• Journal of the Korean Home Economics Association
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• v.35 no.5
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• pp.73-102
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• 1997

The purpose of this study was to identify the specific and empirical contents in terms of first-married stepmother about her stress and efforts to adapt to her stepfamily. This studies relied on the qualitative research method in order to approach stepmother's subjective experience. There were 6 stepmother respondents who were 6 first-marrieds living in Seoul or Kyoungki area. The data was collected by in-depth personal interview.‘Open coding process’, a part of grounded theory procedures were used to analyzed the data. The major findings can be summarized as follows: 1. When focused o stressors, the stress of stepmothers were categorized into 4 categories. Those were the following: 1 When focused on stressors, the stress of stepmothers were categorized into 4 categories. Those were the following: (1) Stepmother's own problem such as stepmother' identity problem; (2) Problems within stepfamily such as problems about relations with husbands, stepchildren, and her own children; (3) Problems of stepmother family's kin such as relational problems with former spouses, in-laws, and her parent; (4) Problems of social relationship such as isolation and alienation in social relationship and neighbors' prejudice about stepmother. 2. In overcoming stress from stepfamily life and adapting to it, 4 categories were identified as important. Contents of 4 categories were such like this: (1) Stepmother's own efforts - (a) give a positive meaning to marriage or remarriage (b) flexible personality (c) situation-accepting attitude (d) exclusive management of household income (e) job (f) perseverance for time to adaptation; (2) Positive feedback within stepfamily - (a) supportive husband (b) sense of unity as a couple (c) psychological reward from stepchildren (d) existence of stepmother's own child (e) behavior for family solidarity (f) family-centered religious life; (3) Stepfamily's relationship with former spouses such as breakdown in relationship with ex-wives or ex-husbands; (4) Support from stepmothers' kin and people in social network with stepmothers. It was concluded that to reduce stress and to help adapt to stepfamily, stepmother should make an effort, and that her stepfamily and her kin should cooperate and support. In addition, negative stereotype of stepmother and stepfamily should disappeared. It was suggested that studies on stepfamily should be vitalized and that programs for preparing remarriage and counseling for stepfamily should be spread.

• Journal of Breast Cancer
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• v.21 no.4
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• pp.415-424
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• 2018

Purpose: Triple-positive breast cancer is defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) positivity. Several systemic breast cancer therapies target hormonal and HER2 responsiveness. We compared clinical outcomes of triple-positive disease with those of HER2-enriched and luminal HER2-negative disease and investigated the clinical efficacy of anti-HER2 therapy for triple-positive disease. Methods: We retrospectively compared overall and recurrence-free survival among cases included in the Korean Breast Cancer Society (KBCS) and Seoul St. Mary's Hospital breast cancer registries and the therapeutic efficacy of trastuzumab for triple-positive and HER2-enriched cases. Results: KBCS registry data (2006-2010; median follow-up, 76 months) indicated that patients with triple-positive breast cancer had intermediate survival between those with luminal A and HER2-enriched subtypes (p<0.001). Trastuzumab did not improve overall survival among patients with triple-positive breast cancer (p=0.899) in contrast to the HER2-enriched subtype (p=0.018). Seoul St. Mary's Hospital registry data indicated similar recurrence-free survival outcomes (p<0.001) and a lack of improvement with trastuzumab among patients with triple-positive breast cancer (median follow-up, 33 months; p=0.800). Multivariate analysis revealed that patients with triple-positive breast cancer had better overall survival than those with HER2-enriched disease and similar survival as those with the luminal A subtype (triple-positive: hazard ratio, 1.258, p=0.118; HER2-enriched: hazard ratio, 2.377, p<0.001). Conclusion: Our findings showed that anti-HER2 therapy was less beneficial for treatment of triple-positive breast cancer than for HER2-enriched subtypes of breast cancer, and the triple-positive subtype had a distinct prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1187-1192
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• 2014

Background: To correlate breast cancer subtypes with prognostic factors, microvessel density (MVD), vascular endothelial growth factor (VEGF) expression and clinical features. Materials and Methods: One hundred cases of primary breast carcinoma were classified using biomarkers on tissue microarray as: luminal A [estrogen receptor (ER)+, HER2-, $Ki-67{\leq}14%$], luminal B [ER+, HER2+ or ER+, HER2-, Ki-67>14%], HER2, triple negative basal-like (TNB) [any basal cytokeratins (CKs, 5, 14, 17) and/or endothelial growth factor receptor (EGFR) expression], and TN without such markers [TNN, null], and assessed for p53, vimentin, VEGF and CD31 immunoperoxidase. Results: Of the 100 cases (mean age, 51 years; mean tumor size, 3.2cm; 56% with nodal metastasis; 89 invasive ductal carcinomas, not otherwise specified, 4 invasive lobular carcinomas, 3 metaplastic carcinomas, and 4 other types) there were 39 luminal A, 18 luminal B, 18 HER2, 15 TNB and 10 TNN. The positivities of basal-like markers in the basal-like subtype were 78.3% for CK5, 40% for CK14, 20% for CK17, 46.7% for EGFR. There was no significant difference in age distribution, tumor size, degree of tubular formation, pleomorphism, lymphovascular invasion, nodal metastasis, MVD, VEGF expression and survival among subgroups. TNs demonstrated significantly higher tumor grade, mitotic count, Ki-67 index, p53 and vimentin and decreased overall survival compared with nonTN. Conclusions: The distribution of breast cancer subtypes in this study was similar to other Asian countries with a high prevalence of TN. The high grade character of TN was confirmed and CK5 expression was found to be common in our basal-like subtype. No significant elevation of MVD or VEGF expression was apparent.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3223-3228
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• 2013

Gene expression profiling (GEP) has identified several molecular subtypes of breast cancer, with different clinico-pathologic features and exhibiting different responses to chemotherapy. However, GEP is expensive and not available in the developing countries where the majority of patients present at advanced stage. The St Gallen Consensus in 2011 proposed use of a simplified, four immunohistochemical (IHC) biomarker panel (ER, PR, HER2, Ki67/Tumor Grade) for molecular classification. The present study was conducted in 75 newly diagnosed patients of breast cancer with large (>5cm) tumors to evaluate the association of IHC surrogate molecular subtype with the clinical response to presurgical chemotherapy, evaluated by the WHO criteria, 3 weeks after the third cycle of 5 flourouracil, adriamycin, cyclophosphamide (FAC regimen). The subtypes of luminal, basal-like and HER2 enriched were found to account for 36.0 % (27/75), 34.7 % (26/75) and 29.3% (22/75) of patients respectively. Ten were luminal A and 14 luminal B (8 HER2 negative and 6HER2 positive). The triple negative breast cancer (TNBC) was most sensitive to chemotherapy with 19% achieving clinical-complete-response (cCR) followed by HER2 enriched (2/22 (9%) cCR), luminal B (1/6 (7%) cCR) and luminal A (0/10 (0%) cCR). Heterogeneity was observed within each subgroup, being most marked in the TNBC although the most responding tumors, 8% developing clinical-progressive-disease. The study supports association of molecular subtypes with response to chemotherapy in patients with advanced breast cancer and the existence of further heterogeneity within subtypes.

• Radiation Oncology Journal
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• v.25 no.4
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• pp.233-241
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• 2007

Purpose: We examined the effect of the dual EGFR/HER2 tyrosine kinase inhibitor, GW572016, on EGFR/HER2 receptor phosphorylation, inhibition of downstream signaling and radiosensitization in either an EGFR or HER2 overexpressing human breast cancer xenograft. Materials and Methods: We established SCID mice xenografts from 4 human breast cancer cell line that overexpressed EGFR or HER 2 (SUM 102, SUM 149, SUM 185, SUM 225). Two series of xenografts were established. One series was established for determining inhibition of the EGFR/HER2 receptor and downstream signaling activities by GW572016. The other series was established for determining the radiosensitization effect of GW572016. Inhibition of the receptor and downstream signaling proteins were measured by the use of immunoprecipitation and Western blotting. For determining the in vivo radiosensitization effect of GW572016, we compared tumor growth delay curves in the following four treatment arms: a) control; b) GW572016 alone; c) radiotherapy (RT) alone; d) GW572016 and RT. Results: GW572016 inhibited EGFR, HER2 receptor phosphorylation in SUM 149 and SUM 185 xenografts. In addition, the p44/42 MAPK (ERK 1/2) downstream signaling pathway was inactivated by GW572016 in the SUM 185 xenograft. In the SUM 225 xenograft, we could not observe inhibition of HER2 receptor phosphorylation by GW572016; both p44/42 MAPK (Erk1/2) and Akt downstream signal protein phosphorylation were inhibited by GW572016. GW572016 inhibited growth of the tumor xenograft of SUM 149 and SUM 185. The combination of GW572016 and RT enhanced growth inhibition greater than that with GW572016 alone or with RT alone in the SUM 149 xenograft. GW572016 appears to act as an in vivo radiosensitizer. Conclusion: GW572016 inhibited EGFR/HER2 receptor phosphorylation and downstream signaling pathway proteins. GW572016 modestly inhibited the growth of tumor in the SUM 185 xenograft and showed radiosensitization in the SUM 149 xenograft. Our results suggest that a better predictor of radiation response would be inhibition of a crucial signaling pathway than inhibition of a receptor.

• Journal of Gastric Cancer
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• v.17 no.1
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• pp.52-62
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• 2017

Purpose: The Trastuzumab for gastric cancer (GC) trial identified human epidermal growth factor receptor 2 (HER2) as a predictor of successful treatment with trastuzumab (HER2 receptor targeting agent) among patients with advanced/metastatic GC. To date, the prevalence of HER2 overexpression in the Korean population is unknown. The present study aimed to assess the incidence of HER2 positivity among GC and gastroesophageal (GE) junction cancer samples and the relationship between HER2 overexpression and clinicopathological characteristics in Korean patients. Materials and Methods: Tumor samples collected from 1,695 patients with histologically proven GC or GE junction enrolled at 14 different hospitals in Korea were examined. After gathering clinicopathological data of all patients, HER2 status was assessed by immunohistochemistry (IHC) at each hospital, and IHC 2+ cases were subjected to silver-enhanced in situ hybridization at 3 central laboratories. Results: A total of 182 specimens tested positive for HER2, whereas 1,505 tested negative. Therefore, the overall HER2-positive rate in this study was 10.8% (95% confidence interval=9.3%-12.3%). The HER2-positive rate was higher among intestinal-type cases (17.6%) than among other types, and was higher among patients older than 70 years and 50 years of age, compared to other age groups. Conclusions: Our evaluation of the HER2 positivity rate (10.8%) among Korean patients with GC and GE junction indicated the necessity of epidemiological data when conducting studies related to HER2 expression in GC and GE junction.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9379-9383
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• 2014

Background: Pathologic complete response (pCR) is one of the most important target end-points of neoadjuvant chemotherapy (NACT) in patients with breast cancer (BC). In present study, we aimed to investigate the relationship between molecular subtypes and NACT in patients with BC. Materials and Methods: Using the Akdeniz University database, 106 patients who received NACT for operable breast cancer were retrospectively identified. Prognostic factors before and after NACT were assessed. According to the molecular subtypes, molecular shifting after NACT and tumoral and nodal response to NACT were analyzed. Results: The distribution of subtypes was: Luminal A, 28.3% (n=30); Luminal B, 31.1% (n=33); HER2-like, 24.5% (n=26); and basal like/triple negative (BL/TN), 16.0% (n=17). According to molecular subtypes, pCR rates in both breast and axillary were 0%, 21.4%, 36.4% and 27.3% for luminal A, luminal B, HER2-like and BL/TN, respectively (p=0.018). Molecular subtype shifting was mostly seen in luminal A type (28.6%) after the NACT. The pCR rate in breast and axillary was significantly higher in patients with HER2-like type BC. Conclusions: In patients with HER-2 like type BC, NACT may be offered in early stages. Additionally, due to molecular shifting, adjuvant treatment schedule should be reviewed again, especially in the luminal A group.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7819-7824
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• 2015

Purpose: To subtype breast cancer (BC) in Saudi women according to the recent molecular classification and to correlate these subtypes with available clinicopathological parameters. Materials and Methods: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (Her2/neu) immunostaining was semi-quantitatively assessed to define molecular subtypes of luminal A and B, HER-2 and triple negative (basal-like) in BC paraffin embedded sections from 115 Saudi female patients diagnosed between 2005 to 2015 at the Department of Pathology, King Fahd Hospital, Almadinah, Saudi Arabia. Results: The most common subtypes were luminal A (47%), followed by luminal B (27.8%) and basal like subtypes (18.3%), whereas HER-2 was the least common subtype (6.9%). Luminal A was predominantly found in the old age group, with low tumor grade (p<0.001) and small tumor size, whereas HER-2 and basal-like subtypes were significantly associated with young age, high tumor grade, lymph node metastasis and lymphovascular invasion (p<0.03, 0.004, 0.05 and 0.04 respectively). All subtypes showed advanced clinical stage at the time of presentation. Conclusions: Molecular subtypes of Saudi BC patients in Almadinah region are consistent with most of the worldwide subtyping. The biological behaviour of each molecular subtype could be expected based on its characteristic clinicopathological features. Along with other prognostic indicators, molecular subtyping would be helpful in predicting prognosis and management of our BC patients. We recommend screening and early diagnosis of BC in our population.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.507-513
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• 2000

ErbB3/HER3 is a cell surface receptor which belongs to the ErbB/HER subfamily of receptor protein tyrosine kinases. When expressed in NIH/3T3 cells, ErbB3 can form heterodimeric coreceptor with endogenous ErbB2. Among known intracellular effectors of the ErbB2/ErbB3 are mitogen-activated protein kinase (MAPK) and phosphoinositide (PI) 3-kinase. In the present study, we studied relative contributions of above two distinct signaling pathways to the heregulin-induced mitogenic response via activated ErbB3. For this, clonal NIH-3T3 cell lines expressing wild-type ErbB3 and ErbB3 mutants were stimulated with $heregulin{\beta}_1$. While cyclin D1 level was markedly high and further increased by treatment of heregulin in cells expressing wild-type ErbB3, the elimination of either Shc binding or PI 3-kinase binding lowered both levels. This result was supported by the reduction of cyclin $D_1$ expression by preteatment with MAPK kinase inhibitor or PI 3-kinase inhibitor before stimulation with heregulin. In accordance with the cyclin $D_1$ expression, elimination of either Shc binding or PI 3-kinase binding reduced the heregulin-induced DNA synthesis and cell growth rate. Our results obtained by the comparison of wild-type and ErbB3 mutants indicate that the full induction of the cell cycle progression through $G_1/S$ phase by ErbB3 activation is dependent on both Shc/MAPK and PI 3-kinase signal transduction pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5511-5515
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• 2012

Introduction: The nuclear factor ${\kappa}B$ (NF-${\kappa}B$) is a super family of transcription factors which plays important roles in development and progression of cancer. The present investigation concerns NF-${\kappa}B$ /p65 activity in human breast cancers with overexpression of ER, PR, HER-2/neu, as well as the significance of p65 expression with regard to menopausal status, stage, grade, tumor size, nodal status, and NPI of invasive ductal carcinomas in Eastern India. Materials and Methods: In this hospital based study 57 breast cancer patients attending a Breast Clinic of a reputed institute of Eastern India were assessed for p65 protein expression in breast tumor tissue samples by Western blotting. ER, PR and HER-2/neu expression was determined by immunohistochemistry. Results: NF-${\kappa}B$/p65 was significantly associated with advanced stage, large tumor size (${\geq}5$ cm), high grade, negative ER, negative PR, and positive HER-2/neu. High NF-${\kappa}B$/p65 expression was more frequent in patients with a high NPI ($NPI{\geq}5.4$, 84.6%) compared with low NPI (<5.4, 44.4%) and this association was statistically significant (p = 0.002). Conclusion: NF-${\kappa}B$/p65 overexpression was associated with advanced stage, large tumor size, high grade, and high NPI which are poor prognostic factors linked to enhanced aggressiveness of the disease. NF-${\kappa}B$/p65 expression implies aggressive biological behavior of breast cancer and this study validates significant association of NF-${\kappa}B$ /p65 overexpression with negative estrogen and progesterone receptor status and overexpression of HER-2/neu oncoprotein. In our good clinical practice, patients with NF-${\kappa}B$ positive tumors need to be treated aggressively.