Shin-Cheh Chen

Correlation of dynamic contrast enhancement MRI parameters with microvessel density and VEGF for assessment of angiogenesis in breast cancer

To investigate the association between parameters obtained from dynamic contrast enhanced MRI (DCE‐MRI) of breast cancer using different analysis approaches, as well as their correlation with angiogenesis biomarkers (vascular endothelial growth factor and vessel density).

Preoperative magnetic resonance imaging evaluation for breast cancers after sonographically guided core-needle biopsy: a comparison study.

AbstractBackground: The aim of the study was to evaluate the efficacy of contrast-enhanced magnetic resonance imaging (MRI) for preoperative assessment of palpable breast cancer after sonographically guided percutaneous core-needle biopsy.n Methods: Thirty-six breast cancers in 35 women that had been diagnosed by sonographically guided core-needle biopsy prior to subsequent MRI were evaluated in this retrospective study. Radiological and pathological reports, multiplicity, retroareolar involvement, and the size of the breast cancers were reviewed. The cancer sizes, as derived from sonography and enhanced MRI, were correlated with histological size in greatest diameter by means of Pearson’s correlation. The threshold value for significance was set at P < .05.n Results: Synchronous breast cancers were revealed in the index cases by means of enhanced MRI (10), sonography (8), and mammography (7). Two of the 36 index cancers (5.6%) benefited from MRI assessment. Retroareolar cancer extension was observed with enhanced MRI in five index cancers. Of these, one was also noted on both a sonogram and a mammogram. Four of the index cancers (11.1%) benefited from the enhanced MRI. Overall, five index cancers (13.9%) benefited from the enhanced MRI. With a gold standard of histology, the mean cancer sizes were underestimated by sonography and overestimated by enhanced MRI. In comparison with sonography, a stronger association was noted between MRI and histological measurements, with coefficients of 0.657 and 0.882, respectively (P < .001).n Conclusions: In a clinical setting, MRI for preoperative assessment of breast cancers is warranted. Minimally invasive, percutaneous core-needle biopsy did not alter the clinical efficacy of the MRI evaluation.

Expression of ROR1 has prognostic significance in triple negative breast cancer

Overexpression of receptor tyrosine kinase-like orphan receptor (ROR1) in a variety of human malignancies is associated with aggressive behaviour. Therapeutic agents targeting ROR1 have shown promising results in vivo and in vitro studies. In breast cancer, high-level expression of ROR1 mRNA is associated with high-grade tumours and metastasis. We investigated the prevalence and prognostic significance of ROR1 expression in triple negative breast cancer (TNBC). ROR1 was immunohistochemically stained on full-face sections of 210 TNBC patient samples. Forty-seven TNBC cases (22.4xa0%) showed strong ROR1 expression, which was associated with shorter disease-free survival (DFS; Pxa0=xa00.00015), distant metastasis-free survival (DMFS; Pxa0=xa00.00013) and overall survival (OS; Pxa0=xa00.026) in univariate analyses. Results were confirmed by multivariate analysis. Seventy TNBC cases (33.3xa0%) with medullary features showed longer OS (Pxa0=xa00.00013). We divided the whole series into two subgroups based on the presence or absence of medullary features. Strong ROR1 expression retained a predictive value of shorter DFS and DMFS in both subgroups. Our study suggests that strong ROR1 expression might be an independent adverse prognostic factor in TNBC patients and may serve as a potential marker for patient selection in ROR1-targeted therapy. More large-scale studies are needed to clarify its potential usefulness.

MRI findings of cancers preoperatively diagnosed as pure DCIS at core needle biopsy.

Background Under-estimation of invasion components occur occasionally at core needle diagnosed ductal carcinoma in situ (DCIS) that may change the prognosis or treatment planning. Purpose To determine whether enhanced magnetic resonance imaging (MRI) features of biopsy-proven ductal cancers in situ help predict the under-estimation of invasive breast cancers. Material and Methods After a retrospective review of the enhanced MRI features on preoperative proven breast ductal cancers in situ by biopsy, tumor morphology (mass and non-mass), enhancing curve patterns, and non-mass enhanced appearances were compared between pure ductal cancers in situ and invasive ductal cancers (IDCs) after surgery. A statistical analysis was performed, and P values <0.05 were deemed significant. Results Twenty-five breast cancers from 24 women were analyzed. Eleven DCIS remained as DCISs, and 14 were upgraded to IDC after surgery. Eight of 14 IDCs (57%) and one of 11 DCISs (9%) presented as mass lesions; otherwise six (43%) IDCs and 10 (91%) DCISs were non-mass lesions (P = 0.013). Among the non-mass cancers, six of 10 DCISs (60%) were focally enhanced and six of 6 IDCs (100%) were segmentally enhanced. The overall cancer sizes measured on enhanced MRI were moderately correlated with histopathology, with a Spearmans rank correlation coefficient of 0.656 (P = 0.001). The mean diameter of the IDCs was larger than that of the pure DCISs on enhanced MRI (2.69 ± 1.42 cm for IDC and 1.62 ± 1.03 cm for DCIS; P = 0.048). The cut-off size was optimally selected at 1.95 cm with a 64% sensitivity and a 77% specificity, using a receiver-operating characteristic curve. The enhancement curves, with washout or persistent rising, were statistically insignificant (P = 0.085 and 0.93, respectively). Conclusion Enhanced MRI provided informative morphology and size features that might help to predict the underestimation of invasiveness in preoperative biopsy-proven DCIS.

Dual-Energy Contrast-Enhanced Spectral Mammography: Enhancement Analysis on BI-RADS 4 Non-Mass Microcalcifications in Screened Women

Background Mammography screening is a cost-efficient modality with high sensitivity for detecting impalpable cancer with microcalcifications, and results in reduced mortality rates. However, the probability of finding microcalcifications without associated cancerous masses varies. We retrospectively evaluated the diagnosis and cancer probability of the non-mass screened microcalcifications by dual-energy contrast-enhanced spectral mammography (DE-CESM). Patients and Methods With ethical approval from our hospital, we enrolled the cases of DE-CESM for analysis under the following inclusion criteria: (1) referrals due to screened BI-RADS 4 microcalcifications; (2) having DE-CESM prior to stereotactic biopsy; (3) no associated mass found by sonography and physical examination; and (4) pathology-based diagnosis using stereotactic vacuum-assisted breast biopsy. We analyzed the added value of post-contrast enhancement on DE-CESM. Results A total of 94 biopsed lesions were available for analysis in our 87 women, yielding 27 cancers [19 ductal carcinoma in situ (DCIS), and 8 invasive ductal carcinoma (IDC)], 32 pre-malignant and 35 benign lesions. Of these 94 lesions, 33 showed associated enhancement in DE-CESM while the other 61 did not. All 8 IDC (100%) and 16 of 19 DCIS (84.21%) showed enhancement, but the other 3 DCIS (15.79%) did not. Overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 88.89%, 86.56%, 72.72%, 95.08% and 87.24%, respectively. The performances of DE-CESM on both amorphous and pleomorphic microcalcifications were satisfactory (AUC 0.8 and 0.92, respectively). The pleomorphous microcalcifications with enhancement showed higher positive predictive value (90.00% vs 46.15%, p = 0.013) and higher cancer probability than the amorphous microcalcifications (46.3% VS 15.1%). The Odds Ratio was 4.85 (95% CI: 1.84–12.82). Conclusion DE-CESM might provide added value in assessing the non-mass screened breast microcalcification, with enhancement favorable to the diagnosis of cancers or lack of enhancement virtually diagnostic for non-malignant lesions or noninvasive subgroup cancers.

Assessment of Breast Specimens With or Without Calcifications in Diagnosing Malignant and Atypia for Mammographic Breast Microcalcifications Without Mass: A STARD-Compliant Diagnostic Accuracy Article.

Abstract Presence of microcalcifications within the specimens frequently signifies a successful attempt of stereotactic vacuum-assisted breast biopsy (VABB) in obtaining a pathologic diagnosis of the breast microcalcifications. In this study, the authors aimed to assess and compare the accuracy and consistency of calcified or noncalcified specimens obtained from same sites of sampling on isolated microcalcifications without mass in diagnosing high-risk and malignant lesions. To the best of our knowledge, an individual case-based prospective comparison has not been reported. With the approval from institutional review board of our hospital (Chang Gung Memorial Hospital), the authors retrospectively reviewed all clinical cases of stereotactic VABBs on isolated breast microcalcifications without mass from our database. The authors included those having either surgery performed or had clinical follow-up of at least 3 years for analysis. All the obtained specimens with or without calcification were identified using specimen radiographs and separately submitted for pathologic evaluation. The concordance of diagnosis was assessed for both atypia and malignant lesions. A total of 390 stereotactic VABB procedures (1206 calcified and 1456 noncalcified specimens) were collected and reviewed. The consistent rates between calcified and noncalcified specimens were low for atypia and malignant microcalcifications (44.44% in flat epithelial atypia, 46.51% in atypical ductal hyperplasia, 55.73% in ductal carcinoma in situ, and 71.42% in invasive ductal carcinoma). The discordance in VABB diagnoses indicated that 41.33% of malignant lesions would be misdiagnosed by noncalcified specimens. Furthermore, calcified specimens showed higher diagnostic accuracy of breast cancer as compared with the noncalcified specimens (91.54 % versus 69.49%, respectively). The evaluation of both noncalcified specimens and calcified specimens did not show improvement of diagnostic accuracy as compared with evaluating calcified specimens alone (91.54% versus 91.54%, respectively). The high prevalence of diagnostic discordance between the calcified and noncalcified specimens indicated the higher value of calcified specimens in diagnosing atypia and malignant microcalcifications. Noncalcified specimens did not provide additional diagnostic benefit from this study. The separation of calcified and noncalcified specimens may facilitate more focused interpretation from pathologists among the large number of specimens.

Dynamic enhanced computed tomography values of locally advanced breast cancers predicting axilla nodal metastasis after neoadjuvant chemotherapy.

Objective: We investigated the differences of dynamic enhanced values between the locally advanced breast cancers with and without axillary nodal metastasis on computed tomography (CT) after neoadjuvant chemotherapy. Methods: The patients with locally advanced breast cancer (greatest diameter >5 cm before chemotherapy) who completed the preoperative neoadjuvant chemotherapy and ready to undertake subsequent surgery received dynamic CT. The CT enhancement values were measured on the main breast cancers in the greatest diameter, and the means of enhancement were compared between the categories with nonmetastasized and metastasized nodal axilla. Results: Thirty-nine patients with locally advanced breast cancers, 15 patients without and 24 with metastasized nodal axilla, were enrolled in this study. The patients with metastasized axilla nodes had significantly higher net maximal enhancement (NME) than that of patients without metastasis (mean, 52.9 ± 23.6 vs 33.6 ± 22.5, respectively; P = 0.02). Using the receiver operating characteristic curve, the cutoff NME in differentiating the nonmetastasized and metastasized axilla nodal status was optimally chosen at 40 Hounsfield, with sensitivity of 88.24%, specificity of 50%, positive predictive value of 71.4%, negative predictive value of 75%, and accuracy of 72.4% after chemotherapy. Conclusion: Additional information of dynamic CT in our results reveals statistically distinguishable NME between those advanced breast cancers with or without axilla nodal metastasis after chemotherapy.

Identification of patients with hormone receptor-positive breast cancer who need adjuvant tamoxifen therapy for more than 5 years

BACKGROUND/PURPOSEnExtended hormonal therapy with tamoxifen for > 5 years has improved disease-free survival (DFS) and overall survival (OS) in hormone receptor (HR)-positive breast cancer patients. The aim of this study was to identify the HR-positive breast cancer women who need adjuvant tamoxifen for > 5 years.nnnMETHODSnBetween 1990 and 2004, 1104 HR-positive breast cancer patients who had received tamoxifen treatment at our institution and had been disease free for at least 6 years were included in this analysis. Univariate and multivariate analyses of prognostic factors for late recurrence were performed using the binary logistic regression model.nnnRESULTSnDuring a median follow-up period of 10.9 years after surgery, 70 patients died and 99 showed recurrence. In multivariate analysis, age < 40 years (p < 0.001) and lymph node metastasis (p < 0.001) were associated with higher rates of recurrence. We stratified patients into high-risk (age < 40 years or positive lymph node status, 536 patients) and low-risk (age > 40 years and negative lymph node status, 566 patients) groups. The recurrence rates were 14.6% and 3.5% in the high-risk and low-risk groups, respectively. Patients in the high-risk group had poorer disease-free survival (p < 0.001) and overall survival (p = 0.010) than those in the low-risk group.nnnCONCLUSIONnOur findings suggest that HR-positive breast cancer women either aged < 40 years or with positive lymph node status were justified in continuing with tamoxifen therapy for > 5 years.

Establishment of two basal-like breast cancer cell lines with extremely low tumorigenicity from Taiwanese premenopausal women

The research of carcinogenetic mechanisms of breast cancer in different ethnic backgrounds is an interesting field, as clinical features of breast cancers vary among races. High premenopausal incidence is distinctive in East-Asian breast cancer. However, human cell lines derived from Asian primary breast tumor are rare. To provide alternative cell line models with a relevant genetic background, we aimed to establish breast cancer cell lines from Taiwanese patients of Han-Chinese ethnicity. Fresh tissue from mammary tumors were digested into organoids, plated and grown in basal serum-free medium of human mammary epithelial cells (HuMEC) with supplements. Cells were further enriched by positive selection with CD326 (epithelial cell adhesion molecule; EpCAM)-coated micro-magnetic beads. Two breast cancer cell lines derived from premenopausal women were successfully established by this method, and named Chang-Gung Breast Cancer 01 (CGBC 01) and 02 (CGBC 02). These two cell lines had a similar phenotype with weak expression of estrogen receptor (ER), progesterone receptor (PR), and without amplification of receptor tyrosine protein kinase erbB-2 (HER2/neu). Genome-wide Single Nucleotide Polymorphism (SNP) array showed multiple copy number alterations in both cell lines. Based on gene expression profiles, CGBC 01 and 02 were clustered into basal-like subtype with reference to the breast cancer cell line gene expression database. The tumorigenicity of both cell lines was extremely low in both anchorage-independence assay and transplantation into the mammary fat pads of nude mice. CGBC 01 and CGBC 02 are low tumorigenic breast cancer cell lines, established from Han-Chinese premenopausal breast cancer patients, which serve as in vitro models in studying the biological features of Asian breast cancer.

Impact of Detection Method and Accompanying Ductal Carcinoma in Situ on Prognosis of T1a,bN0 Breast Cancer

Background: T1a,bN0 breast cancer is not easily detected. Before mammography became widespread, most cases were discovered only after the development of symptoms. The presence of ductal carcinoma in situ (DCIS) affects the detectability of associated invasive cancer; however, the prognostic value of concomitant DCIS is controversial. This study compared the characteristics of screening-detected and symptom-detected T1a,bN0 breast cancer, and investigated the impact of accompanying DCIS on detection and prognosis. Patients and Methods: Data were collected from a single hospital between 2000 and 2009. Of 5,690 primary breast cancers patients, 438 met the criteria for T1a,bN0M0. Logistic regression models were used to identify prognostic indicators and their association with the detection method. Survival analyses were performed to estimate distant relapse-free survival (DRFS) and breast cancer-specific survival (BCSS). Results: Tumors in 79 and 359 patients were detected by screening and development of symptoms, respectively. Symptomatic cancer patients were younger, more likely to receive a mastectomy, and had larger accompanying DCIS lesions; their 10-year DRFS rates were worse than those of patients with screening-detected tumors (91.1% vs. 100% respectively, p=0.049). Patients with large accompanying DCIS (≥2 cm) had markedly worse 10-year DRFS (77.1% vs. 97.4%, p<0.001) and BCSS (94.3% vs. 98.9%, p<0.001). Conclusion: T1a,bN0 breast cancers detected owing to symptoms are more likely to have larger accompanying DCIS. T1a,bN0 patients with large accompanying DCIS have worse DRFS and BCSS. It is important to consider associated DCIS size when evaluating prognosis in T1a,bN0 breast cancer patients.