kaplan–Meier survival curves and log-rank tests compared 5-year OS between groups. Multivariable Cox proportional hazards models assessed RS as an independent predictor, adjusting for age, race, comorbidities, grade, radiation, and insurance status. (3) Results: A total of 1325 women met the selection criteria. The cohort demonstrated significant survival disparities by RS (log-rank p = 0.017). Five-year OS rates were 97.5%, 97.5%, and 93.7% for low, intermediate, and high-risk patients, respectively. Adjusted multivariate analysis confirmed RS as an independent prognosticator: low (HR = 0.31, 95% CI: 0.15–0.75) and intermediate (HR = 0.32, 95% CI: 0.15–0.75) scores correlated with reduced mortality versus high RS. Omission of radiation therapy (HR = 2.68, 95% CI: 1.05–6.86) and higher comorbidity burden (0 comorbidities vs. ≥2: HR = 0.25, 95% CI: 0.10–0.61) were significantly associated with worse survival. (4) Conclusions: Oncotype DX is predictive for OS in IMPC, with high RS (>25) portending poorer outcomes. The survival detriment associated with RT omission aligns with prior studies demonstrating RT benefit in higher-risk cohorts. These findings validate RS as a prognostic tool in IMPC and underscore its potential to refine adjuvant therapy, particularly RT utilization. Future studies should explore RS-driven treatment personalization in IMPC, including comorbidity management and adjuvant radiation to improve outcomes in this distinct patient population.

OBJECTIVES/GOALS: While disease subtypes are critical for precision medicine, most projects use unipartite clustering methods such as k-means which are not fully automated, do not provide statistical significance, and are difficult to interpret. These gaps were addressed through bipartite networks and tested for generalizability on three national databases. METHODS/STUDY POPULATION: Data. All participants with self-reported stroke from the 2010 Health and Retirement Study (HRS), with cases (n=798) having one or more 8 depressive symptoms measured by the Centers for the Epidemiological Study–Depression 8 scale, and controls (n=389) with none of those symptoms. The replication data set consisted of independent identically-defined participants (cases=725, controls=190) from 1998 HRS. Method. (1) Bipartite network analysis and modularity maximization to automatically identify patient-symptom biclusters with significance. (2) Rand Index to measure the replicability of symptom co-occurrences in the replication data. (3) ExplodeLayout to visualize and interpret the subtypes. (4) R libraries to generalize the methods, upload them to CRAN, and then tested on the N3C and All of Us platforms. RESULTS/ANTICIPATED RESULTS: The analysis identified 4 depressive symptom subtypes (https://postimg.cc/Ny8YwXJW) which had significant modularity (Q=0.26, z=3.03, P DISCUSSION/SIGNIFICANCE: We developed generalizable methods to automatically identify biclusters, measure the clustering significance, and visualize the results for interpretation. These methods were successfully tested on three national level data bases. Such generalizable methods should accelerate the analysis of subtypes, and the design of targeted interventions.

The 21-gene recurrence score (RS) is used to predict benefit from chemotherapy in hormone receptor (HR)-positive breast cancer with one to three positive lymph nodes. Prospective–retrospective studies have shown that the RS is prognostic for both systemic and locoregional recurrence in tamoxifen-treated patients. We aimed to assess whether RS could be utilized to predict a survival benefit from postmastectomy radiation therapy (PMRT). The National Cancer Database (NCDB) was used to identify women ≤ 75 years of age with HR+, HER2-negative, T1–3, N1, M0 breast cancer who underwent mastectomy and axillary staging with available RS during the years 2010–2016. Kaplan–Meier and Cox proportional hazards models were used to identify association between treatment and overall survival (OS). Univariate and multivariate analyses were used to identify variables correlating with PMRT and OS. A total of 8907 patients were identified. Of the total, 3203 (36

OBJECTIVES/GOALS: A growing number of older adults in the United States have multiple social determinants of health (SDoH) that are barriers to effective medical care. We used generalizable machine learning methods to identify and visualize subtypes based on participant-reported SDoH profiles, and their association with delayed medical care (self-reported yes/no). METHODS/STUDY POPULATION: Data. All participants aged >=65 in All of Us with complete data on 18 SDoH self-reported variables, selected through consensus by 2 experienced health services researchers, and guided by Andersen’s behavioral model. Covariates included demographics, and the outcome was delayed medical care . Cases (n=4090) consisted of participants with at least one of the 18 SDoH variables, and controls (n=7414) consisted of participants with none of them. Method. (1) Used bipartite network analysis and modularity maximization to identify participant-SDoH biclusters, and visualize them through ExplodeLayout. (2) Used multivariable logistic regression (adjusted for demographics and corrected through Bonferroni) to measure the odds ratio (OR) of each participant bicluster to the outcome, compared with the controls. RESULTS/ANTICIPATED RESULTS: The analysis identified 7 SDoH subtypes (https://postimg.cc/Vd7Pg4xZ) with statistically significant modularity compared with 100 random permutations of the data (All of Us=.51, Random Mean=.38, z=20, P DISCUSSION/SIGNIFICANCE: The results identified 7 distinct subtypes based on SDoH profiles and their risk for delayed medical care, highlighting the importance of addressing specific combinations of barriers, with affordability having the highest risk. Furthermore, the analytical methods used are generalizable and have been made publicly available on CRAN and All of Us.

DNA damage drives genetic mutations that underlie the development of cancer in humans. Multiple pathways have been described in mammalian cells which can repair this damage. However, most work to date has focused upon single lesions in DNA. We present here a combinatorial system which allows assembly of duplexes containing single or multiple types of damage by ligating together six oligonucleotides containing damaged or modified bases. The combinatorial system has dual fluorescent labels allowing examination of both strands simultaneously, in order to study interactions or competition between different DNA repair pathways. Using this system, we demonstrate how repair of oxidative damage in one DNA strand can convert a mispaired T:G deamination intermediate into a T:A mutation. We also demonstrate that slow repair of a T:G mispair, relative to a U:G mispair, by the human methyl-binding domain 4 DNA glycosylase provides a competitive advantage to competing repair pathways, and could explain why CpG dinucleotides are hotspots for C to T mutations in human tumors. Data is also presented that suggests repair of closely spaced lesions in opposing strands can be repaired by a combination of short and long-patch base excision repair and simultaneous repair of multiply damage sites can potentially lead to lethal double strand breaks.

Background Invasive lobular carcinoma (ILC) is traditionally considered less responsive to chemotherapy. Although the Oncotype recurrence score (RS) has been validated to identify high‐risk patients who benefit from chemotherapy, some studies have questioned its relevance in patients with ILC. The objective of this study was to better characterize potential use of the RS in these patients. Methods The National Cancer Database was used to identify women with stage I through III, T1 through T3, N0 or N1, hormone receptor‐positive, HER2‐negative ILC or invasive ductal carcinoma (IDC) who had an available RS between 2010 and 2016. Multivariable Cox regression was used to model the effect of variables on 5‐year overall survival (OS). The Kaplan‐Meier method was used to estimate OS according to the RS, nodal status, and chemotherapy. Results In total, 15,763 patients with ILC and 100,070 with IDC were identified. The mean age of patients with ILC and IDC was 59.2 ± 9.1 and 57.2 ± 9.8, respectively. A lower percentage of patients with ILC versus those with IDC had a high RS, defined as >25 (6.6% vs 16.0%; P < .0001). ILC patients with a high RS who had N0 or N1 disease received approximately 10% less chemotherapy compared with similar patients who had IDC. The results indicated that the RS had statistically significant prognostic value for patients with ILC. In addition, an absolute OS advantage was correlated with the receipt of chemotherapy by patients with ILC who had a high RS with N0 or N1 disease. Conclusions Patients with ILC who have a high RS are treated less often with chemotherapy compared with similar patients who have IDC. Nevertheless, the RS has a prognostic as well as a predictive value in ILC, with an association between OS benefit and chemotherapy receipt in patients who have ILC with a high RS, especially if they have N1 disease. Lay Summary Invasive lobular carcinoma (ILC) is a subtype of breast cancer comprising about 15% of cases. The Oncotype recurrence score (RS) is a genetic test of breast tumors that helps predict which patients might benefit from chemotherapy. Some have doubted the relevance of the RS for patients with ILC. In this study, the authors show that the RS is relevant for patients who have ILC. The RS has the potential of predicting the risk of recurrence and identifying patients with ILC who might benefit from chemotherapy.

Purpose/Objectives Mucinous carcinoma (MC) of the breast is an uncommon variant of breast cancer which has a favorable prognosis. Current guidelines for ER/PR-positive, HER2-negative pure-MC state that endocrine therapy (ET) is only required for tumors ≥3cm and node-positive patients while chemotherapy (CTX) is not required but can be considered for node positive-patients. While radiation therapy (RT) currently remains a part of breast-conserving therapy (BCT) for this histology, the prognostic impact of RT in pure MC remains unclear. Materials/Methods The National Cancer Database (NCDB) was queried (2004-2017) for patients with non-metastatic, histologically confirmed MC who received breast-conserving surgery. Kaplan-Meier analysis was used to evaluate overall survival (OS). Univariate (UVA) and multivariate (MVA) analyses were conducted using Cox proportional hazard models to determine which clinical and treatment factors were prognostic for overall survival. Results A total of 24,837 patients with median age 70 (IQR 61-78) were included in this study. A total of 66% of carcinomas were grade 1 and 34% were grade 2. A total of 79% were pT1, 20% were pT2, and 1% were pT3-4. A total of 96% were pN0 and 4% were pN1-3. A total of 99% were ER+, 92% were PR+, and 96% were HER2-. A total of 61% received RT, 70% received ET, and 8% received CTX. The 10-year OS was 73% for those who received RT and 41% for those who did not. On UVA, RT (HR 0.31, p< 0.0001; CI 0.29-0.33), ET (HR 0.52, p< 0.0001; CI 0.49-0.55), CTX (HR 0.40, p< 0.0001; CI 0.35-0.46), and black race (HR 0.87, p= 0.006; CI 0.79- 0.96) were positive prognostic factors for OS while older age (HR 1.10, p< 0.0001; CI 1.09-1.10), CDCC comorbidity score (HR 1.93, p< 0.0001; CI 1.81- 2.06), and tumor size (HR 1.01, p< 0.0001; CI 1.01-1.02) were negative prognostic factors. On MVA, RT (HR 0.64, p< 0.0001; CI 0.59-0.69) and ET (HR 0.85, p< 0.0001; CI 0.78- 0.91) remained positive prognostic factors while older age (HR 1.08, p< 0.0001; CI 1.08-1.09), CDCC comorbidity score (HR 1.61, p< 0.0001; CI 1.50- 1.73), and tumor size (HR 1.02, p< 0.0001; CI 1.01- 1.02) remained negative prognostic factors; chemotherapy (HR 1.19, p= 0.039; CI 1.01- 1.39) became a negative prognostic factor and black race (HR 0.99, p= 0.92; CI 0.89- 1.12) was no longer prognostic. Conclusion This is the largest study to date on mucinous carcinoma of the breast and the role of RT after breast-conserving surgery. Use of postoperative RT after lumpectomy is associated with improved OS in patients with breast MC, suggesting that post-lumpectomy RT should remain standard of care. Citation Format: Neil Chevli, Kaidi Wang, Waqar Haque, Mary R. Schwartz, Julie Nangia, Jennifer Sasaki, Andrew M. Farach, Sandra S. Hatch, E. Brian Butler, Bin S. Teh. Prognostic impact of radiation therapy in mucinous carcinoma of the breast [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-15.

PURPOSE:The 21-gene RT-PCR recurrence score (RS) is performed in patients with hormone receptor-positive (ER+, PR+), human epidermal growth factor receptor 2 (HER2)-negative, N0 breast cancer to determine which patients will likely benefit from chemotherapy after breast-conserving surgery (BCS). The purpose of this study was to evaluate whether the RS can predict for patients likely to benefit from radiation therapy (RT) after BCS. METHODS AND MATERIALS:The National Cancer Database was queried (2004-2017) for female patients with pT1N0 ER+ PR+ HER2-negative breast cancer treated with BCS who had an available RS. Patients were stratified based on their RS (low risk [LR], 1-10; intermediate risk [IR], 11-25; high risk [HR], 26-100). For each RS cohort, propensity score matching was conducted to create 1:1 matched cohorts of patients who received RT and patients who did not. Kaplan-Meier analysis evaluated overall survival (OS). Univariable and multivariable (MVA) Cox proportional hazard analysis identified clinical and treatment factors prognostic for OS. RESULTS:A total of 79,040 patients met the selection criteria: 18,823 in the LR cohort, 52,341 in the IR cohort, and 7876 in the HR cohort. A total of 92% of patients received RT: 91% in the LR cohort, 93% in the IR cohort, and 92% in the HR cohort. After propensity score matching, the 5-year OS in the LR cohort was 95% for those who received RT and 93% for those who did not (P = .184). In the IR cohort, the 5-year OS was 95% for those who received RT and 93% for those who did not (P = .001). In the HR cohort, the 5-year OS was 95% for those who received RT and 84% for those who did not (P < .001). MVA demonstrated that RT was a positive prognostic factor for OS in both the IR cohort (P = .001) and HR cohort (P < .001). On MVA in the LR cohort, RT (P = .186) was not predictive of improved OS. CONCLUSIONS:An OS benefit was observed with the use of RT in patients with IR or HR RS but not in patients with LR RS. Future prospective evaluation is warranted.

OBJECTIVES/GOALS: Approximately 10% of COVID-19 patients experience multiple symptoms weeks and months after the acute phase of infection. Our goal was to use advanced machine learning methods to identify PASC phenotypes based on their symptom profiles, and their association with critical adverse outcomes, with the goal of designing future targeted interventions. METHODS/STUDY POPULATION: Data. All COVID-19 outpatients from 12 University of Minnesota hospitals and 60 clinics. Independent variables consisted of 20 CDC-defined PASC symptoms extracted from clinical notes using NLP. Covariates included demographics, and outcomes included New Psychological Diagnostic Evaluation, and Number of PASC Hospital Visits (>=5). Cases (n=3235) consisted of patients with at least one symptom, and controls (n=3034) consisted of patients with no symptoms. Method. (1) Used bipartite network analysis and modularity maximization to identify patient-symptom biclusters. (2) Used multivariable logistic regression (adjusted for demographics and corrected through Bonferroni) to measure the odds ratio of each patient bicluster to adverse outcomes, compared to controls, and to each of the other biclusters. RESULTS/ANTICIPATED RESULTS: The analysis identified 6 PASC phenotypes (http://www.skbhavnani.com/DIVA/Images/Fig-1-PASC-Network.jpg), which was statistically significant compared to 1000 random permutations of the data (PASC=.31, Random Median=.27, z=11, P<.01). Three of the clusters (Cluster-1, Cluster-4, and Cluster-5 encircled with ovals in Fig. 1) contained CNS-related symptoms, which had statistically significant risk for one or both of the adverse outcomes. For example, Cluster-1 with critical CNS symptoms (depression, insomnia, anxiety, brain-fog/difficulty-thinking), had a significantly higher OR compared to the controls for New Psychological Diagnostic Evaluation (OR=6.6, CI=4.9-9.1, P-corr<.001), in addition to having a significantly higher ORs for the same outcome compared to all the other clusters. DISCUSSION/SIGNIFICANCE: The results identified distinct PASC phenotypes based on symptom profiles, with three of them related to CNS symptoms, each of which had significantly higher risk for specific adverse outcomes compared to controls. We will test whether these phenotypes replicate in the N3C data, and explore their translation into triage and treatment strategies.

The number of involved lymph nodes negatively affects prognosis in breast cancer patients. Nevertheless, current staging and treatment recommendations do not distinguish between patients with single versus multiple lymphatic micrometastases. In this study, we aim to better characterize these patients. The National Cancer Database was retrospectively queried to identify 486,800 women with stage I–III, estrogen receptor-positive/progesterone receptor-positive/human epidermal growth factor receptor 2-negative (ER+/PR+/HER2−) breast cancer and nodal status of N0, N1mi with 1 (Nmic1) or more (Nmic > 1) involved nodes, and N1 with 1 involved node (N1.1), from 2010 to 2016. Patients with different nodal statuses were compared regarding treatment characteristics, survival, and benefit from chemotherapy by their 21-gene recurrence score (RS). Of the 23,072 N1mi patients, 88.3% were Nmic1 and 11.7% were Nmic > 1. Nmic > 1 patients were younger, had larger and higher-grade tumors, with more lymphovascular invasion, and were more commonly treated by axillary dissection, radiation, and chemotherapy than Nmic1 patients. In that, they were comparable with N1.1 patients. Five-year survival of Nmic > 1 patients (88.1%) was worse than Nmic1 patients (90.1%; p = 0.02), but similar to N1.1 patients (87.9%). Nmic1, Nmic > 1, and N1.1 patients with RS 11–25 exhibited a < 2% absolute survival benefit associated with chemotherapy. With RS > 25, Nmic > 1 patients showed a 3.5% benefit, similar to Nmic1 (4.8%) and lower than N1.1 (10.9%) patients. Nmic > 1 breast cancer patients have worse prognoses than Nmic1 patients, similar to N1.1 patients. Our data suggest those patients with RS 11–25 have minimal benefit from chemotherapy. These findings should be taken into account when discussing prognosis and considering chemotherapy in patients with lymphatic micrometastases.

Purpose: Tubular carcinoma (TC) is an invasive breast cancer with favorable prognosis. While pathology specific guidelines exist for TC regarding adjuvant chemotherapy and endocrine therapy, no recommendations exist regarding locoregional treatment based on tumor histology. Prognostic impact of radiotherapy for patients with TC remains unclear. Materials and methods: The National Cancer Database was queried (2004-2015) for patients with pN0M0 TC who underwent lumpectomy. Chi-square testing compared categorized variables between those who did and did not receive radiotherapy. Kaplan-Meier analysis evaluated overall survival (OS). Cox proportional hazard analysis identified variables prognostic for OS. Patients were divided into age cohorts <60 years and >60 years. Propensity score matching (PSM) was utilized to create similar cohorts. Results: 9705 patients met selection criteria; 6182 (75.1%) received radiotherapy while 2045 (24.9%) did not. After PSM, radiotherapy (HR 0.582; 95% CI 0.494-0.686) and endocrine therapy (HR 0.737; 95% CI 0.623-0.872) were favorable prognostic factors on multivariate Cox regression analysis while age > 60 years (HR 5.131; 95% CI 3.753-7.016), Black race (HR 1.445; 95% CI 1.016-2.055), and Charlson-Deyo comorbidity score > 0 (HR 1.708; 95% CI 1.403-2.079) were unfavorable prognostic factors. After PSM, 5-year OS was 91.7% for those who received radiotherapy and 84.5% for those who did not; 10-year OS was 76.1% and 64.1%, respectively (p < 0.001). Conclusion: This is the largest study to date on TC and the prognostic impact of adjuvant radiotherapy. Postoperative radiotherapy is a favorable prognostic factor for OS in patients with pN0M0 TC, suggesting adjuvant radiotherapy should remain standard of care in these patients. (c) 2021 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 159 (2021) 202-208

571 Background: Based on the results of the CALGB 9343 trial, patients age ≥70 with T1N0 ER/PR+ HER2- breast cancer who are treated with breast conserving surgery (BCS) and endocrine therapy (ET) are candidates for omission of radiotherapy (RT). This trial predated the 21- gene RT-PCR recurrence score (RS) test, which is an assay now available for patients with hormone receptor positive, HER2 negative, node negative breast cancer to determine who will benefit from chemotherapy. Whether the RS can predict for patients most likely to benefit from radiation therapy (RT) following BCS has not been previously examined. The purpose of this study was to use a large database of patients age ≥70 with T1N0 ER/PR+ HER2- disease to determine if RS could predict who would benefit from RT following BCS. Methods: The National Cancer Database (NCDB) was queried (2004-2017) for female patients age ≥70 with pT1N0 ER+ PR+ HER2- breast cancer treated with BCS and ET and who had an available RS. Patients were stratified based on their RS (low risk [LR] = 1-10, intermediate risk [IR] = 11-25, high risk [HR] = 26-99). For survival analysis, propensity score matching (PSM) was conducted overall and for each group to create 1:1 matched cohorts of patients who received radiotherapy and patients who did not. Kaplan-Meier analysis with log-rank testing was used to evaluate overall survival (OS). Univariable (UVA) and multivariable (MVA) analysis were conducted using Cox proportional hazard models to determine which clinical and treatment factors were prognostic for OS. Results: A total of 13,614 patients met the selection criteria: 3,840 in the LR cohort, 8,383 in the IR cohort, and 1,391 in the HR cohort. A total of 79% received RT: 77% in the LR cohort, 79% in the IR cohort, and 85% in the HR cohort. Because PSM could not be efficiently performed in the HR cohort alone, the IR and HR cohort were merged (IRHR) for matching. After PSM, overall the 5-year OS was 90% for those who received RT and 88% for those who did not (p = 0.03). The 5-year OS in the LR cohort was 89% for those who received RT and 89% for those who did not (p = 0.517). In the IRHR cohort, the 5-year OS was 93% for those who received RT and 88% for those who did not (p = 0.004). On MVA in the overall cohort, RT (p = 0.037) was predictive of improved OS while increasing age (p < 0.001) and CDCC comorbidity score (p < 0.001) were predictive of worse OS. On MVA in the LR cohort, RT (p = 0.602) was not predictive of improved OS. However, on MVA in the IRHR cohort, RT (p = 0.004) was a positive prognostic factor for OS. Conclusions: This is the first study investigating the role of RS in this subset of patients eligible for omission of radiotherapy. There is an OS benefit with the use of RT in patients with IRHR RS, but not in patients with LR RS. Pending prospective evaluation, assessment of RS in this older subset of patients is recommended with consideration of RT when RS is ≥11.

Purpose: The utility of post-mastectomy radiotherapy (PMRT) in women with a nodal complete response (CRn) to neoadjuvant chemotherapy (NAC) is unknown. The NSABP B-51 trial is evaluating this question, but has not reported results thus far. Therefore, we sought to answer this question with the National Cancer Database. Methods: The National Cancer Database was queried for women with cT1-4N1-3M0 breast cancer who had undergone NAC and were ypN0 upon mastectomy. Statistics included multivariable logistic regres-sion, Kaplan-Meier overall survival (OS) analysis, Cox proportional hazards modeling, and construction of forest plots. Results: Of 14,690 women, 10,092 (69%) underwent adjuvant PMRT and 4598 (31%) did not. The median follow-up was 55.6 months. In all patients, the 10-year OS was 76.3% for PMRT and 78.6% without (p = 0.412). There were no notable effects of PMRT on OS based on age or the axillary management (num-ber of nodes removed). Specifically, in the NSABP B-51 population of cT1-3 cN1 patients, the 10-year OS was 82.6% for PMRT and 80.0% without (p = 0.250). PMRT benefitted women with increasing cT stage (i.e. cT3-4), increasing ypT stages (with the exception of ypT4 potentially owing to small sample sizes), and cN3 cases (p < 0.05 for all). Conclusions: In the absence of published results from NSABP B-51, this assessment of over 14,000 women from a contemporary US database revealed that PMRT may be most useful for a "moderately-high" risk group - women with more advanced primary and/or nodal disease at diagnosis, yet with tumor biology favorable enough that the disease does not progress or remain stable after NAC. The OS findings notwith-standing, this study cannot exclude potential differences between groups in recurrence-free survival, which is the primary endpoint of NSABP B-51, While the results of the NSABP B-51 will confirm optimal management for patients with limited nodal disease having a CRn following NAC, the present results sug-gest PMRT should remain the standard of care for more advanced disease than NSABP B-51 eligibility criteria. (c) 2021 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 162 (2021) 52-59

Objective: To identify subgroups of hormone receptor-positive (HR+) breast cancer patients that might not benefit from adding endocrine therapy (ET) to their local treatment. Background: De-escalation in breast cancer treatment has included surgery, radiation, and chemotherapy and has often focused on older patient populations. Systemic ET has yet to be de-escalated, though it carries serious side-effects, decreasing quality of life over 5 to 10 years. We hypothesize the 21-gene recurrence score (RS) could identify subgroups of younger patients whose long-term survival is unaffected by adjuvant ET. Methods: The National Cancer Database was used to identify women aged ≥50, with HR+, HER2-negative tumors, ≤3 cm in size, N0 status, and a RS≤25, who underwent breast-conserving surgery in 2010 to 2016. Kaplan-Meier and Cox proportional hazards models were used to identify association between treatment and overall survival (OS). Results: Of the 45,217 patients identified, 80.6% were 50 to 69 years old. 42,632 (94.3%) patients received ET and 2585 (5.7%) did not. The 5-year OS was 96.4% for patients receiving ET and 93.1% for those who did not (P < 0.001). After adjusting for all covariates, patients aged 50 to 69 with RS < 11 showed no statistically significant improvement in OS when adding ET to surgery, with or without radiation (P = 0.40). With RS 11 to 25, there was a significant improvement of OS with ET plus radiation (P < 0.001). Conclusions: Local treatment only, with de-escalation of long-term ET, for patients aged 50 to 69 with RS < 11, seems not to impact OS and should have an anticipated quality of life improvement. Prospective studies investigating this approach are warranted.

Several studies have shown that COVID-19 patients with prior comorbidities have a higher risk for adverse outcomes, resulting in a disproportionate impact on older adults and minorities that fit that profile. However, although there is considerable heterogeneity in the comorbidity profiles of these populations, not much is known about how prior comorbidities co-occur to form COVID-19 patient subgroups, and their implications for targeted care. Here we used bipartite networks to quantitatively and visually analyze heterogeneity in the comorbidity profiles of COVID-19 inpatients, based on electronic health records from 12 hospitals and 60 clinics in the greater Minneapolis region. This approach enabled the analysis and interpretation of heterogeneity at three levels of granularity (cohort, subgroup, and patient), each of which enabled clinicians to rapidly translate the results into the design of clinical interventions. We discuss future extensions of the multigranular heterogeneity framework, and conclude by exploring how the framework could be used to analyze other biomedical phenomena including symptom clusters and molecular phenotypes, with the goal of accelerating translation to targeted clinical care.

Background: Sweet Syndrome, or acute febrile neutrophilic dermatosis, is a non-infectious, painful rash accompanied by fever, leukocytosis and skin biopsy showing neutrophilic dermal inflammation. It is either idiopathic, drug-induced or malignancy associated (MASS). MASS is uncommon in cervical cancer, and usually signals diagnosis, progression or recurrence. Clinical Course: Two months following chemoradiation for stage IIIC2(r) squamous cell carcinoma (SCC) of the cervix, a 55-year-old female developed painful papules and plaques on her left toes. One week later she developed fever and the rash spread to her body. Labs revealed leukopenia and an elevated erythrocyte sedimentation rate. Punch biopsy showed neutrophilic dermal inflammation with papillary dermal edema and was negative for infectious immunohistochemistry. The clinical presentation and histopathological features were consistent with, and met diagnostic criteria for Sweet Syndrome. One month following Sweet Syndrome diagnosis and four months following chemoradiation, positron emission tomography scan revealed recurrence in the pelvic lymph nodes. At this time, she had residual rash on her thighs that responded to oral methylprednisolone. She declined further chemotherapy for recurrent SCC and opted for palliative care. Conclusion: We present a rare case of MASS in cervical cancer associated with recurrence two months after chemoradiation.

Background: In invasive breast cancer, HER2 is a well-established negative prognostic factor. However, its significance on the prognosis of ductal carcinoma in situ (DCIS) of the breast is unclear. As a result, the impact of HER2-directed therapy on HER2-positive DCIS is unknown and is currently the subject of ongoing clinical trials. In this study, we aim to determine the possible impact of HER2-directed targeted therapy on survival outcomes for HER2-positive DCIS patients. Materials and methods: The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven DCIS diagnosed from 2004-2015. Patients were divided into two groups based on the adjuvant therapy they received: systemic HER2-directed targeted therapy or no systemic therapy. Statistics included multivariable logistic regression to determine factors predictive of receiving systemic therapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. Results: Altogether, 1927 patients met inclusion criteria; 430 (22.3%) received HER2-directed targeted therapy; 1497 (77.7%) did not. Patients who received HER2-directed targeted therapy had a higher 5-year OS compared to patients that did not (97.7% vs. 95.8%, p = 0.043). This survival benefit remained on multivariable analysis. Factors associated with worse OS on multivariable analysis included Charlson-Deyo Comorbidity Score >= 2 and no receipt of hormonal therapy. Conclusion: In this large study evaluating HER2-positive DOS patients, the receipt of HER2-directed targeted therapy was associated with an improvement in OS. The results of currently ongoing clinical trials are needed to confirm this finding.

This is the first study investigating the predictive value of RS in patients treated with BCS with respect to use of RT. The results suggest that patients with an IR or HR RS may be more likely to benefit from postoperative RT than patients with a LR RS, as an OS benefit was observed with RT use in patients with IR or HR RS, but not in patients with LR RS. Further prospective evaluation is warranted to define the use of RS to guide management with RT.