• 제목/요약/키워드: Receptor, epidermal growth factor

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Clinical Differences in Triple-Positive Operable Breast Cancer Subtypes in Korean Patients: An Analysis of Korean Breast Cancer Registry Data

  • You, Sun Hyong;Chae, Byung Joo;Eom, Yong Hwa;Yoo, Tae-Kyung;Kim, Yong-seok;Kim, Jeong Soo;Park, Woo-Chan
    • 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.

Predicting Successful Conservative Surgery after Neoadjuvant Chemotherapy in Hormone Receptor-Positive, HER2-Negative Breast Cancer

  • Ko, Chang Seok;Kim, Kyu Min;Lee, Jong Won;Lee, Han Shin;Lee, Sae Byul;Sohn, Guiyun;Kim, Jisun;Kim, Hee Jeong;Chung, Il Yong;Ko, Beom Seok;Son, Byung Ho;Ahn, Seung Do;Kim, Sung-Bae;Kim, Hak Hee;Ahn, Sei Hyun
    • Journal of Breast Disease
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    • 제6권2호
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    • pp.52-59
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    • 2018
  • Purpose: This study aimed to determine whether clinicopathological factors are potentially associated with successful breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC) and develop a nomogram for predicting successful BCS candidates, focusing on those who are diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative tumors during the pre-NAC period. Methods: The training cohort included 239 patients with an HR-positive, HER2-negative tumor (${\geq}3cm$), and all of these patients had received NAC. Patients were excluded if they met any of the following criteria: diffuse, suspicious, malignant microcalcification (extent >4 cm); multicentric or multifocal breast cancer; inflammatory breast cancer; distant metastases at the time of diagnosis; excisional biopsy prior to NAC; and bilateral breast cancer. Multivariate logistic regression analysis was conducted to evaluate the possible predictors of BCS eligibility after NAC, and the regression model was used to develop the predicting nomogram. This nomogram was built using the training cohort (n=239) and was later validated with an independent validation cohort (n=123). Results: Small tumor size (p<0.001) at initial diagnosis, long distance from the nipple (p=0.002), high body mass index (p=0.001), and weak positivity for progesterone receptor (p=0.037) were found to be four independent predictors of an increased probability of BCS after NAC; further, these variables were used as covariates in developing the nomogram. For the training and validation cohorts, the areas under the receiver operating characteristic curve were 0.833 and 0.786, respectively; these values demonstrate the potential predictive power of this nomogram. Conclusion: This study established a new nomogram to predict successful BCS in patients with HR-positive, HER2-negative breast cancer. Given that chemotherapy is an option with unreliable outcomes for this subtype, this nomogram may be used to select patients for NAC followed by successful BCS.

두경부 암의 표적 지향적 방사선 치료 (Targeted Therapies and Radiation for the Treatment of Head and Neck Cancer)

  • 김귀언
    • Radiation Oncology Journal
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    • 제22권2호
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    • pp.77-90
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    • 2004
  • 종양 발생 과정에 관여되고 있는 분자 생물학적 기전을 직접 공격해 보자고 하는 치료 방침은 암 치료에 있어서 아주 유망한 치료방법의 하나로 인정되고 있다. Epidermal growth factor receptor (EGFR) 수용체에 여러 ligands가 결합하게 되면 발암 단계에서부터 암의 진행 과정과 전이 과정 그리고 방사선에 대한 저항성과 관련된 여러 가지중요한 신호전달체계를 활성화시킨다. 특히 진행된 두경부 암 환자들에서 EGFR이 과발현 된 경우에는 매우 불량한 예후를 나타내고 있기 때문에 이러한 signaling pathway의 selective targeting을 위한 많은 임상 시도가 이루어지고 있다. 현재까지 알려진 표적치료 항암제로는 크게 EGFR에 대한 monoclonal antibody와 tyrosin kinase Inhibitors로 대별될 수 있는데 이와 같은 약제들은 여러 xenograft에서 고무적인 실험 결과들이 입증되어 곧 바로 임상 현장에서 적용되고 있다. 그러나 기대와는 달리 EGFR Inhibitor 단독으로 치료한 초기 임상연구 결과들을 보면 극히 소수의 환자에서만 미미한 효과를 나타내고 있고, 방사선 치료와의 병용치료에서도 괄목할만한 항암 효과를 보여주지 않고 있다. 그럼에도 불구하고 많은 실험적 데이터로부터 여러 가지 생물학적 이점이 밝혀져 있고 또 미래 지향적인 치료법의 하나로 각광을 받고 있기 때문에 현재 많은 연구자들은 어떤 환자 군에서 이러한 표적 치료가 도움이 될 것이며, 방사선 치료 또는 항암 치료와는 어떤 방식으로 조합할 것인지, 또 그 순서는 어떻게 할 것이며, 또 환자 선정에 있어 reliable marker는 무엇인지, 어떻게 체내에서 신호 전달체계의 효과적인 차단을 확인할 수 있겠는지, 또한 multiple targ리ed therapy가 필 요하도록 하는 targeted agent에 대 한 Intrinsic 또는 acquired resistance의 기전은 무엇인지 등등, 현재 당면하고 있는 많은 문제점을 규명하고자 노력하고 있다. 특히 EGFR-signaling pathway를 표적으로 하는 표적 지향적 방사선 치료를 위한 translation research의 적절한 모델이 되고 있는 두경부 암 환자에서 이러한 제반 문제점을 해결하기 위해서는 더 많은 임상 연구와 함께 well-Integrated laboratory clinical research program이 필요할 것으로 생각된다 또한 EGFR antagonist 외에도 anglogenlc pathway나 cell-cycle pathway를 표적으로 하는 새로운 약제들이 계속 개발되고 있고 이에 관한 연구가 활발히 진행 중이다. 따라서 이 고찰에서는 두경부 암 환자에서 이러한 약제들을 방사선 치료와 병용하였을 때의 임상 연구 결과들을 재검토해 보고 부가적으로 EGFR blockade에 따르는 내성 문제 그리고 방사선 치료를 병용하면서 여러 표적을 동시에 차단시키는 multiple-targeted therapy의 개발 현황을 간략히 소개하고자 한다

Knockdown of GCF2/LRRFIP1 by RNAi Causes Cell Growth Inhibition and Increased Apoptosis in Human Hepatoma HepG2 Cells

  • Li, Jing-Ping;Cao, Nai-Xia;Jiang, Ri-Ting;He, Shao-Jian;Huang, Tian-Ming;Wu, Bo;Chen, De-Feng;Ma, Ping;Chen, Li;Zhou, Su-Fang;Xie, Xiao-Xun;Luo, Guo-Rong
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권6호
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    • pp.2753-2758
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    • 2014
  • Background: GC-binding factor 2 (GCF2) is a transcriptional regulator that represses transcriptional activity of the epidermal growth factor receptor (EGFR) by binding to a specific GC-rich sequence in the EGFR gene promoter. In addition to this function, GCF2 has also been identified as a tumor-associated antigen and regarded as a potentially valuable serum biomarker for early human hepatocellular carcinoma (HCC) diagnosis. GCF2 is high expressed in most HCC tissues and cell lines including HepG2. This study focused on the influence of GCF2 on cell proliferation and apoptosis in HepG2 cells. Materials and Methods: GCF2 expression at both mRNA and protein levels in HepG2 cells was detected with reverse transcription (RT) PCR and Western blotting, respectively. RNA interference (RNAi) technology was used to knock down GCF2 mRNA and protein expression. Afterwards, cell viability was analyzed with a Cell Counting Kit-8 (CCK-8), and cell apoptosis and caspase 3 activity by flow cytometry and with a Caspase 3 Activity Kit, respectively. Results: Specific down-regulation of GCF2 expression caused cell growth inhibition, and increased apoptosis and caspase 3 activity in HepG2 cells. Conclusions: These primary results suggest that GCF2 may influence cell proliferation and apoptosis in HepG2 cells, and also provides a molecular basis for further investigation into the possible mechanism at proliferation and apoptosis in HCC.

누드마우스의 흉강에 폐암세포주의 주입에 의한 종양형성과 HER2/neu와 TGF-${\beta}_1$의 발현 (Tumorigenesis after Injection of Lung Cancer Cell Line (SW-900 G IV) into the Pleural Cavity of Nude Mice)

  • 박억숭;김송명;김종인
    • Journal of Chest Surgery
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    • 제43권6호
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    • pp.588-595
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    • 2010
  • 배경: 종양의 종류에 따라 발현되는 종양 항원의 종류도 다양하며 그 발현률의 차이는 더욱 다양하다. 이와 같은 이유로 폐암의 치료연구를 위해서는 인체를 대신할 만한 동물 모형이 절대 필요하다. 저자는 편평상피세포암의 세포주를 배양하여 Nude mice의 흉강 내에 주입하는 방법으로 종양형성을 시도하여 종양형성의 성공 유무와 조직학적 변화와 함께 폐암과 관련 있는 EGFR (epidermal growth factor receptor)의 수용기 중 하나인 HER2/neu 종양 유전자와 세포 성장 억제 작용과 악성화 과정에서의 저항성으로 작용하는 TGF-${\beta}_1$을 각각 정량 하도록 하여 인공적인 동소 폐암의 경우 암유전자의 발현에 관하여 조사해보고자 하였다. 대상 및 방법: 면역성이 없는 20마리의 수컷생쥐 (Male BALB/c nude mice)로 5마리를 대조군으로 하였으며, 나머지 15마리는 실험군으로 하고 체중은 20~25 gm (Orient, Japan)의 범위에 있었다. HER2/neu는 채혈하여 보관된 혈액의 혈청을 분리하여 CLIA (chemiluminiscent immunoassay) 법으로 정량적으로 측정하였으며 TGF-${\beta}_1$은 immunosandwitch법을 이용하여 정량 분석하였다. 통계학적 분석을 위하여 SPSS통계(SPSS Version10.0, USA)프로그램을 이용하였으며 Student T test를 하였으며 p값이 0.05 미만인 경우를 유의성이 있는 것으로 간주하였다. 결과: 정상 대조군에서나 인위적으로 주입한 폐암 세포주에 의한 폐암이 만들어진 이후에도 HER2/neu 유전자의 증폭은 전혀 반응을 나타내지 못하였다. 하지만 TGF-${\beta}_1$ 대조군의 정량치는 $28,490{\pm}8,549pg/mL$이었고 폐암 세포 주입군은 $42,362{\pm}14,449pg/mL$로 유의하게 1.48배 높게 나왔다(p<0.483). HER2/neu 유전자와 TGF-${\beta}_1$은 유의한 상관관계가 없는 것으로 나타났다. 결론: TGF-${\beta}_1$유전자는 대조군에 비하여 1.48배 정도의 증폭이 발현되었다. TGF-${\beta}_1$의 증폭은 Nude mice에서 발암에 의한 생체 치유 억제 기전이 확실히 작동하고 있다는 것을 의미하며, 인체의 조기 폐암의 발견에 역할을 가능케 하는 정량 검사법으로 이용할 수도 있을 것이다.

IP-10에 의한 기도상피세포에서의 TNF-α 유도 MUC5AC발현 억제: 특발성폐섬유증 환자의 적은 객담과의 연관성 (IP-10 Decreases TNF-α Induced MUC5AC Expression in Human Airway Epithelial Cells: a Possible Relation with Little Sputum Production in Idiopathic Pulmonary Fibrosis)

  • 김승준;강춘미;유문빈;윤형규;김영균;김관형;문화식;박성학;송정섭
    • Tuberculosis and Respiratory Diseases
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    • 제64권5호
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    • pp.347-355
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    • 2008
  • 연구배경: 특발성폐섬유증 환자의 전형적인 증상은 운동호흡곤란과 마른기침으로, 객담이 적은 원인에 대해서 아직까지 잘 알려져 있지 않다. Interferon-${\gamma}$ inducible protein-10 (IP-10)은 여러 호흡기질환과 관련되는데 폐 내로 염증을 유입시키는데 중요한 역할을 한다. 본 연구는 특발성폐섬유증 환자에서 객담이 적은 기전으로 IP-10이 연관성이 있는지에 대해 연구하였다. 방법: 특발성폐섬유증 환자를 대상으로 기관지폐포세척액에서 IP-10의 농도를 ELISA로 측정하였다. IP-10이 기도 점액소 발현에 미치는 영향을 간접적으로 알아보기 위해 NCI-H292 세포(점막표피모양 암종 세포주)에서 IP-10을 전처치한 이후 tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)로 자극하여 발현정도를 측정하였다. 이때 점액소 발현과 관련되는 기전으로 epidermal growth factor receptor-mitogen activated protein kinase (EGFR-MAPK)의 신호전달 경로를 알아 보았다. 결과: IP-10의 기관지폐포세척액내 농도는 특발성폐섬유증 환자가 건강 대조군에 비해 유의하게 높았다. IP-10의 전처치는 NCI-H292 세포에서 TNF-${\alpha}$ 유도 MUC5AC 점액소 발현을 감소시켰는데 이 때 EGFR-MAPK 신호전달 경로의 차단과 관련되었다. 결론: 특발성폐섬유증 환자의 적은 객담은 IP-10의 발현증가와 일부 관련 가능성이 있으며, 이때 IP-10의 작용은 MUC5AC 점액소 유전자 발현에 필요한 EGFR-MAPK 신호전달 경로의 차단과 관련될 것으로 생각한다.

Correlation between Ki67 and Histological Grade in Breast Cancer Patients Treated with Preoperative Chemotherapy

  • Petric, Militza;Martinez, Santiago;Acevedo, Francisco;Oddo, David;Artigas, Rocio;Camus, Mauricio;Sanchez, Cesar
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권23호
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    • pp.10277-10280
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    • 2015
  • Background and Aim: Breast cancer (BC) is a heterogeneous disease and cell proliferation markers may help to identify subtypes of clinical interest. We here analyzed the correlation between cell proliferation determined by Ki67 and HG in BC patients undergoing preoperative chemotherapy (PCT). Materials and Methods: We obtained clinical/pathological data from patients with invasive BC treated at our institution from 1999 until 2012. Expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor type 2 (HER2) and Ki67 were determined by immuno-histochemistry (IHC). Clinicopathological subtypes were defined as: Luminal A, ER and/or PR positive, HER2 negative, HG 1 or 2; Luminal B, ER and/or PR positive, HER2 negative or positive and/or HG 3; triple negative (TN), ER, PR and HER2 negative independent of HG; HER2 positive, ER, PR negative and HER2 positive, independent of HG. By using Ki67, a value of 14% separated Luminal A and B tumors, independently of the histological grade. We analyzed correlations between Ki67 and HG, to define BC subtypes and their predictive value for response to PCT. Results: 1,560 BC patients were treated in the period, 147 receiving PCT (9.5%). Some 57 had sufficient clinicopathological information to be included in the study. Median age was 52 years (26-72), with 87.7% invasive ductal carcinomas (n=50). We performed IHC for Ki67 in 40 core biopsies and 50 surgical biopsies, 37 paired samples with Ki67 before and after chemotherapy being available. There was no significant correlation between Ki67 and HG (p=0.237), both categorizing patients into different subtypes. In most cases Ki67 decreased after PCT (65.8%). Only 3 patients had pathologic complete response (cPR). Conclusions: In our experience we did not find associations between Ki67 and HG. Determination of clinicopathological luminal subtypes differs by using Ki67 or HG.

Risk Factors for Stage IV Breast Cancer at the Time of Presentation in Turkey

  • Uyeturk, Ummugul;Tatli, Ali Murat;Gucuk, Sebahat;Oksuzoglu, Berna;Ulas, Arife;Avci, Nilufer;Ozbay, Mehmet Fatih;Gunduz, Seyda;Akinci, Muhammed Bulent;Salim, Derya Kivrak;Sonmez, Ozlem Uysal;Akdag, Fatma;Ergenc, Hasan
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권12호
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    • pp.7445-7449
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    • 2013
  • Background: Breast cancer (BC) is the one of the most common cancers in women. It is also a leading cause of death. Unfortunately, some patients initially present with distant metastases and are diagnosed with stage IV disease that is nearly always, by then, incurable. This retrospective analysis investigated the risk factors for stage IV BC that may underlie such late presentation. Materials and Methods: In all, 916 patients with BC who visited the medical oncology polyclinic of eight different centres in Turkeybetween December 2011 and January 2013 were analysed. Results: A total of 115 patients (12.6%) presented with stage IV disease. In univariate analysis; to comparing these with patients at other stages, no statistical difference was found for median diagnosis age or age at menarche (p=0.611 and p=0.820), whereas age at menopause and age at first live birth were significant (p=0.018 and p=0.003). No difference was detected in terms of accompanying diseases, use of oral contraceptives and hormone replacement therapy, smoking, alcohol consumption and the rate of family history of BC between the patients (p=0.655, p=0.389, p=0.762, p=0.813, p=0.229, p=0.737). However, screening methods were employed less often, the rate of illiteracy was higher, and the rate of other cancers was higher in patients with stage IV BC (p=0.022, p=0.022, p=0.018). No statistical difference was observed between the patients in terms of tumour histopathology, and status of oestrogen receptor, progesterone receptor, or human epidermal growth factor-2 receptor (p=0.389, p=0.326, p=0.949, p=0.326). Grade 3 tumours were more frequent in patients with stage IV disease (p<0.001). On multivariate analysis, risk factors for stage IV breast cancer at the time of presentation were found to be age at first live birth and educational level (p=0.003 and p=0.047). Conclusions: Efforts should be made to perform mammography scans, in particular, at regular intervals through national training programs for all women, particularly those with family histories of breast and other types of cancer, and to establish early diagnosis of BC long before it proceeds to stage IV. Additionally, women's education had better be upgraded. In order to make women aware of BC, national education-programmes must be organised.

Clinicopathologic Characteristics and Prognostic Factors in Patients with Operable HER-2 Overexpressing Breast Cancer

  • Liu, Ai-Na;Sun, Ping;Liu, Jian-Nan;Ma, Jin-Bo;Qu, Hua-Jun;Zhu, Hua;Yu, Cai-Yan;Zhang, Liang-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권4호
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    • pp.1197-1201
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    • 2012
  • Objective: To study the relationship between clinical pathologic characteristics, treatment modalities and prognostic factors in HER-2 (Human Epidermal growth factor Receptor-2) overexpressed breast carcinoma. Materials and Methods: Major clinico-pathological factors including therapeutic modalities and survival status of 371 breast cancer patients with HER2 over-expression, teated at Yantai Yuhuangding Hospital from March of 2002 to December of 2010 were retrospectively studied, with special attention focused on survival-related factors. Results: The median age of the total 371 patients in this study was 48 years at time of diagnosis, among which, the leading pathological type was infiltrating ductal carcinoma (92.5%); 62.8% presented with a primary tomor larger than 2 cm in diameter at diagnosis, 51.0% had axillary lymph node (ALN) metastases; ER (Estrogen receptor)/PR (Progesterone receptor) double negative occured in 52.8% of cases, and PCNA (proliferation cell nuclear antigen) (+++) was found in 55.1%. HER-2 overexpressed patients were usually in advanced stage when the diagnosis was made (72.8% at stages IIA~IIIC). The prognosis and survival were assessed in 259 patients with complete follow-up data. 5-year DFS (disease-free survival) and OS (overall survival) rate was 68.0% and 78.0% respectively. Univariate analysis revealed that age, tumor size, ALN metastases, LVSI (lymph-vascular space involvement), PCNA status, hormonal therapy, chemotherapy cycles, and HER-2 overexpression, correlated closely with the prognosis. ALN metastases, LVSI, PCNA status and chemotherapy cycles were independent predictors of survival. Conclusions: HER-2 overexpressed breast cancer has special clinical and pathological characteristics, with advanced clinical stages and high rate of ER/PR double negative. Lymph node metastases, LVSI, PCNA and chemotherapy cycles are independent predictors of prognosis.

Inflammatory Breast Cancer: a Single Centre Analysis

  • Gogia, Ajay;Raina, Vinod;Deo, Suryanarayan Vishnu;Shukla, Nootan Kumar;Mohanti, Bidhu Kalyan;Sharma, Daya Nand
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권7호
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    • pp.3207-3210
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    • 2014
  • Background: Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer characterized by rapidly progressive breast erythema, pain and tenderness, oedema and paeu d'orange appearance. It accounts for 1-3% of all newly diagnosed cases of breast cancer in the west. Data on IBC from India are lacking. The aim of our study was to assess the clinical-pathological parameters and outcome of IBC at, All India Institute of Medical Sciences, a large tertiary care centre. Materials and Methods: We screened 3,650 breast cancer cases registered from January 2004 to December 2012 and found 41 cases of IBC. Data included demographics as well as clinical, radiological and histopathological characteristics, and were collected from clinical case records using the International Classification of Diseases code (C-50). Patients who presented with IBC as a recurrence, or who had a neglected and advanced breast cancer that simulated an IBC were excluded from this study. Results: The median age was 45 years (range 23-66). The median duration of symptoms was 5 months. The American Joint Committee on Cancer stage (AJCC) distribution was Stage III - 26 and IV - 15 patients. Estrogen receptor (ER), progesterone receptor (PR) positivity and human epidermal growth factor receptor 2 (HER2/neu) positivity were 50%, 46% and 60%, respectively. Triple negativity was found in 15% of the cases. All the non metastatic IBC patients received anthracycline and/ or taxane based chemotherapy followed by modified radical mastectomy, radiotherapy and hormonal therapy as indicated. Pathological complete remission rate was 15%. At a median follow-up of 30 months, the 3 year relapse free survival and overall survival were 30% and 40%respectively. Conclusion: IBC constituted 1.1% of all breast cancer patients at our centre. One third of these had metastatic disease at presentation. Hormone positivity and Her2 neu positivity were found in 50% and 60% of the cases, respectively.