OBJECTIVE: To evaluate if uterine myoma is associated with breast cancer. METHODS: This case-control study used a nationwide database in Taiwan. We identified 24,315 patients with newly diagnosed breast cancer as cases and matched them with 24,281 patients without breast cancer on age, sex, urbanization, income, and initial diagnosis date. Patients with prior mastectomy were excluded. We used logistic regression analysis to assess the association between uterine myoma and breast cancer while adjusting for confounders. We evaluated the impact of surgical removal of uterine myoma on subsequent breast cancer among patients with uterine myoma. RESULTS: We found that 2,892 (11.9%) patients with newly diagnosed breast cancer and 2,541 (10.5%) patients without breast cancer had a history of uterine myoma. The association between breast cancer and uterine myoma was significant (adjusted odds ratio [aOR]=1.14; 95% confidence interval [CI]=1.07–1.21; p<0.001). This association remained in patients who used hormone (aOR=1.20; 95% CI=1.08–1.33; p=0.001) or who did not use hormone (aOR=1.11; 95% CI=1.03–1.19; p=0.005) within 5 years prior to the index date. Surgical removal of uterine myoma was not associated with a decreased risk of breast cancer (aOR=0.99; 95% CI=0.88–1.10; p=0.795). CONCLUSION: A minor increased risk of breast cancer was found in women with a history of uterine myoma. This association remained in patients with recent hormone use. Removal of uterine myoma was not associated with decreased risk of breast cancer.
Breast Neoplasms* ; Breast* ; Case-Control Studies* ; Diagnosis ; Female ; Hormone Replacement Therapy ; Humans ; Leiomyoma* ; Logistic Models ; Mastectomy ; National Health Programs ; Odds Ratio ; Taiwan ; Urbanization ; Uterus

OBJECTIVE: Uterine myoma which results in the magnitude of ovarian cancer remains uncertain. This study aimed to assess the association between women with previous uterine myoma and the risk of ovarian cancer. METHODS: This population-based case-control study was conducted using the Taiwan National Health Insurance Research Database between 2006 and 2010. We identified 4,088 adult women with newly diagnosed ovarian cancer with 16,348 women without ovarian cancer matched for age, urbanization level, income and initial diagnosis date. Logistic regression analyses were used to evaluate the variables associated with ovarian cancer. In addition, the effect of surgical interventions on the risk of ovarian cancer was also evaluated. RESULTS: Women with previous uterine myoma were more likely than those who did not to have ovarian cancer (adjusted odds ratio [aOR]=2.26; 95% confidence interval [CI]=2.06−2.49). Patients with uterine myoma who either received (aOR=1.79; 95% CI=1.51−2.13) or did not receive hormone replacement therapy (aOR=2.51; 95% CI=2.24−2.82) experienced a significantly higher risk of ovarian cancer than those without uterine myoma, respectively. However, patients with uterine myoma who underwent either myomectomy (aOR=0.55; 95% CI=0.39−0.77) or hysterectomy (aOR=0.33; 95% CI=0.26−0.42) had a significantly lower risk of ovarian cancer. CONCLUSION: The results revealed that a significantly higher risk of ovarian cancer in women with previous uterine myoma, through an indirect mechanism. Furthermore, a lower risk of ovarian cancer was observed in women who underwent surgical removal of the uterine myoma.
Adult ; Case-Control Studies ; Diagnosis ; Female ; Hormone Replacement Therapy ; Humans ; Hysterectomy ; Leiomyoma ; Logistic Models ; National Health Programs ; Odds Ratio ; Ovarian Neoplasms ; Taiwan ; Urbanization

BACKGROUNDEarly detection with screening mammography can potentially reduce breast cancer mortality rates. To achieve an efficient screening, a peer review system provides a compensatory double-check reviewing, will hopefully to prevent the omission of detectable lesions and reduce unnecessary recall.

METHODSIn 2009, 4643 initial mammographic screenings reported by 74 screening radiologists had negative results with a recall rate of less than 5%. In the same year, 2538 initial positives screened by 18 screening radiologists had a recall rate higher than 15%. Those 7181 randomized screenings were evenly distributed for reassessment by 39 reviewing radiologists. The disagreement of assessments between the reviewers and screening radiologists was recorded. The differential rate was defined as the number of the disagreements divided by the number of audited films reviewed by a screening radiologist. The equality of the differential rates for each screening radiologists with negative and positive assessments was compared by a Chi-square test. The performance of the 39 auditors was measured by the Kendall's tau statistic. P values less than 0.05 were considered statistically significant.

RESULTSThe mean differential rate for screening radiologists of negative assessments was 6.7% (P = 0.588), while 35.0% for positive assessments were significant (P < 0.001). The result indicated that most of the initial negative assessments reported by the screening radiologists were generally accepted by the reviewers but not the positive assessments. With respect to the 39 reviewers, there was no significant evidence for the association of the difference rates between negative and positive assessments. Nine reviewers were found to have their differential rate for negative and positive assessments larger than the average of the population. Eleven reviewers were found to have their differential rates smaller than the average for both. Thirteen reviewers had their differential rates smaller than the average for negative assessments but larger than the average for positive assessments. The opposite condition was found for six reviewers. The Kendall's tau statistic was 0.038 (P = 0.735).

CONCLUSIONSReviewers usually agreed with the opinion of the initial screening doctors who reported negative findings. Therefore, a 5% recall rate as the lower range of reviewing negatives may be still too high. The recall rate of more than 15% was significantly related to improper interpretation, especially when the differential rate is 25% or higher, a warning to the underperforming screening radiologist is recommended. An ideal reviewer should interpret films independently. Reviewers with tendencies to be followers or contrarians should not be enrolled in the reviewing system.

Breast Neoplasms ; diagnostic imaging ; Early Detection of Cancer ; Female ; Humans ; Mammography ; Peer Review ; Reproducibility of Results ; Taiwan

BACKGROUND/OBJECTIVES: Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of α-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha (PPARα). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by PPARα. MATERIALS/METHODS: The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among PPARα homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate (PPARα agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA. RESULTS: PPARα ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, PPARα activation increased hepatic Acox, Fads1, Fads2 and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex. CONCLUSIONS: LCPUFA enzyme expression was altered by PPARα. Either PPARα deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.
Animals ; Brain ; Brain-Derived Neurotrophic Factor ; Clofibrate ; Docosahexaenoic Acids ; Fatty Acid Desaturases ; Liver ; Mice ; Peroxisomes ; PPAR alpha ; Retina ; RNA, Messenger

Diabetic nephropathy (DN) is a hyperglycemia-induced progressivedevelopment of renal insufficiency. Excessive glucose can increase mitochondrialreactive oxygen species (ROS) and induce cell damage, causing mitochondrial dysfunction.Our previous study indicated that cilostazol (CTZ) can reduce ROS levelsand decelerate DN progression in streptozotocin (STZ)-induced type 1 diabetes.This study investigated the potential mechanisms of CTZ in rats with DN and in highglucose-treated mesangial cells. Male Sprague–Dawley rats were fed 5 mg/kg/day ofCTZ after developing STZ-induced diabetes mellitus. Electron microscopy revealedthat CTZ reduced the thickness of the glomerular basement membrane and improvedmitochondrial morphology in mesangial cells of diabetic kidney. CTZ treatmentreduced excessive kidney mitochondrial DNA copy numbers induced by hyperglycemiaand interacted with the intrinsic pathway for regulating cell apoptosis as anantiapoptotic mechanism. In high-glucose-treated mesangial cells, CTZ reduced ROSproduction, altered the apoptotic status, and down-regulated transforming growthfactor beta (TGF-) and nuclear factor kappa light chain enhancer of activated B cells(NF-B). Base on the results of our previous and current studies, CTZ decelerationof hyperglycemia-induced DN is attributable to ROS reduction and thereby maintenanceof the mitochondrial function and reduction in TGF- and NF-B levels.

Diabetic nephropathy (DN) is a hyperglycemia-induced progressivedevelopment of renal insufficiency. Excessive glucose can increase mitochondrialreactive oxygen species (ROS) and induce cell damage, causing mitochondrial dysfunction.Our previous study indicated that cilostazol (CTZ) can reduce ROS levelsand decelerate DN progression in streptozotocin (STZ)-induced type 1 diabetes.This study investigated the potential mechanisms of CTZ in rats with DN and in highglucose-treated mesangial cells. Male Sprague–Dawley rats were fed 5 mg/kg/day ofCTZ after developing STZ-induced diabetes mellitus. Electron microscopy revealedthat CTZ reduced the thickness of the glomerular basement membrane and improvedmitochondrial morphology in mesangial cells of diabetic kidney. CTZ treatmentreduced excessive kidney mitochondrial DNA copy numbers induced by hyperglycemiaand interacted with the intrinsic pathway for regulating cell apoptosis as anantiapoptotic mechanism. In high-glucose-treated mesangial cells, CTZ reduced ROSproduction, altered the apoptotic status, and down-regulated transforming growthfactor beta (TGF-) and nuclear factor kappa light chain enhancer of activated B cells(NF-B). Base on the results of our previous and current studies, CTZ decelerationof hyperglycemia-induced DN is attributable to ROS reduction and thereby maintenanceof the mitochondrial function and reduction in TGF- and NF-B levels.

PURPOSE: The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)–mutant lung adenocarcinoma patients with acquired resistance after firstline EGFR–tyrosine kinase inhibitor (TKI) treatment. MATERIALS AND METHODS: We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFR mutation status. RESULTS: A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression-free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). CONCLUSION: PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746-A750 mutation are associated with the frequency of T790M mutation.
Adenocarcinoma* ; Disease-Free Survival ; Epidermal Growth Factor* ; Exons ; Humans ; Lung Neoplasms ; Lung* ; Mutation Rate ; Odds Ratio ; Phosphotransferases ; Point Mutation ; Prevalence ; Receptor, Epidermal Growth Factor* ; Sequence Deletion