• Journal of Breast Cancer
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• 제21권4호
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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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• 제14권6호
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• pp.3779-3784
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• 2013

Aims: To determine the clinical, pathological and prognostic features associated with triple-negative breast cancer (TNBC). Methods: Clinical and histologic data of 21,749 breast cancer patients who were treated at Tianjin Medical University Cancer Institute and Hospital between July 2002 and December 2011 were collected. Patients were divided into two groups: those with TNBC and those with other types of breast cancer. Patients and tumor characteristics were compared between the two groups using the Chi-square test. The prognostic results of 9,823 patients in the study population were also analyzed to determine long-term survival rates in the two groups of breast cancer patients. Results: Among the breast cancer patients treated in our hospital between 2003 and 2011, 10.4%-13.5% of them had triple-negative breast cancers. Data analyses revealed significant differences in disease onset age, family history of breast cancer, tumor size, tumor histologic grade, lymph note positivity and metastatic status between TNBC and non-TNBC patients. There were also significant differences in 5-year, 7-year and 9-year disease-free and 7-year and 9-year overall survival probability between the groups. Conclusions:TNBC are associated with younger disease onset age, larger tumor size, higher rate of axillary lymph node positivity, and higher tumor histologic grade. TNBC is also related to family history of breast cancer, increased metastatic risk and poor prognosis.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10505-10508
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• 2015

Background: Breast cancer is an important cause of death among women. One way of classifying different forms of breast cancer is by molecular features, usually in terms of the four subtypes: luminal A, luminal B, HER2-enriched, and triple negative. Objectives: This study aimed to investigate the association between molecular subtypes and survival among breast cancer patients treated with radiotherapy. Materials and Methods: A retrospective cohort study was conducted. The subjects were 272 breast cancer patients who had received treatment in the radiotherapy unit at Srinagarind Hospital, Thailand, between 1 January, 1999, and 31 May, 2009. The end of the study was 1 June, 2014. Overall survival was defined as the time elapsing between initial registration at the radiotherapy unit and death or the end of the study. Survival curves were estimated by the Kaplan-Meier method, and a multivariate analysis was performed using Cox's proportional hazard regression model. Results: The patient mean age was $47.5{\pm}10.4$ at the time of diagnosis. Of the 272 patients, 146 (53.7%) were classified as luminal A, 12 (4.4%) as luminal B, 30 (11.0%) as HER2-enriched, and 84 (30.9%) as triple negative. The overall survival rates at 1, 3 and 5 years were 87.1%, 68.4% and 59.2%, respectively. According to molecular subtypes, HER2-enriched patients had the lowest 5-year survival rate (30.0 %, 95%CI: 15.02-46.55). The median follow-up time was 8.37 years. In the Cox model analysis a higher risk of death was found for patients with HER2-enriched ($HR_{adj}=3.34$, 95%CI:1.96-5.67), triple negative ($HR_{adj}=2.17$, 95%CI: 1.44-3.27), and stage IIlB ($HR_{adj}=2.20$, 95%CI: 1.16-4.17) cancers. Conclusions: The worst survival rates were among patients classified as HER2-enriched, triple negative and at stage IIIB. Early detection and an advanced treatment modality are needed to help these patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9739-9745
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• 2014

Purpose: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. Materials and Methods: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. Results: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Conclusions: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2109-2114
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• 2012

Background: Ethnic variation in tumor characteristics and clinical presentation of breast cancer is increasingly being emphasized. We studied the tumor characteristics and factors which may influence the presentation and prognosis of triple negative breast cancers (TNC) in a cohort of Chinese women. Methods: A prospective cohort of 1800 Chinese women with breast cancer was recruited in a tertiary referral unit in Hong Kong between 1995 and 2006 and was followed up with a median duration of 7.2 years. Of the total, 216 (12.0%) had TNC and 1584 (88.0%) had non-TNC. Their clinicopathological variables, epidemiological variables and clinical outcomes were evaluated. Results: Patients with TNC had similar age of presentation as those with non-TNC, while presenting at earlier stages (82.4% were stage 1-2, compared to 78.4% in non-TNC, p=0.035). They were likely to be associated with grade 3 cancer (Hazard Ratio(HR)=5.8, p<0.001). TNC showed higher chance of visceral relapse (HR=2.69, p<0.001), liver metastasis (HR=1.7, p=0.003) and brain metastasis (HR=1.8, p=0.003). Compared with non-TNC group, TNC had similar 10-year disease-free survival (82% vs 84%, p=0.148), overall survival (78% vs 79%, p=0.238) and breast cancer-specific mortality (18% vs 16%, p=0.095). However, TNC showed poorer 10-year stage 3 and 4 specific survival (stage 3: 53% vs. 67%, p=0.010; stage 4: 0% vs. 40%, p=0.035). Conclusions: Chinese women with triple negative breast cancer do not have less aggressive biological behavior compared to the West and presentation at a later stage results in worse prognosis compared with those with non triple negative breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1115-1118
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• 2016

Background: There is controversy about ablation efficacy of low or high doses of radioiodine-131 (RAI) in patients with differentiated thyroid cancers (DTC). The purpose of this prospective study was to determine efficacy of 30 mCi and 100 mCi of RAI to achieve successful ablation in patients with low to intermediate risk DTC. Materials and Methods: This prospective cross sectional study was conducted from April 2013 to November 2015. Inclusion criteria were patients of either gender, 18 years or older, having low to intermediate risk papillary and follicular thyroid cancers with T1-3, N0/N1/Nx but no evidence of distant metastasis. Thirty-nine patients were administered 30 mCi of RAI while 61 patients were given 100 mCi. Informed consent was acquired from all patients and counseling was done by nuclear physicians regarding benefits and possible side effects of RAI. After an average of 6 months (range 6-16 months; 2-3 weeks after thyroxin withdrawal), these patients were followed up for stimulated TSH, thyroglobulin (sTg) and thyroglobulin antibodies, ultrasound neck (U/S) and a diagnostic whole body iodine scan (WBIS) for ablation outcome. Successful ablation was concluded with stimulated Tg< 2ng/ml with negative antibodies, negative U/S and a negative diagnostic WBIS (triple negative criteria). ROC curve analysis was used to find diagnostic strength of baseline sTg to predict successful ablation. Results: Successful ablation based upon triple negative criteria was 56% in the low dose and 57% in the high dose group (non-significant difference). Based on a single criterion (follow-up sTg<2 ng/ml), values were 82% and 77% (again non-significant). The ROC curve revealed that a baseline sTg level ${\leq}7.4ng/ml$ had the highest diagnostic strength to predict successful ablation in all patients. Conclusions: We conclude that 30 mCi of RAI has similar ablation success to 100 mCi dose in patients with low to intermediate risk DTC. A baseline $sTg{\leq}7.4ng/ml$ is a strong predictor of successful ablation in all patients. Low dose RAI is safer, more cost effective and more convenient for patients and healthcare providers.

• 대한전자공학회논문지SD
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• 제39권12호
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• pp.1033-1044
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• 2002

본 논문에서는 grounded-plate PMOS 게이트 (GPPG) 강유전체 메모리 셀을 이용한 새로운 FRAM 설계기술을 제안하였다 GPPG 셀은 PMOS와 강유전체 커패시터로 구성되며 셀 plate 는 ground 에 접지 된다. 제안된 FRAM 에서는 비트라인이 V/sub DD/로 precharge 되고, negative 전압 워드라인 기법이 사용되며, negative 펄스 restore 동작을 이용한다 GPPG 셀을 이용한 FRAM 구조는 셀 plate 구동기폭 사용하지 않으므로 메모리 셀 efficiency를 극대화 할 수 있는 장점이 있다. 또한 기존의 common-plate 셀과는 달리 제안된 FRAM 구조는 데이터의 읽기 및 쓰기 동작 시 강유전체 커패시터에 V/sub DD/거 충분한 전압이 가해지므로 저 전압 동작에 제한이 없다. 아울러 제안된 FRAM 구조는 필요한 8 비트 데이터만 선택하는 column-path 회로를 사용하므로 메모리 array 전력소모를 최소화 할 수 있다. 끝으로 0.5-um, triple-well/1-polycide/2-metal 공정을 이용한 4-Mb FRAM 설계를 통해 GPPG 셀 FRAM architecture 실현 가능성을 확인하였다.

• 대한전자공학회논문지SD
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• 제42권10호
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• pp.1-8
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• 2005

본 논문에서는 강유전체 메모리의 셀 효율을 높이기 위해 PMOS-gating 셀을 이용한 설계기법을 기술하였다. PMOS-gating 셀은 PMOS access 트랜지스터와 강유전체 커패시터로 이루어지며 커패시터의 플레이트는 ground에 고정된다. 아울러 read/write 동작시 비트라인이 $V_{DD}$로 precharge 되고, negative 전압 워드라인 기법이 사용되며, negative 펄스 restore 동작을 이용한다. 이는 셀 플레이트 구동없이 단순히 워드라인과 비트라인만 구동하여 메모리 셀의 데이타를 저장하고 읽어낼 수 있는 설계 방식으로, 기존의 셀 플레이트를 구동하는 FRAM 대비 메모리 셀 효율을 극대화 할 수 있어, multi-megabit 이상의 집적도에서 경쟁력 있는 칩 면적 구현이 가능하다. $0.25-{\mu}m$ triple-well 공정을 적용한 2.5-V, 1-Mb FRAM 시제품 설계를 통해 제안한 설계기술을 검증하였고, 시뮬레이션 결과 48 ns의 access time, 11 mA의 동작전류 특성을 보였다. 레이아웃 결과 칩 면적은 $3.22\;mm^{2}$ 이며, 기존의 셀 플레이트 구동기를 사용하는 FRAM 대비 약 $20\;\%$의 셀 효율을 개선하였다.

• BMB Reports
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• 제48권6호
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• pp.342-347
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• 2015

The expression of epidermal growth factor receptor (EGFR) is an important diagnostic marker for triple-negative breast cancer (TNBC) cells, which lack three hormonal receptors: estrogen and progesterone receptors as well as epidermal growth factor receptor 2. EGFR transactivation can cause drug resistance in many cancers including TNBC, but the mechanism underlying this phenomenon is poorly defined. Here, we demonstrate that insulin treatment induces EGFR activation by stimulating the interaction of EGFR with insulin-like growth factor receptor 1 (IGF-1R) in the MDA-MB-436 TNBC cell line. These cells express low levels of EGFR, while exhibiting high levels of IGF-1R expression and phosphorylation. Low-EGFRexpressing MDA-MB-436 cells show high sensitivity to insulinstimulated cell growth. Therefore, unexpectedly, insulin stimulation induced EGFR transactivation by regulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells. [BMB Reports 2015; 48(6): 342-347]

• Biomolecules & Therapeutics
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• 제24권1호
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• pp.62-66
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• 2016

Amygdalin, D-mandelonitrile-${\beta}$-D-glucoside-6-${\beta}$-glucoside, belongs to aromatic cyanogenic glycoside group derived from rosaceous plant seed. Mounting evidence has supported the anti-cancer effects of amygdalin. However, whether amygdalin indeed acts as an anti-tumor agent against breast cancer cells is not clear. The present study aimed to investigate the effect of amygdalin on the proliferation of human breast cancer cells. Here, we show that amygdalin exerted cytotoxic activities on estrogen receptors (ER)-positive MCF7 cells, and MDA-MB-231 and Hs578T triple-negative breast cancer (TNBC) cells. Amygdalin induced apoptosis of Hs578T TNBC cells. Amygdalin downregulated B-cell lymphoma 2 (Bcl-2), upregulated Bcl-2-associated X protein (Bax), activated of caspase-3 and cleaved poly ADP-ribose polymerase (PARP). Amygdalin activated a pro-apoptotic signaling molecule p38 mitogen-activated protein kinases (p38 MAPK) in Hs578T cells. Treatment of amygdalin significantly inhibited the adhesion of Hs578T cells, in which integrin ${\alpha}5$ may be involved. Taken together, this study demonstrates that amygdalin induces apoptosis and inhibits adhesion of breast cancer cells. The results suggest a potential application of amygdalin as a chemopreventive agent to prevent or alleviate progression of breast cancer, especially TNBC.