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Jae-Cheol Jo,
Myoung Joo Kang,
Jeong Eun Kim,
Jin-Hee Ahn,
Kyung Hae Jung,
Gyungyub Gong, Hak Hee Kim,
Seung Do Ahn,
Su Ssan Kim,
Byung Ho Son,
Sei Hyun Ahn,
Sung-Bae Kim
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ABSTRACT: BACKGROUND: Leptomeningeal metastasis (LM) is one of the major problems in the management of metastatic breast cancer; typically, LM has a devastating prognosis and often represents a terminal event. The present study analyzed the clinical features and outcome of LM in patients with breast cancer. METHODS: The medical records of patients diagnosed with LM from breast cancer at Asan Medical Center, between 2002 and 2012, were reviewed retrospectively. RESULTS: Of 95 LM patients, 38 (40 %) had an ECOG performance status (PS) ≤ 2, and the median age was 47 years (range 26-72 years). At the time of LM diagnosis, 46 patients (48.4 %) presented with coincidental failure of systemic disease control. Seventy-eight patients (82.1 %) underwent intrathecal (IT) chemotherapy, resulting in cytologic negative conversion in 26 patients, and 46 patients (48.4 %) received systemic chemotherapy. The median overall survival (OS) time was 3.3 months, and 7.8 % of the patients survived for more than 1 year. OS tended to be higher in patients who achieved cytologic negative conversion from IT chemotherapy than in those who did not (4.5 vs. 2.4 months, P = 0.088). Multivariate analysis demonstrated that ECOG PS ≤ 2, controlled extracranial disease at the time of LM diagnosis, and systemic chemotherapy after LM diagnosis were independent factors associated with survival. CONCLUSIONS: The prognosis of patients with LM from breast cancer is poor. Systemic chemotherapy, in addition to intrathecal chemotherapy, might confer a survival benefit, even after the detection of LM.
Cancer Chemotherapy and Pharmacology 05/2013; · 2.83 Impact Factor
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ABSTRACT: OBJECTIVE. The purpose of our study was to assess the diagnostic performance of breast MRI in evaluating residual disease in patients after excisional biopsy for breast cancer on the basis of both morphologic and kinetic features. MATERIALS AND METHODS. Of 5304 breast MRI examinations performed between January 2007 and December 2011, 308 evaluated postoperative sites after excisional biopsy of breast cancer. Among these, 203 patients who were not treated with chemotherapy or radiotherapy before MRI and underwent definitive surgery within 30 days after MRI were enrolled. MRI findings were analyzed on the basis of contrast-enhanced subtraction images. The enhancement patterns were classified into four categories: no enhancement (P1), thin regular rim enhancement (P2), thick or irregular rim enhancement (P3), and nodular or nonmasslike enhancement (P4) around the postoperative sites. The enhancement kinetics were assessed as follows: persistent, plateau, and washout pattern. RESULTS. From 207 breast MRI examinations in 203 patients, 144 breasts had residual breast cancer at histopathologic examination after definitive surgery. When P1 and P2 were considered negative for residual cancer and P3 and P4 were considered positive, the sensitivity, specificity, positive and negative predictive values, and accuracy were 79.9%, 73.0%, 87.1%, 61.3%, and 77.8%, respectively. The specificity and positive predictive value improved to 90.5% and 91.7%, when analyzed with washout enhancement kinetics as another positive finding for residual cancer. A statistically significant trend of decreasing specificity and positive predictive value (p < 0.05) was found with the passage of a time interval between excision and breast MRI. CONCLUSION. Although the overlapping features of the postsurgical changes and malignant lesions remain as the limitations, dynamic contrast-enhanced breast MRI is a useful tool for residual disease prediction after excisional biopsy for breast cancer. Combined use of morphologic and kinetic evaluation parameters improved the diagnostic performance. We do not recommend that MRI be unreasonably delayed after excisional biopsy considering the risk of prolonging definitive surgery.
American Journal of Roentgenology 05/2013; 200(5):1167-73. · 2.78 Impact Factor
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ABSTRACT: We evaluated the impact of three automatic optimization of parameters (AOP) modes of digital mammography on the dose and image quality.
Computerized Imaging Reference Systems phantoms were used. A total of 12 phantoms with different thickness and glandularity were imaged. We analyzed the average glandular dose (AGD) and entrance surface exposure (ESE) of 12 phantoms imaged by digital mammography in three modes of AOP; namely standard mode (STD), contrast mode (CNT), and dose mode (DOSE). Moreover, exposure factors including kVp, mAs, and target/filter combination were evaluated. To evaluate the quality of the obtained digital image, two radiologists independently counted the objects of the phantoms.
According to the AOP modes, the score of masses and specks was sorted as CNT>STD=DOSE. There was no difference in the score of fiber among the three modes. The score of image preference was sorted as CNT>STD>DOSE. The AGD, ESE, and mAs were sorted as CNT>STD>DOSE. The kVp was sorted as CNT=STD>DOSE. The score of all test objects in the phantom image was on a downtrend with increasing breast thickness. The score of masses was different among the three groups; 20-21%>30%>50% glandularity. The score of specks was sorted as 20-21%=30%>50% glandularity. The score of fibers was sorted as 30%>20-21%=50% glandularity. The score of image preference was not different among the three glandularity groups. The AGD, ESE, kVp, and mAs were correlated with breast thickness, but not correlated with glandularity.
The DOSE mode offers significant improvement (19.1-50%) in dose over the other two modes over a range of breast thickness and breast glandularity with acceptable image quality. Owning knowledge of the three AOP modes may reduce unnecessary radiation exposure by utilizing the proper mode according to its purpose.
Journal of Breast Cancer 03/2013; 16(1):90-96. · 0.32 Impact Factor
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ABSTRACT: PURPOSE: To compare the performance of radiologists in the use of conventional ultrasound (US) and automated breast volume ultrasound (ABVU) for the characterization of benign and malignant solid breast masses based on breast imaging and reporting data system (BI-RADS) criteria. MATERIALS AND METHODS: Conventional US and ABVU images were obtained in 87 patients with 106 solid breast masses (52 cancers, 54 benign lesions). Three experienced radiologists who were blinded to all examination results independently characterized the lesions and reported a BI-RADS assessment category and a level of suspicion of malignancy. The results were analyzed by calculation of Cohen's κ coefficient and by receiver operating characteristic (ROC) analysis. RESULTS: Assessment of the agreement of conventional US and ABVU indicated that the posterior echo feature was the most discordant feature of seven features (κ = 0.371 ± 0.225) and that orientation had the greatest agreement (κ = 0.608 ± 0.210). The final assessment showed substantial agreement (κ = 0.773 ± 0.104). The areas under the ROC curves (Az) for conventional US and ABVU were not statistically significant for each reader, but the mean Az values of conventional US and ABVU by multi-reader multi-case analysis were significantly different (conventional US 0.991, ABVU 0.963; 95 % CI -0.0471 to -0.0097). The means for sensitivity, specificity, positive predictive value, and negative predictive value of conventional US and ABVU did not differ significantly. CONCLUSION: There was substantial inter-observer agreement in the final assessment of solid breast masses by conventional US and ABVU. ROC analysis comparing the performance of conventional US and ABVU indicated a marginally significant difference in mean Az, but not in mean sensitivity, specificity, positive predictive value, or negative predictive value.
Breast Cancer 10/2012; · 1.36 Impact Factor
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ABSTRACT: Pathologic complete response (pCR) has been suggested as a surrogate prognostic indicator in breast cancer patients treated with neoadjuvant chemotherapy. We assessed whether the likelihood of pCR and survival is associated with the immunohistochemistry-based molecular subtypes.
We retrospectively analyzed the records of 276 patients with breast cancer who received neoadjuvant chemotherapy between January 2000 and January 2010. Patients were classified into four molecular subtypes based on the immunohistochemistry profiles of estrogen receptor, progesterone receptor, and HER2/neu. Logistic regression was used to analyze variables associated with pCR.
The pCR was achieved in 45 patients (16.3%). The triple negative subtype was an independent predictive factor for pCR (odds ratio, 3.21; 95% confidence interval, 1.20-8.56; p=0.020), and the ERBB-2 subtype showed a trend for higher pCR rates (odds ratio, 3.03; 95% confidence interval, 0.93-9.89; p=0.067) compared with the luminal A subtype. In 99 patients with HER2/neu-positive breast cancer, pCR rates were higher in those who received trastuzumab (31.7%) than those treated with conventional chemotherapy regimens (17.2%, p=0.023). The pCR was significantly associated with prolonged progression-free survival (p=0.008). The triple negative subgroup had shorter progression-free survival (p=0.001) and overall survival (p=0.001) than the other subgroups.
We demonstrated that the triple negative and ERBB-2 subtypes are more likely to obtain pCR when neoadjuvant chemotherapy is given, compared to the luminal A subtype. Despite the high pCR rate, the triple negative subtype showed worse survival outcomes, paradoxically, primarily due to patients who had residual disease.
Journal of breast cancer. 06/2012; 15(2):203-10.
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ABSTRACT: With the widespread use of PET/CT, incidental hypermetabolic foci unrelated to the known malignancy have been described with increasing frequency.
To determine the frequency and clinical significance of incidental focal hypermetabolic uptake in the breast as detected by 18F-FDG PET/CT, and to explore factors differentiating benign and malignant breast uptake.
From January 2005 to June 2010, a total of 51,971 whole-body FDG PET/CT examinations were performed in our clinic. After excluding 7254 sets of PET/CT data from patients known to have breast cancer, we retrospectively identified patients showing incidental focal hypermetabolic activity in the breast. Of 44,717 PET/CT examinations conducted on 32,988 patients, we identified 131 patients with no previous known or suspected benign and malignant breast disease. The etiology, mean SUV(max), and diameter of breast lesions were assessed. We also compared the presentation of the lesions on CT, mammography, and ultrasonography.
Of the 131 patients, 60 were histologically diagnosed with breast lesions, including 32 with malignant and 28 with benign lesions. An additional 11 patients were followed-up for more than 2 years and were clinically considered to have benign lesions. The remaining 60 patients who had neither histologic confirmation nor followed-up for more than 2 years were excluded. Therefore, 71 patients were finally included. The mean SUV(max) of 39 benign lesions and 32 malignant lesions were 2.02 ± 1.52 and 3.71 ± 3.83, respectively (P = 0.0001). At a cut-off value of 2.3, the rate of malignancy and specificity of the mean SUVmax for differentiating benign and malignant breast lesions were 61.3%, 76.3, respectively. The CT data from PET/CT revealed that the mean diameters of benign and malignant lesions were 1.19 ± 0.97 cm and 2.26 ± 1.96 cm, respectively (P = 0.0009).
Incidental focal 18F-FDG uptake in the breast as detected by PET/CT was indicative of malignancy in 45% of patients. Both mean SUV(max) and diameter were greater for malignant than benign lesions.
Acta Radiologica 05/2012; 53(5):530-5. · 1.37 Impact Factor
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ABSTRACT: The aim of this study was to determine whether tumor size, MRS parameters and apparent diffusion coefficient (ADC) measurements could be applied to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). Ninety patients with breast cancer (median size, 4.5 cm; range, 1.6-9.5 cm) were evaluated with single-voxel (1) H MRS and dynamic contrast-enhanced MRI. Diffusion-weighted imaging was performed in 41 of these patients using a 1.5-T scanner before and after completion of NAC. Pre- and post-treatment measurements and changes in tumor size, MRS parameters [absolute and normalized total choline-containing compound (tCho) integral and tCho signal-to-noise ratio (SNR)] and ADCs in pCR versus non-pCR were compared using the nonparametric Mann-Whitney test. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance of each parameter. After NAC, 30 patients (33%) showed pCR and 60 (67%) showed non-pCR. At pretreatment, ADC was the only significant parameter in differentiating between pCR and non-pCR [(0.83 ± 0.05) × 10(-3) versus (0.97 ± 0.14) × 10(-3) mm(2) /s] (p = 0.014). Post-treatment measurements after completion of NAC and changes in tumor size (both p < 0.001), MRS parameters (p = 0.027 and p = 0.020 for absolute tCho integral, p = 0.036 and p = 0.023 for normalized tCho integral, and p = 0.032 and p = 0.061 for tCho SNR) and ADC (p = 0.003 and p < 0.001) were significantly different between the pCR and non-pCR groups, except for changes in tCho SNR. In ROC analysis, the areas under the ROC curve (AUCs) of 0.63-0.73 were obtained for tumor size and MRS parameters. AUCs for pre- and post-treatment ADC and changes in ADC were 0.75, 0.80 and 0.96, respectively. The optimal cut-off of the percentage change in ADC for predicting pCR was 40.7%, yielding 100% sensitivity and 91% specificity. Patients with pCR showed significantly lower pretreatment ADCs than those with non-pCR. The change in ADC after NAC was the most accurate predictor of pCR. Copyright © 2012 John Wiley & Sons, Ltd.
NMR in Biomedicine 05/2012; 25(12):1349-59. · 3.21 Impact Factor
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ABSTRACT: The purpose of this article is to determine whether the peak integral and signal-to-noise ratio (SNR) of total choline-containing compounds obtained by MR spectroscopy (MRS) correlate with histologic biomarkers currently used for predicting prognosis in patients with breast cancer.
Single-voxel proton MRS using a 1.5-T scanner was performed in 184 patients (mean age, 48 years; range, 28-72 years) with breast cancer. We obtained absolute total choline-containing compound peak integral, total choline-containing compound peak integral normalized for the volume of interest, and SNR after MRI. On surgical pathology, pathologic subtype and prognostic factors such as nuclear grade, histologic grade, estrogen receptor (ER), HER-2≠neu, extensive intraductal component (EIC), lymphovascular invasion, and lymph node metastasis were also evaluated. Statistical analysis was performed using Mann-Whitney U test and Spearman rank correlation.
The total choline-containing compound SNR, absolute total choline-containing compound peak integral, and normalized total choline-containing compound integral were significantly higher for invasive ductal carcinoma, cancer of high nuclear or histologic grade, and EIC-negative cancer (p < 0.001) than for in situ or other invasive carcinomas (p = 0.005), cancer of low nuclear or histologic grade (p = 0.009), and EIC-positive cancer (p = 0.017). There was a significant difference in the total choline-containing compound SNR between ER-positive and -negative groups (p = 0.007) and between triple-negative and non-triple-negative groups (p = 0.002). A positive correlation was found between the volume of interest (p < 0.001), tumor size (p = 0.011), and three MRS parameters (p = 0.003).
Our study suggests that proton MRS can play a role in predicting prognostic indicators of tumor aggressiveness in patients with newly diagnosed breast cancer.
American Journal of Roentgenology 05/2012; 198(5):W488-97. · 2.78 Impact Factor
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Inho Han,
Byeong-Ju Kwon,
Barbora Vagaska,
Bong-Jin Kim,
Jae Kyeong Kang,
Mi Hee Lee, Hak Hee Kim,
Jong-Chul Park,
Kang-Kyun Wang,
Yong-Rok Kim,
Jun-Sung An,
Ji-Min Lee,
Chae-Young Hyun,
Jae-Hwan Jeong,
Soo-Jin Lim
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ABSTRACT: Plasma surface modifications of polymer scaffolds using biomolecules such as oxygen, nitrogen, and other active grafting molecules
have been studied to enhance biological responses such as cell attachment, spreading, and proliferation. According to the
reports, nitrogen grafting requires corrosive or mixture gas environment, or post treatment. This study aimed to evaluate
a simple atmospheric pressure plasma surface modification in order to graft nitrogen derivatives and to promote biological
responses. In this study, a polycarprolactone (PCL) film was modified within 10 min by argon atmospheric pressure discharge
(Ar-APGD). Excited argon atoms, nitrogen atoms, oxygen atoms, and hydroxyl functional groups were observed from the optical
emission spectra of the discharge. Decreased carbonyl functional groups and ether functional groups were observed; notably,
immobilized nitrogen was observed on the PCL surface after the Ar-APGD treatment. Promoted neonatal Human Dermal Fibroblast
(nHDF) growth patterns were observed on the Ar-APGD-treated surface.
Keywordsbiodegradable polymer–plasma–atmospheric pressure–surface modification–neonatal human dermal fibroblast
Macromolecular Research 04/2012; 19(11):1134-1141. · 1.15 Impact Factor
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ABSTRACT: PurposeTo evaluate significance of nipple enhancement of Paget’s disease in contrast enhanced (CE) breast MRI.
MethodsTen patients of biopsy proven Paget’s disease were included in this study. Preoperative mammogram and ultrasonogram (US) were
obtained in all 10 patients, and 8 patients underwent CE breast MRI prior to surgery. Mammographic and US findings were reviewed
retrospectively. On MRI, morphology (flattening or asymmetry or thickening) and enhancement of pathologically involved nipple
were analyzed comparing with the opposite side, and also reviewed the abnormal enhancing lesion in the breast parenchyma.
ResultsMorphologic changes of the nipple were detected in 2 out of 10 patients by mammogram and 6 out of 10 patients by US. On MRI,
morphologic change was also revealed in 7 patients and abnormal enhancement of involved nipple was observed in all 8 patients.
Associated parenchymal enhancing lesions were proved to be DCIS (7 out of 10) and invasive ductal carcinoma (2 out of 10).
Remaining one patient had no underlying breast parenchymal malignancy.
ConclusionCE breast MRI allows for the correct detection of nipple involvement of Paget’s disease even when clinical information or
mammographic/US findings are not provided.
KeywordsPaget’s disease-Breast-Breast cancer-Magnetic resonance imaging
Archives of Gynecology and Obstetrics 04/2012; 282(2):157-162. · 1.28 Impact Factor
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ABSTRACT: The purpose of this study was to prospectively evaluate interobserver agreement on lesion detection and characterization in the review of automated ultrasound images of the breast by five radiologists.
From August to October 2009, bilateral whole-breast ultrasound examinations were performed with an automated technique and with a handheld device for 55 women consecutively scheduled to undergo diagnostic ultrasound. Three-dimensional volume data from automated ultrasound were reviewed by five radiologists, who were unaware of the results of ultrasound with a handheld device and mammography and of the clinical information. If a lesion was detected with automated ultrasound, clock-face position, distance from the nipple, largest diameter, and BI-RADS final assessment category were evaluated. If the lesion was a mass, shape, orientation, margin, echogenicity, and posterior feature were analyzed. Intraclass correlation coefficients and kappa statistics were used for statistical analysis.
At least two observers identified 145 lesions with automated ultrasound. Among 725 possible detections, 587 (81%) detections were made. Individual investigators detected between 74% (107/145) and 88% (127/145) of the lesions. The rate of detection of lesions larger than 1.2 cm was 92%. Most lesions detected only with handheld ultrasound (11/12, 92%) or automated ultrasound (34/36, 94%) were cysts or probably benign masses. All intraclass correlation coefficients for lesion location and size exceeded 0.75, indicating high reliability. Substantial agreement was found for mass shape (κ = 0.71), orientation (κ = 0.72), margin (κ = 0.61), and BI-RADS final assessment category (κ = 0.63).
Detection of lesions larger than 1.2 cm in greatest diameter was reliable. High reliability was obtained for reporting lesion size and location. Substantial agreement was obtained for description of key feature and final assessment category.
American Journal of Roentgenology 09/2011; 197(3):747-54. · 2.78 Impact Factor
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ABSTRACT: The objective of our study was to prospectively evaluate the diagnostic accuracy of optical diffusion breast imaging in patients who underwent conventional ultrasound followed by surgery or biopsy.
We performed optical diffusion breast imaging after conventional ultrasound of 193 patients (mean age, 47 years) with 217 lesions. All patients underwent ultrasound-guided core needle biopsy or surgery. One of six radiologists reviewed conventional ultrasound features, assessed a BI-RADS category, and reviewed optical diffusion imaging results for each lesion. Surgery and biopsy results were used as reference standards. We compared the diagnostic accuracy including the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of conventional ultrasound alone and of conventional ultrasound followed by optical diffusion imaging. In addition, we prospectively investigated if total hemoglobin level or oxygen saturation level is the most reliable indicator in optical diffusion imaging.
Of the 217 breast lesions, 108 were malignant and 109 were benign. For differentiation of malignant from benign lesions, conventional ultrasound was associated with a sensitivity of 100%, specificity of 27.5%, PPV of 57.8%, NPV of 100%, and accuracy of 63.6%. The supplemental use of optical diffusion imaging after conventional ultrasound was associated with a sensitivity of 98.1%, specificity of 41.3%, PPV of 62.4%, NPV of 95.7%, and accuracy of 69.7%. The area under the receiver operating characteristic curve was 0.738 for total hemoglobin level and 0.502 for oxygen saturation level. The cutoff value was 0.195 mmol/L for total hemoglobin, with 68.4% sensitivity and 69.7% specificity.
Optical diffusion imaging might be a good supplemental tool to increase the diagnostic accuracy of conventional ultrasound in differentiating malignant from benign breast lesions.
American Journal of Roentgenology 09/2011; 197(3):732-9. · 2.78 Impact Factor
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Geundoo Jang,
Sung Sook Lee,
Jin-Hee Ahn,
Kyung Hae Jung,
Hyunjoo Lee,
Gyungyub Gong, Hak-Hee Kim,
Seung Do Ahn,
Byung Ho Son,
Sei-Hyun Ahn,
Sung-Bae Kim
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ABSTRACT: The incidences and clinical aggressiveness of intracranial metastases have not been as well characterized in patients with triple-negative (TN) breast cancer as in patients with human epidermal growth factor 2-positive (HER2+) breast cancer. Patients diagnosed with brain metastases from primary breast cancer, as determined by computed tomography and/or magnetic resonance imaging, at Asan Medical Center from January 1990 to July 2006 were identified and classified into three subtypes: TN, HER2+, and other. The clinical features and outcomes of these three groups were compared. Of the 7,872 patients diagnosed with primary breast cancer, 198 developed brain metastases; of these, 61 patients with unknown estrogen receptor, progesterone receptor, and HER2 status were excluded. Of the remaining 137 patients, 44 (32%) were classified as TN, 69 (50%) as HER2+, and 24 (18%) as other. Clinical parameters, including performance status and previous adjuvant chemotherapy and/or radiotherapy, were well balanced among groups, except that earlier staged tumors (I and II) were more prevalent in the TN than in the HER2+ and other (59 vs. 36 vs. 38%, P = 0.01). At a median follow-up of 99 months, the median times from initial diagnosis to brain metastasis (20 vs. 32 vs. 45 months, P = 0.01) and to first distant metastasis at any site (16 vs. 23 vs. 23 months, P = 0.005) were significantly shorter in TN than in the HER2+ and other. Median overall survival (OS) from primary cancer diagnosis was significantly shorter in the TN than in the HER2+ and other (31 vs. 39 vs. 57 months, P = 0.02), but survival after brain metastasis was similar (5.9 vs. 5.2 vs. 8.8 months, P = 0.31). Compared with other breast cancer phenotypes, TN breast cancer was characterized by earlier brain and other distant metastases and shorter OS, despite a higher proportion of tumors diagnosed at early stages.
Breast Cancer Research and Treatment 07/2011; 128(1):171-7. · 4.43 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the differential radiologic findings of pure mucocele-like tumor and mucocele-like tumor associated with atypical ductal hyperplasia (ADH) or malignancy of the breast according to BI-RADS and sonographic cystic mass classification.
During a 10-year period, 72 mucocele-like tumors in 68 women were diagnosed histologically at three institutions. We retrospectively reviewed the mammographic (n = 69) and ultrasound (n = 72) findings of the 72 lesions according to the BI-RADS lexicon. The radiologic findings were correlated with the pathologic results.
Mammography showed 53 lesions had calcifications without (n = 39) or with (n = 14) a mass. Calcifications of intermediate concern or associated with higher probability of malignancy were found more frequently in mucocele-like tumors associated with ADH or malignancy than in pure mucocele-like tumors (92.3% vs 62.9%, p = 0.019). At ultrasound, 69 of the mucocele-like tumors (95.8%) were seen as a cystic mass. Cysts with thick septations, clustered cysts, and complex masses were more frequently seen in mucocele-like tumors associated with ADH or malignancy (89.7% vs 32.5%, p < 0.001). The positive predictive value for BI-RADS category 4 was 13.3% (95% CI, 6.9-24.2%) and was 50% for BI-RADS category 5 (95% CI, 15-85%).
Mucocele-like tumors associated with ADH or malignancy were more frequently seen as clustered cysts, cysts with thick septations, and complex masses associated with calcifications of intermediate concern or higher probability of malignancy. BI-RADS can be used in the management of mucocele-like tumors.
American Journal of Roentgenology 06/2011; 196(6):1424-30. · 2.78 Impact Factor
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ABSTRACT: Fulvestrant, a potent estrogen receptor (ER) antagonist with a novel mechanism of action, has shown efficacy in pretreated patients with advanced breast cancer. We assessed the efficacy and tolerability of fulvestrant in Korean postmenopausal women.
Of the 25 candidates identified at Asan Medical Center, Seoul, Korea, six were deemed ineligible due to inadequate baseline and follow-up imaging. The 19 patients included in this retrospective analysis received the approved dose of fulvestrant (250 mg intramuscular injection, once per month) as second- (n=8), third- (n=7), or fourth-line (n=4) endocrine therapy.
At a median follow-up of 7.4 months (range, 1.2-34.8 months), the 19 patients received a median of four cycles (range, 1-34 cycles) of fulvestrant. Median time to progression was 5.5 months (95% confidence interval [CI], 0.4-10.7 months), and median overall survival was 17.9 months (95% CI, 2.7-33.1 months). Among 17 evaluable patients, one (5.3%) achieved a partial response, 10 (52.6%) showed stable disease, and six (31.6%) showed progressive disease. The clinical benefit rate was 26.3%. Four patients (21.1%) reported adverse events, but all were grade 1 or 2.
Fulvestrant was effective and well tolerated in patients with advanced breast cancer who had been previously treated with several lines of endocrine and chemotherapeutic agents.
Journal of breast cancer. 06/2011; 14(2):135-9.
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ABSTRACT: Derivation of human induced pluripotent stem (iPS) cells could enable their widespread application in future. Establishment of highly efficient and reliable methods for their preservation is a prerequisite for these applications. In this study, we developed a vitrification solution comprising ethylene glycol (EG) and sucrose as well as carboxylated ε-poly-l-lysine (PLL); this solution inhibited devitrification. Human iPS cells were vitrified in 200-μL vitrification solutions comprised 6.5M EG, 0.75 M sucrose and 0 or 10%w/v carboxylated PLL with 65 mol% of the amino groups converted to carboxyl groups [PLL (0.65)] in a cryovial by directly immersing in liquid nitrogen. After warming, attached colony and recovery rates of human iPS cells vitrified by adding PLL (0.65) were significantly higher than those for cells without PLL (0.65) and vitrification solution (DAP213: 2M dimethyl sulfoxide, 1M acetamide and 3M propylene glycol). Furthermore, even after warming at room temperature, attached colony and recovery rates of iPS cells vitrified with PLL (0.65) were reduced to a lesser extent than those vitrified with either DAP213 or EG and sucrose without PLL (0.65). This could be attributed to inhibition of devitrification by PLL (0.65), as differential scanning calorimetry indicated less damage after vitrification with PLL (0.65). In addition, human iPS cells vitrified in the solution with PLL (0.65) had normal karyotypes and maintained undifferentiated states and pluripotency as determined by immunohistochemistry and teratoma formation. Addition of PLL (0.65) successfully vitrified human iPS cells with high efficiency. We believe that this method could aid future applications and increase utility of human iPS cells.
Cryobiology 05/2011; 63(2):76-83. · 2.06 Impact Factor
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ABSTRACT: To investigate the effects of (-)epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, on cell growth, cell cycle and phosphorylated nuclear factor-κB (pNF-κB) expression in neonatal human dermal fibroblasts (nHDFs).
The proliferation and cell-cycle of nHDFs were determined using WST-8 cell growth assay and flow cytometry, respectively. The apoptosis was examined using DNA ladder and Annexin V-FITC assays. The expression levels of pNF-κB and cell cycle-related genes and proteins in nHDFs were measured using cDNA microarray analyses and Western blot. The cellular uptake of EGCG was examined using fluorescence (FITC)-labeled EGCG (FITC-EGCG) in combination with confocal microscopy.
The effect of EGCG on the growth of nHDFs depended on the concentration tested. At a low concentration (200 μmol/L), EGCG resulted in a slight decrease in the proportion of cells in the S and G(2)/M phases of cell cycle with a concomitant increase in the proportion of cells in G(0)/G(1) phase. At the higher doses (400 and 800 μmol/L), apoptosis was induced. The regulation of EGCG on the expression of pNF-κB was also concentration-dependent, whereas it did not affect the unphosphorylated NF-κB expression. cDNA microarray analysis showed that cell cycle-related genes were down-regulated by EGCG (200 μmol/L). The expression of cyclins A/B and cyclin-dependent kinase 1 was reversibly regulated by EGCG (200 μmol/L). FITC-EGCG was found to be internalized into the cytoplasm and translocated into the nucleus of nHDFs.
EGCG, through uptake into cytoplasm, reversibly regulated the cell growth and expression of cell cycle-related proteins and genes in normal fibroblasts.
Acta Pharmacologica Sinica 05/2011; 32(5):637-46. · 1.95 Impact Factor
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ABSTRACT: Conditioned medium from adipose derived stem cells (ADSC-CM) stimulates both collagen synthesis and migration of fibroblasts, and accelerates wound healing in vivo. Recently, the production and secretion of growth factors has been identified as an essential function of adipose-derived stem cells (ADSCs). However, the main soluble factor of ADSC-CM which mediates paracrine effects and its underlying mechanism has not been elucidated yet. In this study, we considered transforming growth factor-beta1 (TGF-β1) as a strong candidate for paracrine effect of ADSC-CM and investigated collagen synthesis and hyaluronic acid synthase (HAS) expression. After ADSC-CM addition, collagen type I, type III, HAS and hyaluronic acid (HA) expressions on human dermal fibroblasts (HDFs) were evaluated. Furthermore, to clarify effects of TGF-β1 as a paracrine mediator, TGF-β1 antibody and external supplementary TGF-β1 were treated to HDFs. Collagens type I, type III, HAS-1 and HAS-2 mRNA expressions of HDFs were greatly increased by ADSC-CM treatment, however there was no change in TGF-β1 antibody treated HDFs compared with non-treated control. These results strongly demonstrate that TGF-β1 plays an important role as a paracrine mediator of ECM synthesis. The fact that TGF-β1 contained in ADSC-CM not only accelerates collagen deposition but also increase hyaluronic acid synthesis of HDFs through HAS-1 and HAS-2 expression was also elucidated in this study. Therefore, ADSC-CM shows promise for the treatment of cutaneous wounds and accelerates granulation formation during healing process.
Cytotechnology 01/2011; 63(1):57-66. · 1.21 Impact Factor
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ABSTRACT: The objective of our study was to retrospectively determine the positive predictive value of each descriptor and of combined descriptors for microcalcifications to predict the risk of malignancy as well as the appropriate final assessment category.
A total of 308 needle-localized open breast biopsies for mammographically detected microcalcifications were performed in 295 women (age range, 33-71 years; mean age, 52 years) during 7 years. Thirteen patients had bilateral microcalcifications that were studied separately. Two breast radiologists retrospectively reviewed the microcalcifications with regard to their morphology, distribution, and extent and to associated findings and final assessment category, after which they categorized them into nine combined descriptors. Surgical pathology served as the reference standard for malignant lesions and follow-up of at least 12 months served as the reference for benign lesions. The Fisher's exact test, including odds ratios, was used for statistical analysis.
Of the 308 needle-localized open breast biopsies, 144 (47%) were malignant and 164 (53%) were benign. For combined descriptors of morphology and distribution, the odds ratios of malignancy regarding the higher probability of malignancy and ductal distribution were as follows: 0 for typically benign morphology or scattered distribution, 93.00 for intermediate concern and regional, 33.53 for intermediate concern and clustered, 5.00 for intermediate concern and ductal, 24.00 for higher probability of malignancy and regional, and 1.13 for higher probability of malignancy and clustered.
Each descriptor and combined descriptors for microcalcifications and the final assessment category could help to predict the risk of malignancy.
American Journal of Roentgenology 12/2010; 195(6):1466-71. · 2.78 Impact Factor
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ABSTRACT: Inflammatory pseudotumor of the breast is a very rare cause of breast mass. To our knowledge, only a few cases have been described in the English literature. In this case, the lesion appeared on mammography as a round high-density mass with ill-defined margins and on sonography as an irregular mass of complex echogenicity with ill-defined margins and an echogenic rim. The lesion was resected with no evidence of local recurrence after 3 years.
Journal of Clinical Ultrasound 10/2009; 38(1):52-5. · 0.81 Impact Factor
