The Association between Oxaliplatin-Induced Peripheral Neuropathy, Sociodemographic, and Clinical Characteristics with Falls in Older Adults with Colorectal Cancer.

Our purpose was to investigate the associations between oxaliplatin-induced peripheral neuropathy (OIPN), sociodemographic, and clinical characteristics of older colorectal cancer patients with falls. The study population consisted of older adults diagnosed with colorectal cancer obtained from the Surveillance, Epidemiology, and End Results database combined with Medicare claims. OIPN was defined using specific (OIPN 1) and broader (OIPN 2) definitions of OIPN, based on diagnosis codes. Extensions of the Cox regression model to accommodate repeated events were used to obtain overall hazard ratios (HR) with 95% confidence intervals and the cumulative hazard of fall. The unadjusted risk of fall for colorectal cancer survivors with vs. without OIPN 1 at 36 months of follow-up was 19.6% vs. 14.3%, respectively. The association of OIPN with time to fall was moderate (OIPN 1, HR = 1.37, 95% CI: 1.04, 1.79) to small (OIPN 2, HR = 1.24, 95% CI: 1.01, 1.53). Memantine, opioids, cannabinoids, prior history of fall, female sex, advanced age and disease stage, chronic liver disease, diabetes, and chronic obstructive pulmonary disease all increased the hazard rate of fall. Incorporating fall prevention in cancer care is essential to minimize morbidity and mortality of this serious event in older colorectal cancer survivors.

The association between sociodemographic, clinical, and potentially preventive therapies with oxaliplatin-induced peripheral neuropathy in colorectal cancer patients.

PURPOSE: The purpose of this retrospective cohort study was to evaluate whether several potentially preventive therapies reduced the rate of oxaliplatin-induced peripheral neuropathy (OIPN) in colorectal cancer patients and to assess the relationship of sociodemographic/clinical factors with OIPN diagnosis. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results database combined with Medicare claims. Eligible patients were diagnosed with colorectal cancer between 2007 and 2015, ≥ 66 years of age, and treated with oxaliplatin. Two definitions were used to denote diagnosis of OIPN based on diagnosis codes: OIPN 1 (specific definition, drug-induced polyneuropathy) and OIPN 2 (broader definition, additional codes for peripheral neuropathy). Cox regression was used to obtain hazard ratios (HR) with 95% confidence intervals (CI) for the relative rate of OIPN within 2 years of oxaliplatin initiation. RESULTS: There were 4792 subjects available for analysis. At 2 years, the unadjusted cumulative incidence of OIPN 1 was 13.1% and 27.1% for OIPN 2. For both outcomes, no therapies reduced the rate of OIPN diagnosis. The anticonvulsants gabapentin and oxcarbazepine/carbamazepine were associated with an increased rate of OIPN (both definitions) as were increasing cycles of oxaliplatin. Compared to younger patients, those 75-84 years of age experienced a 15% decreased rate of OIPN. For OIPN 2, prior peripheral neuropathy and moderate/severe liver disease were also associated with an increased hazard rate. For OIPN 1, state buy-in health insurance coverage was associated with a decreased hazard rate. CONCLUSION: Additional studies are needed to identify preventive therapeutics for OIPN in cancer patients treated with oxaliplatin.

Characteristics Associated With Nonreceipt of Surveillance Testing and the Relationship With Survival in Stage II and III Colon Cancer.

We investigated characteristics of patients with colon cancer that predicted nonreceipt of posttreatment surveillance testing and the subsequent associations between surveillance status and survival outcomes. This was a retrospective cohort study of the Surveillance, Epidemiology, and End Results database combined with Medicare claims. Patients diagnosed between 2002 and 2009 with disease stages II and III and who were between 66 and 84 years of age were eligible. A minimum of 3 years' follow-up was required, and patients were categorized as having received any surveillance testing (any testing) versus none (no testing). Poisson regression was used to obtain risk ratios with 95% confidence intervals for the relative likelihood of No Testing. Cox models were used to obtain subdistribution hazard ratios with 95% confidence intervals for 5- and 10-year cancer-specific and noncancer deaths. There were 16,009 colon cancer cases analyzed. Patient characteristics that predicted No Testing included older age, Black race, stage III disease, and chemotherapy. Patients in the No Testing group had an increased rate of 10-year cancer death that was greater for patients with stage III disease (subdistribution hazard ratio = 1.79, 95% confidence interval: 1.48, 2.17) than those with stage II disease (subdistribution hazard ratio = 1.41, 95% confidence interval: 1.19, 1.66). Greater efforts are needed to ensure all patients receive the highest quality medical care after diagnosis of colon cancer.

Unplanned emergency department visits and hospital admissions of older adults under treatment for cancer in the ambulatory/community setting.

PURPOSE: This study aims to identify the incidence and risk/protective factors for (1) unplanned emergency department (ED) visits and hospital admissions (HA) and (2) nausea/vomiting/dehydration (NVD) at time of treatment in older adults under treatment for cancer. MATERIALS AND METHODS: This is a exploratory retrospective cohort study of adults (60 and older) with cancer. Adults were included if they had a new cancer diagnosis and were being treated with chemotherapy. Study outcomes included the number of ED visits and HA (cycles 1-4) and NVD at the time of receiving chemotherapy (cycles 2-4). Repeated measures, Poisson regression was used to obtain risk ratios with 95% confidence intervals for independent predictors of outcomes. RESULTS: Of 402 study participants, 20% experienced an ED visit, and 18% experienced a HA. Common reasons for ED visits were pain (23.5%) and NVD (20.4%). Common reasons for HA were infection (34.4%) and NVD (22.2%). Multivariate analysis showed risk factors for ED visits included chemotherapy cycle 1, having esophageal cancer, being treated with ≥ 3 chemotherapy agents, and increasing levels of functional impairment. Risk factors for HA included chemotherapy cycle 1, increasing levels of functional impairment, intravenous fluids between treatment, and being prescribed antiemetics for home use. Predictors of NVD at time of chemotherapy treatment included Hispanic ethnicity, insurance status, cancer type, chemotherapy emetic potent, treatment frequency, intravenous fluids between cycles, and number of home antiemetics. CONCLUSION: Unplanned ED visits and HA occur in older adults under treatment for cancer due to numerous treatment-related side effects. Helping older adults identify and manage side effects early may reduce the number of unplanned admissions.

Surveillance Colonoscopy in Older Stage I Colon Cancer Patients and the Association With Colon Cancer-Specific Mortality.

OBJECTIVES: Guideline-issuing groups differ regarding the recommendation that patients with stage I colon cancer receive surveillance colonoscopy after cancer-directed surgery. This observational comparative effectiveness study was conducted to evaluate the association between surveillance colonoscopy and colon cancer-specific mortality in early stage patients. METHODS: This was a retrospective cohort study of the Surveillance, Epidemiology, and End Results database combined with Medicare claims. Surveillance colonoscopy was assessed as a time-varying exposure up to 5 years after cancer-directed surgery with the following groups: no colonoscopy, one colonoscopy, and ≥ 2 colonoscopies. Inverse probability of treatment weighting was used to balance covariates. The time-dependent Cox regression model was used to obtain inverse probability of treatment weighting-adjusted hazard ratios (HRs), with 95% confidence intervals (CIs) for 5- and 10-year colon cancer, other cancer, and noncancer causes of death. RESULTS: There were 8,783 colon cancer cases available for analysis. Overall, compared with patients who received one colonoscopy, the no colonoscopy group experienced an increased rate of 10-year colon cancer-specific mortality (HR = 1.63; 95% CI 1.31-2.04) and noncancer death (HR = 1.36; 95% CI 1.25-1.49). Receipt of ≥ 2 colonoscopies was associated with a decreased rate of 10-year colon cancer-specific death (HR = 0.60; 95% CI 0.45-0.79), other cancer death (HR = 0.68; 95% CI 0.53-0.88), and noncancer death (HR = 0.69; 95% CI 0.62-0.76). Five-year cause-specific HRs were similar to 10-year estimates. DISCUSSION: These results support efforts to ensure that stage I patients undergo surveillance colonoscopy after cancer-directed surgery to facilitate early detection of new and recurrent neoplastic lesions.

The association between post-treatment surveillance testing and survival in stage II and III colon cancer patients: An observational comparative effectiveness study.

BACKGROUND: The best strategy for surveillance testing in stage II and III colon cancer patients following curative treatment is unknown. Previous randomized controlled trials have suffered from design limitations and yielded conflicting evidence. This observational comparative effectiveness research study was conducted to provide new evidence on the relationship between post-treatment surveillance testing and survival by overcoming the limitations of previous clinical trials. METHODS: This was a retrospective cohort study of the Surveillance, Epidemiology, and End Results database combined with Medicare claims (SEER-Medicare). Stage II and III colon cancer patients diagnosed from 2002 to 2009 and between 66 to 84 years of age were eligible. Adherence to surveillance testing guidelines-including carcinoembryonic antigen, computed tomography, and colonoscopy-was assessed for each year of follow-up and overall for up to three years post-treatment. Patients were categorized as More Adherent and Less Adherent according to testing guidelines. Patients who received no surveillance testing were excluded. The primary outcome was 5-year cancer-specific survival; 5-year overall survival was the secondary outcome. Inverse probability of treatment weighting (IPTW) using generalized boosted models was employed to balance covariates between the two surveillance groups. IPTW-adjusted survival curves comparing the two groups were performed by the Kaplan-Meier method. Weighted Cox regression was used to obtain hazard ratios (HRs) with 95% confidence intervals (CIs) for the relative risk of death for the Less Adherent group versus the More Adherent group. RESULTS: There were 17,860 stage II and III colon cancer cases available for analysis. Compared to More Adherent patients, Less Adherent patients experienced slightly better 5-year cancer-specific survival (HR = 0.83, 95% CI 0.76-0.90) and worse 5-year noncancer-specific survival (HR = 1.61, 95% CI 1.43-1.82) for years 2 to 5 of follow-up. There was no difference between the groups in overall survival (HR = 1.04, 95% CI 0.98-1.10). CONCLUSIONS: More surveillance testing did not improve 5-year cancer-specific survival compared to less testing and there was no difference between the groups in overall survival. The results of this study support a risk-stratified, shared decision-making surveillance strategy to optimize clinical and patient-centered outcomes for colon cancer patients in the survivorship phase of care.

Segmental Arterial Mediolysis: Abdominal Imaging of and Disease Course in 111 Patients.

OBJECTIVE: The purpose of this study is to identify the imaging characteristics of segmental arterial mediolysis (SAM) at presentation and establish the longitudinal course of disease. MATERIALS AND METHODS: We retrospectively identified patients with SAM at a single institution from 2000 through 2015. Diagnosis was based on published guidelines with multidisciplinary consensus. Imaging studies obtained at initial evaluation were reviewed to evaluate imaging findings and vascular territory distribution. All subsequent follow-up imaging studies were reviewed to assess for progression, stability, or regression. RESULTS: We identified 111 patients (79 men and 32 women; median age, 51 years) who met the diagnostic criteria for SAM. Abdominal pain was the most common presentation (74%), followed by flank pain (21%). SAM most commonly affected the renal arteries (47%), superior mesenteric artery (46%), celiac trunk (46%), hepatic artery (23%), iliac arteries (18%), and splenic artery (14%). The most common imaging findings were dissection (86%), aneurysm (57%), beading or webs (28%), occlusion (19%), and a rind or wall thickening (15%). The 247 available follow-up imaging studies for 97 patients (median follow-up, 12 months) showed progression in 19 patients (20%), with either stability or regression observed in the remaining patients. CONCLUSION: SAM most commonly affects the renal arteries, superior mesenteric artery, and celiac artery. Dissections and aneurysms are the most common imaging findings. Follow-up imaging studies show stability or regression in most patients.

Predictors of guideline treatment nonadherence and the impact on survival in patients with colorectal cancer.

BACKGROUND: This study investigated the effect of comorbidity, age, health insurance payer status, and race on the risk of patient nonadherence to NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon and Rectal Cancers. In addition, the prognostic impact of NCCN treatment nonadherence on overall survival was assessed. PATIENTS AND METHODS: Patients with CRC who received primary treatment at Memorial University Medical Center from 2003 to 2010 were eligible for this study. Modified Poisson regression was used to obtain risk ratios for the outcome of nonadherence with NCCN Guidelines. Hazard ratios (HRs) for the relative risk of death from all causes were obtained through Cox regression. RESULTS: Guideline-adherent treatment was received by 82.7% of patients. Moderate/severe comorbidity, being uninsured, having rectal cancer, older age, and increasing tumor stage were associated with increased risks of receiving nonadherent treatment. Treatment nonadherence was associated with 3.6 times the risk of death (HR, 3.55; 95% CI, 2.16-5.85) in the first year after diagnosis and an 80% increased risk of death (HR, 1.80; 95% CI, 1.14-2.83) in years 2 to 5. The detrimental effect of nonadherence declined with increasing comorbidity and varied according to age. CONCLUSIONS: Although medically justifiable reasons exist for deviating from NCCN Guidelines when treating patients with colorectal cancer (CRC), those who received nonadherent treatment had much higher risks of death, especially in the first year after diagnosis. This study's results highlight the importance of cancer health services research to drive quality improvement efforts in cancer care for patients with CRC.

Characteristics associated with breastfeeding behaviors among urban versus rural women enrolled in the Kansas WIC program.

The Special Supplemental Nutrition Program for Women, Infants and Children (WIC) is a public nutritional assistance program for low-income women and their children up to age five. This study provides insight into maternal characteristics associated with breastfeeding among urban versus rural women. A secondary analysis was conducted using the Pregnancy Nutrition Surveillance System dataset of women enrolled in the Kansas WIC program in 2011. Geographic residency status was obtained through application of the Census tract-based rural-urban commuting area codes. Descriptive variables included maternal demographics, health, and lifestyle behaviors. A multivariable binary logistic regression was used to obtain adjusted odds ratios with 95 % confidence intervals. The outcome variable was initiation of breastfeeding. A P value of ≤0.05 was considered statistically significant. The total sample size was 17,067 women. Statistically significant differences regarding socio-demographics, program participation, and health behaviors for urban and rural WIC participants were observed. About 74 % of all WIC mothers initiated breastfeeding. Urban women who were Hispanic, aged 18-19, high school graduates, household income >$10,000/year, and started early prenatal care were more likely to breastfeed. Urban and rural women who were non-Hispanic black with some high school education were less likely to breastfeed. Increased breastfeeding initiation rates are the result of a collaborative effort between WIC and community organizations. Availability of prenatal services to rural women is critical in the success of breastfeeding promotion. Findings help inform WIC program administrators and assist in enhancing breastfeeding services to the Kansas WIC population.

The effect of methodology in determining disparities in in-hospital mortality of trauma patients based on payer source.

A retrospective registry review of adult patients admitted to a Level I trauma center sought to determine whether results regarding in-hospital mortality associated with payer source vary on the basis of methodology. Patients were categorized into 4 literature-derived definitions (Definition 1: insured and uninsured; Definition 2: commercially insured, publicly insured, and uninsured; Definition 3: commercially insured, Medicaid, Medicare, and uninsured; and Definition 4: commercially insured, Medicaid, and uninsured). In-hospital mortality differences were found in Definitions 2 and 3, and when reclassifying dual-eligible Medicare/Medicaid into socioeconomic and age indicators. Variations in methodology culminated in results that could be interpreted with differing conclusions.

Geographic residency status and census tract socioeconomic status as determinants of colorectal cancer outcomes.

OBJECTIVES: We examined the impact of geographic residency status and census tract (CT)-level socioeconomic status (SES) on colorectal cancer (CRC) outcomes. METHODS: This was a retrospective cohort study of patients diagnosed with CRC in Georgia for the years 2000 through 2007. Study outcomes were late-stage disease at diagnosis, receipt of treatment, and survival. RESULTS: For colon cancer, residents of lower-middle-SES and low-SES census tracts had decreased odds of receiving surgery. Rural, lower-middle-SES, and low-SES residents had decreased odds of receiving chemotherapy. For patients with rectal cancer, suburban residents had increased odds of receiving radiotherapy, but low SES resulted in decreased odds of surgery. For survival, rural residents experienced a partially adjusted 14% (hazard ratio [HR] = 1.14; 95% confidence interval [CI] = 1.07, 1.22) increased risk of death following diagnosis of CRC that was somewhat explained by treatment differences and completely explained by CT-level SES. Lower-middle- and low-SES participants had an adjusted increased risk of death following diagnosis for CRC (lower-middle: HR = 1.16; 95% CI = 1.10, 1.22; low: HR = 1.24; 95% CI = 1.16, 1.32). CONCLUSIONS: Future efforts should focus on developing interventions and policies that target rural residents and lower SES areas to eliminate disparities in CRC-related outcomes.

Racial and Ethnic Variations in Pre-Diagnosis Comorbidity Burden and Health-Related Quality of Life Among Older Women with Breast Cancer.

BACKGROUND: This study examined racial/ethnic differences in comorbidity burden and health-related quality of life (HRQOL) among older women before breast cancer diagnosis. METHODS: From Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) linked data resource, 2513 women diagnosed with breast cancer at ≥ 65 years between 1998 and 2012 were identified and grouped based on comorbidity burden using latent class analysis. Pre-diagnosis HRQOL was measured using SF-36/VR-12 and summarized to physical (PCS) and mental component summary (MCS) scores. The adjusted least-square means and 95% confidence intervals were obtained according to comorbidity burden and race/ethnicity. The interactions were examined with 2-way ANOVA. RESULTS: The latent class analysis revealed four comorbid burden classes, with Class 1 being the most healthy and Class 4 being the least healthy. African American (AA) and Hispanic women were more likely to be in Class 4 than non-Hispanic white (NHW) women (18.6%, 14.8%, and 8.3%, respectively). The mean PCS was 39.3 and differed by comorbidity burden and race/ethnicity (Pinteraction < 0.001). There were no racial/ethnic differences in Classes 1 and 2, while NHW women reported significantly lower PCS scores than AA women in Classes 3 and 4. The mean MCS was 51.4 and differed by comorbidity burden and race/ethnicity (Pinteraction < 0.001). There was no racial/ethnic difference in Class 3; however, AA women reported lower MCS scores than Asian/Pacific Islander women in Class 1, and AA and Hispanic women reported lower MCS scores than NHW women in Classes 2 and 4. CONCLUSION: Comorbidity burden negatively affected HRQOL but differentially for racial/ethnic groups. As the comorbidity burden increases, NHW women are more concerned with physical HRQOL, while AA and Hispanic women are more concerned with mental HRQOL.

Association between adjuvant radiation treatment and breast cancer-specific mortality among older women with comorbidity burden: A comparative effectiveness analysis of SEER-MHOS.

BACKGROUND: The National Comprehensive Cancer Network suggested that older women with low-risk breast cancer (LRBC; i.e., early-stage, node-negative, and estrogen receptor-positive) could omit adjuvant radiation treatment (RT) after breast-conserving surgery (BCS) if they were treated with hormone therapy. However, the association between RT omission and breast cancer-specific mortality among older women with comorbidity is not fully known. METHODS: 1105 older women (≥65 years) with LRBC in 1998-2012 were queried from the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey data resource and were followed up through July 2018. Latent class analysis was performed to identify comorbidity burden classes. A propensity score-based inverse probability of treatment weighting (IPTW) was applied to Cox regression models to obtain subdistribution hazard ratios (HRs) and 95% CI for cancer-specific mortality considering other causes of death as competing risks, overall and separately by comorbidity burden class. RESULTS: Three comorbidity burden (low, moderate, and high) groups were identified. A total of 318 deaths (47 cancer-related) occurred. The IPTW-adjusted Cox regression analysis showed that RT omission was not associated with short-term, 5- and 10-year cancer-specific death (p = 0.202 and p = 0.536, respectively), regardless of comorbidity burden. However, RT omission could increase the risk of long-term cancer-specific death in women with low comorbidity burden (HR = 1.98, 95% CI = 1.17, 3.33), which warrants further study. CONCLUSIONS: Omission of RT after BCS is not associated with an increased risk of cancer-specific death and is deemed a reasonable treatment option for older women with moderate to high comorbidity burden.

Health insurance and neighborhood poverty as mediators of racial disparities in advanced disease stage at diagnosis and nonreceipt of surgery for women with breast cancer.

BACKGROUND: In our recent study, advanced disease stage and nonreceipt of surgery were the most important mediators of the racial disparity in breast cancer survival. The purpose of this study was to quantify the racial disparity in these two intermediate outcomes and investigate mediation by the more proximal mediators of insurance status and neighborhood poverty. METHODS: This was a cross-sectional study of non-Hispanic Black and non-Hispanic White women diagnosed with first primary invasive breast cancer in Florida between 2004 and 2015. Log-binomial regression was used to obtain prevalence ratios (PR) with 95% confidence intervals (CIs). Multiple mediation analysis was used to assess the role of having Medicaid/being uninsured and living in high-poverty neighborhoods on the race effect. RESULTS: There were 101,872 women in the study (87.0% White, 13.0% Black). Black women were 55% more likely to be diagnosed with advanced disease stage at diagnosis (PR, 1.55; 95% CI, 1.50-1.60) and nearly twofold more likely to not receive surgery (PR, 1.97; 95% CI, 1.90-2.04). Insurance status and neighborhood poverty explained 17.6% and 5.3% of the racial disparity in advanced disease stage at diagnosis, respectively; 64.3% remained unexplained. For nonreceipt of surgery, insurance status explained 6.8% while neighborhood poverty explained 3.2%; 52.1% was unexplained. CONCLUSIONS: Insurance status and neighborhood poverty were significant mediators of the racial disparity in advanced disease stage at diagnosis with a smaller impact on nonreceipt of surgery. However, interventions designed to improve breast cancer screening and receipt of high-quality cancer treatment must address additional barriers for Black women with breast cancer.

Multi-Modal Neurorehabilitation for Persisting Post-Concussion Symptoms.

Treatment of the chronic sequela that persist after a mild traumatic brain injury has been challenging with limited efficacy. The aim of this work was to report outcomes obtained from persons who met the criteria of persisting post-concussive symptoms (PPCS), utilizing a novel combination of modalities in a structured neurorehabilitation program. This work was designed as a retrospective, pre-post chart review of objective and subjective measures collected from 62 outpatients with PPCS a mean of 2.2 years post-injury, before and after a multi-modal 5-day treatment protocol. The subjective outcome measure was the 27-item modified Graded Symptom Checklist (mGSC). Objective outcome measures were motor speed/reaction time, coordination, cognitive processing, visual acuity, and vestibular function. Interventions included non-invasive neuromodulation, neuromuscular re-education exercises, gaze stabilization exercises, orthoptic exercises, cognitive training, therapeutic exercises, and single/multi-axis rotation therapy. Pre-post differences in measures were analyzed using the Wilcoxon signed-rank test, with effect size determined by the rank-biserial correlation coefficient. Pre-post treatment comparisons for the subjective mGSC overall, combined symptom measures, individual components of the mGSC, and cluster scores significantly improved for all items. Moderate strength relationships were observed for the mGSC composite score, number of symptoms, average symptom score, feeling in a "fog," "don't feel right," irritability, and physical, cognitive, and affective cluster scores. Objective symptom assessment significantly improved for trail making, processing speed, reaction time, visual acuity, and Standardized Assessment of Concussion. Patients suffering from PPCS ∼2 years after injury may have significant benefits with some moderate effect sizes from an intensive, multi-modal neurorehabilitation program.

Disparities in late stage diagnosis, treatment, and breast cancer-related death by race, age, and rural residence among women in Georgia.

The objectives of this study were to examine the outcomes of late stage breast cancer diagnosis, receiving first course treatment, and breast cancer-related death by race, age, and rural/urban residence in Georgia. The authors used cross-sectional and follow-up data (1992-2007) for Atlanta and Rural Georgia cancer registries that are part of the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (N = 23,500 incident breast cancer cases in non-Hispanic whites or non-Hispanic African Americans). Multilevel modeling and Cox proportional hazard models revealed that compared to whites, African American women had significantly increased odds of late stage diagnosis (odds ratio [OR] = 2.08, p = 0.0001) and unknown tumor stage (OR = 1.27, p = 0.0001), decreased odds of receiving radiation (OR = 0.93, p = 0.041) or surgery (OR = 0.50, p = 0.0001), and increased risk of death following breast cancer diagnosis (hazard rate ratio [HR] = 1.50, p = 0.0001). Increased age was significantly associated with the odds of late/unknown stage at diagnosis, worse treatment, and survival. Women residing in rural areas had significantly decreased odds of receiving radiation and surgery with radiation (OR = 0.59, p = 0.0001), and for receiving breast-conserving surgery compared to mastectomy (OR = 0.73, p = 0.005). Factors affecting each level of the breast cancer continuum are distinct and should be examined separately. Efforts are needed to alleviate disparities in breast cancer outcomes in hard-to-reach populations.

Multiple mediation analysis of racial disparity in breast cancer survival.

BACKGROUND: Racial (Black vs. White) disparities in breast cancer survival have proven difficult to mitigate. Targeted strategies aimed at the primary factors driving the disparity offer the greatest potential for success. The purpose of this study was to use multiple mediation analysis to identify the most important mediators of the racial disparity in breast cancer survival. METHODS: This was a retrospective cohort study of non-Hispanic Black and non-Hispanic White women diagnosed with invasive breast cancer in Florida between 2004 and 2015. Cox regression was used to obtain unadjusted and adjusted hazard ratios (HR) with 95% confidence intervals (CI) for the association of race with 5- and 10-year breast cancer death. Multiple mediation analysis of tumor (advanced disease stage, tumor grade, hormone receptor status) and treatment-related factors (receipt of surgery, chemotherapy, radiotherapy, and hormone therapy) was used to determine the most important mediators of the survival disparity. RESULTS: The study population consisted of 101,872 women of whom 87.0% (n = 88,617) were White and 13.0% were Black (n = 13,255). Black women experienced 2.3 times (HR, 2.27; 95% CI, 2.16-2.38) the rate of 5-year breast cancer death over the follow-up period, which decreased to a 38% increased rate (HR, 1.38; 95% CI, 1.31-1.45) after adjustment for age and the mediators of interest. Combined, all examined mediators explained 73% of the racial disparity in 5-year breast cancer survival. The most important mediators were: (1) advanced disease stage (44.8%), (2) nonreceipt of surgery (34.2%), and (3) tumor grade (18.2%) and hormone receptor status (17.6%). Similar results were obtained for 10-year breast cancer death. CONCLUSION: These results suggest that additional efforts to increase uptake of screening mammography in hard-to-reach women, and, following diagnosis, access to and receipt of surgery may offer the greatest potential to reduce racial disparities in breast cancer survival for women in Florida.

Disruption of the NHR4 domain structure in AML1-ETO abrogates SON binding and promotes leukemogenesis.

AML1-ETO is generated from t(8;21)(q22;q22), which is a common form of chromosomal translocation associated with development of acute myeloid leukemia (AML). Although full-length AML1-ETO alone fails to promote leukemia because of its detrimental effects on cell proliferation, an alternatively spliced isoform, AML1-ETO9a, without its C-terminal NHR3/NHR4 domains, strongly induces leukemia. However, full-length AML1-ETO is a major form of fusion product in many t(8;21) AML patients, suggesting additional molecular mechanisms of t(8;21)-related leukemogenesis. Here, we report that disruption of the zinc-chelating structure in the NHR4 domain of AML1-ETO by replacing only one critical amino acid leads to rapid onset of leukemia, demonstrating that the NHR4 domain with the intact structure generates inhibitory effects on leukemogenesis. Furthermore, we identified SON, a DNA/RNA-binding domain containing protein, as a novel NHR4-interacting protein. Knock-down of SON by siRNA resulted in significant growth arrest, and disruption of the interaction between AML1-ETO and endogenous SON rescued cells from AML1-ETO-induced growth arrest, suggesting that SON is an indispensable factor for cell growth, and AML1-ETO binding to SON may trigger signals inhibiting leukemogenesis. In t(8;21) AML patient-derived primary leukemic cells and cell lines, abnormal cytoplasmic localization of SON was detected, which may keep cells proliferating in the presence of full-length AML1-ETO. These results uncovered the crucial role of the NHR4 domain in determination of cellular fate during AML1-ETO-associated leukemogenesis.

Trends in Breast Cancer Survival by Race-Ethnicity in Florida, 1990-2015.

BACKGROUND: This study was conducted to evaluate trends in survival, by race-ethnicity, for women diagnosed with breast cancer in Florida over a 26-year period. METHODS: This was a retrospective cohort study of women diagnosed with invasive breast cancer in Florida between 1990 and 2015. Data were obtained from the Florida Cancer Data System. Women in the study were categorized according to race (white/black) and Hispanic ethnicity (yes/no). Cumulative incidence estimates of 5- and 10-year breast cancer-related death with 95% confidence intervals (CI) were obtained by race-ethnicity, according to diagnosis year. Subdistribution hazard models were used to obtain subdistribution HRs (sHR) for the relative rate of breast cancer death accounting for competing causes. RESULTS: Breast cancer mortality decreased for all racial-ethnic groups, and racial-ethnic minorities had greater absolute and relative improvement for nearly all metrics compared with non-Hispanic white (NHW) women. However, for the most recent time period (2010-2015), black women still experienced significant survival disparities with non-Hispanic black (NHB) women, having twice the rate of 5-year [sHR = 2.04; 95% confidence interval (CI), 1.91-2.19] and 10-year (sHR = 2.02; 95% CI, 1.89-2.16) breast cancer-related death. Adjustment for covariates substantially reduced the excess rate of breast cancer-related death for black women. CONCLUSIONS: Despite efforts to improve disparities in breast cancer outcomes for underserved women in Florida, black women continue to experience significant survival disparities. IMPACT: These results highlight the need for targeted approaches to eliminate disparities in breast cancer survival for black women.