Adjuvant tamoxifen adherence in men with early-stage breast cancer.

BACKGROUND: Most breast cancers (BCs) in men are hormone receptor-positive. Adjuvant tamoxifen is part of the standard treatment of these patients. Small, single-institution studies have suggested that men have high rates of discontinuing adjuvant endocrine treatment. The authors examined rates of tamoxifen discontinuation and medication adherence in a large population-based cohort of male patients with BC. METHODS: In the Surveillance, Epidemiology, and End Results-Medicare database, male patients with invasive nonmetastatic BC, diagnosed between 2007 and 2013, who were ≥65 years old, had Part D coverage, and had tamoxifen prescriptions within 1 year of diagnosis were identified. Adherence was defined as a medication possession ratio of ≥80% among those patients who were filling tamoxifen prescriptions. Logistic regression model was used to assess predictors of tamoxifen adherence. RESULTS: A total of 451 patients met eligibility criteria. The median age at diagnosis was 75 years. The median follow-up was 32.5 months. The rates of tamoxifen discontinuation were 15.8%, 24.3%, 31.3%, 36.9%, and 48.3% at 1, 2, 3, 4, and 5 years after diagnosis, respectively. Among the men who were still taking tamoxifen, the corresponding adherence rates were 76.9%, 73.6%, 68.7%, 64.8%, and 60.2%. In the adjusted model, significant predictors of lower adherence included residing in a high poverty area (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.28-2.12) and a Charlson comorbidity score of ≥2 (OR, 0.46; 95% CI, 0.22-0.97). CONCLUSION: Older men with breast cancer have high rates of tamoxifen discontinuation, with 48% of all patients discontinuing tamoxifen before the end of year 5. Additionally, even among those patients continuing tamoxifen, a substantial number of patients are nonadherent. Further research should evaluate potentially modifiable reasons for treatment discontinuation and lack of adherence to tamoxifen.

Variation in Use of High-Cost Technologies for Palliative Radiation Therapy by Radiation Oncologists.

BACKGROUND: Understanding the sources of variation in the use of high-cost technologies is important for developing effective strategies to control costs of care. Palliative radiation therapy (RT) is a discretionary treatment and its use may vary based on patient and clinician factors. METHODS: Using data from the SEER-Medicare linked database, we identified patients diagnosed with metastatic lung, prostate, breast, and colorectal cancers in 2010 through 2015 who received RT, and the radiation oncologists who treated them. The costs of radiation services for each patient over a 90-day episode were calculated, and radiation oncologists were assigned to cost quintiles. The use of advanced technologies (eg, intensity-modulated radiation, stereotactic RT) and the number of RT treatments (eg, any site, bone only) were identified. Multivariable random-effects models were constructed to estimate the proportion of variation in the use of advanced technologies and extended fractionation (>10 fractions) that could be explained by patient fixed effects versus physician random effects. RESULTS: We identified 37,361 patients with metastatic lung cancer, 3,684 with metastatic breast cancer, 5,323 with metastatic prostate cancer, and 8,726 with metastatic colorectal cancer, with 34%, 27%, 22%, and 9% receiving RT within the first year, respectively. The use of advanced technologies and extended fractionation was associated with higher costs of care. Compared with the patient case-mix, physician variation accounted for a larger proportion of the variation in the use of advanced technologies for palliative RT and the use of extended fractionation. CONCLUSIONS: Differences in radiation oncologists' practice and choices, rather than differences in patient case-mix, accounted for a greater proportion of the variation in the use of advanced technologies and high-cost radiation services.

Comparative Analysis of Proposed Strategies for Incorporating Biologic Factors into Breast Cancer Staging.

BACKGROUND: Tumor biology is an important prognostic factor in breast cancer. This study aimed to compare three staging systems incorporating both biologic factors and anatomic staging (AJCC 8th-edition pathologic prognostic staging, Bioscore, and Risk Score) in a large population-based cohort. METHODS: The Surveillance, Epidemiology and End Results program was used to select patients with primary stages 1-4 breast cancer diagnosed in 2010. Patients with inflammatory carcinoma, those with missing data for biologic factors, and those with stages 1-3 disease not treated with surgery were excluded from the study. Estimates of 5-year disease-specific survival (DSS) were calculated using the Kaplan-Meier method. The Harrel concordance index (C-index) and the Akaike Information Criterion were used to compare each model in terms of predicting DSS. RESULTS: The study included 21,901 patients with a median age of 60 years. The median follow-up period was 52 months. All the staging models stratified DSS, with a stepwise decrease in DSS for each increase in risk category or score. The C-index of each model incorporating biologic factors was higher than the C-index for anatomic staging alone (C-index: 0.832 vs. 0.856 for AJCC pathologic prognostic staging, 0.856 for Bioscore, and 0.864 for Risk Score, all p < 0.001). The staging systems incorporating biologic factors did not differ significantly in terms of model fit. CONCLUSION: Staging systems incorporating biologic factors perform better than anatomic staging alone. Implementation of the AJCC 8th-edition pathologic prognostic staging was an important initial step in the inclusion of tumor biology in staging. Given its simplicity and ease of use, the Risk Score should be given consideration as an alternative staging system.

How we use hospice: Hospice enrollment patterns and costs in elderly ovarian cancer patients.

OBJECTIVE: To describe disparities in patterns of hospice use and end-of-life costs among ovarian cancer patients. METHODS: Using Texas Cancer Registry-Medicare data, ovarian cancer patients deceased 2005-2012 with >12 months of continuous Medicare coverage before death were included. Descriptive statistics and multivariable logistic regressions were used to evaluate patterns of hospice use. Cost and resource utilization was obtained from Medicare claims and analyzed using a non-parametric Mann-Whitney test. RESULTS: 2331 patients were assessed: 1788 (77%) white, 359 (15%) Hispanic, 158 (7%) black and 26 (1%) other. 1756 (75%) enrolled in hospice prior to death but only 1580 (68%) died with hospice. 176 (10%) of 1756 patients unenrolled and died without hospice. 346 (20%) unenrolled from hospice multiple times. From 2008 to 2012, patients were less likely to unenroll from hospice prior to death. Black patients were more likely to unenroll from hospice prior to death (OR 2.07 [1.15-3.73]; p = 0.02) compared to white patients. The median amount paid by Medicare during the last six months of life was $38,530 for those in hospice compared to $49,942 if never enrolled in hospice (p < 0.0001) and was higher for black and Hispanic patients compared to white patients. 30% hospice unenrolled patients and 40% multiply enrolled hospice patients received at least one life extending or invasive care procedure following unenrollment from hospice. CONCLUSION: Recently, more patients remain enrolled in hospice, but black patients have a higher risk of unenrollment. Hospice enrollment was associated with lower costs as long as a patient did not unenroll from hospice.

Hospitalization by cytotoxic chemotherapy regimen among older women with stage IV breast cancer.

BACKGROUND: Older patients with cancer are at risk for increased side effects of treatment. Our goal was to inform treatment for older patients by analyzing the relationship between chemotherapy regimen and hospitalization among older women receiving palliative cytotoxic chemotherapy for breast cancer. METHOD: We identified women aged 66-99 years with stage IV de novo breast cancer diagnosed between 2010 and 2013 who received any of the 10 most common cytotoxic chemotherapy-containing regimens in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The primary outcome was hospitalization or death within 30 days of starting a new line of chemotherapy. Generalized linear mixed effects models with patient-specific random effects were used for multivariable analysis of the association between chemotherapy regimen and this outcome. Additional covariates included number of prior lines of therapy; time since diagnosis; hormone receptor and HER2 status; sites of metastatic disease; and age, race, and marital status. The unit of analysis was each new line of chemotherapy. RESULTS: Of 972 lines of chemotherapy initiated among 693 patients, 188 (19%) were followed by hospitalization or death within 30 days. After adjustment, there was significant variation in this outcome by chemotherapy regimen (P = .03); compared with capecitabine, hospitalization/death rates were higher with cyclophosphamide + docetaxel (odds ratio [OR], 2.71; 95% confidence interval [CI], 1.31-5.59), cyclophosphamide + doxorubicin (OR, 2.45; 95% CI, 1.19-5.03), docetaxel (OR, 2.49; 95% CI, 1.19-5.21), and gemcitabine (OR, 3.51; 95% CI, 1.72-7.19). CONCLUSION: Treatment regimen was associated with significant variation in 30-day hospitalization or death among older women receiving cytotoxic chemotherapy for stage IV de novo breast cancer.

Acute myeloid leukemia and myelodysplastic syndrome after adjuvant chemotherapy: A population-based study among older breast cancer patients.

BACKGROUND: Chemotherapy for early breast cancer is associated with a small risk of developing myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). The aim of this study was to determine the risk of developing AML or MDS after modern adjuvant chemotherapy in older breast cancer patients and to further define the risk of individual chemotherapy regimens. METHODS: Patients diagnosed with stage I to III breast cancer from 2003 to 2009 were identified in the Surveillance, Epidemiology, and End Results-Medicare and Texas Cancer Registry-Medicare linked databases. The development of AML/MDS, chemotherapy use, and comorbidities were identified with International Classification of Diseases, Ninth Revision and Healthcare Common Procedure Coding System codes. Analyses included descriptive statistics, cumulative incidences, and Cox proportional hazards models to estimate the hazard of AML/MDS after adjustments for clinically relevant covariates. RESULTS: In all, 92,110 patients were included; after a median follow-up of 85 months, the overall rates per 1000 person-years were 0.65 for AML and 1.56 for MDS. Patients who received an anthracycline (A) or anthracycline and taxane (A+T) regimen were more likely to develop AML (hazard ratio [HR] for A, 1.70; 95% confidence interval [CI], 1.16-2.50; HR for A+T, 1.68; 95% CI, 1.22-2.30) or MDS (HR for A, 2.18; 95% CI, 1.70-2.80; HR for A+T, 1.62; 95% CI, 1.29-2.03) than patients who did not receive chemotherapy. Patients using docetaxel and cyclophosphamide (TC) were not at increased risk for AML or MDS. CONCLUSIONS: Adjuvant chemotherapy is associated with a small but significant increase in the risk of AML and MDS, especially with regimens that include A. Longer follow-up is needed to confirm that risk is not increased with the recently adopted TC regimen. Cancer 2018;124:899-906. © 2017 American Cancer Society.

Adherence to treatment guidelines and survival for older patients with stage II or III colon cancer in Texas from 2001 through 2011.

BACKGROUND: Treatment guidelines for colon cancer recommend colectomy with lymphadenectomy of at least 12 lymph nodes for patients with stage I to stage III disease as surgery adherence (SA) and adjuvant chemotherapy for individuals with stage III disease. Herein, the authors evaluated adherence to these guidelines among older patients in Texas with colon cancer and the associated survival outcomes. METHODS: Using Texas Cancer Registry data linked with Medicare data, the authors included patients with AJCC stage II and III colon cancer who were aged ≥66 years and diagnosed between 2001 and 2011. SA and adjuvant chemotherapy adherence rates to treatment guidelines were estimated. The chi-square test, general linear regression, survival probability, and Cox regression were used to identify factors associated with adherence and survival. RESULTS: The rate of SA increased from 47.2% to 84% among 6029 patients with stage II or stage III disease from 2001 to 2011, and the rate of adjuvant chemotherapy increased from 48.9% to 53.1% for patients with stage III disease during the same time period. SA was associated with marital status, tumor size, surgeon specialty, and year of diagnosis. Patient age, sex, marital status, Medicare state buy-in status, comorbidity status, and year of diagnosis were found to be associated with adjuvant chemotherapy. The 5-year survival probability for patients receiving guideline-concordant treatment was the highest at 87% for patients with stage II disease and was 73% for those with stage III disease. After adjusting for demographic and tumor characteristics, improved cancer cause-specific survival was associated with the receipt of stage-specific, guideline-concordant treatment for patients with stage II or stage III disease. CONCLUSIONS: The adherence to guideline-concordant treatment among older patients with colon cancer residing in Texas improved over time, and was associated with better survival outcomes. Future studies should be focused on identifying interventions to improve guideline-concordant treatment adherence. Cancer 2018;124:679-87. © 2017 American Cancer Society.

Genome-wide identification of genes probably relevant to the adaptation of schizothoracins (Teleostei: Cypriniformes) to the uplift of the Qinghai-Tibet Plateau.

BACKGROUND: Molecular adaptation to the severe environments present during the uplift of the Qinghai-Tibet Plateau has attracted the attention of researchers. The divergence of the three specialization groups of schizothoracins (Primitive, Specialized and Highly Specialized) may correspond to the three phases of plateau uplift. Based on the transcripts of representative species of the three specialized groups and an outgroup, genes in schizothoracins that may have played important roles during the adaptation to new environments were investigated. RESULTS: The contigs of Gymnodiptychus dybowskii and Schizothorax pseudaksaiensis were compared with those of Gymnocypris przewalskii ganzihonensis and the outgroup Sinocyclocheilus angustiporus, and 5,894 ortholog groups with an alignment length longer than 90 nt after deleting gaps were retained. Evolutionary analyses indicated that the average evolutionary rate of the branch leading to the Specialized group was faster than that of the branch leading to the Highly Specialized group. Moreover, the numbers of gene categories in which more than half of the genes evolved faster than the average values of the genome were 117 and 15 along the branches leading to the Specialized and Highly Specialized groups, respectively. A total of 40, 36, and 55 genes were likely subject to positive selection along the branches leading to the Primitive, Specialized and Highly Specialized groups, respectively, and many of these genes are likely relevant to adaptation to the cold temperatures, low oxygen concentrations, and strong ultraviolet radiation that result from elevation. CONCLUSIONS: By selecting representative species of the three groups of schizothoracins and applying next-generation sequencing technology, several candidate genes corresponding to adaptation to the three phases of plateau uplift were identified. Some of the genes identified in this report that were likely subject to positive selection are good candidates for subsequent evolutionary and functional analyses of adaptation to high altitude.

Estimating regimen-specific costs of chemotherapy for breast cancer: Observational cohort study.

BACKGROUND: One goal for high-quality patient care is communicating treatment costs to patients, yet cost information can be elusive. This is especially relevant for breast cancer care, for which numerous guideline-concordant adjuvant chemotherapy regimens exist. The objective of the current study was to generate cost estimates for such regimens from payers' and patients' perspectives in a large, insured US population. METHODS: Adult women who had incident breast cancer diagnosed between 2008 and 2012 (from the MarketScan database), had no secondary malignancy within 1 year of diagnosis, and received chemotherapy within 3 months of diagnosis were included (n = 14,643). Total and out-of-pocket costs were calculated using all claims within 18 months of diagnosis and were normalized to 2013 US dollars. The extended estimating equations method was used to assess cost by regimen adjusting for demographic and clinical factors. RESULTS: Among patients who did and did not receive trastuzumab, the median insurance payments were $160,590 and $82,260, respectively, and the median out-of-pocket payments were $3381 and $2724, respectively. Among patients who did not receive trastuzumab, 25% paid more than $4712, and 10% of patients paid more than $7041. For patients who did receive trastuzumab, 25% paid more than $5604, and 10% paid more than $8384. Among patients who were covered by high-deductible health plans, the median out-of-pocket cost was $5158, 25% paid at least $8128, and 10% paid ≥ $11,344. CONCLUSIONS: The costs of breast cancer chemotherapy vary widely across regimens, and patients bear a substantial out-of-pocket burden. Cancer 2016;122:3447-3455. © 2016 American Cancer Society.

Acceptability of Personalized Lung Cancer Screening Program Among Primary Care Providers.

Current lung cancer screening (LCS) guidelines rely on age and smoking history. Despite its benefit, only 5%-15% of eligible patients receive LCS. Personalized screening strategies select individuals based on their lung cancer risk and may increase LCS's effectiveness. We assess current LCS practices and the acceptability of personalized LCS among primary care providers (PCP) in Texas. We surveyed 32,983 Texas-based PCPs on an existing network (Protocol 2019-1257; PI: Dr. Shete) and 300 attendees of the 2022 Texas Academy of Family Physicians (TAFP) conference. We analyzed the responses by subgroups of interest. Using nonparametric bootstrap, we derived an enriched dataset to develop logistic regression models to understand current LCS practices and acceptability of personalized LCS. Response rates were 0.3% (n = 91) and 15% (n = 60) for the 2019-1257 and TAFP surveys, respectively. Most (84%) respondents regularly assess LCS in their practice. Half of the respondents were interested in adopting personalized LCS. The majority (66%) of respondents expressed concerns regarding time availability with the personalized LCS. Most respondents would use biomarkers as an adjunct to assess eligibility (58%), or to help guide indeterminate clinical findings (63%). There is a need to enhance the engagement of Texas-based PCPs in LCS. Most of the respondents expressed interest in personalized LCS. Time availability was the main concern related to personalized LCS. Findings from this project highlight the need for better education of Texas-based PCPs on the benefits of LCS, and the development of efficient decision tools to ensure successful implementation of personalized LCS. PREVENTION RELEVANCE: Personalized LCS facilitated by a risk model and/or a biomarker test is proposed as an alternative to existing programs. Acceptability of personalized approach among PCPs is unknown. The goal of this study is to assess the acceptability of personalized LCS among PCPs.

Estimating sojourn time and sensitivity of screening for ovarian cancer using a Bayesian framework.

BACKGROUND: Ovarian cancer is among the leading causes of gynecologic cancer-related death. Past ovarian cancer screening trials using combination of cancer antigen 125 testing and transvaginal ultrasound failed to yield statistically significant mortality reduction. Estimates of ovarian cancer sojourn time-that is, the period from when the cancer is first screen detectable until clinical detection-may inform future screening programs. METHODS: We modeled ovarian cancer progression as a continuous time Markov chain and estimated screening modality-specific sojourn time and sensitivity using a Bayesian approach. Model inputs were derived from the screening arms (multimodal and ultrasound) of the UK Collaborative Trial of Ovarian Cancer Screening and the Prostate, Lung, Colorectal and Ovarian cancer screening trials. We assessed the quality of our estimates by using the posterior predictive P value. We derived histology-specific sojourn times by adjusting the overall sojourn time based on the corresponding histology-specific survival from the Surveillance, Epidemiology, and End Results Program. RESULTS: The overall ovarian cancer sojourn time was 2.1 years (posterior predictive P value = .469) in the Prostate, Lung, Colorectal and Ovarian studies, with 65.7% screening sensitivity. The sojourn time was 2.0 years (posterior predictive P value = .532) in the United Kingdom Collaborative Trial of Ovarian Cancer Screening's multimodal screening arm and 2.4 years (posterior predictive P value = .640) in the ultrasound screening arm, with sensitivities of 93.2% and 64.5%, respectively. Stage-specific screening sensitivities in the Prostate, Lung, Colorectal and Ovarian studies were 39.1% and 82.9% for early-stage and advanced-stage disease, respectively. The histology-specific sojourn times ranged from 0.8 to 1.8 years for type II ovarian cancer and 2.9 to 6.6 years for type I ovarian cancer. CONCLUSIONS: Annual screening is not effective for all ovarian cancer subtypes. Screening sensitivity for early-stage ovarian cancers is not sufficient for substantial mortality reduction.

Personal history of cancer as a risk factor for second primary lung cancer: Implications for lung cancer screening.

BACKGROUND: Personal history of cancer is an independent risk factor for lung cancer but is omitted from existing lung cancer screening eligibility criteria. In this study, we assess the lung cancer risk among cancer survivors and discuss potential implications for screening. METHODS: This was a retrospective, secondary analysis of data from the Surveillance, Epidemiology and End Results (SEER) registry and the MD Anderson Cancer Center (MDACC). We estimated the standardized incidence ratios (SIRs) for lung cancer by site of first primary cancer using data from SEER. We assessed the lung cancer risk among head and neck cancer survivors from MDACC using cumulative incidence and compared the risk ratios (RR) by individuals' screening eligibility status. RESULTS: Other than first primary lung cancer (SIR: 5.10, 95% CI: 5.01-5.18), cancer survivors in SEER with personal history of head and neck cancer (SIR: 3.71, 95% CI: 3.63-3.80) had the highest risk of developing second primary lung cancer, followed by bladder (SIR: 1.86, 95% CI: 1.81-1.90) and esophageal cancers (SIR: 1.78, 95% CI: 1.61-1.96). Head and neck cancer survivors had higher risk to develop lung cancer compared to the National Lung Screening Trial's subjects, (781 vs. 572 per 100,000 person-years, respectively). Head and neck cancer survivors ineligible for lung cancer screening seen at MDACC had significantly higher lung cancer risk than head and neck cancer survivors from SEER (RR: 1.9, p < 0.001). CONCLUSION: Personal history of cancer, primarily head and neck cancer, is an independent risk factor for lung cancer and may be considered as an eligibility criterion in future lung cancer screening recommendations.

Surgical Approach and Persistent Opioid Use in Medicare Patients Undergoing Lung Cancer Resection.

BACKGROUND: Robotic and video-assisted thoracoscopic surgery (VATS) approaches for lung resection are associated with decreased inpatient opioid use compared with open surgery. Whether these approaches affect outpatient persistent opioid use remains unknown. METHODS: Non-small cell lung cancer patients aged 66 years or more who underwent lung resection between 2008 and 2017 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Persistent opioid use was defined as filling an opioid prescription 3 to 6 months after lung resection. Adjusted analyses were performed to evaluate surgical approach and persistent opioid use. RESULTS: We identified 19,673 patients: 7479 (38%) underwent open surgery, 10,388 (52.8%) VATS, and 1806 (9.2%) robotic surgery. Persistent opioid use was 38% in the entire cohort, including 27% of opioid naïve patients, and highest after open surgery (42.5%), followed by VATS (35.3%) and robotic (33.1%, P < .001). In multivariable analyses, robotic (odds ratio 0.84; 95% CI, 0.72-0.98; P = .028) and VATS (odds ratio 0.87; 95% CI, 0.79-0.95; P = .003) approaches were both associated with decreased persistent opioid use compared with open surgery in opioid naïve patients. At 12 months, patients resected using a robotic approach had the lowest oral morphine equivalent per month compared with VATS (133 vs 160, P < .001) and open surgery (133 vs 200, P < .001). Among chronic opioid patients, surgical approach was not associated with postoperative opioid use. CONCLUSIONS: Persistent opioid use after lung resection is common. Both robotic and VATS approaches were associated with decreased persistent opioid use compared with open surgery among opioid naïve patients. Whether a robotic approach yields additional long-term advantages over VATS warrants further investigation.

The complete mitochondrial genome of Schizothorax eurystomus Kessler, 1872 (Cypriniformes, Cyprinidae).

Schizothorax eurystomus, Kessler 1872 is a unique economic fish in Xinjiang, China that is rarely seen in the market. Next-generation sequencing (NGS) was used to determine the complete mitochondrial genome of S. eurystomus collected from the Yarkand River in Xinjiang. The results showed that the mitochondrial genome is a circular, 16,488-bp-long nucleotide with the typical vertebrate genome structure of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a control region. The termination-associated sequence (TAS), central conserved sequence block (CSB), and conserved sequence block were detected in the control region. Phylogenetic analysis placed S. eurystomus in a fully supported clade with S. biddulphi, and that clade was sister to S. yunnanensis. To our knowledge, this is the first study on the complete mitochondrial genome of S. eurystomus from the Yarkand River in Xinjiang, and it provides baseline genetic information for future studies.

Chromosomal-scale genome assembly of the near-extinction big-head schizothorcin (Aspiorhynchus laticeps).

The big-head schizothorcin (Aspiorhynchus laticeps) is an endemic and near-extinction freshwater fish in Xinjiang, China. In this study, a chromosome-scale genome assembly of A. laticeps was generated using PacBio and Hi-C techniques. The PacBio sequencing data resulted in a 1.58 Gb assembly with a contig N50 of 1.27 Mb. Using Hi-C scaffolding approach, 88.38% of the initial assembled sequences were anchored and oriented into a chromosomal-scale assembly. The final assembly consisted of 25 pseudo-chromosomes that yielded 1.37 Gb of sequence, with a scaffold N50 of 44.02 Mb. BUSCO analysis showed a completeness score of 93.7%. The genome contained 48,537 predicted protein-coding genes and 58.31% of the assembly was annotated as repetitive sequences. Whole genome duplication events were further confirmed using 4dTv analysis. The genome assembly of A. laticeps should be valuable and important to understand the genetic adaptation and endangerment process of this species, which could lead to more effective management and conservation of the big-head schizothorcin and related freshwater fish species.

Association of a novel functional promoter variant (rs2075533 C>T) in the apoptosis gene TNFSF8 with risk of lung cancer--a finding from Texas lung cancer genome-wide association study.

Published genome-wide association studies (GWASs) have identified few variants in the known biological pathways involved in lung cancer etiology. To mine the possibly hidden causal single nucleotide polymorphisms (SNPs), we explored all SNPs in the extrinsic apoptosis pathway from our published GWAS dataset for 1154 lung cancer cases and 1137 cancer-free controls. In an initial association analysis of 611 tagSNPs in 41 apoptosis-related genes, we identified only 10 tagSNPs associated with lung cancer risk with a P value<10(-2), including four tagSNPs in DAPK1 and three tagSNPs in TNFSF8. Unlike DAPK1 SNPs, TNFSF8 rs2181033 tagged other four predicted functional but untyped SNPs (rs776576, rs776577, rs31813148 and rs2075533) in the promoter region. Therefore, we further tested binding affinity of these four SNPs by performing the electrophoretic mobility shift assay. We found that only rs2075533T allele modified levels of nuclear proteins bound to DNA, leading to significantly decreased expression of luciferase reporter constructs by 5- to -10-fold in H1299, HeLa and HCT116 cell lines compared with the C allele. We also performed a replication study of the untyped rs2075533 in an independent Texas population but did not confirm the protective effect. We further performed a mini meta-analysis for SNPs of TNFSF8 obtained from other four published lung cancer GWASs with 12 214 cases and 47 721 controls, and we found that only rs3181366 (r2=0.69 with the untyped rs2075533) was associated to lung cancer risk (P=0.008). Our findings suggest a possible role of novel TNFSF8 variants in susceptibility to lung cancer.

Association of Endocrine Therapy and Dementia in Women with Breast Cancer.

PURPOSE: Prior studies have reported differing results regarding the association between endocrine therapy (ET) in the treatment of breast cancer and dementia risk. However, existing findings may be limited by common sources of bias and confounding. Here we investigate the association of ET utilized in the definitive setting to treat non-metastatic breast cancer with dementia risk accounting for multiple potential sources of bias and confounding. PATIENTS AND METHODS: We conducted a retrospective study in SEER-Medicare of women aged ≥ 66 years with non-metastatic breast cancer. We examined the risk of all-cause dementia among ET users versus non-ET users using multivariable regression models, accounting for the competing risk of death, and using a start of the follow-up period as 12-months following breast cancer diagnosis for both groups to avoid immortal time bias. RESULTS: Among 25,777 individuals there were 2,869 incident dementia cases. We found a statistically significantly decreased risk of any dementia among ET users in unadjusted and adjusted models that completely attenuated when accounting for the competing risk of death (hazard ratio, 0.98; 95% confidence interval, 0.90-1.07). CONCLUSION: When accounting for common sources of bias and confounding we did not find evidence to support an association between ET in the definitive treatment of non-metastatic breast cancer and dementia risk. These results suggest that ET may not be associated with dementia risk.

Risks of Multiple Skin Cancers in Organ Transplant Recipients: A Cohort Study in 2 Administrative Data Sets.

IMPORTANCE: There are limited reports on the risks of multiple primary skin cancers in organ transplant recipients (OTRs). OBJECTIVE: To determine the risks over time and risk factors for OTRs developing (1) any skin cancer posttransplant, (2) a subsequent skin cancer after the first posttransplant skin cancer in the data sets used in the study, and (3) 10 or more skin cancers. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from Optum deidentified electronic health record data set (7.7 million patients) and Truven Health MarketScan insurance claims data set (161 million patients) from 2007 to 2017. Skin cancers were identified using diagnosis plus treatment codes for basal cell carcinoma, squamous cell carcinoma, and melanoma; OTRs were identified using 4 or more diagnosis codes for organ transplant. Data analysis took place from January 1, 2007, to December 31, 2017. MAIN OUTCOMES AND MEASURES: Cumulative risks of (1) any skin cancer treatment posttransplant, (2) a subsequent skin cancer treatment after the first posttransplant skin cancer treatment in our data, and (3) 10 or more skin cancer treatments in OTRs. A Wei-Lin-Weissfeld marginal model was used to evaluate risk factors for any skin cancer. RESULTS: A total of 7390 OTRs in Optum and 133 651 in MarketScan were identified, 4.5% and 13.3% of which had had at least 1 skin cancer treatment, respectively. At 2 years after the initial posttransplant skin cancer in the data sets, OTRs had a 44.0% to 57.0% risk of a subsequent skin cancer treatment and a 3.7% to 6.6% risk of having 10 or more skin cancer treatments. Statistically significant risk factors for any skin cancer included age, history of skin cancer, and history of actinic keratosis in both data sets, and male sex and thoracic transplant in MarketScan. CONCLUSIONS AND RELEVANCE: In this retrospective cohort study, approximately half of the OTRs who developed at least 1 posttransplant skin cancer developed a subsequent skin cancer within 2 years, and approximately 1 in 20 developed 10 or more skin cancers. Identifying OTRs at highest risk for multiple primary skin cancers may help target strategies for prevention and early detection.

Prescription Patterns, Initiation, and 5-Year Adherence to Adjuvant Hormonal Therapy Among Commercially Insured Patients With Breast Cancer.

BACKGROUND: Tamoxifen and aromatase inhibitors (AIs) are used as adjuvant hormonal therapy (AHT) for early-stage hormone receptor-positive (HR+) breast cancer. Treatment for 5 years reduces cancer mortality by 30%. Despite this benefit, adherence to AHT has been suboptimal. Here, we evaluated AHT initiation and patient adherence in women with private health insurance. MATERIALS AND METHODS: Female patients with breast cancer ≥ 18 years of age who underwent mastectomy or lumpectomy between 1999 and 2015 were identified in the IBM MarketScan Research Database. AHT initiation and adherence rates were estimated for all AHT users regardless of HR+ status. Initiation rates were standardized using HR+ breast cancer incidence rates in the Surveillance, Epidemiology, and End Results (SEER) program. Adherence was defined as medication possession ratio ≥ 80%. Risk ratios, odds ratios, and their 95% CIs were calculated for factors associated with patients' initiation and adherence. RESULTS: Among 80,224 patients, the raw initiation rate was 71.8% and the standardized rate was 87.5%. We found 61.2% patients initiated treatment with AIs and 38.8% with tamoxifen. Patients' 1-year adherence rate was 84.4% and the 5-year rate was 65.2%. Prescription by mail-in order, using a single AHT regimen, 50 to 69 years of age, monthly out-of-pocket drug payment ≤ $11, in US dollars, no depression, no comorbidity, living in the Northeast, treatment in recent years, and receipt of a combination of chemotherapy, radiation, and surgery were associated with better adherence. CONCLUSION: Five-year AHT adherence rates are low among female patients with breast cancer with private health insurance. Effective approaches to improve AHT adherence are needed.

Shared Decision-Making for Lung Cancer Screening: How Well Are We "Sharing"?

BACKGROUND: Lung cancer screening (LCS) reduces lung cancer mortality, but it also carries a range of risks. Shared decision-making (SDM) is a process of engaging patients in their health care decisions and is a vital component of LCS. RESEARCH QUESTION: What is the quality of SDM among patients recently assessed for LCS? STUDY DESIGN AND METHODS: Cross-sectional study of screened patients recruited from two academic tertiary care centers in the South Central Region of the United States. Self-reported surveys assessed patient demographics, values related to outcomes of LCS, knowledge, SDM components including receipt of educational materials, and decisional conflict. RESULTS: Recently screened patients (n = 266) possessed varied LCS knowledge, answering an average of 41.4% of questions correctly. Patients valued finding cancer early over concerns about harms. Patients indicated that LCS benefits were presented to them by a health care provider far more often than harms (68.3% vs 20.8%, respectively), and 30.7% reported they received educational materials about LCS during the screening process. One-third of patients had some decisional conflict (33.6%) related to their screening decisions, whereas most patients (86.6%) noted that they were involved in the screening decision as much as they wanted. In multivariate models, non-White race and having less education were related to lower knowledge scores. Non-White patients and former smokers were more likely to be conflicted about the screening decision. Most patients (n = 227 [85.3%]) indicated that a health care provider had discussed smoking cessation or abstinence with them. INTERPRETATION: Among recently screened patients, the quality of decision-making about LCS is highly variable. The low use of educational materials including decision aids and imbalance of conveying benefit vs risk information to patients is concerning. A structured approach using decision aids may assist with providing a balanced presentation of information and may improve the quality of SDM.