Breast Neoplasms: Kim Y

Park SK, Kang D, McGlynn KA, Garcia-Closas M, Kim Y, Yoo KY, Brinton LA. · Department of Preventive Medicine, Seoul National University College of Medicine, Yeongeon-dong, Jongro-gu, Seoul 110-799, Seoul, Republic of Korea. · Breast Cancer Res. · Pubmed #18205956 links to  free full text

Abstract: INTRODUCTION: Various perinatal factors, including birth weight, birth order, maternal age, gestational age, twin status, and parental smoking, have been postulated to affect breast cancer risk in daughters by altering the hormonal environment of the developing fetal mammary glands. Despite ample biologic plausibility, epidemiologic studies to date have yielded conflicting results. We investigated the associations between perinatal factors and subsequent breast cancer risk through meta-analyses. METHODS: We reviewed breast cancer studies published from January 1966 to February 2007 that included data on birth weight, birth order, maternal age, gestational age, twin status, and maternal or paternal smoking. Meta-analyses using random effect models were employed to summarize the results. RESULTS: We found that heavier birth weights were associated with increased breast cancer risk, with studies involving five categories of birth weight identifying odds ratios (ORs) of 1.24 (95% confidence interval [CI] 1.04 to 1.48) for 4,000 g or more and 1.15 (95% CI 1.04 to 1.26) for 3,500 g to 3,999 g, relative to a birth weight of 2,500 to 2,599 g. These studies provided no support for a J-shaped relationship of birthweight to risk. Support for an association with birthweight was also derived from studies based on three birth weight categories (OR 1.15 [95% CI 1.01 to 1.31] for > or =4,000 g relative to <3,000 g) and two birth weight categories (OR 1.09 [95% CI 1.02 to 1.18] for > or =3,000 g relative to <3,000 g). Women born to older mothers and twins were also at some increased risk, but the results were heterogeneous across studies and publication years. Birth order, prematurity, and maternal smoking were unrelated to breast cancer risk. CONCLUSION: Our findings provide some support for the hypothesis that in utero exposures reflective of higher endogenous hormone levels could affect risk for development of breast cancer in adulthood.

Aihara T, Kim Y, Takatsuka Y. · Department of Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo, Japan. · Ann Oncol. · Pubmed #11886007 links to  free full text

Abstract: BACKGROUND: This study was conducted to investigate the efficacy and toxicity of weekly docetaxel administration in patients with metastatic breast cancer. PATIENTS AND METHODS: Thirty-seven women were treated with 1 h infusions of docetaxel at 40 mg/m2/week after pre-medication with 8 mg dexamethazone. Each cycle consisted of three consecutive weekly treatments followed by a 1 week rest. All patients were assessed for toxicity; five patients were not assessable for clinical response, time to progression (TTP) and overall survival (OS) because of early treatment failure, but they were included in intention-to-treat analysis. RESULTS: Patients received a median of four cycles (range, 1-9), with a median dose intensity of 28 mg/m2/week (range 22-30) and a median relative dose intensity of 0.95 (range 0.73-1.0). No patients showed complete response, whereas 14 had partial response, which accounted for 38% of objective response rate [95% confidence interval (CI) 22% to 53%]. In addition, three patients (8%, 95% CI 0% to 17%) had stable disease over 6 months. Clinical responses were achieved at a median of three cycles (range 1-4 cycles). The median TTP and OS were 5 and 12 months, respectively. The weekly docetaxel regimen was generally well tolerated. About half of the patients experienced grade > or = 1 neutropenia; only 19% had grade 3/4 neutropenia, including one case of grade 4. No febrile neutropenia was observed and fluid retention syndrome was uncommon. Non-hematologic toxicity, however, such as asthenia/fatigue, nail damage, tearing or hearing disorders, was seen with successive treatment cycles. CONCLUSIONS: Weekly docetaxel at 40 mg/m2/week is an active and feasible regimen for patients with metastatic breast cancer.

Kim J, Lee J, Chang E, Kim S, Suh K, Sul J, Song I, Kim Y, Lee C. · Department of Surgery, Research Institute for Medical Science, College of Medicine, Chungnam National University, 640 Daesadong Jung-Ku, Daejeon 301-721, South Korea. · World J Surg. · Pubmed #19259728 No free full text.

Abstract: BACKGROUND: This study was designed to determine whether a preoperative fluorodeoxyglucose (FDG) positron emission tomography (PET) integrated with computed tomography (CT) (FDG-PET/CT) could be used as a guide for axillary node dissection (AND) or sentinel lymph node biopsy (SNB) in breast cancer patients. METHODS: Between February 2007 and April 2008, we performed FDG-PET/CT scans in 137 biopsy-proven breast cancer patients planning to have an SNB to select patients for either AND (PET/CT N+) or SNB (PET/CT N0). In performing SNB, we also performed additional non-SNB (ADD), which was enlarged at the lower axilla. RESULTS: Twenty-seven patients with positive scans underwent complete AND as a primary procedure, and 110 patients with negative scans underwent SNB + ADD. There were 8 cases of false negative scans, and no case of false positive scan. The overall sensitivity, specificity, positive predictive value, and overall accuracy of FDG-PET/CT in predicting axillary metastasis were 77.1%, 100%, 100%, and 94.2%, respectively. In a subset of 110 patients with SNB + ADD, 104 patients had histologically negative SN, and 6 patients had positive SN in frozen section. Among 110 SNB + ADD cases, there were only 8 cases (7.3%) of positive axillary basins in permanent biopsy, including two cases of late positives that had micrometastases in the SN only. Through selective SNB + ADD based on an FDG-PET/CT, we have spared 27 unnecessary SNBs (true positive scans). CONCLUSIONS: FDG-PET/CT is a specific imaging modality for predicting axillary node metastasis, and allows for a selective approach to either AND or SNB. A selective SNB + ADD based on an FDG-PET/CT reduced both unnecessary SNBs and positive axillary basins, enhancing the identification rates of SN and the accuracy of SNB.

Kim Y, Park SK, Han W, Kim DH, Hong YC, Ha EH, Ahn SH, Noh DY, Kang D, Yoo KY. · Division of Cancer Prevention, National Cancer Control Research Institute, National Cancer Center, Goyang, Korea. · Cancer Epidemiol Biomarkers Prev. · Pubmed #19190159 No free full text.

Abstract: High-density lipoprotein cholesterol (HDL-C) has been suggested to be associated with breast cancer. However, the roles of HDL-C and hypertriglyceridemia on breast cancer still have been controversial. The goal of this study was to investigate the association between HDL-C with breast cancer risk, stratifying by menopausal status, and body mass index. The hormonal receptor status of breast has been proposed to modify the effect of HDL-C on breast cancer. Multicenter hospital-based case-control study was conducted from November 2004 to December 2005 in Korea. After one to two individual matchings by age (+/-5 years) and menopausal status, 690 cases and 1,380 controls were included in the analysis. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by conditional, unconditional, and multinomial logistic regressions. Protective effect of HDL-C on breast cancer was only observed among premenopausal women with an OR (95% CI) of 0.49 (0.33-0.72) for HDL-C > or = 60 versus <50 mg/dL (P(trend) < 0.01). Only nonobese premenopausal women had a significant decreased risk (OR, 0.34; 95% CI, 0.22-0.53). OR (95% CI) of low HDL-C (<50 mg/dL) and high triglyceride (TG; > or = 150 mg/dL) category was 2.20 (1.32-3.67) on estrogen receptor-negative and progesterone receptor-negative breast cancer compared with high HDL-C (> or = 50 mg/dL) and low TG (<150 mg/dL) category. This study suggests that higher level of HDL-C may reduce breast cancer risk among premenopausal women. Estrogen receptor-negative and progesterone receptor-negative breast cancer was associated with dyslipidemia, which implicates that association among HDL-C, TG, and breast cancer may be modified by receptor status.

Lee JY, Kang MB, Jang SH, Qian T, Kim HJ, Kim CH, Kim Y, Kong G. · Department of Pathology, College of Medicine, Hanyang University, Seongdong-Gu, Seoul, Republic of Korea. · Oncogene. · Pubmed #19079342 No free full text.

Abstract: Inhibitor of differentiation-1 (Id-1) has been accepted as a putative oncogene to promote oncogenic processes through inactivation of tumor suppressors and activation of growth promoting pathways. Here, we show that Id-1 activates the Akt pathway by inhibition of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) transcription through downregulation of p53. Id-1 negatively regulated both p53 and PTEN at the transcriptional level. In promoter assay with serial deletion and chromatin immunoprecipitation assay, the binding of p53 to the PTEN promoter was reduced by Id-1, suggesting that Id-1 regulates PTEN transcription through its p53 modulation. This led to Akt phosphorylation at Ser473 and the activation of the Akt-mediated canonical Wnt signaling pathway. The glycogen synthase kinase-3beta phosphorylation at Ser9, stabilization and nuclear localization of beta-catenin, T-cell factor (TCF)/lymphoid enhancer factor transactivation activity and cyclin D1 expression were enhanced by Id-1. On the other hand, Akt-mediated p27(Kip1) phosphorylation at Thr157 and its cytosolic localization were also increased in Id-1 overexpressing MCF7 cells. In conclusion, our results disclose Id-1 as a novel PTEN inhibitor that could activate the Akt pathway and its downstream effectors, the Wnt/TCF pathway and p27(Kip1) phosphorylation and suggest that the oncogenic function of Id-1 may be partly attributed to its PTEN inhibition in human breast carcinogenesis.

Kim JE, Kim HS, Shin YJ, Lee CS, Won C, Lee SA, Lee JW, Kim Y, Kang JS, Ye SK, Chung MH. · Department of Pharmacology, Seoul National University College of Medicine, Seoul 110-799, Korea. · Exp Mol Med. · Pubmed #18985009 links to  free full text

Abstract: Tumor migration/invasion is the main cause of tumor progression and STAT3 is needed to enhance tumor migration/invasion by up-regulating MMP-9. Thus, agents that inhibit STAT3 activation may be used as an anticancer drug. We present herein that 6-methyl-2-propylimino-6, 7-dihydro-5H-benzo [1, 3]-oxathiol- 4-one (LYR71) , a derivative of trimeric resveratrol, has an anticancer activity through inhibition of STAT3 activation. We found that LYR71 suppressed STAT3 activation and inhibited the expression and activity of MMP-9 in RANTES-stimulated breast cancer cells. In addition, LYR71 reduced RANTES-induced MMP-9 transcripts by blocking STAT3 recruitment, dissociating p300 and deacetylating histone H3 and H4 on the MMP-9 promoter. Furthermore, LYR71 inhibited tumor migration/invasion in RANTES-treated breast cancer cells and consequently blocked tumor progression in tumor-bearing mice. Taken together, the results of this study suggest that LYR71 can be therapeutically useful due to the inhibition effect of STAT3-mediated MMP-9 expression in breast cancer cells.

Hara E, Matsuoka Y, Hakamata Y, Nagamine M, Inagaki M, Imoto S, Murakami K, Kim Y, Uchitomi Y. · Section of Psychiatry and Behavioral Science at Tokyo Medical and Dental University Graduate School, Tokyo. · J Neuropsychiatry Clin Neurosci. · Pubmed #18806233 links to  free full text

Abstract: Although smaller hippocampi and amygdalae were found in cancer survivors with intrusions, associations between cancer-related posttraumatic stress disorder (PTSD) and these volumes are unknown. The authors performed MRI volumetric analyses of these regions in 15 cancer survivors with PTSD, 15 cancer survivors without PTSD, and 15 healthy comparison subjects. The authors also examined the correlation between PTSD symptom scores of the Impact of Event Scale and these volumes in the PTSD group. These volumes were not significantly different among the groups, but the intrusion score was inversely associated with the hippocampal volume. Results suggest intrusions, not PTSD diagnosis, might be associated with hippocampal volume.

Trombetta M, Julian T, Miften M, McWilliams W, Kim Y, Parda D. · Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, PA 15212, USA. · Brachytherapy. · Pubmed #18786865 No free full text.

Abstract: PURPOSE: To examine the feasibility of using the MammoSite brachytherapy applicator in the retreatment of the previously irradiated breast. METHODS AND MATERIALS: Between March 2004 and March 2007, three patients previously treated with external beam radiotherapy were retreated using the MammoSite brachytherapy device. Two patients were treated for an ipsilateral breast tumor recurrence after breast conservation surgery and postoperative irradiation, whereas the third patient developed an in-field breast cancer likely associated with Hodgkin's disease mantle irradiation 27 years before. The recurrent histology of two was ductal carcinoma in situ ([DCIS] one originally presenting as infiltrating ductal carcinoma [IDC] and the other as DCIS), whereas the Hodgkin's disease patient presented with IDC. All patients received a twice-daily tumor dose of 3400 cGy at 340 cGy/fraction. The mean maximum skin dose was 53.4% (range, 49.5-60.3%) of the prescribed dose. RESULTS: With a mean followup of 32 months, no patient developed a local recurrence. Cosmesis in all three cases as graded by the National Surgical Adjuvant Breast and Bowel Project, cosmesis criteria was excellent (Grade I) in all cases. Dosimetric calculations demonstrated that the device allows for appropriate local irradiation while sparing the previously irradiated skin of the involved breast as defined by the protocol standard. CONCLUSIONS: Use of the MammoSite device in the treatment of the previously irradiated breast is feasible and may provide adequate local control as well as acceptable cosmesis in carefully selected patients.

Lee JY, Jang KS, Shin DH, Oh MY, Kim HJ, Kim Y, Kong G. · Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea. · Cancer Res. · Pubmed #18519679 links to  free full text

Abstract: Mel-18, a polycomb group (PcG) protein, has been suggested as a tumor suppressor in human breast cancer. Previously, we reported that Mel-18 has antiproliferative activity in breast cancer cells. However, its functional mechanism has not been fully elucidated. Here, we investigated the role of Mel-18 in human breast cancer. We saw an inverse correlation between Mel-18 and phospho-Akt, which were expressed at low and high levels, respectively, in primary breast tumor tissues from 40 breast cancer patients. The effect of Mel-18 on cell growth was examined in two breast cancer cell lines, SK-BR-3 and T-47D, which express relatively low and high levels of endogenous Mel-18, respectively. On Mel-18 overexpression in SK-BR-3 cells, cell growth was attenuated and G(1) arrest was observed. Likewise, suppression of Mel-18 by antisense expression in T-47D cells led to enhanced cell growth and accelerated G(1)-S phase transition. In these cells, cyclin-dependent kinase (Cdk)-4 and Cdk2 activities were affected by Mel-18, which were mediated by changes in cyclin D1 expression and p27(Kip1) phosphorylation at Thr(157), but not by INK4a/ARF genes. The changes were both dependent on the phosphatidylinositol 3-kinase/Akt signaling pathway. Akt phosphorylation at Ser(473) was reduced by Mel-18 overexpression in SK-BR-3 cells and enhanced by Mel-18 suppression in T-47D cells. Akt-mediated cytoplasmic localization of p27(Kip1) was inhibited by Mel-18 in SK-BR-3 cells. Moreover, Mel-18 overexpression showed reduced glycogen synthase kinase-3beta phosphorylation, beta-catenin nuclear localization, T-cell factor/lymphoid enhancer factor promoter activity, and cyclin D1 mRNA level. Taken together, we established a linear relationship between Mel-18-->Akt-->G(1) phase regulators.

Shafee N, Smith CR, Wei S, Kim Y, Mills GB, Hortobagyi GN, Stanbridge EJ, Lee EY. · Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, CA 92697, USA. · Cancer Res. · Pubmed #18451150 links to  free full text

Abstract: The majority of BRCA1-associated breast cancers are basal cell-like, which is associated with a poor outcome. Using a spontaneous mouse mammary tumor model, we show that platinum compounds, which generate DNA breaks during the repair process, are more effective than doxorubicin in Brca1/p53-mutated tumors. At 0.5 mg/kg of daily cisplatin treatment, 80% primary tumors (n = 8) show complete pathologic response. At greater dosages, 100% show complete response (n = 19). However, after 2 to 3 months of complete remission following platinum treatment, tumors relapse and become refractory to successive rounds of treatment. Approximately 3.8% to 8.0% (mean, 5.9%) of tumor cells express the normal mammary stem cell markers, CD29(hi)24(med), and these cells are tumorigenic, whereas CD29(med)24(-/lo) and CD29(med)24(hi) cells have diminished tumorigenicity or are nontumorigenic, respectively. In partially platinum-responsive primary transplants, 6.6% to 11.0% (mean, 8.8%) tumor cells are CD29(hi)24(med); these populations significantly increase to 16.5% to 29.2% (mean, 22.8%; P < 0.05) in platinum-refractory secondary tumor transplants. Further, refractory tumor cells have greater colony-forming ability than the primary transplant-derived cells in the presence of cisplatin. Expression of a normal stem cell marker, Nanog, is decreased in the CD29(hi)24(med) populations in the secondary transplants. Top2A expression is also down-regulated in secondary drug-resistant tumor populations and, in one case, was accompanied by genomic deletion of Top2A. These studies identify distinct cancer cell populations for therapeutic targeting in breast cancer and implicate clonal evolution and expansion of cancer stem-like cells as a potential cause of chemoresistance.

Kim Y, Johnson M, Trombetta MG, Parda DS, Miften M. · Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, PA 15212-4772, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18406895 No free full text.

Abstract: PURPOSE: To measure the interfraction changes of the MammoSite applicator and evaluate their dosimetric effect on target coverage and sparing of organs at risk. METHODS AND MATERIALS: A retrospective evaluation of the data from 19 patients who received 10 fractions (34 Gy) of high-dose-rate partial breast irradiation was performed. A computed tomography-based treatment plan was generated for Fraction 1, and a computed tomography scan was acquired just before the delivery of each fraction to ensure a consistent shape of the balloon. The eccentricity, asymmetry, and planning target volume (PTV) for plan evaluation purposes (PTV_EVAL), as well as trapped air gaps, were measured for all patients. Furthermore, 169 computed tomography-based treatment plans were retrospectively generated for Fractions 2-10. Interfraction dosimetric variations were evaluated using the %PTV_EVAL coverage, target dose homogeneity index, target dose conformal index, and maximum doses to the organs at risks. RESULTS: The average variation of eccentricity and asymmetry from Fraction 1 values of 3.5% and 1.1 mm was -0.4% +/- 1.6% and -0.1 +/- 0.6 mm. The average trapped air gap volume was dramatically reduced from before treatment (3.7 cm(3)) to Fraction 1 (0.8 cm(3)). The PTV_EVAL volume change was insignificant. The average variation for the %PTV_EVAL, target dose homogeneity, and target dose conformal index from Fraction 1 values of 94.7%, 0.64, and 0.85 was 0.15% +/- 2.4%, -0.35 +/- 2.4%, and -0.34 +/- 4.9%, respectively. The average Fraction 1 maximum skin and ipsilateral lung dose of 3.2 Gy and 2.0 Gy varied by 0.08 +/- 0.47 and -0.16 +/- 0.29 Gy, respectively. CONCLUSION: The interfraction variations were patient specific and fraction dependent. Although the average interfraction dose variations for the target and organs at risk were not clinically significant, the maximum variations could be clinically significant.

Kim Y, Kashy DA, Wellisch DK, Spillers RL, Kaw CK, Smith TG. · Behavioral Research Center, American Cancer Society, 250 Williams St. NW., Atlanta, GA 30303, USA. · Ann Behav Med. · Pubmed #18365297 No free full text.

Abstract: BACKGROUND AND PURPOSE: Although evidence suggests that survivors and spousal caregivers tend to experience somewhat similar levels of distress and that the survivor's distress affects his/her own quality of life, the degree to which each person's distress has an independent effect on their partner's quality of life is unknown. Thus, this study aimed to examine the dyadic effects of psychological distress on the quality of life of couples dealing with cancer. METHODS: A total of 168 married survivor-caregiver dyads participating in the American Cancer Society's Study of Cancer Survivors-I and Quality of Life Survey for Caregivers provided complete data for study variables. Participating survivors were diagnosed with either breast or prostate cancer approximately 2 years prior to participating in the study. RESULTS: Using the Actor Partner Interdependence Model, results revealed that although each person's psychological distress is the strongest predictor of their own quality of life, partner's distress and (dis)similarity in distress of the couple also play significant roles in one's quality of life. In addition, the adverse effect of having a partner who is less emotionally resourceful was especially pronounced on men's physical health. CONCLUSIONS: Our systematic investigation provided valuable evidence for identifying the subgroup of cancer survivors and their spouses who are vulnerable to poor quality of life due to their mutual psychological distress. These findings suggest that couples may benefit from interventions that enhance their ability to manage psychological distress, particularly the wife's, which may improve the mental and physical health of both partners when they are dealing with cancer.

Kim Y, Parda DS, Trombetta MG, Colonias A, Werts ED, Miller L, Miften M. · Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212, USA. · Med Phys. · Pubmed #18196791 No free full text.

Abstract: A dosimetric comparison was performed on external-beam three-dimensional conformal partial breast irradiation (PBI) and whole breast irradiation (WBI) plans for patients enrolled in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 protocol at our institution. Twenty-four consecutive patients were treated with either PBI (12 patients) or WBI (12 patients). In the PBI arm, the lumpectomy cavity was treated to a total dose of 38.5 Gy at 3.85 Gy per fraction twice daily using a four-field noncoplanar beam setup. A minimum 6 h interval was required between fractions. In the WBI arm, the whole breast including the entirety of the lumpectomy cavity was treated to a total dose of 50.4 Gy at 1.8 Gy per fraction daily using opposed tangential beams. The lumpectomy cavity volume, planning target volume for evaluation (PTV_EVAL), and critical structure volumes were contoured for both the PBI and WBI patients. Dosimetric parameters, dose volume histograms (DVHs), and generalized equivalent uniform dose (gEUD) for target and critical structures were compared. Dosimetric results show the PBI plans, compared to the WBI plans, have smaller hot spots in the PTV_EVAL (maximum dose: 104.2% versus 110.9%) and reduced dose to the ipsilateral breast (V50: 48.6% versus 92.1% and V100: 10.2% versus 50.5%), contralateral breast (V3: 0.16% versus 2.04%), ipsilateral lung (V30: 5.8% versus 12.7%), and thyroid (maximum dose: 0.5% versus 2.0%) with p values < or = 0.01. However, similar dose coverage of the PTV_EVAL (98% for PBI and 99% for WBI, on average) was observed and the dose difference for other critical structures was clinically insignificant in both arms. The gEUD data analysis showed the reduction of dose to the ipsilateral breast and lung, contralateral breast and thyroid. In addition, preliminary dermatologic adverse event assessment data suggested reduced skin toxicity for patients treated with the PBI technique.

Kim H, Chung H, Kim HJ, Lee JY, Oh MY, Kim Y, Kong G. · Department of Pathology, College of Medicine, Hanyang University, Seongdong-gu, Seoul, Republic of Korea. · Breast Cancer Res Treat. · Pubmed #18158619 No free full text.

Abstract: Although increasing evidence supports the protective role of inhibitor of differentiation and DNA binding-1 (Id-1) against anticancer drug-induced apoptosis, the underlying molecular mechanisms seem to vary depending on the tumor system. Here, we examined the direct role of Id-1 in MCF-7 breast cancer cells by ectopically overexpressing Id-1 under serum-free condition, where the endogenous Id-1 expression was suppressed. Id-1 expression resulted in increased number of viable cells, reduced Bax expression, enhanced Bcl-2 expression, but no change in Bcl-xL expression. The expression of nuclear factor-kappaB (NF-kappaB) was augmented, while those of p53 and IkappaB were reduced. Such changes in p53 and NF-kappaB pathways were also functional, as assessed by real-time polymerase chain reactions and reporter assays of their known downstream targets, p21 and Il-6, as well as Bax and Bcl-2 genes. Finally, Id-1 played a protective role against taxol-induced apoptosis in breast cancer cells as assessed by MTT assay and apoptotic cell count upon taxol treatment (0-200 nM). Reduced Bax expression and enhanced Bcl-2 expression by Id-1 were also noted in the presence of taxol. Taken together, we present a molecular mechanism where Id-1 regulates p53 and NF-kappaB pathways, which in turn regulates Bax and Bcl-2 genes, thus providing a survival advantage under exogenous stress such as serum-free or taxol treatment in MCF-7 breast cancer cells. In this regard, inactivation of Id-1 may provide a potential therapeutic strategy leading to inhibition of breast cancer progression and anti-cancer drug resistance.

Chen Y, Gunawan E, Kim Y, Low KS, Soh CB, Thi LL. · Biomed. Eng. Res. Centre, Nanyang Technol. Univ., Singapore. · Conf Proc IEEE Eng Med Biol Soc. · Pubmed #17945730 No free full text.

Abstract: This paper presents a generic framework for the modeling of ultra-wideband (UWB) signal propagation in human breast, which facilitates system-level simulations and provides performance prediction. The clutter associated with the breast tissue heterogeneity is modeled through several key parameters depending on the tissue compositions. Subsequently, important channel properties such as the backscatter energy and the probability density function of time-of-arrival are derived. The modified Hermite polynomials, which fit well into the real pulse shapes, are then used to model the UWB signals. Armed with the channel/signal model preliminaries, three metrics are proposed, namely, the mean clutter response, the clean tumor response, and the worst-case clutter response. The generalized model provides a parsimonious way to study the effects of tissue structures, pulse templates, and array setup on the performance of a specified UWB imaging system. Numerical examples are used to demonstrate the usefulness of the proposed approach.

Hakamata Y, Matsuoka Y, Inagaki M, Nagamine M, Hara E, Imoto S, Murakami K, Kim Y, Uchitomi Y. · Division of Adult Mental Health, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan. · Neurosci Res. · Pubmed #17923164 No free full text.

Abstract: The neurobiological basis of cancer-related post-traumatic stress disorder (PTSD) has never been studied. We investigated brain structural alterations and the longitudinal courses in patients with cancer-related PTSD. Baseline scans using magnetic resonance imaging were performed in 14 cancer survivors with PTSD, 100 without PTSD, and 70 healthy subjects. Follow-up scans were performed 2 years later in 76 cancer survivors (PTSD, n=9; non-PTSD, n=67). Using voxel-based morphometry, the gray matter volume (GMV) of the cancer survivors with PTSD was compared with the GMVs of those without PTSD and of the healthy subjects. The effects of the interactions between the diagnosis and the timing of the GMV measurements were examined. The GMV of the right orbitofrontal cortex (OFC) was significantly smaller in cancer survivors with PTSD than in those without PTSD or healthy subjects. The interaction between the diagnosis and the timing of the right OFC's GMV measurement was not significant. The OFC, which is thought to be involved in the extinction of fear conditioning and the retrieval of emotional memory, might play an important role in the pathophysiology of PTSD. Moreover, the OFC's GMV may remain constant after the development of cancer-related PTSD.

Kim Y, Morrow GR. · Behavioral Research Center, American Cancer Society, Atlanta, Georgia 30303, USA. · J Pain Symptom Manage. · Pubmed #17604591 No free full text.

Abstract: Although the degree of a patient's anxiety and symptoms of post-treatment nausea have been suggested as predictors of anticipatory nausea, little attention has been given to the impact of family support on the development of anticipatory nausea. This study examines the role of family support in the development of the severity of anticipatory nausea, both directly and mediated through a patient's anxiety. Five hundred thirty-nine patients with breast cancer were studied. The results from latent growth modeling showed that family support was associated with the severity of anticipatory nausea mediated by the levels of a patient's anxiety and post-treatment nausea severity. In addition, family support had a direct impact on the severity level of anticipatory nausea. The findings suggest that helping patients and their families communicate in more satisfactory and supportive ways and maintain an organized family system might be beneficial in reducing the symptoms of chemotherapy-related nausea.

Kim Y, Wellisch DK, Spillers RL, Crammer C. · Behavioral Research Center, American Cancer Society, Atlanta 30303, USA. · Support Care Cancer. · Pubmed #17516094 No free full text.

Abstract: INTRODUCTION: This study examined the effects of the survivor's cancer type (gender-specific vs nongender-specific) and the female caregiver's spirituality and caregiving stress on the caregiver's psychological distress. Cancer caregivers, who were nominated by cancer survivors, participated in a nationwide quality-of-life survey with 252 caregivers providing complete data for the variables. PATIENTS AND METHODS: Breast and ovarian cancer were categorized as gender-specific types of cancer (GTC+), whereas kidney, lung, non-Hodgkin's lymphoma (NHL), and skin melanoma cancers were GTC-. Spirituality, caregiving stress, and psychological distress were measured using the functional assessment of chronic illness therapy--spiritual well-being, stress overload subscale, and profile of mood states--short form, respectively. RESULTS AND DISCUSSION: Hierarchical regression analyses revealed that female caregivers whose care recipient was diagnosed with a nongender specific type of cancer (GTC- group) reported higher psychological distress than did the GTC+ group. The GTC- group also reported lower spirituality and higher caregiving stress related to higher psychological distress than did the GTC+ group. In addition, the beneficial effect of spirituality on reducing psychological distress was more pronounced among the GTC- group or when caregiving stress increased. CONCLUSIONS: Our findings suggest that female caregivers of survivors with a nongender-specific cancer may benefit from programs designed to reduce their psychological distress, and caregivers who are low in spirituality need help to derive faith and meaning in the context of cancer care.

Kim Y, Choi JY, Lee KM, Park SK, Ahn SH, Noh DY, Hong YC, Kang D, Yoo KY. · Departments of Preventive Medicine, Seoul National University College of Medicine, Yongon-dong Chongno-gu, Seoul, Republic of Korea. · Eur J Cancer Prev. · Pubmed #17297388 No free full text.

Abstract: Lactation might have a crucial role in an extraordinary increase in breast cancer incidence in Korea, as the proportion of mothers who practised breast-feeding fell dramatically. This hospital-based case-control analysis has been carried out since 1997 to evaluate whether lactation is associated with breast cancer risk in Korean women. Among the eligible study participants, a total of 753 histologically confirmed incident cases and an equal number of controls were included in the analysis. The risk was estimated using unconditional logistic regression models. Family history, older at menopause, more full-term pregnancies increased the risk of breast cancer. Breast cancer risk decreased according to the total months of breast-feeding (P for trend=0.03). Average duration of breast-feeding of 11-12 months reduced risk of breast cancer by 54% compared with the duration of 1-4 months (odds ratio, 0.46; 95% confidence interval, 0.30-0.70). The decreasing risk trend according to average months of breast-feeding was also statistically significant (P for trend=0.02). Moreover, a reduced risk of breast cancer was apparent when analysis was restricted to the first breast-fed child (P for trend=0.006). This study confirms that lactation has an apparent dose-dependent protective effect against breast cancer in Korean women.

Yoo KY, Kim Y, Park SK, Kang D. · Department of Preventive Medicine, Seoul National University College of Medicine, 410-769, Korea. · Asian Pac J Cancer Prev. · Pubmed #17250452 No free full text.

Abstract: Not only the incidence but the mortality of breast cancer has been steadily increasing in Korea over the last twenty years, and it became the most common female neoplasm in 2002. In fact, the increase in the rate of breast cancer mortality in Korea over the past 10 years has been higher than anywhere else in the world, and it is particularly noteworthy that more than half of the incident cases occur among those younger than 50 years of age. The rapid westernization of dietary habits and changes in reproductive behavior of Korean women presumably played a central role in this extraordinary increase in breast cancer occurrence. A large-scale multi-center case-control analysis showed that an older age, a family history of breast cancer, early menarche, late menopause, late full-term pregnancy, never-having had a breast-fed child, and postmenopausal obesity are breast cancer risk factors in Korea. Environmental and genetic factors are known to play interactive roles in human carcinogenesis and recent studies have shown that genetic polymorphisms may predispose individuals to breast cancer via gene-to-environment or gene-to-gene interactions. Thus research into genetic variation in xenobiotic metabolism, estrogen metabolism, DNA repair, cytokine metabolism, or cell cycle control may give insights into both the etiology and prevention of breast cancer. Epidemiologic evidence obtained from migrant and lifestyle change studies and investigations of main risk factors strongly suggests that breast cancer will further increase in Korea. Future predictions point to a 2- to 3-fold increase in incidence by 2020. Here, we briefly introduce health education programs and breast cancer campaigns, in the broad context of the Korean National Cancer Control Program.

Poole AJ, Li Y, Kim Y, Lin SC, Lee WH, Lee EY. · Department of Biological Chemistry, University of California, Irvine, CA 92697-4037, USA. · Science. · Pubmed #17138902 links to  free full text

Abstract: Women with mutations in the breast cancer susceptibility gene BRCA1 are predisposed to breast and ovarian cancers. Why the BRCA1 protein suppresses tumor development specifically in ovarian hormone-sensitive tissues remains unclear. We demonstrate that mammary glands of nulliparous Brca1/p53-deficient mice accumulate lateral branches and undergo extensive alveologenesis, a phenotype that occurs only during pregnancy in wild-type mice. Progesterone receptors, but not estrogen receptors, are overexpressed in the mutant mammary epithelial cells because of a defect in their degradation by the proteasome pathway. Treatment of Brca1/p53-deficient mice with the progesterone antagonist mifepristone (RU 486) prevented mammary tumorigenesis. These findings reveal a tissue-specific function for the BRCA1 protein and raise the possibility that antiprogesterone treatment may be useful for breast cancer prevention in individuals with BRCA1 mutations.

Martin MY, Keys W, Person SD, Kim Y, Ashford RS, Kohler C, Norton P. · University of Alabama at Birmingham, Birmingham Alabama Division of Preventive Medicine, 35294-4410, USA. · J Cancer Educ. · Pubmed #16122362 No free full text.

Abstract: BACKGROUND: African American women are more likely to be diagnosed at later stages of breast cancer. METHODS: A total of 15 residents participated in a program to increase their self-efficacy in communication skills relevant to understanding and responding to African American cultural issues associated with mammography screening. RESULTS: Physicians reported increasing confidence in their ability to elicit barriers to mammography; assess cultural beliefs and norms; assess perceived health benefits and emotional adjustment; engage in emotional talk; motivate; and negotiate and build partnerships with patients. CONCLUSIONS: A brief program can increase physician communication skills to meet the needs of a diverse population.

Erblich J, Brown K, Kim Y, Valdimarsdottir HB, Livingston BE, Bovbjerg DH. · Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1130, New York, NY 10029-6574, USA. · Patient Educ Couns. · Pubmed #15653247 No free full text.

Abstract: Women who undergo genetic counseling concerning their increased risk of developing breast cancer confront large quantities of complex information in a short period of time. Clinical reports have suggested that many women may not retain what they learned during counseling. A validated questionnaire to measure their knowledge, however, is lacking. In this study, we describe the development and validation of a questionnaire to assess knowledge of information typically included in genetic counseling for breast cancer. Items were empirically derived from detailed content analyses of actual genetic counseling sessions. The instrument's content validity was high, as evidenced by high levels of independent interrater agreement (0.93) on items. Subsequent data reduction and confirmatory factor analytic techniques yielded a highly reliable (alpha = 0.92) 27-item Breast Cancer Genetic Counseling Knowledge Questionnaire (BGKQ). Direct comparison of this questionnaire to a scale previously developed in the literature (BCHK; [Breast Cancer Res. Treat. 53 (1999) 69]) supported the utility of the new questionnaire for evaluation of knowledge after counseling. Compared to non-counseled groups (n = 45), women who had undergone genetic counseling (n = 28) scored significantly higher (P < 0.0001) on the BGKQ, but not on the other questionnaire, establishing the BGKQ's criterion validity. The BGKQ may, thus, provide a useful clinical and research tool for assessing knowledge of information provided during genetic counseling and exploring the potential impact of distress on knowledge, as well as the impact of knowledge on screening behaviors.

Kim Y, Duhamel KN, Valdimarsdottir HB, Bovbjerg DH. · Mount Sinai School of Medicine, USA. · Psychooncology. · Pubmed #15543540 No free full text.

Abstract: The experience of breast cancer in a close family member can be a major life stressor for many women as evidenced by various psychosocial and biological indicators. However, existing studies have found considerable variability in the levels of psychological distress among women with family histories of breast cancer (FHBC). Based on cognitive processing models, we examined moderating effects of recent life events on the impact of having a family member with breast cancer and psychological distress. Specifically, we hypothesized that negative recent life events would be associated with greater psychological distress and that positive recent life events would be associated with less psychological distress, and these patterns will be more prominent among women with FHBC than women without FHBC. Women with (FHBC+, N = 59) and women without (FHBC-, N = 94) FHBC completed measures of recent life events, cancer-specific distress (intrusion and avoidance) and general distress. Results indicated that among FHBC+ women, negative life events were associated with higher levels of breast cancer-specific intrusion and positive life events were associated with lower levels of breast cancer-specific avoidance. These results support the application of cognitive processing models for understanding variability in women's psychological adjustment to their FHBC. Psychological interventions designed to facilitate coping with negative life events and to increase the occurrence of positive events may be warranted.

Lee A, Kim Y, Han K, Kang CS, Jeon HM, Shim SI. · Department of Clinical Pathology, College of Medicine, Catholic University of Korea, Seoul, Korea. · Arch Pathol Lab Med. · Pubmed #15508191 No free full text.

Abstract: CONTEXT: The traditional triple test for breast cancer diagnosis is physical examination, mammography, and aspiration cytology. However, the accuracy of mammography on young women with nonatrophied breasts is poor compared with that for women older than 50 years, and additional methods for diagnosis of breast cancer are needed. OBJECTIVE: To investigate whether carcinoembryonic antigen (CEA), CA 15-3, and CA 125 concentrations in breast aspiration fluid are useful as breast cancer biochemical markers and whether APC and cyclin D2 gene promoter hypermethylation could be regarded as a breast cancer molecular marker. DESIGN: CEA, CA 15-3, and CA 125 concentrations were measured, and methylation status of the APC gene promoter 1A and the promoter region of the cyclin D2 gene were analyzed using a methylation-specific polymerase chain reaction assay of ex vivo breast aspiration fluid obtained from 49 samples of excised breast tissue. SETTING: The specimens were collected during a 1-year period in the tertiary care teaching hospital in Seoul, Korea. PATIENTS: Forty-nine patients with breast masses were surgically treated. Thirty-four patients had breast cancer, and 15 had benign breast disease. RESULTS: Aspiration fluid CEA concentrations were significantly higher in breast cancer cases than in cases of benign breast disease (mean, 69.90 ng/mg protein vs 0.68 ng/mg protein, respectively; P < .001). At 90% specificity of the assay (CEA, 2.13 ng/mg protein), the corresponding sensitivity for breast cancer detection was 62%, according to the receiver operating characteristic curve drawn. The APC gene promoter 1A and the promoter region of the cyclin D2 gene were methylated in 42% (14/33) and 70% (23/33) of the breast cancer aspiration fluid samples, respectively. A cumulative incidence of methylation of these 2 genes was 85% (28/33). The APC and cyclin D2 gene promoters were both unmethylated in the aspiration fluids from 19 women with nonmalignant breast disease. CONCLUSIONS: Breast aspiration fluid CEA concentration and the methylation of the APC gene promoter 1A and the promoter region of the cyclin D2 gene can be used as tumor markers to overcome some of the limitations of aspiration cytology. In combination with the mammogram and physical examination, assays for these markers could be used to help determine a definitive diagnosis when cytologic results are suspicious for malignancy.