scholarly journals Insulin-Regulated Aminopeptidase in Women with Breast Cancer: A Role beyond the Regulation of Oxytocin and Vasopressin

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3252
Author(s):  
María Jesús Ramírez-Expósito ◽  
Basilio Dueñas-Rodríguez ◽  
María Pilar Carrera-González ◽  
Joaquín Navarro-Cecilia ◽  
Jose Manuel Martínez-Martos
Keyword(s):  
Breast Cancer ◽  
Glucose Transporter ◽  
Neoadjuvant Treatment ◽  
Women Patients ◽  
Angiotensin Iv ◽  
High Affinity ◽  
High Affinity Binding Site ◽  
Insulin Dependent ◽  
Glucose Transporter Type 4

Insulin-regulated aminopeptidase (IRAP) is the only enzyme known to cleave oxytocin and vasopressin; however, it is also the high-affinity binding site for angiotensin IV (AngIV) receptor type 4 (AT4) ligands and it is related to insulin-dependent glucose transporters through the translocation of the glucose transporter type 4 (GLUT4). Previous studies have demonstrated an association between IRAP activity and the number and size of mammary tumors in an animal model of breast cancer (BC). Also, a highly significant increase in IRAP activity has been found in BC tissue from women patients. Here, we found no changes in circulating IRAP in premenopausal (preMP) women, but it increased significantly in postmenopausal (postMP) women not treated with neoadjuvant chemotherapy (NACH). However, in women treated with NACH, IRAP activity increased in both preMP and postMP women. Two years of follow-up indicated lower levels of IRAP activity in untreated preMP women, but a return to control levels in untreated postMP women, while IRAP activity returned to control levels in women treated with NACH. Circulating oxytocin decreased in both preMP and postMP women during the follow-up period. Differences in Oxytocin appeared between preMP and postMP women treated with NACH, but not in women who were not treated with NACH. On the contrary, circulating vasopressin increased in untreated and treated preMP and postMP women, with most of the differences related to the hormonal status as well as the neoadjuvant treatment during the two year follow-up We propose that IRAP is involved in mechanisms related not only to oxytocin and/or vasopressin regulation, but also to the local mammary RAS through AngIV and its role in glucose transportation through the IRAP/GLUT4 system.

Randomized trial of chemoendocrine therapy started before or after surgery for treatment of primary breast cancer.

1995 ◽  
Vol 13 (3) ◽  
pp. 547-552 ◽  
Author(s):  
T J Powles ◽  
T F Hickish ◽  
A Makris ◽  
S E Ashley ◽  
M E O'Brien ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Adjuvant Therapy ◽  
Randomized Trial ◽  
Response Rate ◽  
Neoadjuvant Treatment ◽  
Operable Breast Cancer ◽  
Chemoendocrine Therapy ◽  
Primary Operable Breast Cancer

PURPOSE To evaluate in a randomized clinical trial systemic chemoendocrine therapy used as primary (neo-adjuvant) treatment before surgery in women with primary operable breast cancer. PATIENTS AND METHODS Patients aged less than 70 years with clinically palpable, primary operable breast cancer diagnostically confirmed by fine-needle aspiration cytology (FNAC) and suitable for treatment with surgery, radiotherapy, cytotoxic chemotherapy, and tamoxifen were considered eligible. Patients randomized to neoadjuvant treatment received four cycles of chemo-therapy for 3 months before surgery followed by another four cycles after surgery, and were compared with patients randomized to adjuvant therapy who received eight cycles of chemotherapy over 6 months after surgery. RESULTS Of 212 patients who were randomized to receive either adjuvant (n = 107) or neoadjuvant (n = 105) chemoendocrine therapy, 200 are now assessable for response. The two groups are comparable for age, menopausal status, disease stage, and surgical requirements. The overall clinical response rate was 85%, with a complete histologic response rate of 10%. There was a significant reduction in the requirement for mastectomy in patients who received neoadjuvant treatment (13%) as compared with those who received adjuvant therapy (28%) (P < .005). Symptomatic and hematologic acute toxicity was low and similar for adjuvant and neoadjuvant therapy. The median follow-up period for patients in this trial is 28 months, during which time four patients have relapsed locally and 20, including one of the local relapses, have developed metastatic disease, 19 of whom have died. The follow-up period is too brief to evaluate relapse rate or survival duration. CONCLUSION This trial confirms previous reports of a high rate of response to neoadjuvant therapy, but is the first to include small primary cancers and to show, in the context of a randomized trial, a reduction in the requirement for mastectomy. Until disease-free and overall survival data are available from the larger National Surgical Adjuvant Breast and Bowel Project (NSABP)-18 trial, such neoadjuvant treatment cannot be recommended outside of a clinical trial.

Cardiac safety and efficacy of concomitant liposomal doxorubicin, docetaxel, and trastuzumab as neoadjuvant therapy in HER2-overexpressing breast cancer: A retrospective analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 583-583
Author(s):  
Christine Brunner ◽  
Thomas Jaeger ◽  
Christoph Suppan ◽  
Elisabeth Mueller-Holzner ◽  
Zerina Jasarevic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Liposomal Doxorubicin ◽  
Pathological Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Left Ventricular Ejection ◽  
Cardiac Safety ◽  
Multicenter Analysis

583 Background: Concurrent therapy of trastuzumab, anthracycline and taxane for the neoadjuvant treatment of breast cancer (BC) results in an improved rate of pathological complete response (pCR). However, there is considerable concern about the cardiac safety of this combination. The use of liposomal doxorubicin might be a valuable alternative with lower cardiotoxicity. We report cardiac safety and pCR-rate of a single arm, retrospective, multicenter analysis of neoadjuvant treatment for BC with liposomal doxorubicin, trastuzumab, and docetaxel. Methods: In this study 84 women with BC and HER2 overexpression were investigated in 3 oncological departments in Austria. All patients were treated with liposomal doxorubicin (50 - 60 mg/m²), docetaxel (75 mg/m²) and concurrent with trastuzumab for 6 cycles as neoadjuvant therapy. All patients were free of cardiovascular disease and had a left ventricular ejection fraction (LVEF) of ≥ 55%. Cardiac function was by LVEF and was examined at regular intervals(cycles 0-3, cycle 6, FU). Clinical response was evaluated by diagnostic breast imaging after cycles 3 and 6. All patients underwent surgery after neoadjuvant chemotherapy. The absence of any residual invasive cancer in the breast and axilla was defined as pathological complete response (pCR). Median follow up was 2.4 years. Results: Median age of the patients was 50 years. After 6 cycles of treatment the pCR rate was 46%. In this cohort a negative estrogen-and/or progesteron receptor was predictive for pCR (p<0.001). No patient progressed during treatment. None of the patients suffered symptomatic heart failure. Only one patient (1.6%) with asymptomatic LVEF of 45% was observed during follow-up. Conclusions: In this multicenter analysis we observed a considerably high rate of pCR in HER2-positive BC treated with liposomal doxorubicin, docetaxel and trastuzumab. The addition of liposomal doxorubicin instead of conventional doxorubicin or epirubicin entails a very favorable cardiotoxicity profile. This regimen is a safe treatment option in patients with HER-2 positive breast cancer.

Neoadjuvant chemotherapy with docetaxel, carboplatin, and weekly trastuzumab (TCH) activity in HER2-positive early breast cancer: Results after a median follow-up of 4.5 years.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 140-140 ◽  
Author(s):  
Hans-Christian Kolberg ◽  
Leyla Akpolat-Basci ◽  
Miltiades Stephanou ◽  
Carla Hannig ◽  
Cornelia Liedtke
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Neoadjuvant Treatment ◽  
Outcome Data ◽  
Lymph Node Status ◽  
Her2 Positive ◽  
Excellent Outcome ◽  
Er Positive ◽  
Positive Breast Cancer

140 Background: Most patients with HER2-positive receive chemotherapy and trastuzumab. Data from adjuvant trials have shown that the combination of docetaxel, carboplatin and weekly trastuzumab (TCH) is well tolerated and as effective as anthracycline containing regimes. Previous investigations on neoadjuvant treatment with TCH showed pCR-rates in the range of 40%, however, survival data have not yet been presented. Here we present 4.5-year follow-up data for a cohort of 51 patients treated with neoadjuvant TCH. Methods: We treated 51 patients with operable HER2-positive breast cancer with a neoadjuvant schedule of docetaxel (75 mg/m2) and carboplatin (AUC 6) q3w and trastuzumab (2(4)mg/kg) q1w. Lymph node involvement was verified by SLNB or core-cut-biopsy. Mean age at diagnosis was 55 years, 68.6% had ER positive tumors, 39.2% presented with grade 3 disease and 49% of patients were node-positive. Patients were monitored by ultrasound. After 6 cycles of chemotherapy all patients had surgery. Axillary dissection was performed in case of positive lymph node status prior to TCH. After surgery trastuzumab was continued q3w up to one year. Results: Side effects were mild, no grade III/IV toxicities occurred and no case of cardiomyopathia was observed. 21 (41.18%) patients achieved a pCR, 18 (72.0%) patients converted from cN+ to ypN0. Outcome data at a median follow-up of 53.6 months are as follows (see table). Conclusions: Outcome following neoadjuvant TCH as observed in our analysis compares well to outcome data observed in adjuvant trastuzumab trials such as HERA or BCIRG006. Particularly among patients with ER positive disease and those experiencing axillary conversion we observed an excellent outcome. Importantly, TCH was well tolerated in our cohort. Therefore our data support the use of TCH as neoadjuvant therapy regimen for patients with HER-positive breast cancer. [Table: see text]

Computer Techniques for Detection of Breast Cancer and Follow Up Neoadjuvant Treatment

2021 ◽  
pp. 72-106
Author(s):  
Adriel dos Santos Araujo ◽  
Roger Resmini ◽  
Maira Beatriz Hernandez Moran ◽  
Milena Henriques de Sousa Issa ◽  
Aura Conci
Keyword(s):  
Breast Cancer ◽  
Collective Intelligence ◽  
Selection Process ◽  
Neoadjuvant Treatment ◽  
Preoperative Treatment ◽  
Analysis Process ◽  
Breast Abnormality ◽  
Geometric Descriptors ◽  
Preliminary Study

This chapter explores several steps of the thermal breast exams analysis process in detecting breast abnormality and evaluating the response of pre-surgical treatment. Topics concerning the process of acquiring, storing, and preprocessing these exams, including a novel segmentation proposal that uses collective intelligence techniques, will be discussed. In addition, various approaches to calculating statistical and geometric descriptors from thermal breast examinations are also considered of this chapter. These descriptors can be used at different stages of the analysis process of these exams. In this sense, two experiments will be presented. The first one explores the use of genetic algorithms in the feature selection process. The second conducts a preliminary study that intends to analyze some descriptors, already used in other works, in the process of evaluating preoperative treatment response. This evaluation is of fundamental importance since the response is directly associated with the prognosis of the disease.

Evaluation of TOP2A and TIMP-1 as predictive markers of pathologic complete response to neoadjuvant anthracycline-based chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11503-e11503
Author(s):  
Joyce Maria L. Maia ◽  
Elizabeth Santana Santos ◽  
Rafael Costa Lessa ◽  
Felipe D'Almeida Costa ◽  
Stephania Bezerra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Predictive Biomarker ◽  
Complete Response ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Her2 Breast Cancer ◽  
Pre Treatment

e11503 Background: Factors predictive of response to anthracyclines can help selecting patients who really benefit from its use. HER2 amplification, TOP2A aberrations, and changes in tissue inhibitor of metalloproteinase (TIMP-1) expression in breast carcinomas have been shown to be associated with incremental benefit from anthracycline chemotherapy. Methods: We retrospectively analyzed data on the outcome of patients undergoing neoadjuvant anthracycline-based chemotherapy. Evaluated nuclear TOP2A protein expression and cytoplasmatic TIMP-1 expression in tumor cells in breast cancer biopsies by immunohistochemistry (IHC) and reviewed the pathological responses after completion of neoadjuvant treatment. Results: From 2002 to 2012, data from 97 patients was reviewed. Sixty four patients had the paraffin blocks corresponding to the pre-treatment biopsy to analysis the TOP2A and forty nine to TIMP-1. Patients were considered positive for TOP2A if the level of expression in IHC was higher than 20% and graduated TIMP-1 as weak, moderate or strong expression. Thirty percent of the patients achieved pathologic complete response (pCR) in pos-treatment surgical specimens. There was an association between TOP2A IHC expression and tumor pathological complete response (pCR) with higher pCR in TOPO2A positive tumors (pCR 44% vs 14%; p=0.008). There was no association between TIMP-1 expression and pCR. A moderate or strong TIMP-1 expression was associated with higher disease-free survival in multivariate analysis (p=0,005). No difference in PFS and OS was observed between patients with pCR after a median follow-up of 36 months. Conclusions: The expression of TOP2A seems to be a promising predictive biomarker of pCR to antracycline-based neoadjuvant chemotherapy in HER2 breast cancer. The predictive value and form of assessment of TIMP-1 remain uncertain. These findings should be better evaluated in prospective neoadjuvant trials.

scholarly journals PERFIL EPIDEMIOLÓGICO DAS PACIENTES COM CÂNCER DE MAMA SUBMETIDAS A QUIMIOTERAPIA NEOADJUVANTE EM UM HOSPITAL DE SÃO LUIS-MA

2018 ◽  
Vol 5 (2) ◽  
pp. 21-24
Author(s):  
FERNANDO HENRIQUE RIBEIRO DO COUTO CORREA
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Treatment ◽  
Epidemiological Data ◽  
Cross Sectional Study ◽  
Cáncer De Mama ◽  
Breast Cancer Patients ◽  
Cross Sectional ◽  
Epidemiological Profile ◽  
Surgical Treatments

RESUMO Introdução: Anualmente são diagnosticados aproximadamente um milhão de novos casos de câncer, existindo uma prevalência de 4,4 milhões de mulheres que padecem dessa enfermidade. A quimioterapia neoadjuvante, é definida como qualquer tratamento quimioterápico prescrito antes do tratamento cirúrgico, com base nos resultados obtidos, passou-se a indicar o tratamento neoadjuvante em pacientes com tumores operáveis, permitindo a utilização de tratamentos cirúrgicos menos invasivos e  mais eficientes. Metodologia: Estudo retrospectivo, de corte transversal  para avaliar o perfil clínico-epidemiológico de pacientes com câncer de mama sob acompanhamento do Serviço de Mastologia do Hospital do Câncer Aldenora Belo (HCAB) na cidade de São Luis-MA  com uma amostragem de 56 pacientes durante o período de janeiro de 2015 a dezembro de 2015. RESULTADOS: Os resultados referem-se a 56 pacientes com dados clínico-epidemiológicos. Conclusão:  Os resultados encontrados demonstram a evolução no tratamento do câncer de mama avançado, o que é uma realidade em nossa região, devido a falta de programas de acesso ao rastreamento, principalmente no interior do Estado, o que permitiria diagnósticos precoces e tratamentos mais eficazes e menos lesivos a paciente.   Palavras-chave: Oncologia. Mama. Neoplasias. ABSTRACT Introduction: Approximately one million new cases of cancer are diagnosed annually, with a prevalence of 4.4 million women suffering from this disease. Neoadjuvant chemotherapy is defined as any chemotherapy treatment prescribed before the surgical treatment, based on the results obtained, it was indicated the neoadjuvant treatment in patients with operable tumors, allowing the use of less invasive and more efficient surgical treatments. Methodology: Retrospective, cross-sectional study to evaluate the clinical-epidemiological profile of breast cancer patients under follow-up of the Mastology Service of the Aldenora Belo Cancer Hospital (HCAB) in the city of São Luis-MA with a sample of 56 patients during the period from January 2015 to December 2015. RESULTS: The results refer to 56 patients with clinical-epidemiological data. Conclusion: The results show the evolution in the treatment of advanced breast cancer, which is a reality in our region, due to the lack of access programs to the tracing, mainly in the interior of the State, which would allow early diagnosis and more effective treatments and less harmful to the patient. Keywords: Oncology. Mama. Neoplasms.

Long-term standard sentinel node biopsy after neoadjuvant treatment in breast cancer: a single institution ten-year follow-up

2020 ◽  
Author(s):  
Sabrina Kahler-Ribeiro-Fontana ◽  
Eleonora Pagan ◽  
Francesca Magnoni ◽  
Elisa Vicini ◽  
Consuelo Morigi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sentinel Node ◽  
Sentinel Node Biopsy ◽  
Neoadjuvant Treatment ◽  
Single Institution ◽  
Node Biopsy
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