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Purpose Dynamic changes of body image and quality of life (QoL) in breast cancer patients were not commonly investigated. We aimed to compare the dynamic changes in QoL and body image of breast cancer survivors receiving breast-conserving surgery or total mastectomy within 5-10 years after surgery. Methods Patients with non-metastatic breast cancer who received surgery were invited to complete the World Health Organization Quality of Life-Brief (WHOQOL-BREF) questionnaire and the Body Image Scale (BIS) within 10 years after surgery. We applied kernel smoothing methods to capture the dynamic changes of the patients' QoL and body image within 5 years after surgery. We also constructed multiple linear regression models to identify predictive factors for QoL and body image. Results A total of 581 patients were collected, and 211 of them received breast-conserving surgery. There were no statistically significant differences in QoL and body image for breast-conserving surgery versus total mastectomy, but the former showed fluctuating trends. BIS was a predictor of every item and domain in the WHOQOL-BREF in the multiple linear regression model, and explanatory of the trends of dynamic change over time. Patients without lymph node dissection seemed to have less positive feelings but were more satisfied with sexual activities. Conclusion Body image is predictive of the QoL of breast cancer patients. Dynamic changes of body image and QoL would be useful for shared decision-making regarding surgery in breast cancer patients.

This paper presents a three-phase magnetic guidance system to navigate magnetic drugs to the targeted position with induced magnetic forces on the magnetic drugs. A magnetic-vector controlled three-phase exciter has been developed for the magnetic guidance. A 15:1 reduced-scale prototype of the proposed magnetic guidance system is constructed to verify the feasibility of the magnetic navigation.

Background. Endoscopy-assisted breast surgery performed through minimal axillary and/or periareolar incisions is a viable option for patients with breast cancer. In this study, we report the preliminary results of patients with breast cancer who underwent endoscopy-assisted total mastectomy (EATM) followed immediately by pedicled transverse abdominis musculocutaneous (TRAM) flap reconstruction. Methods. Patients in this study comprised women with breast cancer who received EATM and pedicled TRAM flap reconstruction. Clinicopathologic characteristics, type of surgery, complications, and rate of recurrence were recorded. The cosmetic outcomes were evaluated objectively by the surgeons and subjectively by the patients at 3-month postoperative follow-up. Results. A total of 48 patients underwent 49 EATM procedures followed by pedicled TRAM flap reconstruction. Of them, 79.6% underwent endoscopic-assisted nipple-sparing mastectomy and 20.4% received endoscopic-assisted skin-sparing mastectomy. The types of cancer among these patients included ductal carcinoma in situ in 34.7%, stage I cancer in 36.7%, stage II cancer in 24.5%, and stage IIIa cancer in 4.1% patients. Mean tumor size was 2.1 ± 1.4 cm. There were no cases of flap failure. Partial nipple areolar complex ischemia/necrosis occurred in 4 (10.3%) patients; however, all cases resolved after conservative treatment. In the aesthetic outcome evaluation, EATM + TRAM were associated with 89.8% good, 8.2% fair, and 2% unsatisfactory result. No local recurrence was observed during the follow-up period. Conclusion. EATM followed immediately by pedicled TRAM flap reconstruction is a safe procedure and results in good cosmetic outcome in women with early-stage breast cancer.

Purpose Metaplastic carcinoma of the breast (MCB) is a rare histological subtype of breast cancer with an incidence of less than 0.1%–0.5%. Due to its rarity, the clinical characteristics and prognostic significance of MCB compared with other common breast cancers (like infiltrating ductal carcinoma [IDC], and infiltrating lobular carcinoma [ILC]) are not clear, and controversial among different reports. Methods We performed a collective comparison study of multi-institutional cases to evaluate the clinical characteristics and prognostic status of MCB to compare with IDC and ILC. A case control analysis was performed to minimize the bias from clinicopathologic factors between IDC and MCB. Disease free survival (DFS) and overall survival (OS) between groups were compared. Results Forty-five MCB patients were enrolled from the 4 medical centers and compared with 1777 IDC and 53 ILC patients from the CCH cancer registry database comprise the current study. Compared with IDC, MCB was associated with older age, larger tumor size, a lesser lymph node positive rate, a higher likelihood of distant metastasis, higher tumor grade, lower ER-positive tumor, and higher triple negative breast cancer subtype (TNBC). MCB was associated with worse OS ( p = 0.031) than IDC, but no difference in DFS ( p = 0.071); however, MCB was not statistically different from ILC in both DFS and OS ( p = 0.289 and 0.132, respectively). Compared with the case-controlled IDC group, MCB patients had poorer OS ( p = 0.040), but no difference in DFS ( p = 0.439). Conclusion MCB is associated with poorer OS than IDC, and this was related to tumor behavior rather than clinicopathologic factors.

Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin ® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.

The aim of this study was to analyze and determine the prognostic value of the Breast Imaging Reporting and Data System (BI-RADS) classification in Taiwanese patients with breast cancer.Nine hundred ninety-eight patients with breast cancer were diagnosed between January 1, 1999, and August 31, 2005, and 491 (49%) of them were classified as BI-RADS 5. Overall survival and disease-free survival were estimated with the Kaplan-Meier method and compared across the two groups (BI-RADS 5 versus BI-RADS 0-4) using the log-rank test. Univariate and multivariate analyses were used to identify the prognostic factors.The median follow-up time was 81.8 months. Kaplan-Meier analysis showed a significant difference between the two subgroups in five-year overall survival (P = 0.001) and five-year disease-free survival (P0.0001). On univariate analysis, the mammographic findings (BI-RADS 5 versus BI-RADS 0-4) were statistically significantly associated with five-year overall survival and disease-free survival, as were tumor size, lymph-node status, tumor grade, estrogen-receptor status, progesterone-receptor status, and HER-2 status. On multivariate analysis, only the mammographic findings, lymph-node status, HER-2 status, and tumor grade were significant factors related to five-year overall survival and disease-free survival.The BI-RADS classification is a reliable prognostic and predictive factor. Patients with BI-RADS 5 breast cancer showed a worse pattern of relapse than that of BI-RADS 0-4 breast cancer patients.

Preclinical data indicate that the combination of docetaxel, cisplatin and trastuzumab (TCH) may have the potential for clinically significant activity against breast cancers that overexpress the her2/neu gene (HER2). An open-label phase II trial was designed to investigate the response rate and toxicity profile of TCH in breast cancer patients with a primary tumor 2-5 cm in diameter (T2) in its original size.Thirty breast cancer patients with HER2-overexpressing tumors were enrolled. Patients received 6 cycles of docetaxel at 60 mg/m(2) and cisplatin at 50 mg/m(2) given on day 1 and then every 21 days. Trastuzumab was given on day 1, cycle 1 (4 mg/kg), and then continued weekly at 2 mg/kg for 1 year or until disease progression. Tumor measurements were obtained at baseline as well as after 3 and 6 cycles of chemotherapy.We identified 29 breast cancer patients in Taiwan, of whom 13 (44.8%) had pathological complete responses. No cardiac toxicity was observed. Hematologic grade 4 or 3 toxicities were observed in 1 of 28 patients. Non-hematologic grade 4 or 3 toxicities with a reverse pattern were observed in 6 of 29 patients.The results of our study indicate that TCH neoadjuvant chemotherapy is feasible and active in T2 HER2-overexpressing breast cancer patients in terms of pathological complete response rate, complete response, partial response and manageable toxicities.

In this study, the genetic polymorphisms associated with breast cancer in southern Taiwan were investigated. Two categories of genes were analyzed: (1) BRCA1, BRCA2, and Rad51, the DNA repair factors involved in homologous recombinational repair; and (2) CYP1A1, COMT, GST, and NAT2, the xenobiotic-metabolizing enzymes (XME) involved in estrogen metabolism. We found that the number of deletions and/or mutations in the GST genes was highly correlated with the occurrence of breast cancer. These data suggest that the GST enzymes, which detoxify the catechol estrogen quinones, are important target molecules for screening in populations at high risk of breast cancer.

Objective. In this study, quantitative characterization of sonographic image texture and its correlation with histopathologic findings was developed for facilitating clinical diagnosis. A statistical feature matrix was applied to quantify the texture difference (ie, the dissimilarity) of the sonographic images for malignant and benign breast tumors. Methods. Thirty-three patients were recruited for this study. Imaging was performed on a commercially available sonographic imaging system in clinical use. The parameters used for image acquisition were kept the same during clinical examination. Results. On the basis of dissimilarity values, 3 phenomena were noted in the relatively large malignancies studied. First, stellate carcinoma showed the least dissimilarity on sonographic images; second, circumscribed carcinoma showed the most dissimilarity; and third, malignant tissue mixed with fibrous and cellular parts (dense lymphocyte infiltration and prominent intraductal tumors) had dissimilarity values in between. Image textures with smaller dissimilarity values (especially for those values

Background: To formulate individually tailored therapy for patients with early-stage breast cancer, it is necessary to identify biomarkers for predicting metastasis and survival. Methods: A homogeneous cohort of 92 T1-2N0M0 breast carcinoma patients with a long-term follow-up were divided into two groups: the metastasis group (n = 41) and the disease-free group (n = 51). We evaluated the ability of risk discrimination of six biomarkers, including S100A4, Met, bcl-2, p53, survivin, and HER-2/neu, in early-stage breast cancer. Results: In multiple logistic regression analysis, only S100A4 expression (odds ratio = 5.37, p = 0.008) and Met expression (odds ratio = 6.91, p = 0.002) were independent predictors of distant relapse. Multivariate Cox models showed S100A4 and Met expressions were associated with 10-year disease-free survival (DFS) (risk ratio 3.2 and 4.0, respectively); however, tumor size and histological grade were not significant predictors. The 10-year DFS of T1-2N0M0 patients was 55.4%. T1-2N0M0 patients with S100A4-positive tumors had a significantly worse 10-year DFS than those with S100A4-negative tumors (29.0 vs. 68.9 %, p = 0.001). The 10-year DFS in T1-2N0M0 patients with Met-negative tumors was 82.4 vs. 39.7% if Met expression was positive (p = 0.0002). S100A4, but not Met, was still a significant predictor of 10-year DFS in T1N0M0 breast carcinoma patients (p = 0.02). For the T2N0M0 subgroup, both S100A4 and Met were significantly correlated with survival. The 10-year DFS of T2N0M0 patients with S100A4-negative and Met-negative tumors was 92.3%; in those with S100A4-positive and Met-positive tumors, however, it was only 11.8%. Conclusions: S100A4 expression is an indicator of a poor prognosis for T1N0M0 breast cancer. In addition, the combination of S100A4 and Met expression gives the best risk group discrimination in the T2N0M0 subgroup. S100A4 expression appears to be an earlier step in the metastatic progression compared to Met expression in early-stage breast carcinoma.

Background: Patients with breast cancer often receive radiotherapy after mastectomy if they are at a high risk of local recurrence, but the prognosis varies among patients. We conducted a study to evaluate p53, bcl-2 and c-erbB-2 as predictors of prognosis in breast cancer patients receiving post-mastectomy radiotherapy, which has not been well defined in the Taiwanese population. Methods: We recruited 74 consecutive patients with primary operable breast cancer who were treated with mastectomy followed by locoregional radiotherapy and studied the presence of p53, bcl-2 and c-erbB-2 expressions in tumor tissues by immunohistochemical staining. Associations between the protein expressions and clinical outcomes, including local recurrence-free survival (LRFS), metastasis-free survival (MFS) and overall survival (OS), were evaluated. Results: The median follow-up time was 55 months. Expressions of p53, bcl-2 and c-erbB-2 were observed in 14 (19%), 28 (38%) and 39 (53%) patients, respectively. Both p53 and cerbB-2 were significant predictors of MFS. The 5-year MFS for p53-negative and p53-positive tumors were 61.2 and 35.7% (P = 0.01) and 5-year MFS for c-erbB-2-negative and c-erbB-2positive tumors were 71.3 and 42.4% (P = 0.01). Whereas expression of bcl-2 protein is associated with favorable clinicopathological features, it was not related to LRFS, MFS or OS. Multivariate analyses confirmed c-erbB-2 and p53 expressions as predictors of MFS independent of tumor size, histological grading and lymph node involvement. Conclusion: Expressions of p53 and c-erbB-2 are independent predictors of MFS in this Taiwanese population. Further research should be conducted on their application in the treatment and follow-up of patients.

Aim BRCA1, a nuclear phosphoprotein, normally functions as a negative regulator of the cell cycle and may be an active inhibitor of neoplastic progression. Mutation of the BRCA1 gene has been demonstrated in 80% of familial breast cancer. Decreased mRNA levels or aberrant subcellular locations of BRCA1 have been identified in breast cancer lines and in sporadic cases of breast cancer tissues. The expression of BRCA1 in large series of variously differentiated breast carcinomas with correlation with other biological parameters has not been clarified. Methods and results The BRCA1 expression in normal breast tissue (n = 15) and in sporadic cases of invasive ductal carcinoma (n = 108) was determined using immunohistochemistry. BRCA1 expression was correlated with other prognostic parameters including p53, c-erbB-2, bcl-2, oestrogen receptor (ER), histological grade, tumour size, axillary lymph node status and age. BRCA1 was exclusively (100%) localized in the nuclei of normal ductal and lobular epithelia. However, this nuclear expression pattern was variable in breast carcinoma (76.8%). Loss of nuclear BRCA1 expression (22 of 108 cases, 20.4%) correlated well with high histological grade (P

BACKGROUND: Liposarcoma arising within a phyllodes tumor is extremely rare. To the best of our knowledge, a malignant phyllodes tumor with liposarcomatous stroma diagnosed by fine needle aspiration (FNA) has not been reported before. CASE: A 39-year-old female had a malignant phyllodes tumor with liposarcomatous stroma diagnosed by FNA cytology. Two subtypes of liposarcomatous stroma, including lipomalike differentiated and myxoid, were found in the aspirates. The cytologic findings were very representative of the histologic features. CONCLUSION: It is very important to recognize the cytologic features of such rare tumors. An accurate diagnosis preoperatively by FNA permits better therapy planning.

Senescence and epithelial-mesenchymal transition (EMT) have opposing roles in tumor progression, in that, one is a barrier against tumorigenesis, whereas the other is required for invasive malignancies. Here, we report that the DNA damage response (DDR) protein hRAD9 contributes to induction of senescence and inhibition of EMT. Our data show that hRAD9 is frequently downregulated in breast and lung cancers. Loss of hRAD9 expression is associated with tumor stage in breast and lung cancers, as well as with acquisition of an invasive phenotype. Ectopic hRAD9 expression in highly invasive cancer cell lines, H1299 and MDA-MB 231, with low endogenous hRAD9 induced senescence by upregulation of nuclear p21, independent of the p53 status. Ectopic expression of hRAD9 also significantly attenuated cellular migration and invasion in vitro and tumor growth in a xenograft mouse model in vivo. In contrast, silencing hRAD9 in lower invasive cancer cell lines, A549 and MCF7, with high endogenous hRAD9 dramatically increased their migration and invasion abilities, and simultaneously activated EMT. Knockdown of hRAD9 increased, whereas ectopic expression of hRAD9 decreased, the expression of Slug. Moreover, hRAD9 directly bound to the promoter region of slug gene and repressed its transcriptional activity. Taken together, these results suggest that hRAD9 is a potential tumor suppressor in breast and lung cancers and that it is likely to function by upregulating p21 and inhibiting Slug to regulate tumorigenesis.

This study used a Wiggers shock model to investigate the effect of the removal of the intestines on the outcome of hemorrhagic shock.Rats were subjected to laparotomy for the removal of the entire small and large intestines (experimental group) or a sham operation (control group) before bloodshedding. During the period of shock, animals were maintained at 30-35 mm Hg arterial pressure for 2 hours. After reinfusion of the shed blood, rats were observed for over 3 hours for survival. The average volumes (mean +/- SEM) of shed blood were 6.84 +/- 0.23 mL (experimental group) and 6.49 +/- 0.39 mL (control group), with no significant difference between the two (p0.05).This protocol resulted in a 42% mortality (11 of 26) in the control group and 0% mortality (0 of 25) in the experimental group (p0.005, chi2). Moreover, in the survivors, the mean arterial pressure was significantly lower in the control (65.7 +/- 4.3 mm Hg) than in the experimental group (78.2 +/- 3.5 mm Hg) at the end of the experiment (p0.05). Comparing volume status, neither serial hematocrit values nor body weight changes through the experiment had a significant difference between the two groups (p's0.05). Serial quantitation of blood levels of tumor necrosis factor-alpha (TNF-alpha) revealed that systemic TNF-alpha concentrations peaked at 4 hours after shock in both groups. TNF-alpha levels were not reduced by enterectomy. Instead, the peak concentrations were significantly higher in the enterectomized (387.5 +/- 36.5 pg/mL, n = 13) than in the sham-enterectomized group (175.7 +/- 35.9 pg/mL, n = 12,p0.001). Limulus assay, used to detect endotoxins in the blood at 2 hours after restoration of blood volume, showed no endotoxemia in any specimen from either group. Four hours after hemorrhagic shock, blood levels of platelet-activating factor, quantitated by the radioimmunoassay method, were 2.88 +/- 0.18 ng/mL (experimental group, n = 8) and 2.32 +/- 0.32 ng/mL (control group, n = 6). The difference between these two means was not significant (p0.05). Measurement of hepatic adenosine triphosphate (ATP) by the luminometric method showed that hepatic ATP contents were significantly reduced in both groups after shock (p's0.05). However, a higher magnitude of hepatic ATP depletion occurred in the control group; significantly lower amounts of ATP in the liver tissues of the sham-enterectomized group (367 +/- 95 nmol/g, n = 7) than in that of the enterectomized group (870 +/- 100 nmol/g, n = 13) were observed at 5 hours after shock (p0.05).These experimental findings show that, in the absence of the intestines, hemorrhagic shock is associated with both an improved outcome and higher hepatic ATP levels in rats, suggesting the importance of intestinal participation in the process leading to hepatic ATP depletion as well as irreversibility in shock.

Background Pure 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. Methods Data 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. Results The expression of hormonal receptor was higher in MC than those in IDC (P P = 0.023), less axillary lymph node involvement (P P P = 0.042), when compared with those of IDC. Conclusion Our 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.

Background Current guidelines for breast cancer treatment recommend completion axillary lymph node dissection (CALND) following in case of positive sentinel lymph node (SLN) metastasis, which only in 35%–70% shows additional nodal metastases. Several nomograms and scoring systems have been created to predict the risk of metastasis in non-SLNs. The aim of the study was to identify individual patient risk for non-sentinel lymph node metastasis by validating with MSKCC nomogram and to evaluate the variability within a group of SLN-positive breast cancer patients with the final goal of avoiding unnecessary CALND. Patients and methods We retrospectively evaluated 1496 primary breast cancer patients. 324 women with a positive SLN who underwent CALND were identified. The predictive accuracy was measured and compared with the MSKCC nomogram by the area under the receiver operating characteristic curve. Receiver operating characteristic (ROC) curve was drawn on the basis of the sensitivity and specificity, and the area under the curve (AUC) was calculated. Results At least one metastatic non-SLN were identified in 88/324 (27.2%) patients. Tumor size, tumor type, tumor grade, number of positive SLNs and number of negative SLNs were significantly associated with non-SLN status in multivariate analyses. The MSKCC nomogram showed an AUC value of 0.738 (95% confidence interval = 0.682–0.793) after the validation for our collectives. Conclusions The MSKCC nomogram showed a good prediction for the non-SLN metastasis and performed adequately in our patient collective. Therefore, for the use of nomogram, validation with other populations of patients is strongly suggested.

Definitive surgical management of major acute injuries to the second and third portions of the duodenum has been enigmatic. Sometimes, the defect is so large that it is unwise to do primary repair, and resection at this critical portion of the intestinal tract is technically hazardous or impossible. A serosal or mucosal patch technique has been used to repair this kind of duodenal defect with encouraging results. Since the use of this technique has proved effective, such a defect was not necessarily treated with the more complicated pancreaticoduodenectomy and was managed with less morbidity and mortality. But these techniques are still controversial. So, we tried a pedicle flap, called the transverse abdominis musculo-peritoneal (TRAMP) flap, for repair of large duodenal defect. We have used this flap in 25 rabbits, and the specimens were followed up to a period of 3 months. The flap showed satisfactory results and is presented as another option for repair of large duodenal defects.

Importance In neoadjuvant trials, treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancers with dual HER2 blockade resulted in increased pathologic complete response (pCR) rates compared with each targeted agent alone. Amplification and/or overexpression of HER2 currently remains the only biomarker for therapeutic decisions, but it is insufficient to explain the heterogeneous response to anti-HER2 agents. Objective To investigate the ability of clinically and biologically relevant genes and gene signatures (GSs) measured by RNA sequencing to predict the efficacy of anti-HER2 agents. Design, Setting, and Participants The neoadjuvant NeoALTTO trial randomized 455 women with HER2-positive early-stage breast cancer to trastuzumab, lapatinib, or the combination for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide after surgery. The present substudy, which was planned in the NeoALTTO main protocol, evaluated the association of pretreatment gene expression levels defined using RNA sequencing with pCR and event-free survival (EFS). Main Outcomes and Measures Gene expression–based biomarkers using RNA sequencing were examined for their association with response to anti-HER2 therapy and long-term outcome. Results Sequencing data were available for 254 (56%) of the NeoALTTO participants (mean [SD] age of substudy participants, 48.8 [11.2] years). The expression of ERBB2/HER2 was the most significant predictor of pCR, followed by HER2-enriched subtype, ESR1 , treatment arm, ER immunohistochemical analysis scores, Genomic Grade Index, immune, proliferation, and AKT/mTOR GSs. Adjusting for clinicopathological variables and treatment arms, ERBB2/HER2 , HER2-enriched subtype, ESR1, and Genomic Grade Index remained significant. Immune GSs were associated with higher pCR only in the combination arm (odds ratio, 2.1; 95% CI, 1.2-4.0; interaction test P = .01), while the stroma GSs were significantly associated with higher pCR in the single arms and with lower pCR in the combination arm (odds ratio, 0.46; 95% CI, 0.25-0.84; P = .009). None of the evaluated variables was associated with EFS after correction for multiple testing, but this analysis was underpowered. Conclusions and Relevance High levels of ERBB2/HER2 and low levels of ESR1 were associated with pCR in all treatment arms. In the combination arm, high expression of immune and stroma GSs were significantly associated with higher and lower pCR rates, respectively, and should be further explored as candidate predictive markers. Trial Registration clinicaltrials.gov Identifier:NCT00553358

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.

Aims The purpose of this study was to clarify the prognostic significance of triple-negative breast cancer (TNBC) with a tumor size ≤ 1 cm. Materials and methods Patients with primary operable breast cancer with a tumor size ≤ 1 cm were enrolled at Changhua Christian Hospital and National Cheng-Kung University Hospital. Tumors negative for ER, PR, and HER-2 were classified as TNBCs and compared with tumors with any receptor positivity (non-TNBC) for disease-free survival (DFS) and cancer-specific survival (CSS). Results From 1995 to 2006, a total of 377 patients with tumor size ≤ 1 cm were enrolled. Compared with non-TNBC patients, TNBC patients with a tumor size ≤ 1 cm as a whole or in a lymph node-positive subgroup were not associated with a poorer 5-year DFS and CSS. In lymph node-negative patients (pT1a-bN0M0), TNBC was associated with a poorer 5-year CSS but not DFS. Compared with the hormone receptor-positive, HER-2-negative subgroup, TNBC was associated with poorer DFS and CSS. In the multivariate Cox regression hazard analysis, lymph node invasion was the most important cause of disease recurrence and cancer-specific death. Conclusion TNBC is very likely an independent risk factor in small (≤1 cm) node-negative invasive breast cancer. With tumors 1 cm and smaller, lymph node invasion was the single most important prognostic factor.

Background The aims of this study were to determine the accuracy of concurrent core needle biopsy (CNB) and fine needle aspiration biopsy (FNAB) for breast lesions and to estimate the false-negative rate using the two methods combined. Methods Over a seven-year period, 2053 patients with sonographically detectable breast lesions underwent concurrent ultrasound-guided CNB and FNAB. The sonographic and histopathological findings were classified into four categories: benign, indeterminate, suspicious, and malignant. The histopathological findings were compared with the definitive excision pathology results. Patients with benign core biopsies underwent a detailed review to determine the false-negative rate. The correlations between the ultrasonography, FNAB, and CNB were determined. Results Eight hundred eighty patients were diagnosed with malignant disease, and of these, 23 (2.5%) diagnoses were found to be false-negative after core biopsy. After an intensive review of discordant FNAB results, the final false-negative rate was reduced to 1.1% (p-value = 0.025). The kappa coefficients for correlations between methods were 0.304 (p-value < 0.0001) for ultrasound and FNAB, 0.254 (p-value < 0.0001) for ultrasound and CNB, and 0.726 (p-value < 0.0001) for FNAB and CNB. Conclusions Concurrent CNB and FNAB under ultrasound guidance can provide accurate preoperative diagnosis of breast lesions and provide important information for appropriate treatment. Identification of discordant results using careful radiological-histopathological correlation can reduce the false-negative rate.

Background In approximately 80% of breast cancer patients, the hottest sentinel lymph nodes (SLNs) can be used to predict nodal metastasis. We correlate the reliability of using these nodes to predict SLN metastasis with different lymphoscintigraphic patterns in breast cancer. Methods SLN biopsies for T1-2No breast cancer were performed on 467 patients. Lymphoscintigraphic patterns were divided into three groups by the number of draining routes using blue dye and radiocolloid and whether the hottest nodes were the first nodes in the channel. Results The hottest SLNs detected 78 of 87 (90%) cases of SLN metastasis in the 399 patients with successful labeling of both blue dye and radiocolloid in their SLNs. False-negative rates were 0% (single-channel, first node), 58% (multi-channel, first node), and 71% (zero-channel, 0 hottest nodes) (FNR: SingleChanl versus ZeroChanl, P=0.005 and SingleChanl versus MultiChanl, P=0.037; Fisher's exact test). Conclusions We recommend a preoperative lymphoscintigram to distinguish the subset of breast-cancer patients with a single draining channel and whose hottest node is the first node.

We present an unusual case of breast cancer with increased FDG uptake 4 months after chemotherapy. A PET-CT scan displayed results that mimicked multiple lymph node metastases in the right axilla, the mediastinum, and the bilateral pulmonary hilar regions. However, the increased FDG uptake disappeared 17 months later without any additional medical treatment, suggesting the occurrence of flare phenomenon.

Our experience with 73 transverse rectus abdominis myocutaneous (TRAM) flap transfers was reviewed to see the variance in the incidence of complications among three groups of patients undergoing different types of surgical techniques. The TRAM flap was transferred as a free flap in 26 patients, a unipedicled flap in 25 patients, and a microvascularly augmented pedicled flap in 22 patients. Our data demonstrated that the incidence of partial flap loss and fat necrosis in the microvascularly augmented group was significantly lower than that in the unipedicled flap group (P < 0.01), and also lower than that in the free flap group with a statistically marginal significance (P = 0.055). Supplemental surgery is less often required in the microvascularly augmented group than in the conventional TRAM group (P = 0.002). Substantial increase in venous O(2) concentration (P = 0.03), O(2) saturation level (P = 0.007), and pH value (P = 0.002) was noticed following supercharge, and this very fact testifies to the perfusion-promoting effect of the microvascular augmentation maneuver.

Background: Sleep is an important issue for cancer patients and caregivers and poor sleep quality may have deleterious effects on health. This study will examine the correlation between sleep quality and quality of life of breast cancer caregivers. Method: A cross-sectional and correlational design was used to explore the relationship between sleep quality and the quality of life of caregivers. Sixty-one participants were identified by invasive early breast cancer patients, who were diagnosed within the period of 18-month period, as their primary caregivers. The World Health Organization Questionnaire on Quality of Life: BREF-Taiwan version (WHOQOL-BREF-TAIWAN) and the Chinese Pittsburgh Sleep Quality Index (CPSQI) were used to measure the quality of life and sleep quality of caregivers, respectively. Result: Eighty-nine percent of caregivers from this study reported possible sleep difficulties. The scores of CPSQI scores were negatively correlated with the score of every domain of the WHOQOL-BREF-TAIWAN. Discussion: The results suggest that sleep quality may have an impact on several aspects of the quality of life of caregivers. Understanding the correlation between sleep quality and the quality of life of caregivers may assist health professionals in enhancing the sleep quality of caregivers and their ability to care for patients and themselves. Copyright © 2007 John Wiley & Sons, Ltd.

Objective: Early detection is a prerequisite to the effective reduction of morbidity and mortality from breast cancer. The present study intended to employ a high-throughput membrane array to detect a panel of mRNA markers expressed by circulating tumor cells (CTCs) in the peripheral blood of female patients with breast cancer. Methods: Peripheral blood was sampled from 92 breast cancer patients and 100 normal persons. CTCs were detected by using a membrane array technique. The markers used included the pituitary tumor transforming gene 1, survivin, UbcH10 and thymidine kinase 1. Results: The results showed that the membrane array could positively detect 5 cancer cells per 1 ml of peripheral blood in breast cancer cell dilution experiments. For the panel of 4 mRNA markers, sensitivity and specificity were elevated up to 86 and 88%, respectively. Furthermore, it was found that the patients’ clinicopathological characteristics tumor size (p = 0.006), histologic grade (p = 0.012), lymph node metastasis (p = 0.001) and TNM stage (p = 0.006) significantly correlated with the positive detection rate of the multimarker panel. Conclusions: These findings demonstrated that our multimarker membrane array method could detect CTCs in the circulation of breast cancer patients with considerably high sensitivity and specificity.

The objective of this study was mainly to develop and evaluate a membrane array-based method simultaneously detecting the expression levels of a multiple mRNA marker panel in the peripheral blood for used in complementary breast cancer diagnosis. The mRNA markers employed included cytokeratin 19 (CK-19), carcinoembryonic antigen (CEA), c-Met, Her2/neu, and mammaglobin (hMAM). The specimens of peripheral blood were collected from 80 healthy women and 102 female patients with breast cancer. The expression levels of molecular markers were evaluated by real-time Q-PCR and membrane array. Data obtained from real-time Q-PCR and membrane array were subjected to linear regression analysis, revealing that there was a high degree of correlation between the results of these two methods (r=0.979, P

PriB is one of the Escherichia coli varphiX-type primosome proteins that are required for assembly of the primosome, a mobile multi-enzyme complex responsible for the initiation of DNA replication. Here we report the crystal structure of the E. coli PriB at 2.1 A resolution by multi-wavelength anomalous diffraction using a mercury derivative. The polypeptide chain of PriB is structurally similar to that of single-stranded DNA-binding protein (SSB). However, the biological unit of PriB is a dimer, not a homotetramer like SSB. Electrophoretic mobility shift assays demonstrated that PriB binds single-stranded DNA and single-stranded RNA with comparable affinity. We also show that PriB binds single-stranded DNA with certain base preferences. Based on the PriB structural information and biochemical studies, we propose that the potential tetramer formation surface and several other regions of PriB may participate in protein-protein interaction during DNA replication. These findings may illuminate the role of PriB in varphiX-type primosome assembly.

To formulate individually tailored therapy for patients with early-stage breast cancer, it is necessary to identify biomarkers for predicting metastasis and survival.A homogeneous cohort of 92 T1-2N0M0 breast carcinoma patients with a long-term follow-up were divided into two groups: the metastasis group (n = 41) and the disease-free group (n = 51). We evaluated the ability of risk discrimination of six biomarkers, including S100A4, Met, bcl-2, p53, survivin, and HER-2/neu, in early-stage breast cancer.In multiple logistic regression analysis, only S100A4 expression (odds ratio = 5.37, p = 0.008) and Met expression (odds ratio = 6.91, p = 0.002) were independent predictors of distant relapse. Multivariate Cox models showed S100A4 and Met expressions were associated with 10-year disease-free survival (DFS) (risk ratio 3.2 and 4.0, respectively); however, tumor size and histological grade were not significant predictors. The 10-year DFS of T1-2N0M0 patients was 55.4%. T1-2N0M0 patients with S100A4-positive tumors had a significantly worse 10-year DFS than those with S100A4-negative tumors (29.0 vs. 68.9 %, p = 0.001). The 10-year DFS in T1-2N0M0 patients with Met-negative tumors was 82.4 vs. 39.7% if Met expression was positive (p = 0.0002). S100A4, but not Met, was still a significant predictor of 10-year DFS in T1N0M0 breast carcinoma patients (p = 0.02). For the T2N0M0 subgroup, both S100A4 and Met were significantly correlated with survival. The 10-year DFS of T2N0M0 patients with S100A4-negative and Met-negative tumors was 92.3%; in those with S100A4-positive and Met-positive tumors, however, it was only 11.8%.S100A4 expression is an indicator of a poor prognosis for T1N0M0 breast cancer. In addition, the combination of S100A4 and Met expression gives the best risk group discrimination in the T2N0M0 subgroup. S100A4 expression appears to be an earlier step in the metastatic progression compared to Met expression in early-stage breast carcinoma.

Aim: Endoscopic assisted breast surgery (EABS), performed through minimal axillary and/or peri-areolar incisions, could be another option for the management breast cancer. In this study, we report our preliminary results of EABS in the National Cheng-Kung University Hospital (NCKUH), Taipei Medical University Hospital (TMUH) and Changhua Christian Hospital (CCH), Taiwan. Methods: Patients with breast cancer managed by EABS were search from 3 medical centers database. The patients' clinicopathologic characteristics, type of surgery, method of breast reconstruction, complication and recurrence were recorded. (IRB Nr 121229) Results: A total of 220 patients with breast cancer undergone EABS from the above three endoscopic breast surgery centers in Taiwan. All of them were female, and the mean age at diagnosis was 49.5 ± 10.1 years old (range 26 to 80 year). Among these 220 patients, 36(16.4%) underwent endoscopic assisted partial mastectomy (EAPM), and 184 received endoscopic assisted total mastectomy (EATM). In the 184 EATM patients, 46 (25%) received endoscopic assisted skin sparing mastectomy (E-SSM), and 138 (75%) underwent endoscopic assisted nipple sparing mastectomy (E-NSM). The mean pathologic tumor size of these 220 patients was 2.1 ± 1.6 cm (0.1 to 8.5 cm). Lymph node metastasis was found in 33 (15%) patients, 17 patients with lymph node 1-3 positive, and 16 patient with 4-9 lymph nodes metastasis. The post operative stage distribution were 70 (31.8%) ductal carcinoma in situ (DCIS), 75 (34.1%) stage 1, 36(16.4%) stage 2a, 26(11.8%) stage 2b, and 13 (5.9%) stage 3a.Among the 184 EATM patients, 147 (79.9%) received immediate breast reconstruction. Most (57.3%) of them received Gel implant reconstruction, and 42.7% received breast reconstruction with autologous pedicled transverse abdominal myocutaneous (TRAM) flap. Complications (9.6%) follow EABS were all minor, and most of them were wound related. The cosmetic result was scored by surgeons and patients. Conclusions: Endoscopic assisted breast surgery is a safe and highly acceptable operation for the management of Taiwanese women with early stage breast cancer. Disclosure: All authors have declared no conflicts of interest.

Rhodostomin (Rho) is a snake venom protein isolated from Calloselasma rhodostoma. Rho is a disintegrin that inhibits platelet aggregation by blocking the binding of fibrinogen to the integrin αIIbβ3 of platelets. Rho produced in Escherichia coli inhibited platelet aggregation with a KI value of 263 nM. Although functional, Rho produced in E. coli is misfolded based on our 2D and 3D NMR studies. In order to correct the folding problem, Rho was expressed in Pichia pastoris. The recombinant Rho expressed in P. pastoris inhibited platelet aggregation with a resulting KI value of 70 nM. This is the same potency as that of native Rho. CD analysis showed that the secondary structures of Rho are pH-independent and contain 3.5–7.9% α-helix, 48.2–50.5% β-structures, and 42.3–47% coil. The sequential assignment and structure analysis of Rho were obtained using 2D and 3D 15N-edited NMR spectra. These results provide the first direct evidence that highly disulfide-bonded disintegrin can be expressed in P. pastoris with the correct fold. This evidence may serve as the basis for exploring the structure and function relationships as well as the dynamics of disintegrin and its variants. Proteins 2001;43:499–508. © 2001 Wiley-Liss, Inc.

Unilateral breast reconstruction with an extended latissimus dorsi musculocutaneous flap was carried out for 12 women in the National Cheng Kung University Hospital. Eleven patients acquired a good or fair result cosmetically. We analysed the net weight of the flap as well as various anthropometric data to see what effect they have on the final aesthetic outcome. The weight of the flap ranged from 180 to 610 g, and the resected specimen weighed from 160 to 635 g. The flap weight was equivalent to 61%-113% of the specimen weight. A satisfactory result could be achieved when the bulk of the flap attained 70% of the mass resected. We also observed that the aesthetic quality is better when the breast is less ptotic. All of the muscle transfers survived completely without any flap loss. The only complications included one minor wound edge slough and another modest seroma formation at the donor site. This reconstructive method is a viable option for young women with small or medium-sized breasts who anticipate pregnancy in the future. It is especially advisable in Oriental society, since the breast size of the patients is generally smaller and the donor scar is hidden, given the hypertrophic tendency of the lower abdominal scar in Asian people undergoing TRAM flap reconstruction.

Objective The goal of this study is to determine the prognostic and predictive values of the Breast Imaging Reporting and Data System (BI-RADS) classification in breast cancer patients. Patients and methods 1045 patients with breast cancer were disgnosed between January 1, 1999, and December 31, 2007, and 512 (48.9%) of them were classified as BI-RADS 5. Overall survival and disease-free survival were estimated with the Kaplan-Meier method and compared across the two groups (BI-RADS 5 versus BI-RADS 0-4) using the log-rank test. Univariate and multivariate analyses were used to identify the prognostic factors. Results The median follow-up time was 87.8 months. Laplan-Meier analysis showed a significant difference between the two subgroups in five-year overall survival (p Conclusion The BI-RADS classification is a reliable prognostic and predictive factor. Taiwanese breast cancer patients with BI-RADS 5 mammographic finding showed a higher relapse rate than patients with BI-RADS 0-4 mammographic finding. Disclosure All authors have declared no conflicts of interest.

Background Currently, 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. Methods We 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. Results In 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. Conclusion Our 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.