Background and Objectives
We sought to evaluate the impact of chemotherapy sequence on survival by comparing node‐positive invasive lobular carcinoma (ILC) patients who received neoadjuvant (NACT) ...and adjuvant (ACT) chemotherapy.
Methods
cT1‐4c, cN1‐3 ILC patients in the National Cancer Data Base (2004‐2013) who underwent surgery and chemotherapy were divided into NACT and ACT cohorts. Kaplan‐Meier curves and Cox proportional hazards modeling were used to estimate unadjusted and adjusted overall survival (OS), respectively.
Results
Five thousand five hundred fifty‐one (35.6%) of 15 573 ILC patients treated with chemotherapy received NACT. NACT patients had similar rates of pT3/4 disease (26.6% vs 26.2%), nodal involvement (median 3 vs 4), and number of lymph nodes examined (median 13 vs 14) but higher rates of mastectomy (81.8% vs 74.5%, P < 0.001) vs ACT patients. 3.4% of NACT patients experienced pathologic complete response (pCR). Unadjusted 10‐year OS was worse for NACT vs ACT patients (65.1% vs 54.4%, log‐rank P < 0.001). After adjustment for known covariates, NACT continued to be associated with worse OS (hazard ratio HR, 1.38; 95% confidence interval CI, 1.25‐1.52).
Conclusions
In node‐positive ILC, NACT yielded low rates of pCR, was not associated with lower rates of mastectomy or less extensive axillary surgery, and was associated with worse survival vs ACT, suggesting limited benefit for these patients.
Objective: The goal of this study is to use adjunctive classes to improve a predictive model whose performance is limited by the common problems of small numbers of primary cases, high feature ...dimensionality, and poor class separability. Specifically, our clinical task is to use mammographic features to predict whether ductal carcinoma in situ (DCIS) identified at needle core biopsy will be later upstaged or shown to contain invasive breast cancer. Methods: To improve the prediction of pure DCIS (negative) versus upstaged DCIS (positive) cases, this study considers the adjunctive roles of two related classes: atypical ductal hyperplasia (ADH), a non-cancer type of breast abnormity, and invasive ductal carcinoma (IDC), with 113 computer vision based mammographic features extracted from each case. To improve the baseline Model A's classification of pure vs. upstaged DCIS, we designed three different strategies (Models B, C, D) with different ways of embedding features or inputs. Results: Based on ROC analysis, the baseline Model A performed with AUC of 0.614 (95% CI, 0.496-0.733). All three new models performed better than the baseline, with domain adaptation (Model D) performing the best with an AUC of 0.697 (95% CI, 0.595-0.797). Conclusion: We improved the prediction performance of DCIS upstaging by embedding two related pathology classes in different training phases. Significance: The three new strategies of embedding related class data all outperformed the baseline model, thus demonstrating not only feature similarities among these different classes, but also the potential for improving classification by using other related classes.
Acrylamide (AA) has been identified as probably carcinogenic to humans and thus represents a potential public health threat. This study aimed to determine the urinary concentrations of AA and
N
...-acetyl-
S
-(2-carbamoylethyl)-
l
-cysteine (AAMA) in a nationally representative sample (
n
= 1025) of children and adolescents (age range 3–18 years) in South Korea. The AA and AAMA detection rates and geometric mean concentrations were 97%, 19.1 ng/mL, and 98.7%, 26.4 ng/mL, respectively. Although urinary AA levels did not vary widely by age (17.2 ng/mL at 3–6 years, 19.9 ng/mL at 7–18 years), the urinary concentration of AAMA increased with age (18.3 ng/mL at 3–6 years, 30.4 ng/mL at 7–18 years). A multiple linear regression analysis revealed that the urinary levels of AA and AAMA varied significantly by sex, with the adjusted proportional changes indicating rates of 1.47- to 1.48-fold higher at 3–6 years and 1.36- to 1.68-fold higher at 7–18 years among males relative to females. Furthermore, the urinary levels of AA and AAMA correlated with the consumption of certain foods (doughnuts, hotdogs, popcorn, and nachos) among male subjects aged 7–18 years. The urinary concentrations of AA and AAMA increased significantly with the smoking status and passive smoking exposure, with adjusted proportional changes of 1.51 to 1.71-fold higher among smokers relative to non-smokers in the age range of 7–18 years. Exposure to smoking for > 30 min led to adjusted proportional increases in AA and AAMA of 1.51 and 1.77 times in the non-smoking group aged 3–6 years and a 1.52-fold increase in AAMA in the non-smoking group aged 7–18 years. In conclusion, the urinary levels of AA and AAMA were found to associate with age, sex, smoking, and food consumption in a population of Korean children and adolescents.
Arsenic is a human carcinogen. Data on urinary arsenic species analyses of Koreans are limited. This study evaluated the arsenic exposure level, contributing factors, and health effects in Korean ...adults. Dietary intake information and urine samples were obtained from 2044 participants. Arsenic exposure was assessed based on urinary concentrations of arsenic species, such as inorganic arsenic, As(III) and As(V), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and arsenobetaine (AsB), using high-performance liquid chromatography with inductively coupled plasma mass spectrometry, followed by determination of biomarkers, malondialdehyde and c-peptide. The geometric mean concentrations were 30.9 μg/L for the sum of inorganic arsenic and their metabolites, and 84.7 μg/L for the total sum of arsenic measured. Urinary concentrations of arsenic species were influenced by age, inhabitant area (inland or coastal), and seafood intake, which was positively correlated with inorganic arsenic, DMA, and AsB. Rice intake was positively correlated with inorganic arsenic and its metabolites but not with AsB. Additionally, malondialdehyde and c-peptide levels were significantly associated with urinary concentrations of various arsenic species. Seafood and rice are major sources of organic/inorganic arsenic exposure in Korean adults; however, it is necessary to evaluate whether their overconsumption could have a potentially detrimental effect on human health.
Purpose
The purpose of the study was to define quantitative measures of intra-tumor heterogeneity in breast cancer based on histopathology data gathered from multiple samples on individual patients ...and determine their association with distant recurrence-free survival (DRFS).
Methods
We collected data from 971 invasive breast cancers, from 1st January 2000 to 23rd March 2014, that underwent repeat tumor sampling at our institution. We defined and calculated 31 measures of intra-tumor heterogeneity including ER, PR, and HER2 immunohistochemistry (IHC), proliferation, EGFR IHC, grade, and histology. For each heterogeneity measure, Cox proportional hazards models were used to determine whether patients with heterogeneous disease had different distant recurrence-free survival (DRFS) than those with homogeneous disease.
Results
The presence of heterogeneity in ER percentage staining was prognostic of reduced DRFS with a hazard ratio of 4.26 (95% CI 2.22–8.18,
p
< 0.00002). It remained significant after controlling for the ER status itself (
p
< 0.00062) and for patients that had chemotherapy (
p
< 0.00032). Most of the heterogeneity measures did not show any association with DRFS despite the considerable sample size.
Conclusions
Intra-tumor heterogeneity of ER receptor status may be a predictor of patient DRFS. Histopathologic data from multiple tissue samples may offer a view of tumor heterogeneity and assess recurrence risk.
In this study, 27 chemicals found in household products, which became an issue in Korea were screened for the agonistoc and antagonistic effects against human estrogen receptor using official ...Organization for Economic Cooperation and Development (OECD) in vitro assays, STTA assay using ERα-HeLa-9903 cell line and BG1Luc ER TA assay. In the case of human ER agonist screening by two assays, all tested chemicals did not show agonist effect against ER. In ER antagonist test by BG1Luc ER TA assay, five surfactants α-dodecyl-ω-hydroxypoly(oxyethylene), alcohols C16-18 ethoxylated, nonylphenol, ethoxylated, 3,6,9,12,15,18,21-heptaoxatritriacontan-1-ol, and α-dodecyl-ω-hydroxypoly(oxy-1,2-ethanediyl)) were found to exhibit weak antagonistic activities. The agonist/antagonist effects against human estrogen receptor of various chemicals, used in Korea by OECD test guideline are reported in this study. These results indicated that two OECD in vitro assays will can be applied in Korea by screening of agonistic/antagonistic effects against human ER of various chemicals.
•OECD in vitro assays applied for screening of the agonistic/antagonistic effect against human ER on 27 chemicals.•No chemicals exhibited the agonistic effect against human ER.•Five surfactants have been found week antagonistic activities mediated by binding affinity against ER.
Aggressive breast cancer variants, like triple negative and inflammatory breast cancer, contribute to disparities in survival and clinical outcomes among African American (AA) patients compared to ...White (W) patients. We previously identified the dominant role of anti-apoptotic protein XIAP in regulating tumor cell adaptive stress response (ASR) that promotes a hyperproliferative, drug resistant phenotype. Using The Cancer Genome Atlas (TCGA), we identified 46-88 ASR genes that are differentially expressed (2-fold-change and adjusted p-value < 0.05) depending on PAM50 breast cancer subtype. On average, 20% of all 226 ASR genes exhibited race-related differential expression. These genes were functionally relevant in cell cycle, DNA damage response, signal transduction, and regulation of cell death-related processes. Moreover, 23% of the differentially expressed ASR genes were associated with AA and/or W breast cancer patient survival. These identified genes represent potential therapeutic targets to improve breast cancer outcomes and mitigate associated health disparities.
Bisphenol A (BPA) is considered to be an endocrine disruptor, but the mechanisms by which it disrupts endocrine functions are poorly understood. Here, we have shown that BPA binds both estrogen ...receptor (ER)-α and ER-beta (ER-β) using a fluorescence polarization competitive binding assay. In addition, we found that BPA induced cell proliferation by modulating cell cycle-related genes in the MCF-7 human mammary cancer cell line. Moreover, using a BG1 luciferase ER transactivation assay, we found that BPA has estrogenic activity. Modulating the MAPK pathway by using an ERK inhibitor (PD98059) or a JNK inhibitor (SP600125) had no effect on the ability of BPA to induce estrogenic activity. However, the antiestrogen, ICI 182,780, and the p38 inhibitor, PD 169316 successfully blocked BPA-induced estrogenic activity. Our findings suggest that BPA mimics ER-dependent estrogenic activity by targeting proteins that regulate the cell cycle and p38 MAPK.
Parabens are broad-spectrum antimicrobial agents used in a range of consumer products, including personal care products, cosmetics, and food. Recently, the widespread use of parabens has raised ...concerns about the potential health risks associated with their endocrine-disrupting effect. In the present study, 2541 urine samples were collected and analyzed by liquid chromatography-mass spectrometry for the determination of the concentrations of methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP) and butyl paraben (BuP). The detection rate and geometric mean concentrations of parabens in the general population followed the order MeP (97.7%; 116ng/mL)>EtP (97.2%; 24.7ng/mL)>PrP (96.7%; 11.0ng/mL)>BuP (83.5%; 1.13ng/mL). The composition profiles showed that MeP and EtP accounted for >90% of the urinary paraben concentration. We performed statistical analysis in order to evaluate differences between demographic variables and urinary concentrations. Our results showed that adjusted proportional change of MeP, PrP, and BuP in adults were 2.67–6.13 times higher in females than in males. The urinary concentrations of PrP in adults increased significantly with age. The adjusted proportional changes of MeP and PrP in adults were associated with increased body mass index (BMI). The adjusted proportional changes of BuP and PrP in children and adolescents were 1.44 and 1.69 times higher in females than in males. However, there was no clear association between paraben concentrations and demographic variables in the children and adolescents groups. The estimated daily intake (EDIurine) of MeP and EtP in adults were 301μg/kg bw/day, which is lower than the acceptable daily intake (ADI; 10mg/kg bw/day). In summary, our results revealed that the general population in Korea was exposed to parabens during 2009–2010, and most Koreans are exposed to parabens. The urinary levels of parabens varied by age group with demographic factors in the Korean population. The results of study may be used to establish a nationally representative baseline of exposure to parabens in risk assessment.
•We examined urinary concentrations of 4 paraben compounds in a Korean national survey.•Most Koreans are exposed to parabens (range of geometric means: 1.13–116ng/mL).•Koreans have different ethyl paraben composition profiles compared with other countries.•Urinary parabens vary by age with demographic factors such as sex and BMI.
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