bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contralateral breast cancer risk according to first breast cancer characteristics among United States women from 1992 to 2015.
Authors: Ramin Cody , Withrow Diana , Davis Lynn Brittny , Gierach Gretchen , Berrington de González Amy 
Published: May 2019

1549 Background: After recent advances in breast cancer treatment and increasing uptake of contralateral prophylactic mastectomies, estimates of contralateral breast cancer (CBC) risk by year of diagnosis and other patient characteristics are needed to help inform decision making. Methods: We estimated CBC risk in 399,032 1-year survivors of a first primary breast cancer (stage I-III) in the US Surveillance, Epidemiology, and End Results Database (1992-2015). CBC was defined as an invasive second breast cancer diagnosed in the opposite breast 12+ months after the first breast cancer diagnosis. We estimated standardized incidence ratios (SIRs) and 5-year cumulative incidence of CBC by calendar period, age, breast cancer subtype, and receipt of hormonal therapy for the initial breast cancer. SIRs were calculated as the observed number of CBCs among survivors compared to the expected number of first breast cancers in the general population. Cumulative incidence was estimated in women without contralateral prophylactic mastectomies and accounted for competing risks. Results: Among 399,032 breast cancer survivors, 11,365 cases of CBC were diagnosed through 2015. Risk of CBC was elevated over the entire study period (SIR = 2.23, 95% CI = 2.19-2.27). SIRs for CBC declined over calendar period and this decreasing trend was observed irrespective of age, estrogen receptor (ER) status, and hormonal therapy. Survivors had an overall 5-year cumulative incidence of CBC of 1.49% (95% CI = 1.44%-1.54%), which decreased over time to 1.31% (95% CI = 1.23%-1.41%) in 2008-2014. For recent diagnoses, the 5-year cumulative incidence of CBC was higher after ER-negative (1.80%, 95% CI = 1.55%-2.07%) and triple negative tumors (1.98%, 95% CI = 1.52%-2.55%), and lowest for women who received hormonal therapy (1.01%, 95% CI = 0.90%-1.13%). Conclusions: Although CBC risk is declining in the US from 1992-2015, survivors have approximately twice the risk of an incident breast cancer (in the contralateral breast) compared to the general population. The 5-year cumulative risk of CBC is highest after ER-negative/triple negative tumors highlighting the need for medical surveillance and targeted interventions among these patients.
Predicting future cancer incidence by age and gender.
Authors: Garner Wesley B. , Smith Benjamin D. , Shabason Jacob Ezra , Williams Grant Richard , Martin Michelle Y. , Ballo Matthew T. , VanderWalde Noam Avraham 
Published: May 2019

1559 Background: Cancer remains a substantial and unique burden on society. While the impact of changing demographics on cancer incidence has previously been characterized (Smith et al, JCO, 2009), this has not been done with updated population data. Our objective was to update projections on the number of new cancer diagnoses in the United States by age and gender through 2040. Methods: Population-based cancer incidence data were obtained using SEER 18 delay-adjusted data. Population estimates were made by age, race, and gender using the 2010 US Census data population projections to calculate future cancer incidence rates. Trends in age- adjusted incidence rates for 23 cancer types were calculated as previously described (Edwards et al, Cancer, 2014). Results: From 2020 to 2040 the projected total cancer incidence will increase by almost 30% from 1.86 million to 2.4 million. This increase is due to the projected increase in population growth, particularly in older individuals. The population of older adults will represent a growing proportion of total cancer diagnoses. Specifically, patients ≥65 years old will make up 69% of all new cancer diagnoses, while 13% of new diagnoses will be in patients ≥85 years old by 2040 (see Table). Cancer diagnoses in females are projected to rise 27%, while male cancer diagnoses are projected to increase by 32% from 2020 to 2040. The incidence rates for lung, colorectal, and prostate cancer are expected to decline, while those for thyroid, liver, melanoma and myeloma are expected to increase. Conclusions: The landscape of cancer care will continue to change over the next several decades. The burden of disease will remain substantial and will continue to disproportionately affect older adults. The growing proportion of older cancer patients and changes in site-specific cancer incidence rates remain of particular interest. These projections should help guide future health policy and research priorities. [Table: see text]
Risk of anxiety and depression in breast cancer survivors compared to women who have never had cancer: A population-based cohort study in the United Kingdom.
Authors: Carreira Helena , Williams Rachael , Funston Garth , Stanway Susannah Jane , Bhaskaran Krishnan 
Published: May 2019

1564 Background: Breast cancer survivors are the largest group of cancer survivors in the United Kingdom (UK). Having had a breast cancer diagnosis may adversely affect the patient’s mental health. We aimed to estimate the long-term risk of anxiety and depression in women with history of breast cancer compared to those who have never had cancer. Methods: We conducted a matched population-based cohort study, using data from the Clinical Practice Research Datalink (CPRD) GOLD primary care database. The exposed cohort included all adult women diagnosed with breast cancer between 1987 and 2018; the unexposed group included women with no cancer history, matched to exposed women in a 4:1 ratio on primary care practice and age. Cox regression models stratified on matched set were used to estimate hazard ratios of the association between breast cancer survivorship and anxiety and depression. Results: 59,972 women (mean 62 years; standard deviation (SD) 14.0) had history of breast cancer. The median follow-up time was 3.0 years (SD 4.4), which amounted to 256,186 person-years under observation. The comparison group included 240,387 women followed up over 3.5 years (SD 4.5) (1,163,819 person-years). The incidence of anxiety in breast cancer survivors was 0.08 (95% confidence interval (95%) 0.07-0.08) per 1000 person-years, and the incidence of depression was 70 (95%CI 68-71) per 1000 person-years. The risks of both depression and anxiety were raised in breast cancer survivors compared with controls, and this appeared to be driven by the first 3 years following diagnosis (Table). Conclusions: Breast cancer survivors in the UK had significantly higher risk anxiety and depression diagnosed in primary care for three years following diagnosis than women who never had cancer. Risk of anxiety and depression in breast cancer survivors compared to women who did not have cancer by time since diagnosis. [Table: see text]
Risk of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) in a cohort of 3,546 women prospectively followed after receiving textured breast implants.
Authors: Ghione Paola , Cordeiro Peter G. , Ni Ai , Hu Qunying , Ganesan Nivetha , Galasso Natasha , Dogan Ahmet , Horwitz Steven M. 
Published: May 2019

1565 Background: Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare subtype of T-cell lymphoma, developing in in the fluid or capsule surrounding breast implants, primarily or exclusively in those with textured surfaces. Several prior series have estimated the risk of BIA- ALCL at 1/6920 - 1/3800 women in retrospectively defined cohorts (from diagnosed cases within national or pathology databases), approximating the population at risk from sales records or other estimates (Sirinvasa 2017; Loch-Wilkinson 2017; de Boer 2018). Methods: A prospective cohort study was conducted in the population that underwent breast reconstruction by a single surgeon at Memorial Sloan Kettering Cancer Center (MSKCC) from April 1993 to December 2017. Patients had long-term follow-up, and events related to implants were prospectively recorded. We identified all cases of BIA-ALCL by cross-checking data from internal clinical records, pathology records, and outside reports. Incidence rate per person-years and cumulative incidence when accounting for competing risk were calculated. 134 women who received smooth-surface implants were excluded from the analysis, since these implants have not been associated with BIA-ALCL. Results: From 1993 to 2017, 3546 patients underwent 6023 breast reconstructions using textured surface implants. All reconstructions were performed by a single surgeon (PGC) on patients enrolled in this study. To identify BIA-ALCL occurrence, clinical and pathological data were assessed from a prospective database. Median follow-up was 7 years (range, 3 days - 24.7 years). Eight women developed ALCL after a median exposure of 11.2 years (range, 8.3-15.8 years). Overall risk of BIA-ALCL in this cohort was 0.294 cases per 1000 person-years (1/443 women). Conclusions: This study, evaluating the risk of women with textured breast implants from a prospective database with long-term follow-up, demonstrated that the incidence rate of BIA-ALCL may be higher than previously reported. These results can help inform implant choice for women undergoing breast reconstruction.
Factors associated with breast cancer mortality-per-incident case in low-to-middle income countries (LMICs).
Authors: Chagpar Anees B. , Coccia Mario 
Published: May 2019

1566 Background: Reducing breast cancer mortality is a key healthcare challenge worldwide. We sought to determine the impact of macro-socioeconomic factors on breast cancer age-standardized incidence (ASI) and mortality-per-incident case (MPI) in LMICs. Methods: Data regarding breast cancer ASI and mortality in 78 LMICs were obtained from IARC/WHO. MPI was defined as the age standardized mortality divided by the ASI. Country-level socioeconomic data were obtained from World Bank, UN Development Project, and WHO data sources. Results: In 2018, the median ASI for breast cancer was 26.5 (range; 5-67.3) per 100,000 population in LMICs, with a median MPI of 50.6% (range 27-70%). ASI and MPI were inversely correlated (Spearman rho = -0.236, p = 0.044). Factors associated with ASI and MPI are shown in the table below. We found no factor could discriminate between the highest and lowest quartile in terms of ASI. However, all (except health expenditure as a % of GDP) were significantly different between the highest and lowest quartile in terms of MPI. Conclusions: Results suggest considerable variation in terms of breast cancer MPI within LMICs. Improved rates are seen with increasing GDP, literacy, contraceptive use, and provision of doctors and mammography, but overall % GDP expended on public health does not seem to significantly influence breast cancer MPI. [Table: see text]
Adverse effects of early bilateral oophorectomy on body composition: Results from a nationally representative sample of United States women.
Authors: Karia Pritesh S , Joshu Corinne , Visvanathan Kala 
Published: May 2019

1568 Background: Prior studies suggest that bilateral oophorectomy (BO), a common cancer prevention strategy, may be associated with adiposity. However, the impact of BO on lean mass, a potential marker of healthy aging, and whole-body composition is not known. Declines in lean mass have been linked to physical disability and mortality. We examined the association between BO and total and regional distribution of fat and lean mass in a cross-sectional study. Methods: The study population included women 35-70 years who underwent dual-energy x-ray absorptiometry (DXA) scans at enrollment as part of the National Health and Nutrition Examination Survey 1999-2006 (N = 3,764). Multinomial logistic regression models were used to examine the relationship between prior BO and tertiles of fat and lean mass. Models were adjusted for age, race, education, BMI at age 25, physical activity, smoking, alcohol use, parity, oral contraceptive use and hormone replacement therapy use. Results: Women with prior BO < 45 years (n = 346) had 2.9-times higher odds than women without BO (n = 3,212) of being in the highest compared to the lowest tertile of total fat mass (OR, 2.91; 95% CI, 1.93-4.38) and 2.7-times higher odds of being in the lowest compared to the highest tertile of total lean mass (OR, 2.67; 95% CI, 1.81-3.95). Results were similar when stratified by age at enrollment ( < 45, 45-54, and ≥55). Similarly, among women with normal BMI at enrollment, those with prior BO < 45 years (n = 74) had higher odds of being in the highest tertile of total fat mass (OR, 9.88, 95% CI, 2.21-44.00) and the lowest tertile of total lean mass (OR, 10.09; 95% CI, 2.72-37.46). These differences in body composition were most pronounced in the trunk region. No difference was observed in women with BO ≥45 years compared to women without BO. Conclusions: Women with a history of early BO experience significant changes in body composition, including increased fat mass and decreased lean mass, even while maintaining a normal BMI. If validated in future prospective studies, our results suggest that a comprehensive evaluation of body composition may be warranted in young women who undergo BO.
Racial disparities in cancer survival: A trend analysis based on SEER data (1973-2010).
Authors: Alavi Seyed Navid , Eze Chibuzo , Pandellapalli Poornima 
Published: May 2019

1571 Background: African Americans have higher incidence of cancer and lower survival rates compared to other ethnicities. We studied the 5-year relative survival between black and white races for the most common cancers in the United States. Methods: Data was obtained from the SEER database, the largest population-based cancer database including 28% of US population. Data containing 5-year relative survival from the patients who were diagnosed from 1973 to 2010. We included data for cancers of colorectal, lung, prostate, breast and melanoma, the most common cancers in the United States. Results: For colorectal cancer average 5-year relative survival from 1973 to 2010 is 59.9% for whites and 51.5% for blacks. Same results for lung cancer are 14.6% for whites and 12.2% for blacks, for breast cancer is 84.5% for whites and 71.6% for blacks, for prostate cancer is 86.9% for whites and 80.5% for blacks, and for melanoma is 87.9% for whites and 66.4% for blacks. The average black to white 5-year relative survival ratio is 0.86, 0.84, 0.85, 0.92, and 0.76 for cancers of colorectal, lung, breast, prostate, and melanoma, respectively. This ratio has decreased from 0.89 to 0.86 and from 0.87 to 0.81 for colorectal and lung cancer, respectively and for cancers of breast, prostate and melanoma it has increased from 0.85 to 0.87, from 0.88 to 0.89, and from 0.73 to 0.80 respectively. Conclusions: Our analysis shows that for colorectal and lung cancer the survival rate difference between blacks and whites has increased over 4 decades but for cancers of breast, prostate and melanoma this ratio has decreased. Better understating of the factors contributing to racial differences in cancer survival has potential applicability in policymaking for a better and equal health care delivery.
Relationship of liver cancer with LRP1B or TP53 mutation and tumor mutation burden and survival.
Authors: Wang Longrong , Yan Kai , Zhou Jiamin , Zhang Ning , Wang Miao , Song Jia , Zhao Jing , Zhang Yuzi , Cai Shangli , Zhao Yiming , Wang Lu 
Published: May 2019

1573 Background: Liver cancer (LC), one of the most common causes of cancer-related deaths, is a serious medical problem due to the limited treatment options available for this disease. Immune checkpoint inhibitors (ICIs) that are proved to be beneficial in the treatment of advanced LC. Similar to observations in other cancers, these ICIs as monotherapy may benefit only a fraction of HCC patients. Tumor mutation burden (TMB) is an important predictor for efficacy of ICIs in several solid tumors. However, the research on exploring the association between TMB and mutant genes with high frequency of liver cancer is limited. Besides, previous research on prognostic factors primarily focus on pathological features, probing the effects of genetic variations are urgently needed to study. Methods: Whole-exome sequencing data of 377 liver tumors from the Cancer Genome Altas (TCGA) and next generation sequencing (NGS) data of 655 liver tumors from Chinese clinical dataset were analyzed to explore the associated between LRP1B or TP53 gene alteration and TMB. TMB was defined as total number of somatic non-synonymous mutations in coding region. Results: In total, 9.3% (35/377) of hepatic tumors in TCGA and 7.8% (51/655) in clinical cohort harboring LRP1B mutation. LRP1B mutation was significantly associated with higher TMB in both TCGA cohort (P = 0.0003) and clinical cohort (P = 0.0005). The frequency of TP53 mutation was 28.1% (106/377) in TCGA cohort, however, TP53 mutation represented a greater rate of 54.5% (357/655) in Chinese clinical cohort. TP53 mutation was also associated with higher TMB in the two cohort (P = 0.0005 for the TCGA cohort and P = 0.0010 for the clinical cohort). In addition, prognosis analysis was performed on patients in TCGA cohort. LRP1B statue resulted in significantly shorter overall survival (OS, median, 20.9 vs 61.7 months; HR, 2.22; P = 0.0012), and a decreasing trend on progression-free survival (PFS) without significant difference (median, 8.7 vs 16.6 months; HR, 1.28; P = 0.2839). TP53 mutation was an independent risk factors affecting both OS (HR 1.58, P = 0.0109) and PFS (HR 1.59, P = 0.0027), respectively. Conclusions: The results indicated that LRP1B or TP53 mutation was a poor prognostic factor in LC, and patients harboring any of these two gene mutations might easily benefit from the immunotherapy.
Second interim and first molecular analysis of the EORTC randomized phase III intergroup CATNON trial on concurrent and adjuvant temozolomide in anaplastic glioma without 1p/19q codeletion.
Authors: Van Den Bent Martin J. , Erridge Sara , Vogelbaum Michael A. , Nowak Anna K. , Sanson Marc , Brandes Alba Ariela , Wick Wolfgang , Clement Paul M. , Baurain Jean-Francois , Mason Warren P. , Wheeler Helen , Weller Michael , Aldape Kenneth D. , Wesseling Pieter , Kros Johan M. , Tesileanu Mircea , Golfinopoulos Vassilis , Gorlia Thierry , Baumert Brigitta G. , French Pim 
Published: May 2019

2000 Background: The 1st interim analysis of the CATNON trial showed benefit from adjuvant (adj) temozolomide (TMZ) on overall survival (OS) but remained inconclusive about concurrent (conc) TMZ. A 2nd interim analysis was planned after 356 events. Methods: The 2x2 factorial design phase III CATNON trial randomized 751 adult patients with newly diagnosed non-codeleted anaplastic glioma to either 59.4 Gy radiotherapy (RT) alone; the same RT with concTMZ; the same RT and 12 cycles of adjTMZ or the same RT with both concTMZ and adjTMZ ( doi: 10.1016/S0140-6736(17)31442-3). MGMT promoter methylation ( MGMTmeth) status was re-assessed with the Infinium Methylation EPIC Beadchip using the MGMT_STP27 model. Isocitrate dehydrogenase 1 and 2 ( IDH) mutation (mt) status was assessed with glioma targeted Agilent SureSelect baits sequence using an Illumina HiSeq2500 Rapid PE100. Results: With a median follow-up of 56 months and 356 events, the hazard ratio (HR) for OS adjusted for stratification factors after concTMZ was 0.968 (99.1% CI 0.73, 1.28). 5-year OS was 50.2% with and 52.7% without concTMZ (95% CI [44.4, 55.7] and [46.9, 58.1]). An IDHmt was found in 335 of 480 assessed cases (70%). Median OS was 19 mo (95% CI 16.3, 22.3) in IDHwt tumors and 116 mo (95% CI 82.0, 116.6) in IDHmt tumors. HR for OS after concTMZ in patients with known IDH status. Clinical trial information: NCT00626990. IDHmt was predictive of benefit from adjTMZ ( IDHmt HR: 0.41, 95% CI 0.27, 0.64; IDHwt: HR 1.05, 95% CI 0.73, 1.52; interaction test p = 0.001). In IDHmt patients that received adjTMZ, the HR for OS after concTMZ was 0.71 (95% CI 0.35, 1.42, p=0.32). MGMTmeth was found in 288 of 410 assessed cases (70%), interaction test for concTMZ (p = 0.092) and adjTMZ (p = 0.166) did not reach statistical significance. Conclusions: In the entire study cohort, concTMZ did not increase OS. However, in IDHmt tumors a trend towards benefit of concTMZ is present. AdjTMZ increased OS in IDHmt but not in IDHwt tumors. The ongoing molecular analyses and further follow-up will allow full assessment of efficacy in the molecular subgroups.[Table: see text]
A phase I, open label, perioperative study of AG-120 and AG-881 in recurrent IDH1 mutant, low-grade glioma: Results from cohort 1.
Authors: Mellinghoff Ingo K. , Cloughesy Timothy Francis , Wen Patrick Y. , Taylor Jennie Webster , Maher Elizabeth A. , Arrillaga Isabel , Peters Katherine B. , Choi Changho , Ellingson Benjamin M. , Lin Alexander P. , Thakur Sunitha B , Nicolay Brandon , Lu Min , Le Kha , Yin Feng , Tai Feng , Schoenfeld Steven , Steelman Lori , Pandya Shuchi Sumant , Clarke Jennifer Leigh 
Published: May 2019

2003 Background: AG-120 (ivosidenib [IVO]) is a first-in-class oral inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1) evaluated in 66 glioma patients (pts) in an ongoing phase 1 study. AG-881 (vorasidenib [VOR]) is an oral, potent, brain-penetrant inhibitor of mIDH1/2 evaluated in 52 glioma pts in an ongoing phase 1 study. In an orthotopic glioma model, IVO and VOR reduced 2-hydroxyglutarate (2-HG) by 85% and 98%, respectively, despite different brain:plasma ratios (<0.04 vs 1.33). Methods: Primary endpoint: brain tumor 2-HG concentration with IVO or VOR treatment in mIDH1 low-grade glioma. Pts with recurrent non-enhancing WHO-2016 Grade (Gr) 2 or 3 mIDH1-R132H oligodendroglioma or astrocytoma undergoing craniotomy were randomized 2:2:1 to IVO 500mg QD, VOR 50mg QD, or no treatment for 4 wks preoperatively in Cohort 1. Post-operatively, pts continued to receive IVO or VOR and control pts were randomized 1:1 to IVO or VOR. Tumors were assessed for mIDH1 status, cellularity, 2-HG, and drug concentration. Treated samples were compared to control pts and mIDH1 and wild type (WT) banked reference (ref) samples. Plasma and CSF 2-HG were assessed. Pts with non-evaluable tissue were replaced. Results: As of 29 Nov 2018, 26 pts (17M, 9F; 25 Gr 2, 1 Gr 3) were randomized preoperatively (IVO 10, VOR 11, control 5), 25 received drug (IVO 12, VOR 13). At the data cut, 19 tumors were analyzed with 16 evaluable. Common (>10%) TEAEs (all grade 1/2): diarrhea (36%), hypocalcemia and constipation (each 20%), anemia, hyperglycemia, pruritus, headache and nausea (each 16%), and hypokalemia and fatigue (each 12%). Mean brain:plasma ratio: 0.16 for IVO, 2.4 for VOR. Tumor 2-HG results are shown in Table. Updated data from Cohort 1 will be presented. Conclusions: In Cohort 1 of this phase 1 perioperative study, IVO and VOR were CNS penetrant and lowered 2-HG compared to untreated samples. Cohort 2 is open and will evaluate IVO 250mg BID and VOR 10mg QD. Brain tumor 2-HG concentration. Clinical trial information: NCT03343197. [Table: see text]