MethParquet: an R package for rapid and efficient DNA methylation association analysis adopting Apache Parquet.

SUMMARY: Genome-wide DNA methylation (DNAm) profiling is indispensable for unveiling how DNAm regulates biological pathways and individual phenotypes. However, managing and analyzing extensive DNAm data generated from large cohort studies present computational obstacles. Apache Parquet is a data file format that allows for efficient data storage, retrieval, and manipulation, alleviating computational hurdles associated with conventional row-based formats. We here introduce MethParquet, the first R package leveraging the columnar Parquet format for efficient DNAm data analysis. It can be used for data extraction, methylation risk score calculation, epigenome-wide association analyses, and other standard post-quality control tasks. The package flexibly implements diverse regression models. Via a public methylation dataset, we show the efficiency of this package in reducing running time and RAM usage in large-scale EWAS. AVAILABILITY AND IMPLEMENTATION: The MethParquet R package is publicly available on the GitHub repository https://github.com/ZWangTen/MethParquet. It includes a vignette and a toy dataset derived from a public resource.

Breast Cancer Screening and BI-RADS Scoring Trends Before and During the COVID-19 Pandemic in an Academic Safety-Net Hospital.

BACKGROUND: Little is known about how the COVID-19 pandemic affected screening mammography rates and Breast Imaging Reporting and Data Systems (BI-RADS) categorizations within populations facing social and economic inequities. Our study seeks to compare trends in breast cancer screening and BI-RADS assessments in an academic safety-net patient population before and during the COVID-19 pandemic. PATIENTS AND METHODS: Our single-center retrospective study evaluated women ≥ 18 years old with no known breast cancer diagnosis who received breast cancer screening from March 2019-September 2020. The screening BI-RADS score, completion of recommended diagnostic imaging, and diagnostic BI-RADS scores were compared between the pre-COVID-19 era (from 1 March 2019 to 19 March 2020) and COVID-19 era (from 20 March 2020 to 30 September 2020). RESULTS: Among the 11,798 patients identified, screened patients were younger (median age 57 versus 59 years, p < 0.001) and more likely covered by private insurance (35.9% versus 32.3%, p < 0.001) during the COVID-19 era compared with the pre-COVID-19 era. During the pandemic, there was an increase in screening mammograms categorized as BI-RADS 0 compared with the pre-COVID-19 era (20% versus 14.5%, p < 0.0001). There was no statistically significant difference in rates of completion of diagnostic imaging (81.6% versus 85.4%, p = 0.764) or assignment of suspicious BI-RADS scores (BI-RADS 4-5; 79.9% versus 80.8%, p = 0.762) between the two eras. CONCLUSIONS: Although more patients were recommended to undergo diagnostic imaging during the pandemic, there were no significant differences in race, completion of diagnostic imaging, or proportions of mammograms categorized as suspicious between the two time periods. These findings likely reflect efforts to maintain equitable care among diverse racial groups served by our safety-net hospital.

Association of Race, Ethnicity, Language, and Insurance with Time to Treatment Initiation Among Women with Breast Cancer at an Urban, Academic, Safety-Net Hospital.

INTRODUCTION: Initial treatment for nonmetastatic breast cancer is resection or neoadjuvant systemic therapy, depending on tumor biology and patient factors. Delays in treatment have been shown to impact survival and quality of life. Little has been published on the performance of safety-net hospitals in delivering timely care for all patients. METHODS: We conducted a retrospective study of patients with invasive ductal or lobular breast cancer, diagnosed and treated between 2009 and 2019 at an academic, safety-net hospital. Time to treatment initiation was calculated for all patients. Consistent with a recently published Committee on Cancer timeliness metric, a treatment delay was defined as time from tissue diagnosis to treatment of greater than 60 days. RESULTS: A total of 799 eligible women with stage 1-3 breast cancer met study criteria. Median age was 60 years, 55.7% were non-white, 35.5% were non-English-speaking, 18.9% were Hispanic, and 49.4% were Medicaid/uninsured. Median time to treatment was 41 days (IQR 27-56 days), while 81.1% of patients initiated treatment within 60 days. The frequency of treatment delays did not vary by race, ethnicity, insurance, or language. Diagnosis year was inversely associated with the occurrence of a treatment delay (OR: 0.944, 95% CI 0.893-0.997, p value: 0.039). CONCLUSION: At our institution, race, ethnicity, insurance, and language were not associated with treatment delay. Additional research is needed to determine how our safety-net hospital delivered timely care to all patients with breast cancer, as reducing delays in care may be one mechanism by which health systems can mitigate disparities in the treatment of breast cancer.

Assessing breast cancer-related lymphedema screening and treatment gaps in a safety-net hospital.

BACKGROUND AND OBJECTIVES: We evaluated the unmet breast cancer-related lymphedema (BCRL) treatment and education needs at New England's largest safety-net hospital serving a diverse population by assessing prevalence, risk factors, and treatment. METHODS: This was a retrospective cohort study examining breast cancer surgery patients from September 2016 to September 2021. The primary outcome was BCRL diagnosis. Secondary outcomes included BCRL risk factors, and physical and occupational therapy (PT/OT) referral frequency and completion. RESULTS: Of 639 patients, 17% of patients had documented BCRL, which was significantly associated with axillary lymph node dissection (ALND). There were no racial, insurance, breast radiation, or BMI category differences between patients with and without a BCRL diagnosis. Of those with BCRL, 58% received a PT/OT referral, and 56% completed their referral. There were no racial, insurance, or BMI category differences between those who received a PT/OT referral and those who did not. CONCLUSION: In our high-risk population, rates of documented BCRL were higher than expected, approaching rates of ALND, despite the majority undergoing sentinel lymph node biopsy (SLNB). PT/OT referral and completion rates were low, concerning for an unmet BCRL treatment and education need. No disparities in care delivery were seen, but a program that addresses treatment gaps and ensures accessible and patient-centered BCRL care is urgently needed.

Technical Pearls and Pitfalls of Facial Feminization Surgery: A Review of Techniques From a Single Institutional Practice.

BACKGROUND: Facial feminization surgery (FFS) is an emerging practice that falls under the broader umbrella of gender-affirming surgery. Various approaches exist to feminize the face, yet few published articles describe in detail the techniques of each component procedure. Considering the diversity of interventions employed, the objective of this manuscript is to highlight FFS techniques utilized by the senior author and create a corresponding media gallery. METHODS: All patients with the diagnosis of gender dysphoria that were referred to the senior author for FFS consultation between June 2017 and August 2022 were reviewed. Data were retrospectively collected from electronic medical records according to the institutional review board (IRB)-approved study protocol. Data collected and analyzed included demographics, operative documentation, and postoperative follow-up. Multimedia material was collected intraoperatively and postoperatively. RESULTS: A total of 231 patients underwent 262 operations with a total of 1224 FFS procedures. The average follow-up time was 7.7 ± 11 months. Out of the 262 operations, 24 (9.2%) patients experienced minor complications, including 3 (1.1%) with wound dehiscence, 13 (5.0%) with hematomas, and 14 (5.3%) with postoperative infection requiring antibiotics. Of those, 3 (1.1%) required a return to the operating room for washout or removal of malar implants. CONCLUSION: Although there is a consensus on the fundamental surgical principles to achieve adequate feminization of the facial architecture, the specific techniques to do so differ according to individual practices. As techniques diverge, so do their risk profiles and outcomes; techniques must, thus, align with patients' interventional goals. The material presented here is one of many that can support trainees and junior surgeons as they build a gender-affirming practice.

Mitigating disparities in breast cancer treatment at an academic safety-net hospital.

PURPOSE: Among women with non-metastatic breast cancer, marked disparities in stage at presentation, receipt of guideline-concordant treatment and stage-specific survival have been shown in national cohorts based on race, ethnicity, insurance and language. Little is published on the performance of safety-net hospitals to achieve equitable care. We evaluate differences in treatment and survival by race, ethnicity, language and insurance status among women with non-metastatic invasive breast cancer at a single, urban academic safety-net hospital. METHODS: We conducted a retrospective study of patients with invasive ductal or lobular breast cancer, diagnosed and treated between 2009 and 2014 at an urban, academic safety-net hospital. Demographic, tumor and treatment characteristics were obtained. Stage at presentation, stage-specific overall survival, and receipt of guideline-concordant surgical and adjuvant therapies were analyzed. Chi-square analysis and ANOVA were used for statistical analysis. Unadjusted survival analysis was conducted by Kaplan-Meier method using log-rank test; adjusted 5 year survival analysis was completed stratified by early and late stage, using flexible parametric survival models incorporating age, race, primary language and insurance status. RESULTS: 520 women with stage 1-3 invasive breast cancer were identified. Median age was 58.5 years, 56.1% were non-white, 31.7% were non-English-speaking, 16.4% were Hispanic, and 50.1% were Medicaid/uninsured patients. There were no statistically significant differences in stage at presentation between age group, race, ethnicity, language or insurance. The rate of breast conserving surgery (BCS) among stage 1-2 patients did not vary by race, insurance or language. Among patients indicated for adjuvant therapies, the rates of recommendation and completion of therapy did not vary by race, ethnicity, insurance or language. Unadjusted survival at 5 years was 93.7% for stage 1-2 and 73.5% for stage 3. Adjusting for age, race, insurance status and primary language, overall survival at 5 years was 93.8% (95% CI 86.3-97.2%) for stage 1-2 and 83.4% (95% CI 35.5-96.9%) for stage 3 disease. Independently, for patients with early- and late-stage disease, age, race, language and insurance were not associated with survival at 5-years. CONCLUSION: Among patients diagnosed and treated at an academic safety-net hospital, there were no differences in the stage at presentation or receipt of guideline-concordant treatment by race, ethnicity, insurance or language. Overall survival did not vary by race, insurance or language. Additional research is needed to assess how hospitals and healthcare systems mitigate breast cancer disparities.

Evaluation of obstructive sleep apnea among consecutive patients with all patterns of atrial fibrillation using WatchPAT home sleep testing.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and is associated with significant morbidity, mortality, and financial burden. Obstructive sleep apnea (OSA) is more common in individuals with AF and may impair the efficacy of rhythm control strategies including catheter ablation. However, the prevalence of undiagnosed OSA in all-comers with AF is unknown. DESIGN: This pragmatic, phase IV prospective cohort study will test 250-300 consecutive ambulatory AF patients with all patterns of atrial fibrillation (paroxysmal, persistent, and long-term persistent) and no prior sleep testing for OSA using the WatchPAT system, a disposable home sleep test (HST). The primary outcome of the study is the prevalence of undiagnosed OSA in all-comers with atrial fibrillation. RESULTS: Preliminary results from the initial pilot enrollment of approximately 15% (N = 38) of the planned sample size demonstrate a 79.0% prevalence of at least mild (AHI≥5) OSA or greater in consecutively enrolled patient with all patterns of AF. CONCLUSIONS: We report the design, methodology, and preliminary results of our study to define the prevalence of OSA in AF patients. This study will help inform approaches to OSA screening in patients with AF for which there is currently little practical guidance. CLINICAL TRIAL REGISTRATION: NCT05155813.

Axillary Lymph Node Dissection is Associated with Improved Survival Among Men with Invasive Breast Cancer and Sentinel Node Metastasis.

BACKGROUND: Male breast cancer (MBC) is rare, and management is extrapolated from trials that enroll only women. It is unclear whether contemporary axillary management based on data from landmark trials in women may also apply to men with breast cancer. This study aimed to compare survival in men with positive sentinel lymph nodes after sentinel lymph node biopsy (SLNB) alone versus complete axillary dissection (ALND). PATIENTS AND METHODS: Using the National Cancer Database, men with clinically node-negative, T1 and T2 breast cancer and 1-2 positive sentinel nodes who underwent SLNB or ALND were identified from 2010 to 2020. Both 1:1 propensity score matching and multivariate regression were used to identify patient and disease variables associated with ALND versus SLNB. Survival between ALND and SLNB were compared using Kaplan-Meier methods. RESULTS: A total of 1203 patients were identified: 61.1% underwent SLNB alone and 38.9% underwent ALND. Treatment in academic centers (36.1 vs. 27.7%; p < 0.0001), 2 positive lymph nodes on SLNB (32.9 vs. 17.3%, p < 0.0001) and receipt or recommendation of chemotherapy (66.5 vs. 52.2%, p < 0.0001) were associated with higher likelihood of ALND. After propensity score matching, ALND was associated with superior survival compared with SLNB (5-year overall survival of 83.8 vs. 76.0%; log-rank p = 0.0104). DISCUSSION: The results of this study suggest that among patients with early-stage MBC with limited sentinel lymph node metastasis, ALND is associated with superior survival compared with SLNB alone. These findings indicate that it may be inappropriate to extrapolate the results of the ACOSOG Z0011 and EORTC AMAROS trials to MBC.

Impact of the COVID-19 Pandemic on Delays to Breast Cancer Surgery: Ripples or Waves?

BACKGROUND: Adherence to current recommendations for optimal time from diagnosis to treatment for patients with breast cancer may have been disrupted by the COVID-19 pandemic. This study aimed to evaluate the impact of the pandemic on time to surgery or systemic treatment with chemotherapy or immunotherapy for patients diagnosed with breast cancer. METHODS: Using the National Cancer Database, patients diagnosed with breast cancer in 2020 were compared to those diagnosed from 2018-2019 (Pre-COVID). Sub-analyses were performed for patients who were tested for COVID-19 and those who had a positive result in 2020. Multivariate logistic regression was used assess odds ratios for delayed time to surgery (DTS, defined as > 90 days) or systemic therapy (defined as > 120 days). RESULTS: In total, 230,997 patients were diagnosed with breast cancer in 2018 and 2019 compared to 102,065 in 2020. Of the 2020 cohort, 47,659 (46.7%) received COVID-19 testing; of which, 3,158 (6.6%) resulted positive. A larger proportion of COVID-tested or COVID-positive patients had higher stage at diagnosis. DTS was more likely for patients who were diagnosed in 2020, uninsured or underinsured, non-white, Hispanic, less educated, or age < 70 years. Similar factors were predictive of delay to systemic therapy (less age < 70 years); however, diagnosis in 2020 was not. CONCLUSION: The COVID-19 pandemic was associated with significant DTS for breast cancer but spared time to systemic therapy. Delays disproportionately impacted vulnerable and underserved patient populations. The true clinical effects of these delays may yet be realized for breast cancer patients.

Association of Race, Ethnicity, Insurance, and Language and Rate of Breast-Conserving Therapy Among Women With Nonmetastatic Breast Cancer at an Urban, Safety-Net Hospital.

INTRODUCTION: Breast-conserving therapy (BCT), specifically breast-conserving surgery (BCS) and adjuvant radiation, provides an equivalent alternative to mastectomy for eligible patients. However, previous studies have shown that BCT is underused in the United States, particularly among marginalized demographic groups. In this study, we examine the association between race, ethnicity, insurance, and language and rate of BCS among patients treated at an academic, safety-net hospital. MATERIALS AND METHODS: We conducted a retrospective cohort study of 520 women with nonmetastatic breast cancer diagnosed and treated at an academic, safety-net hospital (2009-2014). We assessed eligibility for BCT and then differences in the rate of BCT among eligible patients by race, ethnicity, insurance, and language. Reasons for not undergoing BCT were documented. RESULTS: Median age was 60 y; 55.9% were non-White, 31.9% were non-English-speaking, 15.6% were Hispanic, and 47.4% were Medicaid/uninsured. Three hundred seventy one (86.3%) underwent BCS; within this group, 324 (87.3%) completed adjuvant radiation. Among patients undergoing mastectomy, 30 patients (36.7%) were eligible for BCT; within this group, reasons for mastectomy included patient preference (n = 28) and to avoid possible re-excision or adjuvant radiation in patients with significant comorbidities (n = 2). Eligibility for BCT varied by ethnicity (Hispanic [100%], Non-Hispanic [92%], P = 0.02), but not race, language, or insurance. Among eligible patients, rate of BCS varied by age (<50 y [84.9%], ≥50 y [92.9%], P = 0.01) and ethnicity (Hispanic [98.5%], Non-Hispanic [91.3%], P = 0.04), but not race, language, or insurance. CONCLUSIONS: At our safety-net hospital, the rate of BCS among eligible patients did not vary by race, language, or insurance. Excluding two highly comorbid patients, all patients who underwent mastectomy despite being eligible for BCT were counseled regarding BCS and expressed a preference for mastectomy. Further research is needed to understand the value of BCT in the treatment of breast cancer, to ensure informed decision-making, address potential misconceptions regarding BCT, and advance equitable care for all patients.

Impact of Patient Primary Language upon Immediate Breast Reconstruction After Mastectomy.

BACKGROUND: Preoperative decision-making in patients who speak a primary language other than English is understudied. We investigated whether patient primary language is associated with differences in immediate breast reconstruction (IBR) after mastectomy. PATIENTS AND METHODS: This retrospective observational study analyzed female patients undergoing mastectomy in the New Jersey State Inpatient Database (2009-2014). The primary outcome was the odds of IBR with a prespecified subanalysis of autologous tissue-based IBR. We used multivariable logistic regression and hierarchical generalized linear mixed models to control for patient characteristics and nesting within hospitals. RESULTS: Of 13,846 discharges, 12,924 (93.3%) specified English as the patient's primary language, while 922 (6.7%) specified a language other than English. Among English-speaking patients, 6178 (47.8%) underwent IBR, including 2310 (17.9%) autologous reconstructions. Among patients with a primary language other than English, 339 (36.8%) underwent IBR, including 93 (10.1%) autologous reconstructions. Unadjusted results showed reduced odds of IBR overall [odds ratio (OR) 0.64, 95% CI 0.55-0.73], and autologous reconstruction specifically (OR 0.52, 95% CI 0.41-0.64) among patients with a primary language other than English. After adjustment for patient factors, this difference persisted among the autologous subgroup (OR 0.64, 95% CI 0.51-0.80) but not for IBR overall. A hierarchical model incorporating both patient characteristics and hospital-level effects continued to show a difference among the autologous subgroup (OR 0.75, 95% CI 0.58-0.97). CONCLUSIONS: Primary language other than English was an independent risk factor for lower odds of autologous IBR after adjustments for patient and hospital effects. Focused efforts should be made to ensure that patients who speak a primary language other than English have access to high-quality shared decision-making for postmastectomy IBR.

Residential Racial Segregation and Disparities in Breast Cancer Presentation, Treatment, and Survival.

OBJECTIVE: To understand the role of racial residential segregation on Black-White disparities in breast cancer presentation, treatment, and outcomes. SUMMARY OF BACKGROUND DATA: Racial disparities in breast cancer treatment and outcomes are well documented. Black individuals present at advanced stage, are less likely to receive appropriate surgical and adjuvant treatment, and have lower overall and stage-specific survival relative to White individuals. METHODS: Using data from the Surveillance, Epidemiology, and End Results program, we performed a retrospective cohort study of Black and White patients diagnosed with invasive breast cancer from 2005 to 2015 within the 100 most populous participating counties. The racial index of dissimilarity was used as a validated measure of residential segregation. Multivariable regression was performed, predicting advanced stage at diagnosis (stage III/IV), surgery for localized disease (stage I/II), and overall stage-specific survival. RESULTS: After adjusting for age at diagnosis, estrogen/progesterone receptor status, and region, Black patients have a 49% greater risk (relative risk [RR] 1.49 95% confidence interval [CI] 1.27, 1.74) of presenting at advanced stage with increasing segregation, while there was no observed difference in Whites (RR 1.04, 95% CI 0.93, 1.16). Black patients were 3% less likely to undergo surgical resection for localized disease (RR 0.97, 95% CI 0.95, 0.99) with increasing segregation, while Whites saw no significant difference. Black patients had a 29% increased hazard of death (RR 1.29, 95% CI 1.04, 1.60) with increasing segregation; there was no significant difference among White patients. CONCLUSIONS: Our data suggest that residential racial segregation has a significant association with Black-White racial disparities in breast cancer. These findings illustrate the importance of addressing structural racism and residential segregation in efforts to reduce Black-White breast cancer disparities.

Undertreatment of Gallbladder Cancer: A Nationwide Analysis.

BACKGROUND: Gallbladder cancer has a high mortality rate and an increasing incidence. The current National Comprehensive Cancer Network (NCCN) guidelines recommend resection for all T1b and higher-stage cancers. This study aimed to evaluate re-resection rates and the associated survival impact for patients with gallbladder cancer. METHODS: Patients with gallbladder adenocarcinoma who underwent resection were identified from the National Cancer Database (2004-2015). Re-resection was defined as definitive surgery within 180 days after the first operation. Propensity scores were created for the odds of a patient having a re-resection. Patients were matched 1:2. Survival analyses were performed using the Kaplan-Meier and Cox proportional hazard methods. RESULTS: The study identified 6175 patients, and 466 of these patients (7.6%) underwent re-resection. Re-resection was associated with younger median age (65 vs 72 years; p < 0.0001), private insurance (41.6% vs 27.1%; p < 0.0001), academic centers (50.4% vs 29.7%; p < 0.0001), and treatment location in the Northeast (22.8% vs 20.4%; p = 0.0011). Compared with no re-resection, re-resection was associated with pT stage (pT2: 47.6% vs 42.8%; p = 0.0139) and pN stage (pN1-2: 28.1% vs 20.7%; p < 0.0001), negative margins on final pathology (90.1% vs 72.6%; p < 0.0001), and receipt of chemotherapy (53.7% vs 35.8%; p < 0.0001). The patients who underwent re-resection demonstrated significantly longer overall survival (OS) than the patients who did not undergo re-resection (median OS, 44.0 vs 23.0 months; p < 0.0001). After propensity score-matching, re-resection remained associated with superior survival (median OS, 44.0 vs 31.0 months; p = 0.0004). CONCLUSIONS: Re-resection for gallbladder cancer is associated with improved survival but remains underused, particularly for early-stage disease.

Chronic Human Pegivirus 2 without Hepatitis C Virus Co-infection.

Most human pegivirus 2 (HPgV-2) infections are associated with past or current hepatitis C virus (HCV) infection. HPgV-2 is thought to be a bloodborne virus: higher prevalence of active infection has been found in populations with a history of parenteral exposure to viruses. We evaluated longitudinally collected blood samples obtained from injection drug users (IDUs) for active and resolved HPgV-2 infections using a combination of HPgV-2-specific molecular and serologic tests. We found evidence of HPgV-2 infection in 11.2% (22/197) of past or current HCV-infected IDUs, compared with 1.9% (4/205) of an HCV-negative IDU population. Testing of available longitudinal blood samples from HPgV-2-positive participants identified 5 with chronic infection (>6 months viremia in >3 timepoints); 2 were identified among the HCV-positive IDUs and 3 among the HCV-negative IDUs. Our findings indicate that HPgV-2 can establish chronic infection and replicate in the absence of HCV.

Association of MRI T2 Signal Intensity With Desmoid Tumor Progression During Active Observation: A Retrospective Cohort Study.

OBJECTIVE: The aim of this study was to identify predictors of desmoid progression during observation. SUMMARY OF BACKGROUND DATA: Untreated desmoids can grow, remain stable, or regress, but reliable predictors of behavior have not been identified. METHODS: Primary or recurrent desmoid patients were identified retrospectively from an institutional database. In those managed with active observation who underwent serial magnetic resonance imaging (MRIs) with T2-weighted sequences, baseline tumor size was recorded, and 2 radiologists independently estimated the percentage of tumor volume showing hyperintense T2 signal at baseline. Associations of clinical or radiographic characteristics with progression-free survival (PFS; by RECIST) were evaluated by Cox regression and Kaplan-Meier statistics. RESULTS: Among 160 patients with desmoids, 72 were managed with observation, and 37 of these had serial MRI available for review. Among these 37 patients, median age was 35 years and median tumor size was 4.7 cm; all tumors were extra-abdominal (41% in abdominal wall). Although PFS was not associated with size, site, or age, it was strongly associated with hyperintense T2 signal in ≥90% versus <90% of baseline tumor volume (as defined by the "test" radiologist; hazard ratio = 11.3, P = 0.003). For patients in the ≥90% group (n = 20), 1-year PFS was 55%, compared with 94% in the <90% group (n = 17). The percentage of baseline tumor volume with hyperintense T2 signal defined by a validation radiologist correlated with results of the test radiologist (ρ = 0.75). CONCLUSION: The percent tumor volume characterized by hyperintense T2 signal is associated with desmoid progression during observation and may help distinguish patients who would benefit from early intervention from those who may be reliably observed.

Racial differences in genomic testing and receipt of endocrine therapy in early-stage breast cancer.

PURPOSE: Genomic testing in early-stage hormone-positive breast cancer is the standard of care. However, decisions based on genomic testing results are predicated on the assumption that patients receive endocrine treatment. We sought to investigate racial differences in genomic testing and adjuvant treatment in breast cancer. METHODS: A retrospective, population-based hospital registry study using the National Cancer Database. Participants included women with stages I-II, ER + breast cancer between 2010 and 2014. Sociodemographic factors were analyzed. Primary outcomes were the utilization of genomic testing and receipt of endocrine therapy. Logistic regression modeling was used to compute crude and adjusted odds of genomic testing and receipt of endocrine therapy. RESULTS: Among a total sample size of 387,008 patients, 147,863 (38.2%) underwent genomic testing. Older age (≥ 70 years) was associated with a lower adjusted odd of genomic testing (OR 0.33; 95% CI 0.32-0.34, p = < 0.0001). Black patients had lower odds of receiving genomic testing on multivariate analysis compared to Whites (OR 0.82; 95% CI 0.80-0.85, p = < 0.0001). In patients who underwent a genomic test, compared to Whites, Blacks had a lower odds of receiving endocrine therapy (OR 0.86; 95% CI 0.80-0.93, p = < 0.0001) even if they did not receive adjuvant chemotherapy (OR 0.90; 95% CI 0.82-0.98, p = 0.014). CONCLUSIONS: In a national sample of breast cancer patients, Black women are less likely to get genomic testing and receive hormonal therapy, even when adjuvant chemotherapy is omitted. A priority in addressing breast cancer disparities is to ensure adherence to hormonal therapy among all women, including those who do not receive adjuvant chemotherapy.

Contralateral Prophylactic Mastectomy Use After Neoadjuvant Chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) for breast cancer increases breast-conserving surgery (BCS) rates, but many women opt for mastectomy with contralateral prophylactic mastectomy (CPM). Here we evaluate factors associated with CPM use in women undergoing mastectomy post-NAC. METHODS: A retrospective institutional NAC database review identified women with clinical stage I-III, unilateral invasive breast cancer undergoing unilateral mastectomy (UM) or CPM mastectomy from 9/2013 to 12/2017. Clinical/pathologic characteristics, imaging, and presence of contraindications to BCS post-NAC were compared, with subset analysis of BCS candidates. The multivariable analysis was adjusted for potential confounders. RESULTS: Five hundred sixty-nine women underwent mastectomy after NAC, 297 (52%) UM and 272 (48%) CPM. On univariable analysis, younger age, BRCA+, lower pre-NAC clinical stage, pathologic complete response, and axillary surgery extent were associated with CPM (all p < 0.01). Favorable post-NAC clinical factors of no residual palpable disease, clinically negative nodes, complete response on breast imaging, and no post-NAC contraindication to BCS were also associated with CPM (all p < 0.01). On multivariable analysis, young age (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.91-0.95), lower pre-NAC stage (OR 0.51, 95% CI 0.34-0.77), and no contraindication to BCS (OR 3.12, 95% CI 2.02-4.82) were significantly associated with CPM. Among the 203 (35%) women who had no contraindications to BCS post-NAC, 145 (71%) underwent CPM. BRCA+ and family history were reasons more frequently cited for mastectomy among CPM than UM (p < 0.001). CONCLUSIONS: CPM was performed in 48% of women undergoing mastectomy after NAC; younger women with earlier-stage cancers were more likely to undergo CPM. While increased use of CPM in women with more favorable disease is medically appropriate, our findings indicate a lost opportunity for use of BCS.

Provider-patient Language Discordance and Cancer Operations: Outcomes from a Single Center Linked to a State Vital Statistics Registry.

INTRODUCTION: Patterns of worldwide immigration have resulted in high rates of discordance between medical providers and the patients they treat. For example, in the USA, 25 million individuals in the USA self-identified that they speak English less than "very well." Previous studies have generated mixed results regarding differences in postoperative outcomes between English proficient (EP) and limited English proficient (LEP) patients. Our objective was to determine whether a difference in outcomes exists for non-English-speaking patients compared to English-speaking patients after operations commonly performed to treat cancer. STUDY DESIGN: A retrospective cohort study was performed in an urban, safety net and tertiary referral medical center over a five-year period. Adult patients undergoing cancer operations were stratified as EP and LEP. We evaluated 30-day revisit to the ED, length of stay (LOS), long-term all-cause mortality, and any major complication on index admission. Regression was used to adjust for baseline comorbidities, case risk, and socioeconomic factors. RESULTS: A total of 2467 patients were included. There was no difference in case risk between language groups, but EP had a larger proportion of high comorbidity scores. Patients in the non-English group were more likely to be uninsured/self-pay and live in neighborhoods with lower median income. After adjustment, we found no difference in long-term mortality [hazard ratio: 0.87 (95% CI 0.52-1.45)]. LEP patients had the same LOS compared to primary EP patients with an IRR of 0.99 (95% CI 0.88-1.10). There was no difference in the odds of revisit to hospital for LEP versus EP, with an OR of 1.08, 95% CI [0.75-1.53] and no difference in major complication (OR 0.76 (95% CI 0.39-1.45). CONCLUSIONS: We found no association between language and outcomes after cancer operations. This lack of difference may reflect local efficacy at treating non-English-speaking patients, and health systems with fewer services for LEP patients might show different results.

Novel structural features drive DNA binding properties of Cmr, a CRP family protein in TB complex mycobacteria.

Mycobacterium tuberculosis (Mtb) encodes two CRP/FNR family transcription factors (TF) that contribute to virulence, Cmr (Rv1675c) and CRPMt (Rv3676). Prior studies identified distinct chromosomal binding profiles for each TF despite their recognizing overlapping DNA motifs. The present study shows that Cmr binding specificity is determined by discriminator nucleotides at motif positions 4 and 13. X-ray crystallography and targeted mutational analyses identified an arginine-rich loop that expands Cmr's DNA interactions beyond the classical helix-turn-helix contacts common to all CRP/FNR family members and facilitates binding to imperfect DNA sequences. Cmr binding to DNA results in a pronounced asymmetric bending of the DNA and its high level of cooperativity is consistent with DNA-facilitated dimerization. A unique N-terminal extension inserts between the DNA binding and dimerization domains, partially occluding the site where the canonical cAMP binding pocket is found. However, an unstructured region of this N-terminus may help modulate Cmr activity in response to cellular signals. Cmr's multiple levels of DNA interaction likely enhance its ability to integrate diverse gene regulatory signals, while its novel structural features establish Cmr as an atypical CRP/FNR family member.