bluuebunny/crossref_metadata_2025 huggingface dataset:
The PHACT Study: Population Health and Cancer Testing.
Authors: Dhawan Mallika Sachdev , Karipineni Silpa , Budge Jason , Mak Julie , Zhou Alicia , Williams Kelly , Cha Kyusun , Munster Pamela N.
Published: May 2019

1531

Background: There is considerable uncertainty on cancer risk and recommendations for genetic testing in various populations. The purpose of this study is to test types and frequencies of cancer risk mutations in large, unaffected multiethnic populations, as well as feasibility and acceptance of general population germline testing. Methods: After consent, germline genetic testing via Color Genomics 30-gene Cancer Risk panel with personal and family cancer history assessment was offered to 500 participants residing in the San Francisco Bay Area. Participants were older than 21 and without a known family history of a cancer risk mutation. Recruitment occurred at random and through various, non-cancer related community events. Genetic counseling through a genetic counselor at UCSF was offered to all participants. Post-participation surveys were sent out to those who completed testing with 195 responses to assess attitudes towards genetic testing. Results: 500 participants completed testing; 35 were found to have a cancer risk mutation (7.0%). The majority of these have been in moderate risk cancer mutations including CHEK2 (1.0%), APC (0.8%), MUTYH (1.4%) and NBN (0.4%); higher risk mutations were found in BRCA1 (0.4%), BRCA2 (0.6%), BRIP1 (0.4%), PMS2 (0.2%) and PALB2 (0.2%). Data via self-reporting and SNP testing via the Color Genomics platform was collected to contextualize the racial, ethnic, and geographic association of these results. Rates of VUS (variants of uncertain significance) differed among the various ethnic groups (p = 0.027) with the lowest rates in Europeans vs. all other ethnicities (16.6% vs. 29%, p = 0.001). 37 (19.8%) out of 187 respondents reported that their genetic testing influenced testing in family members. In those 37 families, 8 additional people were positive for genetic mutations. Cost was the biggest barrier to pursuing prior genetic testing according to most individuals (20% of respondents); others were too busy (12%) or did not feel genetic testing was medically recommended (9%). Conclusions: The PHACT study demonstrates that large population screening of cancer risk mutations is feasible. The number of participants found to have mutations was greater than expected although the majority of these were in moderate risk genes. We found high rates of VUS in non-Europeans, which points to the complexity of population-based genetic testing.
Management of high, moderate, and low penetrance ovarian cancer susceptibility gene mutations: An assessment of current practice patterns.
Authors: Watson Catherine H. , Davidson Brittany Anne , Havrilesky Laura Jean , Lee Paula S. , McNally Leah , Moss Haley , Previs Rebecca A. , Puechl Allison , Secord Angeles Alvarez , Berchuck Andrew , Kauff Noah D.
Published: May 2019

1536

Background: Limited information exists regarding appropriate risk-reduction strategies for women with moderate and low penetrance ovarian cancer (OVCA) susceptibility mutations. We sought to assess current practice patterns for women with these genetic changes through a survey of members of the Society of Gynecologic Oncology (SGO). Methods: All full SGO members were e-mailed a survey consisting of two vignettes: 1) a 35-year-old premenopausal woman who desires pregnancy; 2) a 55-year-old postmenopausal woman with multiple comorbidities. Each vignette contained sub-scenarios in which the patient had either a BRCA1 (RR = 30-60), RAD51C (RR = 5.0) or ATM (RR 1.5-2.0) OVCA susceptibility mutation. Respondents were queried about their preferred management approach. Chi-square test was used for statistical analysis. Results: 193 (15%) of 1284 SGO members responded. 58% were in academic practice. For the premenopausal woman, 52%, 13% and 6% would perform an RRSO prior to age 40 in the setting of a BRCA1, RAD51C and ATM mutation respectively. 47%, 68% and 9% would perform RRSO at 40-50; and 0%, 9% and 23% would perform RRSO at menopause, depending on the gene mutated. For the postmenopausal woman with comorbidities, 98%, 85% and 42% would proceed with RRSO in the setting of a BRCA1, RAD51C and ATM mutation respectively; 2%, 8% and 39% would observe (with/without screening); and 0%, 7% and 19% would do further research prior to proceeding. Distribution of responses for carriers of RAD51C and ATM mutations were different from BRCA1 in both vignettes [p < 0.001]. Conclusions: Respondents were more likely to perform RRSO earlier and more frequently in the setting of a BRCA1 mutation compared to either a RAD51C or ATM mutation. However, there was lack of consensus in management of the moderate and low penetrance OVCA susceptibility mutations. These patterns likely reflect the limited information available regarding the timing and magnitude of risk associated with these genes. Given the immediate and long-term morbidity of oophorectomy, more data regarding age-specific risks and appropriate risk-reduction strategies for moderate and low penetrance OVCA susceptibility mutations is needed.
Implementation of a low-dose computerized tomography (LDCT) lung cancer screening program (LCSP) across a large integrated health system.
Authors: Bjegovich-Weidman Marija , Leh Steven , Malone Daniel , Mendoza-Ayala Raul , Barry-Weers Anne Marie , Dlouhy Laurie , Wesolowski Jody , Mitchell Dorry , Clement Kevin , Amy Bock , Weese James L.
Published: May 2019

1537

Background: The LDCT LCSP was launched as a critical component of our Cancer Program to support tobacco cessation efforts and increase early detection. Initially it was offered as a self-referral low cost screening. The program was expanded when the Affordable Care Act and Center for Medicare/Medicaid Services covered it as a preventative services benefit in January 2015. Methods: 9 LDCT LCSP locations were implemented between 2014-September 2016. Program data are submitted to the American College of Radiology Lung Cancer Data Registry since 2016. In 2017, a Best Practice Alert was created within our electronic health record (EHR) to alert the primary care clinician if his/her patient met criteria for a LDCT. Each of the sites managed their own programs up until September 2018 when a dedicated team (Team) of two nurses and one data support specialist was justified. The Team focus is to increase awareness of the LDCT LCSP and criteria for eligibility, improve tobacco history taking and pack year documentation in the EHR, increase smoking cessation counseling and referral, and facilitate presentation of all Lung RADS category 4 cases for review at one of our two Multidisciplinary Lung Cancer Case Conferences. Standardized management of key incidental findings was developed for coronary artery calcification, non-lung masses, thoracic aortic aneurysm, and critical pulmonary conditions. To date, we have not examined the impact of the LDCT LCSP on smoking cessation rates. All 9 program sites have been named a Screening Center of Excellence by the Lung Cancer Alliance. Results: In 2016, 1849 LDCT Screenings were performed, 4701 (154% increase) in 2017 and 7154 (52.5% increase) in 2018. Cancer Detection rates were 1.3% in 2016, 1.8% in 2017 and 1.3% for January-June 2018. Cancer registry data reports a 9% increase in Stage 0, 1, 2A and a 7.2% decrease in Stage IV at time of diagnosis from 2014-2017. Conclusions: The implementation of a LDCT LCSP has increased the percentage of patients diagnosed at an earlier stage of lung cancer. With standardized management of key incidental findings, we anticipate improvement in early detection and management of cardiac and pulmonary diseases.
Analysis of healthy breast tissue from Komen Tissue Bank shows distinct histology, decreased proliferation, and lower periductal collagen deposition in women with prolonged history of breastfeeding.
Authors: Basree Mustafa , Shinde Neelam , Li Zaibo , Majumder Sarmila , Ramaswamy Bhuvaneswari
Published: May 2019

1538

Background: Epidemiological studies have shown that prolonged breastfeeding is associated with a reduced risk of developing triple negative/basal-like breast cancer (TN/BLBC). We have modeled abrupt involution (AI) following short breastfeeding and gradual involution (GI) of the mammary gland that occurs over time upon prolonged breastfeeding in wild-type FVB/N mice and discovered prominent histological and molecular changes in the AI glands over time. Further, we demonstrated that breast tissue from healthy women who breastfed <6 months showed enrichment in stem-cell and cell renewal pathways. Here, we corroborate those studies using normal human breast tissue obtained from Susan G. Komen for the Cure Tissue Bank (KTB). Methods: FFPE breast tissue sections obtained from KTB (Protocol #2017CO184). Donors were parous women, aged 18 to 45, without history of breast cancer and for whom breastfeeding history was available. H&E sections and TDLU, the primary anatomical source of most breast cancers, of women who breastfed for ≥6 months (GI, n=49) vs. those who breastfed for ≤3 months (AI, n=20) were evaluated by a blinded pathologist. Masson Trichrome stain was used to measure collagen deposition. Ki67 immunohistochemistry was utilized to determine proliferation. Statistical significance was measured using Fisher’s exact t-test and two-sample t-test with a p-value of <0.05. Results: H&E analysis revealed that breast tissue obtained from women in the AI cohort exhibited histological features of inflammation (p-value= 0.025). Using Ki67 IHC (AI, n=15; GI, n=32) and Masson Trichome stain (AI, n=3; GI, n=4), sections in the AI cohort showed 2-fold increase in proliferation of lobular epithelium (p-value= 0.048) and 1.4-fold increase in periductal collagen deposition (p-value= 0.027) when compared to GI cohort. Age, race, and BMI were not statistically different between AI and GI cohorts. Conclusions: Breast tissue from parous women who breastfed ≤3 months is histologically different than tissue of women with ≥6 months history of breastfeeding. We are currently staining more breast tissue samples obtained from KTB. Experiments are underway to assess the long-term effect of breastfeeding on breast epithelial cell hierarchy and biomarkers of inflammation. Understanding this mechanistic link will help in developing prevention strategies, particularly for African-American women who have lower prevalence of breastfeeding and higher incidence of TN/BLBC.
The impact of smoking cessation on breast cancer patients’ survival.
Authors: Jizzini Mazen , Raghavendra Akshara Singareeka , Ibrahim Nuhad K. , Kypriotakis George , Cinciripini Paul M. , Seoudy Kareem , Karam-Hage Maher A.
Published: May 2019

1542

Background: Breast cancer remains to be one of the highest causes of cancer mortality amongst females globally, second only to lung cancer. Smoking is strongly associated with increased all-cause mortality, including breast cancer related death. It has also been shown to have a negative influence on long-term survival after successful breast cancer treatment. Prior studies have shown that smoking cessation may lead to improved prognosis and better outcomes. Methods: This is a retrospective cohort study of breast cancer patients who were identified as smokers, some of who were referred to the tobacco treatment program (TTP) located at MD Anderson Cancer Center. TTP includes careful patient screening, motivational counseling, and pharmacotherapy. We complemented the original data collected by conducting in-depth chart reviews to extract data including patient demographics, date of diagnosis, stage of cancer, smoking status, duration of abstinence and dates of follow-up or death. We then examined associations between smoking status and survival status using multinomial regression models adjusting for biomarkers of disease and personal characteristics. Results: Among all breast cancer patients (N = 31069), we identified those who are smokers (n = 2320) by matching the TTP database with smoking status from our institutional electronic health records. Of those, 740 patients were referred to TTP. Amongst these, 242 patients quit smoking and remained abstinent at the 9 month follow-up. Compared with non-abstainers, those who quit were more likely to be alive with no evidence of disease during the observation time (RR = 1.62, p = 0.045). When analyzed at different stages, the RR went from 1.35 (p = 0.42) to 2.77 (p = 0.34) for stages 3 and 1, respectively. Although the strength of this relationship varied among disease stage, the direction of the relationship remain consistent. Conclusions: Our data shows that smoking cessation is associated with improved survival status amongst breast cancer survivors across all stages. Comprehensive smoking cessation services may improve survivorship when started as early as the time of diagnosis. Further analysis of the association between smoking cessation and other associated medical outcomes will be conducted to further determine the specific impact of cessation programs.
Improving risk assessment of obesity-associated breast cancer.
Authors: Iyengar Neil M. , Gucalp Ayca , Zhou Xi K. , Wang Hanhan , Giri Dilip D. , Williams Samantha , Falcone Domenick J. , Winston Lisle , Landa Jonathan , Kirstein Laurie J. , Morrow Monica , Dannenberg Andrew J.
Published: May 2019

1544

Background: Elevated body mass index (BMI) is associated with increased risk of estrogen receptor (ER)-positive postmenopausal breast cancer. The risk is also elevated in women with a normal BMI but excess body fat. These risks may be driven by breast white adipose tissue inflammation (WATi), which is associated with elevated aromatase levels and systemic metabolic dysfunction (e.g. hyperinsulinemia). We hypothesized that body fat assessment is superior to BMI for detecting the pathophysiology that promotes obesity-related breast cancer, particularly among normal BMI women. Methods: Non-tumorous breast tissue was collected from women undergoing mastectomy for breast cancer treatment or prevention. Breast WATi was detected by the presence of crown-like structures in the breast, which are composed of a dead/dying adipocyte surrounded by CD68+ macrophages. Body composition was measured prior to mastectomy via dual energy X-ray absorptiometry. Exercise behavior was also assessed prior to surgery using the Godin Leisure Time Exercise Questionnaire. Associations among categorical variables were examined using Χ2 or Fisher’s exact test. Relationships between continuous variables were examined using the Spearman correlation. Results: From April 5, 2016 to August 31, 2018, 100 patients were enrolled; median age 49 (range 29 to 82) years. Breast WATi was present in 56/100 (56%) women and was associated with elevated BMI and body fat levels, breast adipocyte hypertrophy, postmenopausal status, metabolic syndrome and decreased physical activity (P < 0.05). Among 39 women with normal BMI, breast WATi was present in 14 (36%) and was associated with elevated body fat levels, breast adipocyte hypertrophy, dyslipidemia, and decreased physical activity (P < 0.05). There was no statistically significant association between BMI and breast WATi in the normal BMI group. Menopausal status and total fat mass had greater sensitivity and specificity for the detection of breast WATi compared to a BMI-based model (AUC 0.843 vs. 0.779, respectively). Conclusions: Measurement of body fat is superior to BMI for predicting breast inflammation, which has been shown to promote obesity-related breast cancer.
Comparison of risk-reducing surgery in women with BRCA and non-BRCA ovarian cancer susceptibility genes.
Authors: Schwartz Zachary Phillip , Zakhour Mae , Li Andrew John , Walsh Christine S. , Rimel Bj , Alvarado Monica , Lentz Scott E , Cass Ilana
Published: May 2019

1547

Background: Risk reducing gynecologic surgery (RRSO) is standard of care for women with BRCA mutations. The optimal management for women with non-BRCA ovarian cancer susceptibility mutations remains unclear. We sought to characterize the practice patterns for these women at our two institutions. Methods: Women with germline ovarian cancer susceptibility genes who had a RRSO were identified from 1/2000-1/2019 in an IRB approved study. All patients were asymptomatic with no suspicion for malignancy at time of RRSO. Clinico-pathologic characteristics were extracted from the medical records. Continuous variables were analyzed with Kruskal-Wallis and categorical variables analyzed with chi square and t-tests. Results: 152 BRCA1, 95 BRCA2, and 63 Non-BRCA mutation carriers were identified—50 Lynch (22 MLH1, 13 MSH2, 13 MSH6, 2 PMS2) and 13 Other (6 BRIP1, 2 RAD51C, 5 RAD51D). There was no difference between age at testing, age at RRSO, and interval between testing and RRSO between groups. Genetic counseling was higher in Non-BRCA patients. Family history of ovarian cancer was more common in women with BRCA1 and Other germline mutations compared to BRCA2 and Lynch. Family and personal history of breast cancer was high in all groups except Lynch carriers. Prophylactic mastectomy was seen mostly in BRCA mutation carriers. Concomitant hysterectomy was performed in the majority of women (BRCA1 59%, BRCA2 57%, and Other 62%), with the highest frequency in Lynch carriers (86%, p<.01). Occult cancer was only seen in BRCA mutation carriers: BRCA1 (7%), BRCA2 (2%), Lynch (0%), Other (0%). Conclusions: In this cohort, women with Non-BRCA mutations are managed similarly to women with BRCA mutations. We observed no occult cancers in Non-BRCA patients. The optimal role of surgery as a risk reducing strategy in this group requires further study. [Table: see text]
Association between breast cancer mortality-to-incidence ratios and state health disparities in the United States.
Authors: Lee Yu-Che , Chang Ko-Yun , Hurley Judith
Published: May 2019

1548

Background: Breast cancer is the most commonly diagnosed cancer and second leading cause of cancer deaths among women in the United States. The cancer mortality-to-incidence ratio (MIR) provides a population-based indicator of cancer survival and has been established previously to evaluate healthcare variations among different countries. We aim to evaluate the association, which has not been investigated before, between MIR of breast cancer and state-level health disparities in the United States. Methods: We used United States Cancer Statistics (USCS) database to calculate 6-year average of MIRs for breast cancer from 2010 to 2015. America’s Health Rankings (AHR) is a platform using weighted measures in 5 different categories (Behaviors, Community & Environment, Policy, Clinical Care and Outcomes) to determine annual state health rankings. Six-year average (2010-2015) of health uninsured rate by state was obtained from the U.S. Census Bureau and 5-year average (2010-2014) of health spending per capita by state was obtained from Centers for Medicare & Medicaid Services. The correlations between breast cancer MIRs and state health variables were calculated by linear regression analyses. Results: From 2010 through 2015, 1,390,357 females were diagnosed with breast cancer and 246,671 females died from breast cancer in the United States. The 6-year average of age-adjusted incidence rate, mortality rate and MIRs were 124.2 ± 1.3 per 100,000 population, 21.1 ± 0.6 per 100,000 and 0.170 ± 0.007, respectively. Among fifty states we included for analyses, Hawaii had the lowest MIR (0.116 ± 0.014) and Nevada had the highest MIR (0.204 ± 0.004). AHR showed Hawaii had the highest health ranking (No. 1) whereas Louisiana had the lowest health ranking (No. 50) in 2015. In our analysis, states with better health rankings, lower health uninsured rates and higher health spending per capita were significantly correlated with lower MIRs (R2 = 0.695, 0.453 and 0.253, respectively; all P < 0.001). Conclusions: The difference of MIRs for breast cancer was strongly associated with state health diversities. These findings suggest that MIR of breast cancer can be an applicable measure to evaluate and reflect the state-level health disparities in the United States. [Table: see text]
Epidemiology and survival in patients with urethral clear cell carcinoma.
Authors: Patel Mausam , Im Jay , Ivy Austin , Maraboyina Sanjay , Kim Thomas
Published: May 2019

1550

Background: Clear cell carcinoma (CCC) of the urethra is a very rare histologic variant of urethral adenocarcinoma. The majority of studies have been case reports and case series with no large population based studies. A retrospective analysis was performed with the National Cancer Institute’s (NCI) Surveillance, Epidemiology, and End Results (SEER) database to establish the epidemiology of urethral CCC and determine the clinical factors associated with survival. Methods: All cases of clear cell carcinoma of the urethra diagnosed from January 1, 1973 to December 31, 2014 were extracted from SEER. Age at diagnosis, sex, marital status, race, grade, stage, surgery, radiation, chemotherapy, overall survival (OS), disease specific survival (DSS), and survival months were extracted for analysis. Descriptive statistics were calculated for all variables. Univariable analysis to assess for differences in survival with respect to covariates was performed using the log rank test. Multivariable analysis was performed with Cox proportional hazards regression models to determine the predictive performance of covariates with respect to OS and DSS, reported as hazard ratio [HR] with 95% CIs. Comparisons were considered statistically significant at P < 0.05. Results: Sixty one cases were extracted for analysis. The mean ± SD was 63.0 ± 13.9 years. Fifty eight (95.1%) patients were female with 53 (86.8%) locoregional cases at presentation. There were 50 (82%), 18 (29.5%), and 12 (23.0%) patients who underwent surgery, radiation, and chemotherapy, respectively. On univariable analysis, the following covariates were associated with both OS and DSS: age, stage, and surgery (all p < 0.001; log rank test). On multivariable analysis, surgery was a predictor for improved OS and DSS (HR, 0.178; 95% CI [0.068; 0.464]) and HR, 0.166; 95% CI [0.196; 2.132], respectively). Additionally, both increasing age and distant disease were associated with worse OS and DSS. Neither radiation nor chemotherapy were significantly associated with OS or DSS. Conclusions: Surgery improves OS and DSS in patients with urethral CCC. While neither radiation nor chemo were significantly associated with survival, additional studies are necessary to determine how these therapeutic interventions may impact prognosis.
Association of geographic clustering of cutaneous T-cell lymphoma in the state of Georgia with environmental exposure to benzene and trichloroethylene.
Authors: Allen Pamela Blair , Clough Lindsay , Bayakly A. Rana , Ward Kevin C. , Khan Mohammad Khurram , Chen Suephy , Flowers Christopher , Switchenko Jeffrey M.
Published: May 2019

1551

Background: Geographic clustering of CTCL has been recently reported in large registries, but its association with environment factors is unknown. Benzene and trichloroethylene (TCE) are two common carcinogenic environmental toxins associated with hematological cancers. We investigated associations between geographic clustering of CTCL incidence in the state of Georgia with benzene and TCE exposure. Methods: We obtained county-level incidence of CTCL within Georgia from the Georgia Cancer Registry between 1999-2015. To account for the demographic structure in each county, standardized incidence ratios (SIR) were calculated by dividing the observed number of cases of CTCL in Georgia by the expected number of cases using national incidence rates by age, sex, and race. Using spatial analyses, we assessed for population-adjusted county-level clustering of SIRs. We also recorded county-level exposure concentration of benzene and TCE between 1996-2014 from the EPA’s National Air Toxics Assessment database. Linear regression analyses on CTCL incidence were performed comparing SIRs to exposure levels of benzene and TCE by county. Results: Our analyses demonstrated significant geographic clustering of CTCL in Georgia (Moran’s I statistic 0.0991, p-value = 0.022). Local spatial tests revealed several statistically significant hot spots throughout Georgia, particularly around Atlanta. This clustering was strongly correlated with benzene (R2 0.0824, p-value 0.0006) and TCE (R2 0.0614, p-value 0.0016) exposure concentration. Among the four most populous counties in Georgia (Cobb, Dekalb, Fulton, and Gwinnett) CTCL incidence was 1.7 to 2.7 times higher than the average county, and benzene and TCE exposure concentration was 3.0 to 6.3 times higher. Conclusions: These results demonstrate non-random geographic clustering of CTCL incidence in Georgia. This is the first analysis to correlate geographic clustering of CTCL with environmental toxic exposures, demonstrating a statistically significant correlation between environmental exposure to benzene and TCE and CTCL incidence within Georgia. [Table: see text]
Insulin resistance measured by the triglyceride-glucose index and risk of obesity-related cancers: An epidemiological investigation in more than 500,000 individuals.
Authors: Fritz Josef , Bjorge Tone , Nagel Gabriele , Concin Hans , Manjer Jonas , Häggström Christel , Stattin Pär , Stocks Tanja , Ulmer Hanno
Published: May 2019

1552

Background: The role of insulin resistance as a mediator in the association of body mass index (BMI) with site-specific cancer risk has, to our knowledge, never been systematically quantified. We aimed to determine to what extent insulin resistance measured as the logarithmized triglyceride glucose product (TyG index) mediates the effect of BMI on risk of obesity-related cancers. Methods: A total of 510,471 individuals from six European cohorts with a mean age of 43.1 years were included in the study. We fitted Cox models, adjusted for relevant confounders, to investigate associations of TyG index with ten common obesity-related cancer sites, and quantified the proportion of the effect of BMI mediated through TyG index. Results: During a median follow-up of 17.2 years, 16 052 individuals developed obesity-related cancers. TyG index was associated with the risk of cancers of the kidney (hazard ratio (HR) per one standard deviation increase 1.13, 95% confidence interval: 1.07-1.20), liver (1.13, 1.04-1.23), pancreas (1.12, 1.06-1.19), colon (1.07, 1.03-1.10), and rectum (1.09, 1.04-1.14). Substantial proportions of the effect of BMI were mediated by TyG index for cancers of the pancreas (42%), rectum (34%), and colon (20%); smaller proportions for kidney (15%) and liver (11%); none for endometrium, ovary and breast (postmenopausal). Conclusions: In this pooled cohort study including more than 500,000 individuals, insulin resistance measured as the logarithmized triglyceride glucose product significantly mediated the effect of overweight and obesity on risk of cancers of the kidney, liver, pancreas, colon, and rectum. In contrast, insulin resistance did not mediate the risk for cancers of the endometrium, ovary and breast. Our results confirm a promoting role of insulin resistance in the pathogenesis of gastrointestinal cancers. Although often claimed, insulin resistance does not appear to connect excess body weight with cancers of the female reproductive organs.
Insurance disparity in the United States cancer survivors’ smoking rates: A trend study from NHIS 2008-2017.
Authors: Zhao Yannan , Zheng-Lin Binbin , Wang Biyun , Hu Xi-Chun , Jiang Changchuan
Published: May 2019

1553

Background: Smoking rates have been decreasing in the U.S over the last decade. Smoking cessation is a critical part of cancer treatment and survivorship care. However, little is known about the trend of smoking rates in U.S. cancer survivors and how it varied by individuals’ insurance coverages. Methods: We conducted a retrospective study to evaluate the temporal trend of smoking rates using the National Health Interview Survey from 2008 through 2017. Adult cancer survivors (n = 20122) were included in the analysis. The outcomes were self-reported current smoking behavior. Insurance coverage was categorized into any private (age ≤65), other coverage (age ≤65), uninsured (age ≤65), Medicare + any private (age > 65), and other coverage (age > 65). We combined every two years data to improve statistical power in the subgroup analysis. Weighted analyses were performed with SAS 9.4 to account for the complex design. Results: The smoking rates in cancer survivors decreased from 18.4% in 2008 to 12.5% in 2017. However, the smoking rates varied remarkably by insurance status (p < 0.001). There was a decreasing trend of smoking rates in participants with any private (age ≤65) (17.3% in 2008/2009 to 12.0% in 2016/2017), Medicare + any private (age > 65) (7.5% in 2008/2009 to 5.9% in 2016/2017), and other coverage (age > 65) (13.2% in 2008/2009 to 9.2% in 2016/2017) whereas the current smoking rates remains high in cancer survivors with other coverage (age ≤65) (40.1% in 2008/2009 to 34.4% in 2016/2017) and uninsured (age ≤65) (43.4% in 2008/2009 to 43,1% in 2016/2017). Conclusions: Cancer survivors report less smoking behaviors over the last decade which is similar to the general population. However, the smoking rate remains dangerously high in non-elderly cancer survivors without any private insurance.
Comorbidity and racial differences in risk of mortality of men with breast cancer.
Authors: Parise Carol , Caggiano Vincent
Published: May 2019

1554

Background: Black men with breast cancer have more concomitant disease and worse survival than white men. Less is known about concomitant disease and survival in Hispanic and Asian/Pacific Islander (API) men with breast cancer. The purpose of this study was to compare differences in survival and risk of mortality of white, black, Hispanic, and Asian/Pacific Islander (API) men with breast cancer with increasing comorbidity. Methods: We identified 1,497 cases of first primary male invasive breast cancer from the California Cancer Registry 2000-2015 with a documented Charlson Comorbidity Index (CCI). The CCI is a weighted index based on the presence of certain comorbid conditions following a cancer diagnosis and weighted by the severity of these conditions. A score of 0 indicates no significant comorbidity and scores of 2 or more are interpreted as a high comorbidity burden. Bivariate associations between race and AJCC stage, tumor grade, estrogen receptor (ER) status, human epidermal growth factor 2 (HER2), and socioeconomic status (SES) were compared using the χ2 Test of Independence. Kaplan Meier Survival analysis was used to compare unadjusted survival among the races. Cox Regression was used to assess risk of mortality for each race when adjusted for factors that had a statistically significant (p < 0.10) bivariate association with race/ethnicity. Analyses were conducted within each level of the CCI (0, 1, and 2 or more). Results: Among men with a CCI of 0 or 2, blacks had worse unadjusted survival than whites. There were no differences in survival for men with a CCI of 1. Stage, SES, ER, and type of surgery all had statistically significant bivariate associations with race/ethnicity. For men with a CCI of 0, Hispanics (HR = 0.367; 95% CI = 0.167, 0.801) and APIs (HR = 0.422; 95% CI = 0.189, 0.941) had a reduced risk of mortality when compared with whites. Black men had the same risk of mortality as white men. There were no differences in risk of mortality by race for men with a CCI of 1 or 2. Conclusions: Black men with breast cancer and no comorbidity have the same risk of mortality as white men while Hispanic and API men have lower risk of mortality. There are no racial disparities in adjusted risk of mortality in men with breast cancer with any concomitant disease.
Burden of thrombocytopenia in adult cancer patients receiving chemotherapy.
Authors: Soff Gerald A. , Shaw Jaime , Kilpatrick Karynsa , Marongiu Andrea , Park Joseph
Published: May 2019

1555

Background: Thrombocytopenia is a common toxicity of chemotherapy, yet there are limited data on its occurrence in routine clinical practice. Methods: Using structured patient-level data from the Flatiron Health EHR-derived database, we assessed risk (3-month cumulative incidence) of chemotherapy-induced thrombocytopenia (CIT) in adult patients (2012-2017) based on platelet counts, overall and by each grade of CIT, cancer type, and chemotherapy regimen (Table); and the co-occurrence of other hematologic abnormalities. Results: Of 15,521 solid tumor patients who initiated chemotherapy, 13% had evidence of CIT within 3 months (platelet count <100x109/L), 4% had grade 3 (25 to <50x109/L) and 2% had grade 4 (<25x109/L) CIT. Of the solid tumors examined, incidence was highest in melanoma patients. In hematologic malignancies (N = 2,537), 3-month risk was even higher with nearly 30%, 16%, and 12% having any grade, grade 3 and 4 CIT, respectively; and the greatest risk being in multiple myeloma patients. Anthracycline-based regimens were associated with the highest risk of CIT (7% grade 3; 4% grade 4), followed by gemcitabine- and platinum-based regimens. Anemia often accompanied first evidence of CIT (49%); isolated thrombocytopenia occurred in 15%. Conclusions: This study provides a current snapshot of CIT risk in a large sample of adult patients undergoing chemotherapy in routine clinical practice, highlighting patients at highest risk for CIT and underscoring the complexity of managing cancer treatment. [Table: see text]
Breast cancer screening adherence at multiple timepoints over eight years among women in a familial cohort.
Authors: Schaeffer Marcy L. , May Betty J , Hogan Brenna C. , Orellana Mikiaila M. , McCullough Michelle C. , Armstrong Deborah Kay , Myers Kelly , Visvanathan Kala
Published: May 2019

1557

Background: Since 2007, U.S. guidelines recommend cancer-free women with ≥20% lifetime breast cancer (BC) risk undergo BC screening with mammogram and breast MRI. There is limited long-term data on BC screening adherence among young, high-risk women. To address this knowledge gap, we examined utilization of multiple BC screening modalities over time. Methods: Eligible women were ≥ 30 years old, had no history of BC/ovarian cancer, an intact breast, are enrolled in the Breast and Ovarian Surveillance Service (BOSS) Cohort, and visited the Johns Hopkins Cancer Genetics Clinic for risk assessment within 2 months of cohort enrollment (N = 374). All screening was self-reported at baseline, 4, and 8 years. A subset has been validated. We categorized women by BC risk (Tyrer-Cuzick version) obtained at the clinic. We examined frequency of screening over follow-up, and defined adherence to annual mammography and breast MRI based on age- and risk-based guidelines. We modeled the association between BC risk and adherence at 4 and 8 years using logistic regression. Results: At baseline, the median age was 47 years, 31% had lifetime risk < 20%, and 69% had risk ≥20%. Frequency of mammography and clinical breast exam over follow-up was > 60%, while frequency of breast MRI and breast ultrasound was < 40%. Twenty-five percent of high-risk women at 4 years and 40% at 8 years did not report any mammography, breast MRI, or breast ultrasound. At 4 years, high-risk women were 85% less adherent [multivariable adjusted OR = 0.15; 95%CI = 0.07, 0.34] to BC screening guidelines compared to women with a risk of < 20% due to low uptake of breast MRI, while at 8 years, high-risk women were also less adherent to mammography [multivariable adjusted OR = 0.42; 95%CI = 0.18, 0.95]. We observed similar associations among women at high-risk at 5- and 10-years. Adherence at 4 years predicted adherence at 8 years. Interestingly, women who did not uptake MRI complied with other health screening including for colorectal cancer. Conclusions: High-risk women were not adherent to risk-appropriate BC screening, and adherence did not improve over time. Low adherence appears specific to BC screening. New approaches to BC screening are urgently needed for this high-risk group.
Incidental atypical hyperplasia/LCIS in mammoplasty specimens and subsequent risk of breast cancer.
Authors: Acevedo Francisco , Armengol Victor Diego , Deng Zhengyi , Tang Rong , Coopey Suzanne , Mazzola Emanuele , Lanahan Conor , Braun Danielle , Yala Adam , Barzilay Regina , Li Clara , Santus Enrico , Colwell Amy , Guidi Anthony , Cetrulo Curt , Garber Judy Ellen , Smith Barbara L. , King Tari A. , Hughes Kevin S.
Published: May 2019

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Background: Proliferative breast lesions with atypia (atypical hyperplasia and lobular carcinoma in-situ (LCIS)) increase the risk of breast cancer (BC). Most cases are diagnosed in the context of an abnormal mammogram. Little is known about BC risk for patients with these lesions who are asymptomatic. Mammoplasty specimens allow us to study breast tissue in asymptomatic healthy women. We previously published the rate of atypia in the largest reported mammoplasty cohort. The aim of this study is to examine the risk of BC in the atypia cohort. Methods: Breast pathology reports were retrospectively reviewed for evidence of atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH) or LCIS in bilateral reduction mammoplasty specimens from five institutions within a single healthcare system between 1990 to 2017. Patients with prior or concurrent BC or prior atypia were excluded. Data was extracted from electronic medical records using natural language processing and manual review to assess subsequent risk of BC. Results: From our mammoplasty cohort of 4771 patients, 295 patients were found to have atypia (6.2%) at baseline. 40 of these patients were lost to follow-up and excluded from the study. For the remaining 255 patients, 13 had severe ADH bordering on ductal carcinoma in situ, 52 had LCIS, 119 had ALH, and 71 had ADH at baseline. The median age at baseline was 52.1 (range 17.9 – 74.3). With a median follow-up of 7.7 years, of the 255 patients 9 patients developed BC (8 invasive carcinomas, 1 ductal carcinoma in situ). 81.3% of the cohort did not receive chemoprevention. Only one patient out of the nine who developed BC received chemoprevention. The risk of developing BC among women with atypia at baseline was 0.5%, 2.9% and 4.1%, at 3, 5 and 10 years respectively. Conclusions: Patients with asymptomatic atypias found in reduction mammoplasty specimens appear to be at lower risk of developing BC than those diagnosed with atypia in the context of an abnormal mammogram. These results may provide guidance on how to manage this group of patients related to future screening and/or chemoprevention.
A real-world evidence study of CDK4/6 inhibitor treatment patterns and outcomes in metastatic breast cancer by gBRCA mutation status.
Authors: McLaurin Kimmie , Dalvi Tapashi , Collins Jenna M , Nordstrom Beth L , McCutcheon Susan , Bennett James C , Murphy Brian R , Singhal Puneet K , Briceno Josefa Maria
Published: May 2019

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Background: Limited data exist on the real-world treatment patterns and effectiveness of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors in the germline BRCA (g BRCA) mutated breast cancer population. Methods: Adults with human epidermal growth factor receptor 2 negative (HER2-), hormone receptor positive (HR+) metastatic breast cancer (mBC) treated with a CDK4/6 inhibitor from 01Jan2013–31Jan2018 were retrospectively selected from the Flatiron Health Oncology electronic medical record database. Patients with known g BRCA status were classified as having g BRCA mutated (g BRCAm) or wild type (g BRCAwt) disease. Time to first subsequent therapy or death (TFST) and overall survival (OS) were calculated from start of the earliest line of therapy with a CDK4/6 inhibitor. Kaplan-Meier (KM) medians were estimated, and TFST and OS compared between g BRCA groups with Cox models stratified by line of therapy and adjusting for demographic and clinical characteristics that modified hazard ratios (HRs) for g BRCA status by > 10%. Results: Of 2968 HER2- HR+ patients with mBC receiving a CDK4/6 inhibitor, g BRCA status was known for 859 (28.9%). Patients with g BRCAm and g BRCAwt received letrozole plus palbociclib (42.4 and 39.8%, respectively), fulvestrant plus palbociclib (32.9 and 30.7%), or other CDK4/6 regimens (24.7 and 29.5%) across all lines. The g BRCAm group had a non-significant, shorter TFST than g BRCAwt (stratified HR 1.24; 95% CI 0.96–1.59). OS was significantly shorter in g BRCAm than g BRCAwt patients (stratified HR 1.50; 95% CI 1.06–2.14). Conclusions: The results of this real-world study suggest that treatment outcomes with CDK4/6 inhibitors may be poorer in patients with g BRCAm compared with g BRCAwt disease. These findings indicate a higher unmet need among patients with g BRCAm, potentially requiring alternative treatment options. [Table: see text]
Unselected germline screening in pancreatic adenocarcinoma yields high rates of pathogenic and likely pathogenic variants (PV) in hereditary cancer susceptibility genes.
Authors: Cremin Carol , Lee Michael , Hong Quan , Hoeschen Carolyn , Kalloger Steve , Karasinska Joanna , Mackenzie Anna , McCullum Mary , Nuk Jennifer E , Topham James Thomas , Sun Sophie , Schaeffer David F. , Renouf Daniel John , Schrader Kasmintan A
Published: May 2019

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Background: Recent literature cites a germline mutation rate of 3.9-15.1% in patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) depending on breadth of genes tested, pre-selection of high-risk history and population substructure. True incidence of germline mutations in PDAC is unknown in unselected population. Methods: All patients (pts) diagnosed with PDAC in the province of British Columbia, Canada and referred to the Hereditary Cancer Program, were eligible to undergo 30 gene Color saliva kit testing under a research protocol, or clinical multigene testing if they met existing local criteria regardless of whether they signed on to the protocol. Any healthcare provider or patients themselves could refer. Results: 243 pts were referred between August 2016 and October 2018 but 25.1% (61) declined and 9.1% (22) died before testing. Of the 141 pts who consented to research protocol and completed germline testing, median age was 64 (46.1-81.0), 68.8% were European, 1.4% Ashkenazi Jewish heritage, 42% male, 61% non-smoker, 24.1% had personal history of a second cancer and 39% had metastatic disease. Baseline characteristics were similar between the PV positive and uninformative group. 20/25 PV were in known PDAC susceptibility genes with cascade screening implications (ATM (9), BRCA2 (4), BRCA2/ATM (1), CDKN2A (4), and MSH2 (2)). Excluding the 3 PV identified through carrier testing (1) and prior research identification (2), the rate of PV in unselected, unrelated PDAC cohort is 22/138 (15.9%). Utilizing previous NCCN criteria for BRCA1/BRCA2 testing or for familial pancreatic cancer did not appear to select for patients with higher risk of PV positive (12/65 (18.4%) PV positive rate versus 13/76 (17.1%) in those that didn’t meet criteria). Previous criteria would have missed 52% (13/25) PV in ATM (6), BRCA2/ATM (1), BRCA2 (2), MSH2 (2), NBN (1), CHEK2 (1). To date, a third of families with PV identified have accessed cascade testing in 38 relatives. Conclusions: Given the high incidence of 15.9% PV in hereditary cancer susceptibility genes, our data support recommendations for universal germline genetic testing of PDAC pts.
Germline mutation profile among Hispanic women with epithelial ovarian cancer (EOC).
Authors: Chavarri Guerra Yanin , Weitzel Jeffrey N. , Blazer Kathleen Reilly , Slavin Thomas Paul , Mejia Rosa , Sand Sharon , Castillo Danielle , Herzog Josef , Villarreal-Garza Cynthia , Mohar Alejandro , Rodriguez Yeny , Mora Alferez Analí Pamela , Hake Christopher R. , Cescon Terrence , Bobolis Kristie , Kerlin Deborah , Komenaka Ian K. , Rice Patricia , Horcasitas Darling J ,   Clinical Cancer Genomics Community Research Network Consortium
Published: May 2019

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Background: Hospital-based studies have reported a 15% prevalence of BRCA1/ BRCA2( BRCA) mutations, with a slightly higher yield of other predisposition genes on multigene panel testing (MGPT) among women with EOC, and National Comprehensive Cancer Network guidelines recommend genetic cancer risk assessment for women with EOC. However, there is limited data about the genetic epidemiology of EOC among underrepresented populations, such as Hispanics. Consequently, we determined the germline mutation profile of Hispanics with EOC, and compared them with non-Hispanics. Methods: We included all women with a personal history of EOC from the U.S. and Latin America (LatAm; Mexico, Colombia, and Peru), enrolled in the Clinical Cancer Genomics Community Research Network registry. We assessed the prevalence of pathogenic variants (PV) in BRCA1/ BRCA2( BRCA) and other genes, contrasting the germline mutation profile between Hispanics living in LatAm, U.S. Hispanics, women of Ashkenazi Jewish (AJ) ancestry in the US, and other U.S. non-Hispanics. Results: Among 1186 women with EOC (209 from LatAm, 254 U.S. Hispanics l, 78 AJ, and 645 other non-Hispanic), 262 (22%) had a PV in BRCAgenes. Hispanics from LatAm and the U.S. had a similar frequency of BRCAmutations to AJ (30.6%, 29.9%, and 38.4%, respectively; p = 0.14); while non-Hispanics showed a significantly lower frequency of BRCAmutations (14.2%, p = 0.03). The most frequently mutated gene was BRCA1(n = 197, 74.6%), followed by BRCA2(n = 67, 25.3%). Among BRCA-negative cases (n = 924), 59% (n = 545) were evaluated by MGPT and PVs were identified in 2.9% [6 Hispanics (1.2%), 3 AJ (3.8%) and 26 Non-Hispanics (4%)]), of which 66% (n = 23) were in mismatch repair genes ( MSH2, MLH1, MSH6, PMS2), and 34% (n = 12) in other EOC-associated genes ( BRIP1, NBN, PALB2, RAD51C, and RAD51D). Clinically actionable PVs in ATM (n = 4; 0.3% ) and CHEK2 (n = 6; 0.5% ) were also observed. Conclusions: Hispanics with EOC have an elevated frequency of PV, similar to that of classic founder populations such as AJ, and significantly higher than other non-Hispanics. This is partially explained by a high prevalence of recurrent LatAm-specific PV, highlighting the importance of conducting genetic studies in underrepresented populations. There was modest incremental benefit of MGPT.