Impact of Neighborhood Disadvantage on Tumor Biology and Breast Cancer Survival.

OBJECTIVE: The aim of this study was to evaluate the association between neighborhood disadvantage and Oncotype DX score, a surrogate for tumor biology, among a national cohort. BACKGROUND: Women living in disadvantaged neighborhoods have shorter breast cancer (BC) survival, even after accounting for individual-level, tumor, and treatment characteristics. This suggests unaccounted social and biological mechanisms by which neighborhood disadvantage may impact BC survival. METHODS: This cross-sectional study included stage I and II, ER + /HER2 - BC patients with Oncotype DX score data from the National Cancer Database (NCDB) from 2004 to 2019. Multivariate regression models tested the association of neighborhood-level income on Oncotype DX score controlling for age, race/ethnicity, insurance, clinical stage, and education. Cox regression assessed overall survival. RESULTS: Of the 294,283 total BC patients selected, the majority were non-Hispanic White (n=237,197, 80.6%) with 7.6% non-Hispanic Black (n=22,495) and 4.5% other (n=13,383). 27.1% (n=797,254) of the population lived in the disadvantaged neighborhoods with an annual neighborhood-level income of <$48,000, while 59.62% (n=175,305) lived in advantaged neighborhoods with a neighborhood-level income of >$48,000. On multivariable analysis controlling for age, race/ethnicity, insurance status, neighborhood-level education, and pathologic stage, patients in disadvantaged neighborhoods had greater odds of high-risk versus low-risk Oncotype DX scores compared with those in advantaged neighborhoods [odds ratio=1.04 (1.01-1.07), P =0.0067]. CONCLUSION AND RELEVANCE: This study takes a translational epidemiologic approach to identify that women living in the most disadvantaged neighborhoods have more aggressive tumor biology, as determined by the Oncotype DX score.

Genetic Ancestry-specific Molecular and Survival Differences in Admixed Patients With Breast Cancer.

OBJECTIVE: We aim to determine whether incremental changes in genetic ancestry percentages influence molecular and clinical outcome characteristics of breast cancer in an admixed population. BACKGROUND: Patients with breast cancer are predominantly characterized as "Black" or "White" based on self-identified race/ethnicity or arbitrary genetic ancestry cutoffs. This limits scientific discovery in populations that are admixed or of mixed race/ethnicity as they cannot be classified based on historical race/ethnicity boxes or genetic ancestry cutoffs. METHODS: We used The Cancer Genome Atlas cohort and focused on genetically admixed patients that had less than 90% European, African, Asian, or Native American ancestry. RESULTS: Genetically admixed patients with breast cancer exhibited improved 10-year overall survival relative to those with >90% European ancestry. Within the luminal A subtype, patients with lower African ancestry had longer 10-year overall survival compared to those with higher African ancestry. The correlation of genetic ancestry with gene expression and DNA methylation in the admixed cohort revealed novel ancestry-specific intrinsic PAM50 subtype patterns. In luminal A tumors, genetic ancestry was correlated with both the expression and methylation of signaling genes, while in basal-like tumors, genetic ancestry was correlated with stemness genes. In addition, we took a machine-learning approach to estimate genetic ancestry from gene expression or DNA methylation and were able to accurately calculate ancestry values from a reduced set of 10 genes or 50 methylation sites that were specific for each molecular subtype. CONCLUSIONS: Our results suggest that incremental changes in genetic ancestry percentages result in ancestry-specific molecular differences even between well-established PAM50 subtypes which may influence disparities in breast cancer survival outcomes. Accounting for incremental changes in ancestry will be important in future research, prognostication, and risk stratification, particularly in ancestrally diverse populations.

ZIP Code to Genomic Code: Neighborhood Disadvantage, Aggressive Breast Cancer Biology, and Breast Cancer Outcomes.

OBJECTIVE: To determine the association between objective (geospatial) and subjective (perceived) measures of neighborhood disadvantage (ND) and aggressive breast cancer tumor biology, defined using validated social adversity-associated transcription factor (TF) activity and clinical outcomes. BACKGROUND: ND is associated with shorter breast cancer recurrence-free survival (RFS), independent of individual, tumor, and treatment characteristics, suggesting potential unaccounted biological mechanisms by which ND influences RFS. METHODS: We quantified TF-binding motif prevalence within promoters of differentially expressed genes for 147 tissue samples prospectively collected on the protocol. Covariate-adjusted multivariable regression analyzed objective and subjective ND scores with 5 validated TFs of social adversity and aggressive biology-pro-inflammatory activity [nuclear factor-κB ( NF-kB ), activator protein 1 ( AP-1 )], sympathetic nervous system (SNS) activity [cyclic 3'-5' adenosine monophosphate response element-binding protein ( CREB )], and protective cellular responses [interferon-regulatory factor ( IRF ) and signal transducer and activator of transcription ( STAT )]. To clinically validate these TFs as prognostic biomarkers of aggressive biology, logistic regression and multivariable Cox proportional-hazards models analyzed their association with Oncotype DX scores and RFS, respectively. RESULTS: Increasing objective ND was associated with aggressive tumor biology (up-regulated NF-kB , activator protein 1, down-regulated IRF , and signal transducer and activator of transcription) and SNS activation (up-regulated CREB ). Increasing subjective ND (eg, threat to safety) was associated with up-regulated NF-kB and CREB and down-regulated IRF . These TF patterns were associated with high-risk Oncotype DX scores and shorter RFS. CONCLUSIONS: In the largest human social genomics study, objective and subjective ND were significantly associated with TFs of aggressive biology and SNS activation. These TFs also correlated with worse clinical outcomes, implicating SNS activation as one potential mechanism behind ND survival disparities. These findings remain to be validated in a national cohort.

Does structural racism impact receipt of NCCN guideline-concordant breast cancer treatment?

PURPOSE: Disparities in breast cancer survival remain a challenge. We aimed to analyze the effect of structural racism, as measured by the Index of Concentration at the Extremes (ICE), on receipt of National Cancer Center Network (NCCN) guideline-concordant breast cancer treatment. METHODS: We identified patients treated at two institutions from 2005 to 2017 with stage I-IV breast cancer. Census tracts served as neighborhood proxies. Using 5-year estimates from the American Community Survey, 5 ICE variables were computed to create 5 models, controlling for economic segregation, non-Hispanic Black (NHB) segregation, NHB/economic segregation, Hispanic segregation, and Hispanic/economic segregation. Multi-level logistic regression models were used to determine the association between individual and neighborhood-level characteristics on receipt of NCCN guideline-concordant breast cancer treatment. RESULTS: 5173 patients were included: 55.2% were Hispanic, 27.5% were NHW, and 17.3% were NHB. Regardless of economic or residential segregation, a NHB patient was less likely to receive appropriate treatment [(OR)Model1 0.58 (0.45-0.74); ORModel2 0.59 (0.46-0.78); ORModel3 0.62 (0.47-0.81); ORModel4 0.53 (0.40-0.69); ORModel5 0.59(0.46-0.76); p < 0.05]. CONCLUSION: To our knowledge, this is the first analysis assessing receipt of NCCN guideline-concordant treatment by ICE, a validated measure for structural racism. While much literature emphasizes neighborhood-level barriers to treatment, our results demonstrate that compared to NHW patients, NHB patients are less likely to receive NCCN guideline-concordant breast cancer treatment, independent of economic or residential segregation. Our study suggests that there are potential unaccounted individual or neighborhood barriers to receipt of appropriate care that go beyond economic or residential segregation.

Associations Between Neighborhood-Level Income and Triple-Negative Breast Cancer in a Majority-Minority Population.

BACKGROUND: Previous studies on disparities in triple-negative breast cancer (TNBC) focus on race/ethnicity, with few exploring the impact of contextual factors such as neighborhood-level income. This study evaluates the effect of neighborhood-level income on disparities in TNBC among a racially and ethnically diverse cohort, after accounting for granular individual-level risk factors of TNBC. PATIENTS AND METHODS: Patients with stage I-IV breast cancer from 2005 to 2017 were identified from our local tumor registry. The primary outcome was diagnosis of TNBC. Using 5-years estimates from the American Community Survey, we obtained median household income for each census tract which was categorized into quartiles. Mixed effects logistic regression was conducted and stratified by race and ethnicity, controlling for individual-level sociodemographic, comorbidities, and tumor characteristics. RESULTS: Among 5377 breast cancer registry patients, 16.5% were diagnosed with TNBC. The majority were Hispanic (50.1%) followed by non-Hispanic Black (NHB) (28.0%). After controlling for individual-level covariables including race and ethnicity, comorbidities, and tumor characteristics, women from low-income neighborhoods had increased odds of TNBC compared with other breast cancer subtypes, compared with those in high-income neighborhoods [odds ratio (OR) 1.33; 95% confidence interval (CI) 1.04, 1.70, p < 0.001]. In stratified analyses, NHB patients from low-income neighborhoods had two times the odds of TNBC diagnosis compared with those from high-income neighborhoods (OR 2.11; 95% CI 1.02, 4.37). CONCLUSION: We found that living in a low-income neighborhood is associated with an increased odds of TNBC independent of granular individual-level TNBC risk factors, particularly NHB race. More striking, NHB living in low-income neighborhoods had increased odds of TNBC compared with NHB living in high-income neighborhoods. Our results suggest potential unaccounted gene-environment and/or social (api)genomic interactions between neighborhood-level income and TNBC subtype development.

A Multi-institutional Analysis of Factors Influencing the Rate of Positive MRI Biopsy Among Women with Early-Stage Breast Cancer.

BACKGROUND: The use of preoperative magnetic resonance imaging (MRI) for early-stage breast cancer (ESBC) is increasing, but its utility in detecting additional malignancy is unclear and delays surgical management (Jatoi and Benson in Future Oncol 9:347-353, 2013. https://doi.org/10.2217/fon.12.186 , Bleicher et al. J Am Coll Surg 209:180-187, 2009. https://doi.org/10.1016/j.jamcollsurg.2009.04.010 , Borowsky et al. J Surg Res 280:114-122, 2022. https://doi.org/10.1016/j.jss.2022.06.066 ). The present study sought to identify ESBC patients most likely to benefit from preoperative MRI by assessing the positive predictive values (PPVs) of ipsilateral and contralateral biopsies. METHODS: A retrospective cohort study included patients with cTis-T2N0-N1 breast cancer from two institutions during 2016-2021. A "positive" biopsy result was defined as additional cancer (PositiveCancer) or cancer with histology often excised (PositiveSurg). The PPV of MRI biopsies was calculated with respect to age, family history, breast density, and histology. Uni- and multivariate logistic regression determined whether combinations of age younger than 50 years, dense breasts, family history, and pure ductal carcinoma in situ (DCIS) histology led to higher biopsy yield. RESULTS: Of the included patients, 447 received preoperative MRI and 131 underwent 149 MRI-guided biopsies (96 ipsilateral, 53 contralateral [18 bilateral]). PositiveCancer for ipsilateral biopsy was 54.2%, and PositiveCancer for contralateral biopsy was 17.0%. PositiveSurg for ipsilateral biopsy was 62.5%, and PositiveSurg for contralateral biopsy was 24.5%. Among the contralateral MRI biopsies, patients younger than 50 years were less likely to have PositiveSurg (odds ratio, 0.02; 95% confidence interval, 0.00-0.84; p = 0.041). The combinations of age, density, family history, and histology did not lead to a higher biopsy yield. CONCLUSION: Historically accepted factors for recommending preoperative MRI did not appear to confer a higher MRI biopsy yield. To prevent delays to surgical management, MRI should be carefully selected for individual patients most likely to benefit from additional imaging.

Nurturing innovation, catalyzing change: Honoring the legacy of Dr. C. Barr Taylor in the eating disorders field.

This Virtual Issue of the International Journal of Eating Disorders honors the legacy of the late Dr. C. Barr Taylor in the eating disorders (EDs) field. For decades, Dr. Taylor led the way in not only conducting the research needed to achieve the ultimate goal of making affordable, accessible, and evidence-based care for EDs available to all, but also nurturing the next generation of scientific leaders and innovators. Articles included in this Virtual Issue are a selection of Dr. Taylor's published works in the Journal in the past decade, spanning original research, ideas worth researching, commentaries, and a systematic review. We hope this Virtual Issue will inspire the next generation of research in EDs, and equally, if not more importantly, the next generation of young investigators in the field. We urge the field to continue and build upon Dr. Taylor's vision-to increase access to targeted prevention and intervention for EDs in innovative and forward-thinking ways-while embracing his unique and powerful mentorship style to lift up early career investigators and create a community of leaders to address and solve our field's biggest challenges.

Effects of neighborhood disadvantage on cortisol and interviewer-rated anxiety symptoms in breast cancer patients initiating treatment.

PURPOSE: Shorter breast cancer (BC) survival outcomes persist by neighborhood disadvantage independent of patient, tumor, and treatment characteristics. This suggests unaccounted mechanisms by which neighborhood disadvantage "gets under the skin" to impact BC survival outcomes. Here, we evaluate the relationship between neighborhood disadvantage and clinical and neuroendocrine markers of stress in BC patients. METHODS: Women with stage 0-III BC were enrolled 2-10 weeks post-surgery and before initiating adjuvant treatment in a study examining stress and stress management processes. Women provided an afternoon-evening (PM) serum cortisol sample and were administered the Hamilton Anxiety Rating Scale (HAM-A). Home addresses were used to determine the Area Deprivation Index (ADI), a validated measure of neighborhood disadvantage. Multiple regression assessed the relationship between ADI and PM serum cortisol and the presence of elevated HAM-A symptoms. RESULTS: Our sample (n = 225) was predominately middle-aged (M = 50.4 years; range 23-70 years), non-Hispanic White (64.3%), with stage I (38.1%), or II (38.6%) disease. The majority (n = 175) lived in advantaged neighborhoods (ADI 1-3). After controlling for age, stage, and surgery type, women from high ADI (4-10) (vs low ADI) neighborhoods had higher PM cortisol levels (ß = 0.19, 95% CI [0.24, 5.00], p = 0.031) and were nearly two times as likely to report the presence of elevated anxiety symptoms (OR = 1.96, 95% CI [1.00, 3.86], p = 0.050). CONCLUSION: Neighborhood disadvantage is significantly associated with higher levels of PM cortisol and elevated anxiety symptoms suggesting stress pathways could potentially contribute to relationships between neighborhood disadvantage and BC survival.

Genomic Characterization of Aggressive Breast Cancer in Younger Women.

PURPOSE: Although breast cancer (BC) risk increases with age, BC in younger women is more aggressive with higher mortality compared with older women. We characterize the genomic landscape of BCs in younger women. METHODS: Clinicopathologic, molecular, and genomic differences across age groups (< 40 years, 40-60 years, > 60 years) in female BC patients were investigated in two large cohorts [AACR-GENIE8.1 (n = 11,594) and METABRIC (n = 2509)]. Cox-proportional regression analyzed the prognostic impact of age groups for disease-specific survival (DSS) and recurrence-free survival (RFS) in METABRIC and progression-free survival (PFS) in GENIE cohorts. Chi-squared test was used to assess statistical associations between genomic alterations and age groups. RESULTS: Survival analysis showed that women < 40 years had shorter DSS [hazard ratio (HR): 1.52, p = 0.005], RFS (HR: 1.4, p = 0.006), and PFS (HR: 1.82, p = 0.0003) compared with women 40-60 years, and shorter RFS (HR: 1.5, p = 0.001) and PFS (HR: 2.95, p < 0.0001) compared with women > 60 years. Molecular subtypes in the METABRIC cohort showed women < 40 years were enriched with basal, and HER2+ subtypes, and less enriched with luminal A and B subtype (p < 0.0001). Characterization of genomic alterations in both cohorts demonstrated that BCs in women < 40 years were more enriched with TP53 mutations (FDR < 0.0001), BRCA1 mutations (FDR = 0.01), ERBB2 amplifications (FDR < 0.001), CDK12 amplifications (FDR < 0.001), and PPM1D amplifications (FDR < 0.001). In contrast, BCs in older women (> 60 years) were more enriched with PIK3CA, KMT2C, and CDH1 mutations (FDR < 0.0001). CONCLUSIONS: BCs in young women are associated with shorter survival and more aggressive genomic features, including mutations in TP53 and BRCA1, and amplifications in ERBB2 and CDK12. These findings have the potential to impact clinical trial design and treatment.

Omission of Completion Lymph Node Dissection in Sentinel Node Biopsy Positive Head and Neck Cutaneous Melanoma Patients.

BACKGROUND: Recent studies evaluating patients with a positive sentinel lymph node biopsy (SLNB+) show no melanoma-specific survival difference between patients undergoing lymph node basin surveillance and completion lymph node dissection (CLND). This has been broadly applied, despite underrepresentation of head and neck (HN) cutaneous melanoma patients. We evaluated whether this was upheld in the HN melanoma cohort. METHODS: Patients with HN melanoma with a SLNB+ were selected from the National Cancer Database (NCDB) from 2012 to 2019. Overall survival (OS) of patients who underwent SLNB only versus SLNB + CLND were compared. Subgroup analyses were performed based on pathologic N (pN) and receipt of immunotherapy. Adjusted hazard ratio (aHR) and 95% confidence interval (CI) were calculated. RESULTS: Analysis of 634 patients with multivariable Cox regression showed no difference in OS in SLNB only versus SLNB + CLND cohorts (hazard ratio [HR] 1.13; 95% confidence interval [CI] 0.71-1.81; p = 0.610). Charlson-Deyo score (CDS) 1 versus 0 (HR 1.70; 95% CI 1.10-2.63; p = 0.016), pN2+ versus pN1 (HR 1.74; 95% CI 1.23-2.45; p = 0.002), and lymphovascular invasion (LVI) versus no (HR 2.07; 95% CI 1.34-3.19; p = 0.001) were associated with worse prognosis. Subgroup analysis by pN showed no OS benefit for CLND in either pN1 (HR 1.04; 95% CI 0.51-2.10; p = 0.922) or pN2+ (HR 1.31; 95% CI 0.67-2.57; p = 0.427) patients or in patients who received immunotherapy (HR 1.32; 95% CI 0.54-3.22; p = 0.549). CONCLUSIONS: This study of SLNB + HN melanoma patients showed no OS difference in SLNB only versus SLNB + CLND. Further studies need to be performed to better define the role of CLND.

Digital guided self-help for eating disorders: thematic analysis of participant text messages to coaches.

Digital guided self-help for eating disorders (GSH-ED) can reduce treatment disparities. Understanding program participants' interests throughout the program can help adapt programs to the service users' needs. Participants were 383 college students receiving a digital GSH-ED, who were each assigned a coach to help them better utilize the intervention through text correspondence. A thematic and affective analysis of the texts participants had sent found they primarily focused on: strategies for changing their ED-related cognitions, behaviors, and relationships; describing symptoms without expressing an active endeavor to change; and participants' relationship with their coach. Most texts also expressed affect, demonstrating emotional engagement with the intervention. Findings suggest that participants in GSH-ED demonstrate high involvement with the intervention, and discuss topics that are similar to those reported in clinician-facilitated interventions. The themes discussed by digital program participants can inform future iterations of GSH-ED, thereby increasing scalability and accessibility of digital evidence-based ED interventions.

Translational Epidemiology: An Integrative Approach to Determine the Interplay Between Genetic Ancestry and Neighborhood Socioeconomic Status on Triple Negative Breast Cancer.

OBJECTIVE: To investigate the impact of global and local genetic ancestry and neighborhood socioeconomic status (nSES), on breast cancer (BC) subtype, and gene expression. BACKGROUND: Higher rates of aggressive BC subtypes [triple negative breast cancer (TNBC)] and worse overall BC survival are seen in black women [Hispanic Black (HB) and non-Hispanic Black (NHB)] and women from low nSES. However, the complex relationship between genetic ancestry, nSES, and BC subtype etiology remains unknown. METHODS: Genomic analysis was performed on the peripheral blood from a cohort of 308 stage I to IV non-Hispanic White (NHW), Hispanic White (HW), HB, and NHB women with BC. Patient and tumor characteristics were collected. Global and local ancestral estimates were calculated. Multinomial logistic regression was performed to determine associations between age, stage, genetic ancestry, and nSES on rates of TNBC compared to estrogen receptor (ER+)/epidermal growth factor receptor 2 (HER2-), ER+/HER2+, and ER-/HER2+ disease. RESULTS: Among 308 women, we identified a significant association between increasing West African (WA) ancestry and odds of TNBC [odds ratio (OR): 1.06, 95% confidence interval (95% CI): 1.001-1.126, P =0.046] as well as an inverse relationship between higher nSES and TNBC (OR: 0.343, 95% CI: 0.151-0.781, P =0.011). WA ancestry remained significantly associated with TNBC when adjusting for patient age and tumor stage, but not when adjusting for nSES (OR: 1.049, 95% CI: -0.987-1.116, P =0.120). Local ancestry analysis, however, still revealed nSES-independent enriched WA ancestral segment centered at χ 2 =42004914 ( p =3.70×10 -5 ) in patients with TNBC. CONCLUSIONS: In this translational epidemiologic study of genetic ancestry and nSES on BC subtype, we discovered associations between increasing WA ancestry, low nSES, and higher rates of TNBC compared to other BC subtypes. Moreover, on admixture mapping, specific chromosomal segments were associated with WA ancestry and TNBC, independent of nSES. However, on multinomial logistic regression adjusting for WA ancestry, women from low nSES were more likely to have TNBC, independent of genetic ancestry. These findings highlight the complex nature of TNBC and the importance of studying potential gene-environment interactions as drivers of TNBC.

Structural Racism and Breast Cancer-specific Survival: Impact of Economic and Racial Residential Segregation.

OBJECTIVE: To analyze the effect of economic and racial/ethnic residential segregation on breast cancer-specific survival (BCSS) in South Florida, a diverse metropolitan area that mirrors the projected demographics of many United States regions. SUMMARY BACKGROUND DATA: Despite advances in diagnosis and treatment, racial and economic disparities in BCSS. This study evaluates these disparities through the lens of racial and economic residential segregation, which approximate the impact of structural racism. METHODS: Retrospective cohort study of stage I to IV breast cancer patients treated at our institution from 2005 to 2017. Our exposures include index of concentration at the extremes, a measurement of economic and racial neighborhood segregation, which was computed at the census-tract level using American Community Survey data. The primary outcome was BCSS. RESULTS: Random effects frailty models predicted that patients living in low-income neighborhoods had higher mortality compared to those living in high-income neighborhoods [hazard ratios (HR): 1.56, 95% confidence interval (CI): 1.23-2.00]. Patients living in low-income non-Hispanic Black and Hispanic neighborhoods had higher mortality compared to those living in high-income non-Hispanic White (NHW) neighborhoods (HR: 2.43, 95%CI: 1.72, 3.43) and (HR: 1.99, 95%CI: 1.39, 2.84), after controlling for patient characteristics, respectively. In adjusted race-stratified analysis, NHWs living in low-income non-Hispanic Black neighborhoods had higher mortality compared to NHWs living in high-income NHW neighborhoods (HR: 4.09, 95%CI: 2.34-7.06). CONCLUSIONS: Extreme racial/ethnic and economic segregation were associated with lower BCSS. We add novel insight regarding NHW and Hispanics to a growing body of literature that demonstrate how the ecological effects of structural racism-expressed through poverty and residential segregation-shape cancer survival.

Impact of genomic assays on treatment and outcomes in locally advanced breast cancer.

PURPOSE: Genomic profiling in early-stage breast cancer provides prognostic and predictive information. Genomic profiling assays have not been validated in locally advanced breast cancer (LABC). We examined a large cancer registry to evaluate genomic profiling in LABC and its effect on treatment decisions and survival. METHODS: Females with ER+/HER2- LABC who did not receive neoadjuvant therapy were selected from the National Cancer Database 2004-2017. We compared characteristics between patients with and without genomic profiling and with low genomic risk, 21-gene recurrence score ≤ 25 or low-risk 70-gene signature, treated with endocrine therapy ± chemotherapy. Propensity score methods were utilized to account for covariates that may have predicted treatment. Univariable and multivariable survival analyses were performed. RESULTS: Of 18,437 patients with LABC, 1258 (7%) had genomic profiling and 1022 (81%) had low genomic risk results. 562 patients (55%) with low genomic risk received chemotherapy and endocrine therapy (chemoendocrine). Patients who received chemoendocrine therapy were younger, had fewer comorbidities, presented with higher stage disease, had higher grade tumors, more frequently had partial mastectomy, and more often received radiation than those who received endocrine therapy alone. On multivariable analysis, endocrine therapy alone was associated with worse OS compared to chemoendocrine therapy (HR 1.77, 95% CI 1.13-2.78, p = 0.013). CONCLUSION: In women with LABC and low genomic risk, endocrine therapy alone was associated with worse OS compared to chemoendocrine therapy. This suggests that genomic profiling is not predictive in LABC. Accordingly, genomic profiling should not be routinely utilized to make adjuvant treatment decisions in LABC in the absence of further data which shows a benefit.

Stalled at the intersection: insurance status and disparities in post-mastectomy breast reconstruction.

PURPOSE: Post-mastectomy breast reconstruction (PMBR) is an important component of breast cancer treatment, but disparities relative to insurance status persist despite legislation targeting the issue. We aimed to study this relationship in a large health system combining a safety-net hospital and a private academic center. METHODS: Data were collected on all patients who underwent mastectomy for breast cancer from 2011 to 2019 in a private academic center and an adjacent public safety-net hospital served by the same surgical teams. Multivariable logistic regression was used to assess the effect of insurance status on PMBR, controlling for covariates that included socioeconomic, demographic, and clinical factors. RESULTS: Of 1554 patients undergoing mastectomy for breast cancer, 753 (48.5%) underwent PMBR, of which 592 (79.9%) were privately insured, 50 (6.7%) Medicare, 68 (9.2%) Medicaid, and 31 (4.2%) uninsured. Multivariable logistic regression showed a significantly higher likelihood of not undergoing PMBR for uninsured (OR 6.0, 95% CI 3.7-9.8; p < 0.0001), Medicare (OR 1.9, (95% CI 1.2-3.0; p = 0.006), and Medicaid (OR 1.5, 95% CI 1.0-2.3; p = 0.04) patients compared with privately insured patients. Age, stage, race and ethnicity, and hospital type confounded this relationship. CONCLUSION: Patients without health insurance have dramatically reduced access to PMBR compared to those with private insurance. Expanding access to this important procedure is essential to achieve greater health equity for breast cancer patients.

Analysis and Interpretation of metagenomics data: an approach.

Advances in next-generation sequencing technologies have accelerated the momentum of metagenomic studies, which is increasing yearly. The metagenomics field is one of the versatile applications in microbiology, where any interaction in the environment involving microorganisms can be the topic of study. Due to this versatility, the number of applications of this omics technology reached its horizons. Agriculture is a crucial sector involving crop plants and microorganisms interacting together. Hence, studying these interactions through the lenses of metagenomics would completely disclose a new meaning to crop health and development. The rhizosphere is an essential reservoir of the microbial community for agricultural soil. Hence, we focus on the R&D of metagenomic studies on the rhizosphere of crops such as rice, wheat, legumes, chickpea, and sorghum. These recent developments are impossible without the continuous advancement seen in the next-generation sequencing platforms; thus, a brief introduction and analysis of the available sequencing platforms are presented here to have a clear picture of the workflow. Concluding the topic is the discussion about different pipelines applied to analyze data produced by sequencing techniques and have a significant role in interpreting the outcome of a particular experiment. A plethora of different software and tools are incorporated in the automated pipelines or individually available to perform manual metagenomic analysis. Here we describe 8-10 advanced, efficient pipelines used for analysis that explain their respective workflows to simplify the whole analysis process.

Axillary Response to Neoadjuvant Therapy in Node-Positive, Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Patients: Predictors and Oncologic Outcomes.

BACKGROUND: One potential benefit of neoadjuvant therapy (NAT) in node-positive, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) patients is axillary downstaging to avoid axillary dissection. OBJECTIVE: The aim of this study was to evaluate axillary response to NAT with chemotherapy (NCT) or endocrine therapy (NET) and identify potential predictors of response. METHODS: A prospectively collected database was queried for node-positive, ER+, HER2- breast cancer patients treated with NAT and surgery from January 2011 to September 2020. Axillary response was categorized into pathologic complete response (pCR) versus no pCR, and was correlated to demographic and clinicopathologic parameters in a logistic regression model. RESULTS: A cohort of 176 eligible patients was identified and 178 breast cancers were included in the study. The overall axillary pCR rate was 12.3% (22/178). NCT and NET achieved response rates of 13.9% (19/137) and 7.3% (3/41), respectively (p = 0.232). A significantly higher axillary pCR rate was identified in patients with clinical stage II at diagnosis (12/60, 20%) compared with stage III (10/118, 8.4%; p = 0.03). NET patients with ypN0 were younger and were treated for a longer period of time (>6 months). Completion axillary dissection was omitted in the majority (73.7%) of NCT patients achieving axillary pCR. CONCLUSIONS: For patients with node-positive, ER+, HER2- breast cancer, a lower burden of disease at the time of diagnosis (stage II) is associated with a significantly higher axillary pCR, enabling those patients to be spared axillary dissection. Further studies are necessary to define the role of genomic profiling in predicting axillary response.

Disparities in Primary Breast Cancer Stage at Presentation Among Hispanic Subgroups.

BACKGROUND: Although the United States (US) Hispanic population consists of diverse communities, prior breast cancer studies often analyze this group in aggregate. Our aim was to identify differences in breast cancer stage at presentation in the US population, with a particular focus on Hispanic subgroups. METHODS: Data from the National Cancer Database (NCDB) from 2004 to 2017 were used to select women with primary breast cancer; individuals were disaggregated by racial and ethnic subgroup and Hispanic country of origin. Ordinal logistic regression was used to create adjusted odds ratios (aORs) with 95% confidence intervals (CIs), with higher odds representing presentation at later-stage breast cancer. Subgroup analysis was conducted based on tumor receptor status. RESULTS: Overall, among 2,282,691 women (5.2% Hispanic), Hispanic women were more likely to live in low-income and low-educational attainment neighborhoods, and were also more likely to be uninsured. Hispanic women were also more likely to present at later-stage primary breast cancer when compared with non-Hispanic White women (aOR 1.19, 95% CI 1.18-1.21; p < 0.01). Stage disparities were demonstrated when populations were disaggregated by country of origin, particularly for Mexican women (aOR 1.55, 95% CI 1.51-1.60; p < 0.01). Disparities worsened among both racial and country of origin subgroups in women with triple-negative disease. CONCLUSION: Later breast cancer stage at presentation was observed among Hispanic populations when disaggregated by racial subgroup and country of origin. Socioeconomic disparities, as well as uncaptured disparities in access and/or differential care, may drive these observed differences. Future studies with disaggregated data are needed to characterize outcomes in Hispanic communities and develop targeted interventions.

The Association of Preoperative Magnetic Resonance Imaging (MRI) With Surgical Management in Patients With Early-Stage Breast Cancer.

INTRODUCTION: The rate of mastectomy in lumpectomy-eligible patients with unilateral breast cancer is increasing. We sought to investigate the association between magnetic resonance imaging (MRI) and surgical management of patients with early-stage breast cancer by comparing the rate of mastectomy as first surgery in patients with and without preoperative MRI. METHODS: A bi-institutional retrospective study included patients diagnosed between 2016 and 2020. Lumpectomy-eligible patients with in situ and invasive cancer were included. Those receiving preoperative therapy, MRI before diagnosis, or with known bilateral cancer were excluded. The risk factors for bilateral and multicentric disease were accounted for. Fisher's exact and chi-square tests compared categorical variables, Wilcoxon two-sample test analyzed continuous variables, and multivariate analyses were performed with Poisson regression. RESULTS: Four hundred twenty-eight participants met inclusion criteria. Patients who received MRI were younger (58 versus 67 y; P < 0.001) and had denser breasts (group 3 or 4; 61% versus 25%; P < 0.001). Mastectomy rate was twice as high in patients undergoing MRI (32% versus 15%, rate ratio 2.16; P < 0.001), which remained significant in multivariate analysis (rate ratio 2.0; P < 0.001). Contralateral mastectomy (12% versus 4%; P = 0.466) and reexcision (13% versus 12%; P = 0.519) rates were similar. Time to surgery was greater in those receiving MRI alone and MRI biopsy (34 [no MRI] versus 45 [MRI] versus 62 [MRI biopsy]; P < 0.001 for both). CONCLUSIONS: MRI receipt is associated with a doubled rate of mastectomy in lumpectomy-eligible patients. Future work is needed to standardize patient selection for MRI to those with the highest likelihood of having additional undiagnosed disease.

Total neoadjuvant therapy is associated with improved overall survival and pathologic response in pancreatic adenocarcinoma.

BACKGROUND: Few studies have evaluated outcomes of total neoadjuvant therapy (TNT) compared with single modality neoadjuvant therapy (SMNT) or surgery first (SF) for pancreatic ductal adenocarcinoma (PDAC). METHODS: A single-institution retrospective review of PDAC patients who underwent pancreatectomy was conducted (1993-2019). Overall survival (OS) estimates from diagnosis and from surgery were determined using Kaplan-Meier methods; Cox proportional hazards models adjusted for covariates. RESULTS: Surgery was performed upfront (SF) in 168 (46.9%), while 111 (31.0%) had chemotherapy or chemoradiation before resection (SMNT), and 79 (22.1%) underwent TNT (chemotherapy and chemoradiation). Resection margins were more frequently R0 in the TNT group (86.1%) compared with SMNT (64.0%) and SF (72%) (p < 0.001). Complete pathologic response was more common in the TNT group (10.1%) compared with SMNT (3.6%) or SF (0.6%) (p = 0.001), resulting in prolonged survival (median OS = 100.2 months). TNT patients demonstrated longer median OS from surgery (33.6 months) compared with SF (19.1 months) and SMNT (17.4 months) (p = 0.010), which persisted after controlling for covariates. CONCLUSIONS: TNT is associated with more frequent complete pathologic response, a higher rate of margin negative resection, and prolonged OS as compared with SF or SMNT. Additional studies to identify subgroups that derive the greatest benefit are warranted.