RESUMEN
Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in breast cancer. We analyzed the prognostic impact of LOXL2 for breast cancer patients and investigated the role of LOXL2 in breast cancer cell lines. Immunohistochemical study of LOXL2 expression was done in samples from 309 patients. Survival analysis was performed using log-rank test and Cox regression hazard model. After identification of LOXL2 expression in breast cancer cell lines, we performed matrigel invasion and wound-healing assays with LOXL2-silenced cell lines. In the human study, LOXL2 was expressed in 16.2 % of patients. Comparing the LOXL2-positive versus negative groups, there was a significantly higher proportion of estrogen receptor-negative patients (54.0 vs. 37.0 %, respectively; p = 0.029) and triple-negative patients (34.0 vs. 18.0 %; p = 0.022) in the positive group. In multivariate analysis for overall survival and metastasis-free survival, positive LOXL2 was demonstrated as a poor prognostic factor (HR 2.27 and 2.10, respectively). In vitro study indicated that LOXL2 silencing induces a mesenchymal-epithelial transition-like process in basal cell lines (MDA-MB-231 and BT549) associated with decreased invasive and migratory properties. These clinical and preclinical data confirm that higher LOXL2 expression is associated with invasiveness of basal-like breast cancer cells and lower survival of breast cancer patients. Our results suggest the clinical value of LOXL2 as a therapeutic target in breast cancer.
Asunto(s)
Aminoácido Oxidorreductasas/análisis , Neoplasias de la Mama/química , Carcinoma/química , Regulación Neoplásica de la Expresión Génica , Proteínas de Neoplasias/análisis , Adulto , Aminoácido Oxidorreductasas/biosíntesis , Aminoácido Oxidorreductasas/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Carcinoma/genética , Carcinoma/mortalidad , Carcinoma/patología , Carcinoma in Situ/química , Carcinoma in Situ/genética , Carcinoma in Situ/mortalidad , Carcinoma in Situ/patología , Línea Celular Tumoral , Movimiento Celular , Colágeno , Supervivencia sin Enfermedad , Combinación de Medicamentos , Transición Epitelial-Mesenquimal , Femenino , Humanos , Hibridación in Situ , Estimación de Kaplan-Meier , Laminina , Persona de Mediana Edad , Terapia Neoadyuvante , Invasividad Neoplásica , Metástasis de la Neoplasia , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Neoplasias Primarias Múltiples/química , Neoplasias Primarias Múltiples/genética , Neoplasias Primarias Múltiples/mortalidad , Neoplasias Primarias Múltiples/patología , Tumor Filoide/química , Tumor Filoide/genética , Tumor Filoide/mortalidad , Tumor Filoide/patología , Pronóstico , Modelos de Riesgos Proporcionales , Proteoglicanos , Interferencia de ARN , ARN Interferente Pequeño/farmacología , Análisis de Supervivencia , Análisis de Matrices Tisulares , Neoplasias de la Mama Triple Negativas/química , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
The age distribution of breast cancer patients in Korea, where most are less than 60 years of age and have recently entered menopause, differs from that in the West. The aim of this study was to evaluate bone mineral density (BMD) changes in Korean breast cancer patients treated with an aromatase inhibitor (AI) either alone or in combination with zoledronic acid (ZA). Changes in BMD of the lumbar spine and hip were evaluated in 107 patients receiving AI treatment, of which 59 were treated in combination with ZA. The mean age of the patients was 54.9 years, and the median follow-up period was 38.2 months. With AI treatment alone, BMD loss was significant (all P < 0.0001) in the lumbar spine and hip 12 months (4.18 and 3.95%, respectively), 24 months (6.28 and 5.44%), and 36 months (8.17 and 6.82%) after treatment. In contrast, the combination treatment resulted in increased BMD in the lumbar spine and hip 12 months (2.45 and 0.89%, respectively), 24 months (3.51 and 1.03%), and 36 months (3.85 and 1.80%) after treatment. BMD loss in the lumbar spine was significantly greater in AI alone-treated women who had entered menopause within the past year compared with those who had entered menopause more than 1 year ago, when measured 12 and 24 months after treatment (P = 0.017 and 0.021, respectively). Importantly, ZA effectively inhibited AI-associated bone loss, independent of the postmenopausal interval. Because the proportion of patients in this study who had recently entered menopause was high, bone loss in Korean breast cancer patients treated with AI alone was higher than data reported from the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial. In conclusion, we have shown that ZA is very effective in preventing AI-induced bone loss in Korean postmenopausal breast cancer patients.
Asunto(s)
Inhibidores de la Aromatasa/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Densidad Ósea/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Difosfonatos/uso terapéutico , Imidazoles/uso terapéutico , Posmenopausia , Adulto , Anciano , Inhibidores de la Aromatasa/efectos adversos , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Corea (Geográfico) , Persona de Mediana Edad , Osteoporosis/inducido químicamente , Osteoporosis/prevención & control , Ácido ZoledrónicoRESUMEN
Bisphosphonates are used routinely to reduce bone-related events in breast cancer patients with bone metastasis. We evaluated the effects of zoledronic acid, a third generation, nitrogen-containing bisphosphonate, to prevent bone metastasis in breast cancer. Zoledronic acid or vehicle alone was administered to nude mice either simultaneously or after intracardiac injection of human breast cancer MDA-MB-231 cells. Nude mice treated with zoledronic acid at early time points showed a lower incidence of bone metastases than did vehicle-treated nude mice, but these differences were not statistically significant. Only 37.5% of mice treated with zoledronic acid at the time of tumor cell inoculation developed bone metastases compared to over 51.8% of mice receiving vehicle alone (P = 0.304). Cell count of apoptosis confirmed by immunohistochemical staining in metastatic bone tissue significantly increased in the zoledronic acid-treated groups compared to non-treated group (1,018.3 vs 282.0; P = 0.046). However, metastatic tumor cells, which invade soft tissue around the bone, did not show extensive apoptosis; there were no differences between the zoledronic acid-treated and control groups. These results suggest that zoledronic acid increases apoptosis of metastatic breast tumor cells in the bone and could therefore reduce metastatic tumor burden. These results support the use of zoledronic acid to reduce the incidence of bone metastasis in breast cancer.
Asunto(s)
Neoplasias Óseas/secundario , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Difosfonatos/farmacología , Imidazoles/farmacología , Animales , Apoptosis/efectos de los fármacos , Conservadores de la Densidad Ósea/farmacología , Neoplasias Óseas/prevención & control , Huesos/efectos de los fármacos , Huesos/patología , Femenino , Humanos , Ratones , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Ácido ZoledrónicoRESUMEN
This study was designed to assess whether histological and biological factors of breast cancer can predict chemoresponse to specific agents. Adenosine triphosphate-based chemotherapy response assay (ATP-CRA) was employed to retrieve chemoresponse to 5-fluorouracil (5-FU), doxetaxel, doxorubicin, epirubicin, and paclitaxel in 49 patients. Tumors with high histologic and nuclear grade have higher response rate to doxorubicin (P<0.05) and palitaxel (P<0.05). Estrogen receptor (ER)-negative tumors respond well to doxorubicin (P=0.038), and progesterone receptor (PR)-negative tumors to 5-FU (P=0.039), doxetaxel (P=0.038), doxorubicin (P=0.000), epirubicin (P=0.010), and paclitaxel (P=0.003). Among the breast cancer subtypes determined by ER, PR, and HER-2 immunohistochemical stains, the HER-2+/ER- subtype has a higher response rate to doxorubicin (P=0.008). This in vitro result suggests that the combination of histologic and nuclear grade, hormone receptor, and HER-2 status can be a predictive factor of response to specific chemotherapy agents. Further in vivo study should be followed for clinical trials.
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Adenosina Trifosfato/metabolismo , Antineoplásicos/uso terapéutico , Neoplasias de la Mama , Ensayos de Selección de Medicamentos Antitumorales/métodos , Receptor ErbB-2/metabolismo , Adulto , Anciano , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Doxorrubicina/uso terapéutico , Epirrubicina/uso terapéutico , Femenino , Fluorouracilo/uso terapéutico , Humanos , Persona de Mediana Edad , Paclitaxel/uso terapéutico , Receptor ErbB-2/genética , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismoRESUMEN
We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression of angiogenic factors and CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2 mRNAs were not statistically different between DCIS and invasive ductal carcinomas, nor did they differ statistically when grouped by tumor size, histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel density and expression of VEGF and TGF-beta1 were not statistically different between DCIS and invasive ductal carcinoma. CD44std expression was significantly increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was also significantly increased in lower clinical stage, histologic grade and nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis was significantly correlated with MT1-MMP mRNA, VEGF and TGF-beta1 expression (p < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2 mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive ductal carcinoma suggest that the invasive potential of breast carcinoma is already achieved before morphologically overt invasive growth is observed. As MT1-MMP mRNA expression is significantly correlated with axillary nodal metastasis, it may be useful as a prognostic indicator of invasive ductal carcinoma. Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer.
Asunto(s)
Neoplasias de la Mama/fisiopatología , Carcinoma in Situ/fisiopatología , Carcinoma Ductal de Mama/fisiopatología , Metaloproteinasas de la Matriz/genética , Neoplasias de la Mama/genética , Carcinoma in Situ/genética , Carcinoma Ductal de Mama/genética , Femenino , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasas de la Matriz Asociadas a la Membrana , ARN Mensajero/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/genéticaRESUMEN
PURPOSE: Tumor response to neoadjuvant chemotherapy (NAC) may adversely affect the identification and accuracy rate of sentinel lymph node biopsy (SLNB). This study was conducted to evaluate the feasibility of SLNB in node-positive breast cancer patients with negative axillary conversion after NAC. MATERIALS AND METHODS: Ninety-six patients with positive nodes at presentation were prospectively enrolled. (18)Fluorodeoxyglucose-positron emission tomography ((18)F-FDG PET) and ultrasonography were performed before and after NAC. A metastatic axillary lymph node was defined as positive if it was positive upon both (18)F-FDG PET and ultrasonography, while it was considered negative if it was negative upon both (18)F-FDG PET and ultrasonography. RESULTS: After NAC, 55 cases (57.3%) became clinically node-negative, while 41 cases (42.7%) remained node-positive. In the entire cohort, the sentinel lymph node (SLN) identification and false-negative rates were 84.3% (81/96) and 18.4% (9/49), respectively. In the negative axillary conversion group, the results of SLNB showed an 85.7% (48/55) identification rate and 16.7% (4/24) false-negative rate. CONCLUSION: For breast cancer patients with clinically positive nodes at presentation, it is difficult to conclude whether the SLN accurately represents the metastatic status of all axillary lymph nodes, even after clinically negative node conversion following NAC.
RESUMEN
Over-expression of the human epidermal growth factor receptor-2 (HER2/neu) has been observed in many cancers, and is associated with a poor prognosis. Recent adjuvant treatment with anti-HER2 monoclonal antibodies in breast cancer has increased the demand for an evaluation of the HER2/neu status in breast cancer. The aim of this study was to investigate the HER2/neu status in breast cancer by a real-time quantitative polymerase chain reaction (PCR) method using LightCycler (Roche Diagnostics, Mannheim, Germany). DNA samples from the fresh tumor tissues of 27 patients with breast cancer were analyzed in parallel using immunohistochemistry (IHC) and the other prognostic parameters including estrogen receptor, progesterone receptor, cytokeratin, and DNA ploidy. Ten (37%) out of 27 cases tested were positive for HER2/neu, while 16 (73%) out of 22 tested positive through an IHC study. The correlation between the DNA aneuploidy and the positive results for HER2/neu were only observed using the real-time PCR method (p < 0.05). There was no significant correlation between the HER2/neu status and the S-phase fractions of the DNA ploidy or other parameters. This study demonstrated that there is marked discordance in the results for the HER2/neu status according to the various methods used. Real-time quantitative PCR for HER2/neu appears to be clinically useful due to its simplicity and ability to produce rapid results.
Asunto(s)
Neoplasias de la Mama/metabolismo , Receptores ErbB/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Femenino , Humanos , Isoformas de Proteínas/metabolismoRESUMEN
To identify the effect of post-operative irradiation to the thyroid gland in patients with breast carcinoma. Seventy seven patients with partial or total mastectomized breast carcinoma who received routine irradiation therapy (Hockey stick method: supraclavicular, internal mammary lymph nodes, and chest wall irradiation with 5,040 rads, divided into 30 treatments) were reviewed in terms of their ipsilateral thyroid gland response. All patients had the bilateral thyroid sizes measured annually by ultrasonography before and after radiation therapy. In the one-year follow-up group (n=77), 32 patients (41.5%) demonstrated decreased ipsilateral thyroid gland size after Hockey Stick irradiation therapy (p=0.428), in the two-year follow-up group (n=37), 26 patients (70.3%) demonstrated decreased gland size after Hockey Stick irradiation (p=0.001), and in the three-year follow-up group (n=21), 15 patients (71.4%) showed a decreased thyroid gland size (p=0.005). Most the patients with breast carcinoma (32/77 at the one-year follow-up, 26/37 at the two-year follow-up, and 15/21 at the three-year follow-up) after post-operative Hockey Stick irradiation therapy showed reduced ipsilateral thyroid gland size. Routine en face treatment of the supraclavicular lymph nodes, using the Hockey Stick method, should be reconsidered.
Asunto(s)
Neoplasias de la Mama/radioterapia , Ganglios Linfáticos/efectos de la radiación , Glándula Tiroides/efectos de la radiación , Femenino , Estudios de Seguimiento , Humanos , Radioterapia/efectos adversos , Glándula Tiroides/patologíaRESUMEN
PURPOSE: The prognosis of breast cancer has been consistently improving. We analyzed our cohort of breast cancer patients with a long-term follow up at a single center over time. MATERIALS AND METHODS: A total of 1889 patients with known cancer stages were recruited and analyzed between January 1991 and December 2005. Patients were classified according to the time periods (1991-1995; 1996-2000; 2001-2005). To determine intrinsic subtypes, 858 patients whose human epidermal growth receptor-2 status and Ki67 were reported between April 2004 and December 2008 were also analyzed. RESULTS: At a median follow up of 9.1 years, the 10-year overall survival (OS) rate was 80.5% for the entire cohort. On multivariate analysis for OS and recurrence-free survival (RFS), the time period was demonstrated to be a significant factor independent of conventional prognostic markers. In the survival analysis performed for each stage (I to III), OS and RFS significantly improved according to the time periods. Adoption of new agents in adjuvant chemotherapy and endocrine therapy was increased according to the elapsed time. In the patients with known subtypes, OS and RFS significantly differed among the subtypes, and the triple-negative subtype showed the worst outcome in stages II and III. CONCLUSION: In the Korean breast cancer cohort with a long-term follow up, our data show an improved prognosis over the past decades, and harbor the contribution of advances in adjuvant treatment. Moreover, we provided new insight regarding comparison of the prognostic impact between the tumor burden and subtypes.
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Neoplasias de la Mama/epidemiología , Supervivencia sin Enfermedad , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , República de Corea , Análisis de Supervivencia , Tasa de Supervivencia , Factores de TiempoRESUMEN
PURPOSE: Liver resection with colorectal liver metastasis widely accepted and has been considered safe and effective therapeutic option. However, the role of liver resection in breast cancer with liver metastasis is still controversial. Therefore, we reviewed the outcome of liver resection in breast cancer patients with liver metastases in a single hospital experiences. MATERIALS AND METHODS: Between January 1991 and December 2006, 2176 patients underwent breast cancer surgery in Gangnam Severance Hospital. Among these patients, 110 cases of liver metastases were observed during follow-up and 13 of these patients received liver resection with potential feasibility to achieve an R0 resection. RESULTS: The median time interval between initial breast cancer and detection of liver metastasis was 62.5 months (range, 13-121 months). The 1-year and 3-year overall survival rates of the 13 patients with liver resection were 83.1% and 49.2%, respectively. The 1-year and 3-year overall survival rates of patients without extrahepatic metastasis were 83.3% and 66.7% and those of patients with extrahepatic metastasis were 80.0% and 0.0%, respectively (p=0.001). CONCLUSION: Liver resection for metastatic breast cancer results in improved patient survival, particularly in patients with solitary liver metastasis and good general condition.
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Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/cirugía , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Adulto , Neoplasias de la Mama/mortalidad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Anti-epidermal growth factor receptor (EGFR) therapy has been tried in triple negative breast cancer (TNBC) patients without evaluation of molecular and clinical predictors in several randomized clinical studies. Only fewer than 20% of metastatic TNBCs showed response to anti-EGFR therapy. In order to increase the overall response rate, first step would be to classify TNBC into good or poor responders according to oncogenic mutation profiles. This study provides the molecular characteristics of TNBCs including EGFR gene copy number changes and mutation status of EGFR and KRAS gene in Korean TNBC patients. Mutation analysis for EGFR, KRAS, BRAF and TP53 from a total of 105 TNBC tissue samples was performed by direct sequencing, peptide nucleic acid-mediated PCR clamping method and real-time PCR. Copy number changes of EGFR gene were evaluated using multiplex ligation-dependent probe amplification. Out of all 105 TNBCs, 15.2% (16/105) showed EGFR copy number changes. Among them, increased or decreased EGFR copy number was detected in 13 (5 single copy gain, 2 amplification and 4 high-copy number amplification) and 3 cases (3 hemizygous deletion), respectively. The mutation frequencies of KRAS, EGFR and TP53 gene were 1.9% (G12V and G12D), 1.0% (exon 19 del) and 31.4%, respectively. There was no BRAF V600E mutation found. Future studies are needed to evaluate the clinical outcomes of TNBC patients who undergo anti-EGFR therapy according to the genetic status of EGFR.
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Receptores ErbB/genética , Proteínas Proto-Oncogénicas/genética , Neoplasias de la Mama Triple Negativas/genética , Proteínas ras/genética , Adulto , Anciano , Variaciones en el Número de Copia de ADN , Análisis Mutacional de ADN , Femenino , Dosificación de Gen , Humanos , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras) , República de Corea , Proteína p53 Supresora de Tumor/genéticaRESUMEN
PURPOSE: Bone is the most frequent site of metastasis among breast cancer patients. We investigated prognostic factors affecting survival following bone-only metastasis in breast cancer patients. MATERIALS AND METHODS: The medical records of breast cancer patients who were treated and followed at Gangnam Severance Hospital retrospectively reviewed to identify patients with bone-only metastasis. RESULTS: The median time from the diagnosis of bone-only metastasis to the last follow-up or death was 55.2 [95% confidence interval (CI), 38.6-71.9] months. The Kaplan-Meier overall survival estimate at 10 years for all patients was 34.9%. In the multivariate Cox regression model, bisphosphonate treatment [hazard ratio=0.18; 95% CI, 0.07-0.43], estrogen receptor positivity (hazard ratio=0.51; 95% CI, 0.28-0.94), and solitary bone metastasis (hazard ratio=0.32; 95% CI, 0.14-0.72) were significantly associated with longer overall survival in the bone-only recurrence group. Among the treatment modalities, only bisphosphonate treatment was identified as a significant prognostic factor. CONCLUSION: Identifying the factors influencing breast cancer mortality after bone-only metastasis will help clarify the clinical course and improve the treatment outcome for patients with breast cancer and bone-only metastasis. Bisphosphonates, as a significant prognostic factor, warrant further investigation.
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Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Adulto , Antineoplásicos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Receptores de Estrógenos/genética , Receptores de Progesterona/genética , Análisis de Regresión , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
BACKGROUND: Probability of recurrence in patients with estrogen receptor (ER)-positive breast cancer remains constant for long periods. We compared tumor burden impact on late versus early recurrence in our cohort with long-term follow-up. METHODS: Five hundred and ninety five patients diagnosed with ER-positive breast cancer between 1989 and 2001 were classified into three groups: early recurrence within 5 years, late recurrence after 5 years, and no recurrence. We identified prognostic factors among the groups using logistic regression analysis. RESULTS: At median follow-up of 11.7 years, among 595 ER-positive women, 98 (16.4%) had early recurrence and 58 (9.7%) had late recurrence. On multivariate analysis, higher nodal stage (N0 vs. N2, odds ratio [OR] 3.189; N0 vs. N3, OR 9.948), higher histologic grade (grade 1 vs. grade 2, OR 3.896; grade 1 vs. grade 3, OR 5.945), age >35 years (OR 0.295), and receiving endocrine therapy (OR 0.293) affected early recurrence. Compared to no recurrence, receiving endocrine therapy (OR 0.285) was solely related to decreased risk of late recurrence. Increased risk of early recurrence was noted with the higher nodal stage when early and no recurrences were compared. This phenomenon was not found in late recurrence. In the last comparison between the early and late recurrence, higher nodal stage (N0 vs. N3, OR 16.779) and higher histologic grade (grade 1 vs. grade 3, OR 18.111) repeatedly weighted for early recurrence. CONCLUSIONS: Nodal burden had an attenuated influence on late recurrence, which suggests that, unlike early recurrence, tumor biology might have a more important role than tumor load for late recurrence in ER-positive disease.
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Neoplasias de la Mama/patología , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Recurrencia Local de Neoplasia/patología , Receptores de Estrógenos/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Terapia Combinada/métodos , Femenino , Humanos , Metástasis Linfática/genética , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: Some recent trials suggest that postoperative adjuvant radiotherapy (RT) may be safely omitted after breast-conserving surgery (BCS) for some patients with ductal carcinoma in situ (DCIS). In this study, we reviewed clinical outcomes of patients with DCIS treated with partial mastectomy (PM) without adjuvant RT. MATERIALS AND METHODS: Medical records of 28 patients (29 breasts) with DCIS who were treated with PM, but without RT, between April 1991 and December 2010 were retrospectively analyzed. Based on established criteria (2.0 cm or less in size and no comedonecrosis), 18 patients were treated without RT after PM. Seven patients (8 breasts) who did not receive RT due to refusal were also included in this study. Three other patients were excluded because data concerning comedonecrosis were not available. RESULTS: For the 25 patients included in this study, the mean age of the 18 patients who met the criteria was 47.9±6.2 years, and 47.6±12.7 years for the 7 patients who did not. The mean sizes of the primary tumors were 0.6±0.4 cm and 0.9±0.3 cm, respectively, in these two groups. Among these 25 patients (26 breasts) treated without RT, we observed no ipsilateral breast tumor recurrence or mortality within a mean follow-up of 84 months. CONCLUSION: Based on this small number of cases, patients with DCIS, who were selected for tumor size less than 2 cm and absence of comedonecrosis, may be treated successfully with BCS; adjuvant RT may be omitted.
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Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Carcinoma Intraductal no Infiltrante/radioterapia , Carcinoma Intraductal no Infiltrante/cirugía , Mastectomía Segmentaria , Radioterapia Adyuvante , Adulto , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
TrkC mediates many aspects of growth and development in the central nervous system. TrkC is expressed in a variety of non-neuronal tissues as well as human cancers. TrkC overexpression may drive tumorigenesis, invasion, and metastatic capability in cancer cells. However, relatively little is known about whether TrkC activity is also essential to maintain the malignant properties in human tumors. TrkC expression leads to the constitutive activation of two major effector pathways, namely the Ras-MAP kinase (MAPK) mitogenic pathway and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway mediating cell survival. However, it remains unclear how TrkC activates Ras-Erk1/2 and/or PI3K-Akt cascades. Here we define some aspects of the molecular mechanisms regulating TrkC-dependent Ras-Erk1/2 and PI3K/Akt activation. We show that endogenous TrkC associated with c-Src in human and mouse cancer cells which express TrkC. TrkC-c-Src complexes were also detected in primary human breast cancer tissues. Suppression of c-Src by RNA interference in highly metastatic 4T1 mammary cancer cells, which express endogenous TrkC, resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and PI3K-Akt. Moreover, inhibition of c-Src expression almost completely blocks colony formation of 4T1 cells in soft agar. Furthermore, in c-Src-deficient SYF cells, TrkC failed to activate the PI3K-Atk pathway, but not the Ras-Erk1/2 pathway. Therefore these data indicate that TrkC induces the PI3K-Akt cascade through the activation of c-Src.
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Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas pp60(c-src)/metabolismo , Receptor trkC/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Línea Celular , Línea Celular Tumoral , Transformación Celular Neoplásica/efectos de los fármacos , Ciclina D1/metabolismo , Activación Enzimática/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/enzimología , Humanos , Indoles/farmacología , Proteínas Sustrato del Receptor de Insulina , MAP Quinasa Quinasa 1/metabolismo , Ratones , Fosforilación/efectos de los fármacos , Unión Proteica/efectos de los fármacos , Proteínas Proto-Oncogénicas pp60(c-src)/química , Proteínas Proto-Oncogénicas pp60(c-src)/deficiencia , ARN Interferente Pequeño/metabolismo , Sulfonamidas/farmacología , Ensayo de Tumor de Célula MadreRESUMEN
In 2002, breast became the most common cancer site in Korean women. Using national breast cancer incidence data during 1993-2002, crude, age-standardized, and age-specific rates for incidence and mortality were calculated. Survival was examined for cases diagnosed during 1993-2002 and followed up to 2004. Observed survival was calculated using the life table method and relative survival using the Ederer II method. Age-standardized incidence rates in female increased from 14.5 in 1993 to 26.2 per 100,000 in 2002. Age-specific incidences showed peaks in women in their forties. Mortality rates increased from 3.7 in 1993 to 4.6 per 100,000 in 2002 and showed peaks in women in their fifties. Five-year relative survival for female breast cancer diagnosed during 1993-2002 was 82.2%. When we examined the secular trends using cases diagnosed 1993-1999 for complete 5-yr followup, the 5-yr relative survival increased from 75.2% in 1993 to 83.5% in 1999. The data from this study will provide valuable information to plan and evaluate actions against breast cancer including national breast cancer screening.
Asunto(s)
Neoplasias de la Mama/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama Masculina/epidemiología , Neoplasias de la Mama Masculina/mortalidad , Factores Epidemiológicos , Femenino , Humanos , Corea (Geográfico)/epidemiología , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Factores de TiempoRESUMEN
Metastasis is the leading cause of death in breast cancer patients and an appropriate detection of metastasis can provide better prognosis and quality treatments. Microwaves can reveal the unique electromagnetic properties of materials, and this study aims to unleash the electromagnetic properties of breast cancer cells, especially, metastasized cancer cells in the lymph nodes, using broad-band microwaves in attempts to detect metastases. To distinguish the cancer-specific patterns of cancer tissues, three primary microwave parameters were assessed, i.e., permittivity in mid-band frequency (3-5 GHz), conductivity in high-band frequencies (25-30 GHz) and slope changes of permittivity at high-band frequencies (15-30 GHz). An additional parameter, Cancer Metastasis Index (CMI), was developed to effectively represent all parameters. Broadband microwave scanning can reveal cancer specific electromagnetic behaviors in all three parameters, and these were reliably reflected by CMI. CMI effectively magnified the difference of the electromagnetic properties between normal nodal tissues and cancer tissues. immunohistochemistries were performed to verify the origin of electromagnetic changes represented by CMI values.