Che Lin

Triple negative breast carcinoma is a prognostic factor in Taiwanese women

BackgroundCurrently, there is a debate as to whether triple negative breast carcinoma (TNBC) has a worse prognosis than non-TNBC. Our aim was to determine whether TNBC is a prognostic factor for survival.MethodsWe identified 1,048 Taiwanese breast carcinoma patients, of whom 167 (15.9%) had TNBC. Data used for analysis were derived from our cancer registry database for women with breast cancer who were diagnosed between 2002 January and 2006 December.ResultsIn the Kaplan-Meier analysis, tumor subgroup (TNBC vs. non-TNBC) was a prognosis factor related to 5-year overall survival. In the univariate analysis, tumor subgroup (TNBC vs. non-TNBC) was a significant factor related to 5-year overall survival, in addition to age, tumor size, lymph node, metastasis, grade, stage, estrogen receptor status, progesterone receptor status, and HER2 overexpression status. In the multivariate analysis, tumor subgroup was not a significant factor related to 5-year disease-free survival (DFS). In node-positive patients, tumor subgroup was a significant factor related to 5-year overall survival, in addition to age, tumor size, metastasis, and grade. In node-negative patients, tumor subgroup was not a significant factor related to 5-year disease-free survival and 5-year overall survival.ConclusionOur results indicated that TNBC patients in Taiwan have worse 5-year overall survival than non-TNBC patients. Notably, in node-positive patients, TNBC played a prognostic role in 5-year overall survival.

Survival Benefit of Tamoxifen in Estrogen Receptor-Negative and Progesterone Receptor-Positive Low Grade Breast Cancer Patients

Purpose This study aimed to analyze the efficacy and prognostic significance of adjuvant tamoxifen in breast cancer patients with various hormone receptor statuses. Methods Typically, 1,260 female breast cancer patients were recruited in this study. The correlation between estrogen receptor (ER)/progesterone receptor (PR) phenotypes and clinical characteristics was investigated, and the survival rate was assessed after 5-year follow-up. Results The 5-year overall survival (85%) was better in women under the age of 50 years. Patients with ER+/PR+ tumors had a better 5-year survival rate (94%); those with ER-/PR- tumors experienced the worst outcome (74% survival rate); whereas single-positive cases were in between. In 97 out of 128 patients with ER-/PR+ tumors, tamoxifen was given as adjuvant hormonal therapy, and it increased the survival benefit in the lower grade group in terms of overall survival and disease-free survival (p=0.01 and p=0.03, respectively). Conclusion For high-grade tumors with ER-/PR+, adjuvant tamoxifen therapy may have no survival benefit, whereas for the patients with low-grade ER-/PR+ tumors, adjuvant tamoxifen therapy is highly suggestive.

CHARACTERIZATION OF BENIGN AND MALIGNANT SOLID BREAST MASSES : HARMONIC VERSUS NONHARMONIC 3D POWER DOPPLER IMAGING

The aim of this study was to compare the diagnostic performance of nonharmonic ultrasound (US) and tissue harmonic imaging (THI) using three-dimensional (3D) power Doppler sonographic technique to classify benign and malignant breast tumors by vascularization. From January 2003 to February 2004, we evaluated 200 patients and one of lobular carcinoma in situ was excluded from the malignant category. One hundred and ninety-nine subjects were enrolled. All subjects with one or more breast masses were studied with 3D power Doppler US nonharmonic and harmonic technologies. Sixteen of 199 subjects were excluded because masses exceeded 3 cm limit of our US probes footprint (n = 5) or no harmonic Doppler information (n = 11). A total of 97 benign and 86 pathologically proven malignant breast tumor images were analyzed. 3D power Doppler US imaging was performed using a Voluson730 US system. Three histogram indices, the vascularization index (VI), flow index (FI) and vascularization-flow index (VFI), on both nonharmonic and harmonic images were calculated for the intratumor and for shells with an outside thickness of 3 mm surrounding the breast lesion. A multilayer perception (MLP) neural network classifier used the vascularity indices to determine whether the breast tumors are benign or malignant. The receiver operating characteristic (ROC) curves are performed to estimate the diagnostic performances for nonharmonic and harmonic methods. ROC curve analysis used overall age, volume, VI, FI and VFI for both intratumor and shells with an outside thickness of 3 mm surrounding the breast lesions in nonharmonic US and THI. The area under the ROC curve (A(Z)) was 0.9086 and 0.9009 (p = 0.3770). The sensitivity was 90.7% and 83.7% (p = 0.72), respectively, and the specificity was 92.8% and 92.8% (p = 1.00), respectively. In conclusion, the performance of 3D power Doppler US with respect to the characterization of solid breast masses as benign or malignant was not significantly improved with tissue harmonic imaging.

Airborne particulate collected from central Taiwan induces DNA strand breaks, Poly(ADP-ribose) polymerase-1 activation, and estrogen-disrupting activity in human breast carcinoma cell lines

The objectives of this investigation were to examine whether airborne particles induce DNA damaging and estrogen-disrupting effects and to explore the relationships between them. In this study, airborne particulate was collected at an urban, a suburban, and a rural site in central Taiwan. The organic solvent extracts of airborne particulate were examined in human MCF-7 and T47D-KBluc breast cancer cells. We observed significant increases in reactive oxygen species (ROS) generation in MCF-7 cells after treatment with the particulate extracts whereas aryl hydrocarbon receptor (AhR) antagonist blocked the particulate-induced ROS generation in cells. Further, induction of CYP1A1 protein expression was confirmed by immunoblots in cells treated with airborne particles, suggesting the roles of AhR status in mediating the particulate-induced toxicity. In addition, we observed that at non-cytotoxic concentration (∼0.01 m3 air equivalent), airborne particles induced decreases in intracellular NAD(P)H and NAD+ in MCF-7 cells. These decreases were completely blocked by three types of poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors. Moreover, we demonstrated increases in the number of DNA strand breaks in MCF-7 cells exposed to airborne particles as measured by the single-cell gel electrophoresis (Comet) assay. Overall, this evidence confirms that airborne particles induce decreases in intracellular NAD(P)H and NAD+ through PARP-1 activation mediated by formation of DNA strand breaks. Furthermore, we confirmed that with series dilution airborne particles (∼10−7–10−2 m3 air equivalent) possess both estrogenic and anti-estrogenic activities as determined by the ERα-mediated reporter gene assay in human T47D-KBluc breast cancer cells. In conclusions, we confirmed that the DNA-damaging activity and estrogenicity of airborne particles varied considerably with concentration (air equivalent). Our findings add further support to the theme that ROS formation is a significant determinant factor in mediating the induction of oxidative DNA damage and repair in human breast cancer cells exposed to airborne particles and that oxidative stress and the subsequent induction of DNA damage may, in part, contribute to airborne particle-induced carcinogenesis.

Pure mucinous carcinoma of the breast: clinicopathologic characteristics and long-term outcome among Taiwanese women

BackgroundPure mucinous carcinoma (MC) is found in about 3.5% of all newly diagnosed breast cancer patients in Taiwan. MC is a relatively rare malignancy of breast cancer, and its nature, behaviors, treatment pattern and long-term follow-up are not well understood. The study aimed to investigate the incidence rate, treatment patterns, and prognostic factors of MC of the breast and the clinical long-term outcomes compared with infiltrating ductal carcinoma not otherwise specified (IDC) in the middle and south Taiwanese women.MethodsData from 93 patients with breast MC were retrospectively reviewed and the clinicopathologic characteristics and survival status were compared with those of 2,674 patients with IDC.ResultsThe expression of hormonal receptor was higher in MC than those in IDC (P <0.001). MC also demonstrated lower Her2/neu gene over-expression (P = 0.023), less axillary lymph node involvement (P <0.0001), lymphovascular invasion (P <0.0001) and higher 10-year overall survival rate (P = 0.042), when compared with those of IDC.ConclusionOur data confirm the less aggressive behavior of MC compared to IDC. MC showed favorable clinicopathologic characteristics in tumor grade, hormone receptor status and lymph node involvement in the middle and south Taiwanese women.

Cumulative body burdens of polycyclic aromatic hydrocarbons associated with estrogen bioactivation in pregnant women: protein adducts as biomarkers of exposure.

The objective of this research was to simultaneously analyze protein adducts of quinonoid metabolites of naphthalene and endogenous estrogen in serum albumin (Alb) derived from healthy pregnant women in Taiwan and to explore the correlations among them. The isomeric forms of cysteinyl adducts of naphthoquinones, including 1,2-naphthoquinone (1,2-NPQ) and 1,4-naphthoquinone (1,4-NPQ) as well as estrogen quinones, including estrogen-2,3-quinones (E2-2,3-Q) and estrogen-3,4-quinones (E2-3,4-Q), are characterized after adduct cleavage. Results showed that the median levels of cysteinyl adducts of 1,2-NPQ and 1,4-NPQ on serum albumin were 249-390 and 16.0–24.8 pmol g−1, respectively. Logged levels of 1,2-NPQ-Alb were correlated with logged levels of 1,4-NPQ-Alb (correlation coefficient r = 0.551, P < 0.001). Cysteinyl adducts of E2-2,3-Q-1-S-Alb, E2-2,3-Q-4-S-Alb, and E2-3,4-Q-2-S-Alb were detected in all subjects with median levels at 275-435, 162-288, and 197-254 pmol g−1, respectively. We also found a positive relationship between logged levels of E2-2,3-Q-4-S-Alb and those of E2-3,4-Q-2-S-Alb (r = 0.770, P < 0.001).We noticed that median levels of E2-2,3-Q-derived adducts (E2-2,3-Q-1-S-Alb plus E2-2,3-Q-4-S-Alb) in pregnant women were greater than those of E2-3,4-Q-2-S-Alb (∼2–3-fold). Taken together, this evidence lends further support to the theme that cumulative concentration of E2-3,4-Q is a significant predictor of the risk of breast cancer. Furthermore, we noticed that levels of 1,2-NPQ-Alb are positively associated with levels of E2-3,4-Q-2-S-Alb (r = 0.522, P < 0.001) and those of E2-2,3-Q-4-S-Alb (r = 0.484, P < 0.001). Overall, this evidence suggests that environmental exposure to polycyclic aromatic hydrocarbons may modulate estrogen homeostasis and enhance the production of reactive quinone species of endogenous estrogen in humans.

A 10-year Follow-up of Triple-negative Breast Cancer Patients in Taiwan

OBJECTIVE This study aimed to investigate whether triple-negative breast cancer has a worse prognosis; here, we present the 10-year follow-up results of triple-negative breast cancer patients in Taiwan. METHODS We identified 2858 breast cancer patients in Taiwan, of whom 416 (14.6%) had triple-negative breast cancer. Data used for analysis were derived from those breast cancer patients who were diagnosed between January 1996 and December 2006. RESULTS In the Kaplan-Meier analysis, tumor subgroup (triple-negative breast cancer vs. non-triple-negative breast cancer) was a prognostic factor related to 10-year breast cancer death-specific survival and disease-free survival. The results of univariate analysis showed that tumor subgroup was a significant factor related to 10-year disease-free survival and breast cancer death-specific survival, as well as menopausal status, tumor size, lymph node, metastasis, grade, stage, estrogen receptor status, progesterone receptor status and her2/neu gene expression status. Similarly, the multivariate analysis also revealed that tumor subgroup was a significant factor related to 10-year breast cancer death-specific survival and disease-free survival, in addition to tumor size, lymph node, metastasis and grade. CONCLUSIONS It was suggested that triple-negative breast cancer patients in Taiwan have worse 10-year survival. Notably, in node-positive patients, triple-negative breast cancer played a prognostic role in 10-year breast cancer death-specific survival.

Investigation of the cumulative body burden of estrogen-3,4-quinone in breast cancer patients and controls using albumin adducts as biomarkers

Both 17β-estradiol-2,3-quinone (E2-2,3-Q) and 17β-estradiol-3,4-quinone (E2-3,4-Q) are reactive metabolites of estrogen. Elevation of E2-3,4-Q to E2-2,3-Q ratio is thought to be an important indicator of estrogen-induced carcinogenesis. Our current study compared the cumulative body burden of these estrogen quinones in serum samples taken from Taiwanese women with breast cancer (n=152) vs healthy controls (n=75) by using albumin (Alb) adducts as biomarkers. Results clearly demonstrated the presence of cysteinyl adducts of E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb in all study population at levels ranging from 61.7-1330 to 66.6-1,590 pmol/g, respectively. Correlation coefficient between E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb was 0.610 for controls and 0.767 for breast cancer patients (p<0.001). We also noticed that in premenopausal subjects with body mass index (BMI) less than 27, background levels of E2-3,4-Q-2-S-Alb was inversely proportional to BMI with about 25% increase in E2-3,4-Q-2-S-Alb per 5 kg/m(2) decrease in BMI (p<0.001). In addition, we confirmed that mean levels of E2-3,4-Q-2-S-Alb in breast cancer patients were ∼5-fold greater than in those of controls (p<0.001). Overall, this evidence suggests that disparity in estrogen disposition and the subsequent elevation of cumulative body burden of E2-3,4-Q may play a role in the development of breast cancer.

Hemoglobin adducts as biomarkers of estrogen homeostasis: elevation of estrogenquinones as a risk factor for developing breast cancer in Taiwanese women.

The aim of this study was to establish a methodology to analyze estrogen quinone-derived adducts, including 17β-estradiol-2,3-quinone (E2-2,3-Q) and 17β-estradiol-3,4-quinone (E2-3,4-Q), in human hemoglobin (Hb). The methodology was then used to measure the levels of these adducts in Hb derived from female breast cancer patients (n=143) as well as controls (n=147) in Taiwan. Our result confirmed that both E2-2,3-Q- and E2-3,4-Q-derived adducts, including E2-2,3-Q-4-S-Hb and E2-3,4-Q-2-S-Hb, were detected in all breast cancer patients with median levels at 434 (215-1472) and 913 (559-2384) (pmol/g), respectively. Levels of E2-2,3-Q-4-S-Hb correlated significantly with those of E2-3,4-Q-2-S-Hb (r=0.622-0.628, p<0.001). By contrast, median levels of these same estrogen quinone-derived adducts in healthy controls were 71.8 (35.7-292) and 139 (69.1-453) (pmol/g). This translated to ~6-fold increase in mean values of E2-2,3-Q-4-S-Hb and E2-3,4-Q-2-S-Hb in breast cancer patients compared to those in the controls (p<0.001). Our findings add further support to the theme that cumulative body burden of estrogen quinones is an important indicator of breast cancer risk. We hypothesize that combination of genetic events and environmental factors may modulate estrogen homeostasis and enhance the production of estrogen quinones which lead to subsequent generation of pro-mutagenic DNA lesions in breast cancer patients.

Adjuvant Tamoxifen Influences the Lipid Profile in Breast Cancer Patients

Background: Currently there is a debate regarding whether tamoxifen used in breast cancer has an impact on lipid profiles. The aim of this study was to determine whether tamoxifen has an impact on the serum lipid profile in Taiwanese women. Patients and Methods: Data of 109 patients were collected from the routine clinical follow-up for women with hormone receptor-positive breast cancer who were treated between July 2005 and March 2008. These patients were divided into 2 subgroups, based on their tumor grade and lymph node status. Subgroup 1 patients had tumor grade I/II and a negative lymph node status. Those patients with tumor grade III or a positive lymph node status were defined as subgroup 2. Results: In the 109 patients, the mean serum total cholesterol (TC) levels after tamoxifen treatment, as well as the serum low-density lipoprotein cholesterol (LDL-C) levels, were lower than the baseline levels, with statistically significant differences. Treatment with tamoxifen lowered the serum TC and LDL-C levels in both subgroups. Conclusions: The results indicate that tamoxifen has an impact on the serum lipid profile of breast cancer patients in Taiwan. Physicians should follow up the lipid profile in these patients.