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1.
Oncología (Ecuador) ; 32(1): 71-85, 30-04-2022.
Article in Spanish | LILACS | ID: biblio-1368949

ABSTRACT

El carcinoma de mama es una enfermedad común, con efectos negativos significativos en la salud predominantemente femenina. Los linfocitos infiltrantes al tumor (TILs) son una manifestación de la respuesta inmune del huésped al cáncer. Este estudio revisa y resume los reportes bibliográficos relacionados con la eficacia pronóstica del porcentaje alto de TILs en cánceres de mama de tipos moleculares rico en HER2 y triple negativo. Se incluyeron estudios y revisiones en inglés buscados en la base de datos PubMed. Un mayor nivel de TILs se corresponde con mejor supervivencia libre de enfermedad tanto en los cánceres triple negativo como los ricos en HER2; por tanto, constituye un marcador histológico que debería ser utilizado rutinariamente en los análisis microscópicos de biop-sias de mama.


Breast cancer is a common disease affecting women, with significant health-related negative effects. Tumor-infiltrating lymphocytes (TILs) are recognized as manifestations of the host's antitumor im-munity. The following study reviews and summarizes reports on the effectiveness of prognosis of high levels of tumor-infiltrating lymphocytes on triple negative and HER2-enriched breast cancer molecular subtypes. Studies and reviews in English from Pubmed's database were included. A higher percentage of tumor- infiltrating lymphocytes is associated with better prognosis and survival rate of triple negative and HER2-enriched breast cancer. Consequently, such histological marker should be routinely used in the microscopic analysis of breast biopsies.


Subject(s)
Humans , Female , Adult , Middle Aged , Breast Neoplasms , Lymphocytes, Tumor-Infiltrating , Receptor, ErbB-2 , Triple Negative Breast Neoplasms
2.
Article in English | WPRIM | ID: wpr-922538

ABSTRACT

OBJECTIVE@#We employed a multidisciplinary approach incorporating theoretical ideas, clinical experience, psychology, physiology, traditional Chinese medicine (CM), modern practice of CM, and oncology to explore the effect of patients' repression of negative emotions and traumatic events on breast cancer (BC) pathogenesis.@*METHODS@#BC female patients, older than 18 years of age, with available pathology reports who were treated at Rabin Medical Center were recruited. All participants completed questionnaires regarding medical history, behavioral tendencies, negative emotions, trauma, symptoms, and pathology (from a CM perspective). Data on tumor characteristics were collected from the pathology reports. The associations were examined using hierarchical binary logistic regressions.@*RESULTS@#A total of 155 BC patients were enrolled. The median age was 52 years, with a range of 26-79; 95% were mothers; 28% had estrogen receptor (ER)-negative BC, 52% had progesterone receptor (PR)-negative BC, 48% had human epidermal growth factor receptor 2-negative BC, and antigen Ki-67 ≥ 20% was reported for 52% of tumors. Statistically significant associations were found between the emotional markers (sense of motherhood failure, and lack of self-fulfillment), avoidance behavior, and physical symptoms that are related to emotional repression based on CM. Significant associations were also found between variables associated with physical symptoms of emotional repression, which involves the production and accumulation of non-substantial phlegm (i.e., "high-lipid Qi-like microscopic phlegm"), avoidance behavior which unconsciously uses "high-lipid Qi-like microscopic phlegm" in order to achieve emotional repression, and tumor parameters including tumor grade, PR status, and Ki-67. Patients with higher levels of "high-lipid Qi-like microscopic phlegm" were more likely to have tumors with worse prognosis (PR-negative, higher grade, and higher Ki-67).@*CONCLUSION@#We demonstrated a relationship between emotional parameters, behavioral tendencies, CM parameters, and oncologic parameters in BC. Additional research is warranted to explore these associations and their relevance to clinical practice.


Subject(s)
Adult , Aged , Breast Neoplasms , Emotions , Female , Humans , Medicine, Chinese Traditional , Middle Aged , Receptor, ErbB-2 , Receptors, Estrogen , Receptors, Progesterone
3.
ABCS health sci ; 46: e021225, 09 fev. 2021. tab
Article in English | LILACS | ID: biblio-1349382

ABSTRACT

INTRODUCTION: Breast cancer is a heterogenous disease with multiple causes and it lacks more investigation related to its risk factors. OBJECTIVE: To evaluate the likelihood of breast cancer subtypes according to the positivity to estrogen and progesterone receptors (ER+ and PR+ respectively), with or without the expression HER2, related to the following risk factors: age, parity, diabetes mellitus, arterial hypertension, occurrence of familiar cancer case and body mass index (BMI). METHODS: The sample with 79 individuals was divided into three subtypes 1 (ER+/PR-), 2 (ER+/PR+) and 3 (RE+/RP+/HER+) and then analyzed by quantitative methods using Ordinal Generalized Linear Models (OGLM) for estimating the marginal effects of risk factors for the studied subtypes, and modeling the heteroscedasticity in terms of error. RESULTS: It were observed the following statistically significant positive effects: (1) age for the tumoral subtype 1 (ER+/PR-) and (2) parity for the subtype 2 (ER+/PR+); while the significant negative effects were: (1) age for subtype 3 (ER+/PR+/HER2+); (2) parity for both 1 (ER+/PR-) and 3 (ER+/PR+/HER2+) subtypes; and arterial hypertension for subtype 1 (ER+/PR-). There were no statistically significant effects for BMI, Diabetes mellitus and occurrence of familiar cancer variables on the studied tumoral subtypes. CONCLUSION: The risk factos age and parity demonstrated varied effects for the breast cancer subtypes according the expression of estrogen, progesterone and HER2 receptors.


INTRODUÇÃO: O câncer de mama é uma doença heterogênea, multifatorial e que necessita de mais estudos relacionados aos fatores de riscos. OBJETIVO: Analisar a probabilidade dos subtipos tumorais do câncer de mama receptores de estrogênio (RE) ou progesterona (RP) positivos, com ou sem expressão de HER2, em relação aos fatores de risco: idade, parto, diabetes mellitus, hipertensão arterial, ocorrência de câncer de mama familiar e índice de massa corporal (IMC). MÉTODOS: A análise da amostra de 79 pacientes dividida nos subtipos 1 (RE+/RP-), 2 (RE+/RP+) e 3 (RE+/RP+/HER+), foi feita por meio de métodos quantitativos usando o Modelo Linear Generalizado Ordinal (MLGO) para estimar os efeitos marginais dos fatores de risco para os subtipos estudados, e ao mesmo tempo modelando a heterocedasticidade do termo de erro. RESULTADOS: Nos resultados foram observados os seguintes efeitos positivos estatisticamente significantes: (1) da idade para o subtipo tumoral 1 (RE+/RP-) e (2) do número de partos para o subtipo 2 (RE+/RP+); enquanto os efeitos negativos significativos foram os seguintes: (1) da idade para o subtipo 3 (RE+/RP+/HER2+); (2) do número de partos para o sutipos 1 (RE+/RP) e 3 (RE+/RP+/HER2+); e da hipertensão arterial para o o subtipo 1 (RE+/RP-). Não foram observados efeitos estatisticamente significativos das variáveis IMC, Diabetes mellitus e ocorrência de câncer de mama familiar sobre os subtipos tumorais estudados. CONCLUSÃO: Os fatores de risco idade e número de partos têm efeitos variados para os subtipos do câncer de mama segundo a expressão de receptores para estrogênio, progesterona e HER2.


Subject(s)
Humans , Female , Breast Neoplasms , Risk Factors , Receptor, ErbB-2 , Parity , Body Mass Index , Diabetes Mellitus , Hypertension
4.
Chinese Medical Journal ; (24): 261-267, 2021.
Article in English | WPRIM | ID: wpr-921259

ABSTRACT

Antibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Breast Neoplasms/drug therapy , Female , Humans , Immunoconjugates/therapeutic use , Receptor, ErbB-2
5.
Chinese Journal of Oncology ; (12): 1001-1006, 2021.
Article in Chinese | WPRIM | ID: wpr-920981

ABSTRACT

Human epidermal growth factor receptor 2 (HER-2) plays an important role in carcinogenesis and development of urothelial carcinoma. Overexpression of HER-2 is associated with poor prognosis of urothelial carcinoma. Although there is no significant benefit from anti-HER-2 targeted therapies of monoclonal antibody and tyrosine kinase inhibitor, Anti-HER-2 antibody-drug conjugate (HER-2-ADC) has shown a promising efficacy in urothelial carcinoma patients with HER-2 overexpression. Therefore, effectively screening the potential beneficiaries of HER-2-ADC drugs has become a new challenge. However, standardized HER-2 scoring system for urothelial carcinoma has yet to be developed. Thus, the Committees organized experts to reach this expert consensus based on the clinical practice of HER-2 expression, gene amplification and mutation testing in urothelial carcinoma, combined with the current research progress and internal discussion of committee members, in order to construct HER-2 testing standard of urothelial carcinoma and improve the accuracy of interpretation, to guide the clinical application.


Subject(s)
Carcinoma, Transitional Cell/genetics , Consensus , Humans , Receptor, ErbB-2/genetics , Urinary Bladder Neoplasms/genetics
6.
Frontiers of Medicine ; (4): 621-628, 2021.
Article in English | WPRIM | ID: wpr-888733

ABSTRACT

Multi-gene assays have emerged as crucial tools for risk stratification in early-stage breast cancer. This study aimed to evaluate the prognostic significance of the 21-gene recurrence score (RS) in Chinese patients with pN0-1, estrogen receptor-positive (ER


Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/pathology , Female , Humans , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Receptor, ErbB-2/genetics , Receptors, Estrogen
8.
Chinese Medical Journal ; (24): 1569-1575, 2021.
Article in English | WPRIM | ID: wpr-887576

ABSTRACT

BACKGROUND@#Although de novo stage IV breast cancer is so far incurable, it has entered an era of individualized treatment and chronic disease management. Based on systemic treatment, whether the surgical resection of primary or metastatic foci of de novo stage IV breast cancer can bring survival benefits is currently controversial. We aimed to explore the clinicopathological factors and current status of the management of de novo stage IV breast cancer in China to provide a reference for clinical decisions.@*METHODS@#Based on the assistance of Chinese Society of Breast Surgery, a retrospective study was conducted to analyze the clinical data of patients with de novo stage IV breast cancer in 33 centers from January 2017 to December 2018. The relationship between basic characteristic (age, menstrual status, family history, reproductive history, pathological type, estrogen receptor [ER] status, progesterone receptor [PR] status, human epidermal growth factor receptor 2 [HER2] status, Ki-67 percentage, and molecular subtype), and metastasis sites (lung metastasis, liver metastasis, and bone metastasis) was examined by Pearson Chi-square tests.@*RESULTS@#A total of 468 patients with de novo stage IV breast cancer were enrolled. The median age of the enrolled patients was 51.5 years. The most common pathological type of primary lesion was invasive carcinoma (97.1%). Luminal A, luminal B, HER2 overexpressing, and triple-negative subtypes accounted for 14.3%, 51.8%, 22.1%, and 11.8% of all cases, respectively. Age, PR status, and HER2 status were correlated with lung metastasis (χ2 = 6.576, 4.117, and 8.643 and P = 0.037, 0.043, and 0.003, respectively). Pathological type, ER status, PR status, and molecular subtype were correlated with bone metastasis (χ2 = 5.117, 37.511, 5.224, and 11.603 and P = 0.024, <0.001, 0.022, and 0.009, respectively). Age, PR status, HER2 status, Ki-67 percentage, and molecular subtype were correlated with liver metastasis (χ2 = 11.153, 13.378, 10.692, 21.206, and 17.684 and P = 0.004, <0.001, 0.001, <0.001, and 0.001, respectively). Combined treatment with paclitaxel and anthracycline was the most common first-line chemotherapy regimen for patients with de novo stage IV breast cancer (51.7%). Overall, 91.5% of patients used paclitaxel-containing regimens. Moreover, 59.3% of hormone receptor-positive patients underwent endocrine therapy.@*CONCLUSIONS@#In 2018, 1.07% of patients from all studied centers were diagnosed with de novo stage IV breast cancer. This study indicated that 95.1% of patients received systemic therapy and 54.2% of patients underwent surgical removal of the primary lesion in China.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms/surgery , China , Female , Humans , Mastectomy , Middle Aged , Prognosis , Receptor, ErbB-2 , Receptors, Progesterone , Retrospective Studies
9.
Chinese Journal of Oncology ; (12): 405-413, 2021.
Article in Chinese | WPRIM | ID: wpr-877505

ABSTRACT

The introduction of cyclin-dependent kinase (CDK) 4/6 inhibitors has revolutionized the clinical management paradigm of hormone receptor (HR) positive/human epidermal growth factor receptor (HER) 2 negative breast cancer. As of today, CDK 4/6 inhibitors including Palbociclib, Ribociclib, and Abemaciclib have been widely approved by regulatory agencies. Randomized clinical trials demonstrated that CDK 4/6 inhibitors in combination with an aromatase inhibitor (AI) or fulvestrant in the first-, second- or later-line setting for HR positive/HER2 negative locally advanced or metastatic breast cancer led to substantial reduction in the risk of disease progression or death. Adverse effects of treatment were manageable and as or better than expected in terms of patient satisfaction. Considering CDK4/6 inhibitors in combination with endocrine therapy being a novel approach in China clinical practice, the panel developed the consensus comprehensively describing the pharmacology properties, monitoring strategy during treatment and adverse events management, to facilitate greater understanding in Chinese oncologists of a whole new therapeutic class of drug, promote accuracy of clinical decision and help reach the ultimate goal of improving survival and quality of life of the target patient population.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , China , Consensus , Cyclin-Dependent Kinase 4 , Cyclin-Dependent Kinase 6 , Humans , Protein Kinase Inhibitors/therapeutic use , Quality of Life , Receptor, ErbB-2
10.
Article in English | WPRIM | ID: wpr-880654

ABSTRACT

OBJECTIVES@#Clarifying the expression of breast cancer receptor is the key to clinical treatment for breast cancer. This study aims to explore the correlation between X-ray and clinical characteristics of 4 molecular subtypes and their receptor types of breast cancer.@*METHODS@#A total of 439 breast cancer patients who confirmed by pathology and performed X-ray examination were enrolled. The X-ray and clinical characteristics of 4 molecular subtypes and the expression of their receptors were analyzed.@*RESULTS@#Luminal A type showed the highest proportion of spiculate masses, and the lowest calcification score, showing significant difference with other 3 subtypes (all @*CONCLUSIONS@#Four molecular subtypes of breast cancer and their receptor expressions are correlated with X-ray and clinical characteristics, which can provide a basis for clinical diagnosis and treatment.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms/genetics , Female , Humans , Receptor, ErbB-2/genetics , Receptors, Estrogen , Receptors, Progesterone , X-Rays
11.
Oncol. (Guayaquil) ; 30(3): 237-249, Diciembre 30, 2020.
Article in Spanish | LILACS | ID: biblio-1145729

ABSTRACT

Introducción: El tratamiento neodyuvante del cáncer de mama HER2 positivo ha ido evolucionando a través del tiempo, con la implementación de nuevas estrategias de manejo terapéutico. Es de esta manera como el trastuzumab, un anticuerpo monoclonal anti-HER2sigue siendo el tratamiento estándar en este subtipo de cáncer, los primeros estudios en los que se evidencia su eficacia son el realizado por el Dr. Buzdar y el estudio NOAH en los cuales las pacientes alcanzaron mayores tasas de respuesta patológica completa en comparación con quimioterapia sola, así como también un mayor número de cirugías conservadoras de mama en lugar de mastectomía.Con el paso de los años se han ido desarrollando nuevas estrategias de manejo terapéutico, así tenemos el doble bloqueo anti-HER2 con los anticuerpos monoclonales trastuzumab y pertuzumab que han mejorado las tasas de respuesta patológica completa. Además se ha incluido al lapatinib un inhibidor de tirosina quinasa como parte de las terapias dirigidas. Se ha dilucidado si las antraciclinas confieren un beneficio adicional al tratamiento neoadyuvante y los estudios demuestran que el beneficio es el mismo queotros esquemas de quimioterapia. Es en realidad la quimioterapia indispensable en la neoadyuvancia, el estudio PHERGain demuestra que existen pacientes que pueden alcanzar respuesta patológica completa solo con el doble bloqueo anti-her2 (trastuzumab y pertuzumab) lo que evitaría la toxicidad innecesaria por quimioterapia, y se podrían desarrollar estrategias para el manejo de aquellas pacientes que no alcanzaron una respuestapatológica completa posterior al doble bloqueo. Aún queda un campo amplio por explorar y con estudios en curso al momento. Palabras claves:DsCS:Receptor ErbB-2, Trastuzumab, Neoplasias de la Mama, Quimioterapia Adyuvante, Ado-Trastuzumab Emtansina


Introduction:The neodyuvanttreatment of HER2 positive breast cancer has evolved over time, with the implementation of new therapeutic management strategies. It is in this way that trastuzumab, an anti-HER2 monoclonal antibody continues to be the standard treatment in this subtype of cancer, the first studies in which its efficacy is evidenced are the one carried out by Dr. Buzdar and the NOAH study in which patients achieved higher rates of complete pathological response compared to chemotherapy alone, as well as a higher number of breast-conserving surgeries rather than mastectomy.Over the years, new therapeutic management strategies have been developed, thus we have the double anti-HER2 blockade with the monoclonal antibodies trastuzumab and pertuzumab that have improved the ratesof complete pathological response. In addition, lapatinib, a tyrosine kinase inhibitor, has been included as part of targeted therapies. It has been elucidated whether anthracyclines confer an additional benefit to neoadjuvant treatment and studies show that the benefit is the same as other chemotherapy regimens.It is actually the essential chemotherapy in neoadjuvant therapy, the PHERGain study shows that there are patients who can achieve a complete pathological response only with the double anti-her2 blockade (trastuzumab and pertuzumab), which would avoid unnecessary toxicity due to chemotherapy, and strategies could be developed for the management of those patients who did not achieve a complete pathological response after double blockade. There is still a wide field to explore and with studies underway at the moment. Keywords:MESH:Receptor, ErbB-2;Trastuzumab; Breast Neoplasms; Chemotherapy, Adjuvant; Ado-Trastuzumab Emtansine


Subject(s)
Humans , Breast Neoplasms , Receptor, ErbB-2 , Trastuzumab , Chemotherapy, Adjuvant , Ado-Trastuzumab Emtansine
12.
Oncol. (Guayaquil) ; 30(3): 249-279, Diciembre 30, 2020.
Article in Spanish | LILACS | ID: biblio-1222453

ABSTRACT

Introducción: Los tumores gliales, dentro de las lesiones neuroepiteliales, son las neoplásicas intraaxiales más comunes. Representan alrededor del 45% de todos los tumores primarios del sistema nervioso central (SNC) y el 77% de todos los tumores primarios malignos del SNC. El promedio de supervivencia media de los pacientes con glioblastoma multiforme (GBM) cuando se utiliza el tratamiento multimodal es de 15-18 meses y de 2 a 5 años con gliomas anaplásicos. Los tratamientos convencionales de los tumores cerebrales incluyen cirugía, radioterapia y quimioterapia. El tratamiento quirúrgico representa la primera aproximación para la gran mayoría de tumores cerebrales, sin embargo, la resección total no siempre es alcanzable en relación con la localización del tumor, de vital importancia para preservar estructuras nerviosas o vasculares. Modalidades de tratamiento agresivas han extendido la supervivencia media, pero la supervivencia a menudo se asocia con un deterioro significativo en la calidad de vida. La eficacia de quimioterapia sistémica está limitada por la presencia de la barrera hemato encefálica (BHE), la que limita el paso de una amplia variedad de agentes anti cancerígenos, la acción de los agentes alquilantes, está limitado por la activación de metil-guanina-metil-transferasa. El advenimiento de los estudios moleculares permite una nueva evaluación de la biología de los gliomas con, un nivel de precisión que promete interesantes avances hacia el desarrollo de terapias específicas eficaces. Las terapias dirigidas bloquean la activación de vías oncogénicas, ya sea a nivel de la interacción ligando-receptor o mediante la inhibición vías de transducción de señales, corriente abajo, inhibiendo así el crecimiento y la progresión del cáncer. El objetivo del presente trabajo fue realizar una revisión bibliográfica acerca de los aspectos relacionados con la patogénesis molecular en la progresión de estos tumores en los adultos, y sus potenciales blancos terapéuticos.


Introduction:Glial tumors, within neuroepithelial lesions, are the most common intraaxial neoplastic. They represent about 45% of all primary central nervous system (CNS) tumors and 77% of all malignant primary CNS tumors. The median median survival of patients with glioblastoma multiforme (GBM) when multimodal treatment is used is 15-18 months and 2-5 years with anaplastic gliomas. Conventional treatments for brain tumors include surgery, radiation therapy, and chemotherapy. Surgical treatment represents the first approach for the vast majority of brain tumors; however, total resection is not always achievable in relation to the location of the tumor, which is vitally important to preserve nerve or vascular structures.Aggressive treatment modalities have extended median survival, but survival is often associated with a significant deterioration in quality of life. The efficacy of systemic chemotherapy is limited by the presence of the blood-brain barrier (BBB), which limits the passage of a wide variety of anticancer agents, the action of alkylating agents, is limited by the activation of methyl-guanine-methyltransferase. The advent of molecular studies allows a new evaluation of the biology of gliomas with, a level of precision that promises interesting advances towards the development of effective specific therapies. Targeted therapies block the activation of oncogenic pathways, either at the level of ligand-receptor interaction or by inhibiting downstream signal transduction pathways, thus inhibiting cancer growth and progression.The objective of the present work was to carry out a bibliographic review about the aspects related to the molecular pathogenesis in the progression of these tumors in adults, and their potential therapeutic targets.


Subject(s)
Breast Neoplasms , Receptor, ErbB-2 , Trastuzumab , Chemotherapy, Adjuvant , Ado-Trastuzumab Emtansine
13.
Oncol. (Guayaquil) ; 30(1): 13-24, Abril. 2020.
Article in Spanish | LILACS | ID: biblio-1140900

ABSTRACT

En el cáncer de mama luminal, la terapia hormonal está indicada en adyuvancia y neoadyuvancia. El estadio metastásico incluye un grupo heterogéneo de tumores que varían de acuerdo con el sitio de metástasis, tiempo de aparición, condición general de las pacientes, entre otras características intrínsecas del tumor. Esto establece tiempos de sobrevida con rangos variables de meses a muchos años. Los estrógenos actúan en receptores de membrana citoplasmática y nuclear: en las células neoplásicas estimulan la transcripción del ARN, con persistencia de la proliferación. El bloqueo de la acción hormonal en el cáncer avanzado encuentra mecanismos de resistencia con el uso de vías de señalización paralelas, este conocimiento ha permitido el desarrollo de inhibidores de CDK 4/6, mTOR y PIK3-CA, que se recomiendan en enfermedad metastásica, con prolongación significativa de la supervivencia global. En crisis visceral aún se mantiene el uso de quimioterapia sistémica secuencial o combinada


For a patient with estrogen receptor positivebreast cancer, the adjuvant and neoadjuvant endocrine therapy has an absolute benefit. The metastatic stage includes a diverse group of tumors that vary according to the site of metastasis, time of appear, general condition of the patients, and other intrinsic characteristics of the tumor. survival in cancer varies according these features, from a few months to many years. Estrogen hormones stimulate nuclear and cytoplasmic receptors. In neoplastic cells, estrogen regulate RNA transcription, with persistence of proliferation. The blocking of hormonal action in metastatic cancer, has resistance mechanisms with the use of parallel signaling pathways, this knowledge has allowed the development of inhibitors of CDK 4/6, mTOR and PIK3-CA, which are recommended in metastatic disease. with significant prolongation of overall survival. In visceral crisis, the use of sequential or combined systemic chemotherapy is still maintained


Subject(s)
Humans , Breast Neoplasms , Receptor, ErbB-2 , Neoplasm Metastasis
14.
Biol. Res ; 53: 13, 2020. tab, graf
Article in English | LILACS | ID: biblio-1100919

ABSTRACT

BACKGROUND: Gallbladder cancer (GBC) is the most common tumor of the biliary tract. The incidence of GBC shows a large geographic variability, being particularly frequent in Native American populations. In Chile, GBC represents the second cause of cancer-related death among women. We describe here the establishment of three novel cell lines derived from the ascitic fluid of a Chilean GBC patient, who presented 46% European, 36% Mapuche, 12% Aymara and 6% African ancestry. RESULTS: After immunocytochemical staining of the primary cell culture, we isolated and comprehensively characterized three independent clones (PUC-GBC1, PUC-GBC2 and PUC-GBC3) by short tandem repeat DNA profiling and RNA sequencing as well as karyotype, doubling time, chemosensitivity, in vitro migration capability and in vivo tumorigenicity assay. Primary culture cells showed high expression of CK7, CK19, CA 19-9, MUC1 and MUC16, and negative expression of mesothelial markers. The three isolated clones displayed an epithelial phenotype and an abnormal structure and number of chromosomes. RNA sequencing confirmed the increased expression of cytokeratin and mucin genes, and also of TP53 and ERBB2 with some differences among the three cells lines, and revealed a novel exonic mutation in NF1. The PUC-GBC3 clone was the most aggressive according to histopathological features and the tumorigenic capacity in NSG mice. CONCLUSIONS: The first cell lines established from a Chilean GBC patient represent a new model for studying GBC in patients of Native American descent.


Subject(s)
Humans , Animals , Male , Middle Aged , Antigens, Tumor-Associated, Carbohydrate/genetics , Indians, South American/genetics , Gallbladder Neoplasms/genetics , Ascitic Fluid/metabolism , Tumor Cells, Cultured , Carcinogenicity Tests , Chile , DNA Fingerprinting , Tumor Suppressor Protein p53/genetics , Cisplatin/pharmacology , Mice, Inbred NOD , Clone Cells/drug effects , Clone Cells/metabolism , Sequence Analysis, RNA , Receptor, ErbB-2/genetics , Genes, erbB-2/genetics , Gene Expression Profiling , Cell Line, Tumor/drug effects , Cell Line, Tumor/metabolism , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Epithelial Cells/metabolism , Keratin-19/genetics , Keratin-7/genetics , Carcinogenesis/genetics , Gallbladder Neoplasms/metabolism , Antineoplastic Agents/pharmacology
15.
Clinics ; 75: e2360, 2020. tab
Article in English | LILACS | ID: biblio-1142774

ABSTRACT

OBJECTIVES: In the Human Epidermal Growth Factor Receptor-2 (HER2) rs1136201 variant, the presence of the G allele may promote cellular alterations and increase breast cancer risk, in addition to enhanced cellular proliferation, tumor aggressiveness, and metastases. The aim of this study was to investigate the presence of the single-nucleotide polymorphism (SNP) variant, rs1136201, within the HER2 gene in women from the Northeastern region of Brazil and breast cancer risk. METHODS: The study included 140 women who were divided into two groups, case (breast cancer) and control (without breast cancer), with 70 women in each group. Peripheral blood of each woman was drawn for the study of genomic Deoxyribonucleic acid (DNA) extracted from leukocytes using the genotyping technique by real-time polymerase chain reaction. RESULTS: The GG genotype occurred in 1 woman in both groups (1.4%) (p=0.32), while the AG genotype occurred in 19 (27.2%) and 13 (18.6%) women in the case and control (p=1.00) groups, respectively. No statistically significant difference in GG and AG genotypes was observed between the case and control groups in premenopausal women (p=1.00). Furthermore, no significant difference in genotypes was observed between the groups, among postmenopausal women (p=0.14). CONCLUSION: In this study, the HER2 rs1136201 polymorphism did not show any statistically significant association with breast cancer, both in premenopausal and postmenopausal women. Nevertheless, further studies with a larger sample size should be performed to assess the association of HER2 polymorphism with breast cancer risk in women from the Northeastern region of Brazil.


Subject(s)
Humans , Female , Breast Neoplasms/genetics , Receptor, ErbB-2/genetics , Brazil , Case-Control Studies , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Genotype
16.
Chinese Medical Journal ; (24): 2552-2557, 2020.
Article in English | WPRIM | ID: wpr-877833

ABSTRACT

BACKGROUND@#Inflammatory breast cancer (IBC) is an aggressive type of cancer with poor prognosis and outcomes. This study aimed to investigate clinicopathological features, molecular characteristics, and treatments among Chinese patients diagnosed with IBC.@*METHODS@#We collected data of 95 patients with IBC who were treated by members of the Chinese Society of Breast Surgery, from January 2017 to December 2018. The data, including demographic characteristics, pathological findings, surgical methods, systemic treatment plans, and follow-up, were obtained using a uniform electronic questionnaire. The clinicopathological features of different molecular types in patients without distant metastases were compared using the Kruskal-Wallis (H) test followed by post hoc analyses.@*RESULTS@#Lymph node metastasis was noted in 75.8% of all patients, while distant metastasis was noted in 21.4%. Pathological findings indicated invasive ductal and lobular carcinomas in 86.8% and 5.3% of cases, respectively. Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) (41.5%) and HR-/HER2+ (20.1%) were the most common biologic subtypes, followed by HR+/HER2+ (19.1%) and HR-/HER2- (19.1%). Stage III IBC was treated via pre-operative neoadjuvant chemotherapy in 87.7% of the cases, predominantly using anthracycline and taxanes. A total of 91.9% of patients underwent surgical treatment. Among them, 77.0% of the patients underwent modified radical mastectomy, 8.1% of whom also underwent immediate breast reconstruction. The Kruskal-Wallis test revealed that the efficacy of chemotherapy significantly differed among those with HR+/HER2- and HR-/HER2- tumors (adjusted P = 0.008), and Ki-67 expression significantly differed in HR-/HER2+ and HR+/HER2+ molecular subtypes (adjusted P = 0.008).@*CONCLUSION@#Our study provides novel insight into clinicopathological characteristics and treatment status among patients with IBC in China, and might provide a direction and basis for further studies.@*TRIAL REGISTRATION@#chictr.org.cn, No. ChiCTR1900027179; http://www.chictr.org.cn/showprojen.aspx?proj=45030.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms/surgery , Chemotherapy, Adjuvant , China , Humans , Inflammatory Breast Neoplasms/surgery , Mastectomy , Neoadjuvant Therapy , Prognosis , Receptor, ErbB-2 , Receptors, Progesterone
17.
Rev. bras. ginecol. obstet ; 41(12): 710-717, Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1057890

ABSTRACT

Abstract Objective To identify the biomarkers of response to neoadjuvant chemotherapy in early luminal breast cancer. Methods A cross-sectional study that included all patients with early or locallyadvanced luminal breast cancer submitted to neoadjuvant chemotherapy between 2013 and 2014. Demographic, clinic and pathologic data were retrieved from patient records. The expressions of the estrogen receptor (ER), the progesterone receptor (PR), and Ki67 were analyzed by immunohistochemistry (IHC). The status of the human epidermal growth factor receptor 2 (HER2) was evaluated by IHC and fluorescent in situ hybridization (FISH). Independent predictors of clinic and pathologic response were evaluated by stepwise logistic regression models and receiver operating characteristic (ROC) curve analysis. Results Out of 298 patients identified, 115 were included in the analysis. Clinical complete response (cCR) was observed in 43.4% of the patients (49/113), and pathologic complete response (pCR) was observed in 7.1% (8/115) of the patients. The independent predictors of cCR were premenopausal status (p < 0.001), low PR expression (≤ 50% versus > 50%; p = 0.048), and Ki67 expression ≥ 14% (versus < 14%; p = 0.01). Patients with cCR were more commonly submitted to breast conserving surgery (34.7% versus 7.8%; p < 0.001). Increasing cut-off points for Ki67 expression were associated with an increase in specificity and a decrease in sensitivity to identify patients with cCR. Conclusion Premenopausal status, lower PR expression and higher Ki67 expression were associated with a higher rate of cCR to neoadjuvant chemotherapy in luminal breast cancer.


Resumo Objetivo Identificar biomarcadores de resposta à quimioterapia neoadjuvante em câncer luminal de mama. Métodos Estudo transversal em que foram incluídas todas as pacientes com câncer luminal de mama em estádio inicial ou localmente avançado que foram submetidas a quimioterapia neoadjuvante nos anos de 2013 e 2014. Dados demográficos, clínicos e patológicos foram obtidos de prontuários médicos. As expressões de receptor de estrogênio (RE), de receptor de progesterona (RP), e de Ki67 foram avaliadas por imuno-histoquímica (IHQ). A expressão do receptor tipo 2 do fator de crescimento epidérmico humano (human epidermal growth factor receptor 2, HER2) foi avaliada por IHQ e hibridização in situ por imunofluorescência (HISI). Análises de regressão logística e de curva de característica de operação do receptor (COR) foram usadas para investigar fatores preditivos independentes de resposta clínica e patológica. Resultados De 298 pacientes identificadas, 115 foram incluídas na análise. Resposta clínica completa (RCc) foi observada em 43.4% das pacientes (49/113), e resposta patológica completa (RPc), em 7.1% (8/115). Os fatores preditivos independentes de RCc foram status menopausal (p < 0.001), baixa expressão de RP (≤ 50% versus > 50%; p = 0.048), e expressão de Ki67 ≥ 14% (versus < 14%; p = 0.01). Pacientes com RCc apresentaram maior probabilidade de serem submetidas a cirurgia conservadora da mama (34.7% versus 7.8%; p < 0.001). Aumento no ponto de corte para expressão de Ki67 foi associado a aumento da especificidade e redução da sensibilidade na identificação de pacientes com RCc. Conclusão Status premenopausal, baixa expressão de RP e maior expressão de Ki67 estiveram associados a maior taxa de RCc à quimioterapia neoadjuvante no câncer luminal de mama.


Subject(s)
Humans , Female , Adult , Breast Neoplasms/genetics , Breast Neoplasms/drug therapy , Menopause , Receptors, Progesterone/genetics , Ki-67 Antigen/genetics , Neoadjuvant Therapy , Antineoplastic Agents/therapeutic use , Receptors, Progesterone/metabolism , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism , Gene Expression , Cross-Sectional Studies , Chemotherapy, Adjuvant , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Ki-67 Antigen/metabolism , Middle Aged
18.
Oncol. (Guayaquil) ; 29(2): 97-109, 30 de Agosto del 2019.
Article in Spanish | LILACS | ID: biblio-1015302

ABSTRACT

Propósito de la revisión: Este artículo tiene la siguiente pregunta de investigación: ¿Se debe considerar la Biología, histología y el fenotipo para la estadificación inicial del Cáncer de Mama? Se realiza una revisión del estudio metabólico del cáncer de mama (CM) con la técnica de la captación de glucosa Fluorada 18-Fluoro-2-Desoxi-D-Glucosa y su medición de intensidad con tomografía por Emisión de positrones (18F-FDG PET/CT). Recientes Hallazgos: La 18F-FDG PET/CT puede detectar metástasis que no son visibles en otras modalidades, el carcinoma ductal invasivo muestra una mayor captación que el carcinoma lobular invasivo. La alta captación de 18F-FDG se ha asociado con un resultado peor y una supervivencia más corta. Extracto: El cáncer de mama es un tipo heterogéneo de malignidad porque varios factores afectan su comportamiento y pronóstico. Debido a esta heterogeneidad, el tratamiento óptimo y la respuesta esperada al tratamiento puede variar sustancialmente para cada paciente. 18F-FDG PET/CT puede proporcionar información relevante sobre el metabolismo, el diagnóstico y el pronóstico del cáncer de mama. Varios estudios han sugerido una correlación entre las características clínico-patológicas del cáncer de mama y los parámetros metabólicos obtenidos por 18F-FDG PET/CT.


Purpose of the review: This article has the following research question: Should biology, histology and phenotype be considered for initial staging of breast cancer? A review of the metabolic study of breast cancer (CM) is performed with the technique of glucose uptake Fluorada 18-Fluoro-2-Deoxy-D-Glucose and its intensity measurement with positron emission tomography (18F-FDG PET / CT). Recent Findings: 18F-FDG PET / CT can detect metastases that are not visible in other modalities, invasive ductal carcinoma shows a higher uptake than invasive lobular carcinoma. The high uptake of 18F-FDG has been associated with a worse outcome and shorter survival. Excerpt: Breast cancer is a heterogeneous type of malignancy because several factors affect its behavior and prognosis. Due to this heterogeneity, the optimal treatment and the expected response to treatment may vary substantially for each patient. 18F-FDG PET / CT can provide relevant information on the metabolism, diagnosis and prognosis of breast cancer. Several studies have suggested a correlation between the clinical-pathological characteristics of breast cancer and the metabolic parameters obtained by 18F-FDG PET / CT.


Subject(s)
Humans , Breast Neoplasms , Receptor, ErbB-2 , Positron-Emission Tomography , Tomography , Diagnosis , Neoplasm Metastasis
19.
Rev. méd. Chile ; 147(5): 557-567, mayo 2019. tab, graf
Article in English | LILACS | ID: biblio-1014264

ABSTRACT

ABSTRACT Background: Breast cancer (BC) is the most common malignancy in women. Aim: To assess the impact of HER2 status on axillary lymph node (ALN) involvement in patients with invasive ductal carcinoma of no special type (IDC-NST) both at diagnosis and during the 4-year postoperative period. Patients and Methods: We retrospectively included 375 women with an early clinical stage of non-luminal IDC-NST who between 2007 and 2013 underwent breast surgery at a clinical hospital. They were divided into phenotype-based groups: HR+HER2-, HR+HER2+, HR-HER2+ and HR-HER2-. Only patients with sentinel lymph node (SLN) macrometastases underwent ALN dissection. If > 3 ALNs were positive, radiotherapy was delivered. All patients were treated with chemotherapy, HER2+ BC patients received trastuzumab, and hormone receptor (HR)-positive BC patients received hormonal therapy. Results: Larger tumor size, higher grade, HR+, HER2+ status, and lymphovascular invasion (LVI) were predictive for ALN metastases at diagnosis. The poorest overall, disease-free, and distant recurrence-free survival (OS, DFS, DRFS) were found in the HR-HER2- group, while the poorest locoregional recurrence-free survival (LRFS) was observed in HR-HER2+ and HR-HER2- groups. HER2 status was not predictor of survival. Conclusions: HER2+ status was predictive for ALN involvement at diagnosis but had no effect on 4-year LRFS in these patients.


Antecedentes: El cáncer de mama es el tumor maligno más común en mujeres. Objetivo: Conocer el impacto del estado HER2 sobre el compromiso ganglionar axilar al momento del diagnóstico y durante los primeros cuatro años después de la cirugía en mujeres con carcinoma ductal invasivo de tipo no especial (IDC-NST). Pacientes y Métodos: Incluimos retrospectivamente a 375 mujeres en etapas clínicas iniciales de IDC-NST que fueron operadas en un hospital clínico. Ellas se dividieron en grupos de acuerdo al fenotipo: HR+HER2-, HR+HER2+, HR-HER2+y HR-HER2-. La disección de ganglios axilares se efectuó solo en las pacientes con macrometástasis en el ganglio centinela. Si había más de tres ganglios comprometidos, se efectuó radioterapia. Todas las pacientes se trataron con quimioterapia. Las pacientes HER2+ recibieron trastuzumab y las pacientes HR+ recibieron hormonoterapia. Resultados: Tumores más grandes, de mayor grado de malignidad, HR+, HER2+ y la invasión linfovascular fueron predictivos de la presencia de metástasis axilares al momento del diagnóstico. La sobrevida más baja se observó en pacientes HR-HER2+. La sobrevida libre de recurrencia locorregional más baja, se observó en pacientes HR-HER2+ y HR-HER2-. HER2 no fue predictor de sobrevida. Conclusiones: En estas mujeres, HER2+fue predictor de la presencia de compromiso ganglionar axilar al momento del diagnóstico pero no de la sobrevida a cuatro años.


Subject(s)
Humans , Female , Adult , Middle Aged , Aged , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Receptor, ErbB-2/analysis , Sentinel Lymph Node/pathology , Axilla , Time Factors , Breast Neoplasms/mortality , Multivariate Analysis , Retrospective Studies , Carcinoma, Ductal, Breast/mortality , Statistics, Nonparametric , Disease-Free Survival , Ki-67 Antigen/analysis , Tumor Burden , Kaplan-Meier Estimate , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Neoplasm Staging
20.
Gac. méd. Méx ; 155(supl.1): 50-55, dic. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1286565

ABSTRACT

Resumen Antecedentes: La clasificación del cáncer de mama en subtipos mediante la expresión de receptores hormonales (RH) y del receptor 2 del factor de crecimiento epidérmico humano (HER2) por inmunohistoquímica (IHQ) es una práctica estándar para la toma de decisiones terapéuticas. Objetivo: Conocer las características y supervivencia de cada subtipo de pacientes, que es indispensable para poder diseñar futuros estudios. Método: Realizamos un estudio retrospectivo evaluando las características clinicopatológicas y la supervivencia por subtipo mediante IHQ en mujeres con cáncer de mama. Resultados: 211 mujeres con cáncer de mama RH(+)/HER2(-), 53 con RH(+)/HER2(+), 16 con HER2(+) y 23 con RH(-)/HER2(-), con una mediana de supervivencia global en meses de 39 (20.5-62.7), 42 (25.5-65), 42 (13.7-67.7) y 26 (11-78), respectivamente, para un cociente de riesgo (HR por sus siglas en inglés, Hazard Ratio): 3.7 (IC 95%: 1.3-10.3) en el grupo triple negativo comparado con RH(+)/HER2(-) (p = 0.01). Conclusión: Los subtipos con RH positivos por IHQ son los más frecuentes y este grupo de pacientes tienen una mejor supervivencia global comparada con las pacientes triple negativo.


Abstract Background: Breast cancer subtype classification according to hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) using immunohistochemistry is the standard practice for therapeutic decision making. Objective: To design future studies information on characteristics and survival of each subtype is essential. Method: We conducted a retrospective study to analyze clinical and pathologic features as well as survival data according to breast cancer immunohistochemistry subtype. Results: There were 211 women with a RH(+)/HER2(-) breast cancer subtype, 53 HR(+)/HER2(+), 16 HER2(+) and 23 HR(-)/HER2(-), with a median overall survival in months of 39 (20.5-62.7), 42 (25.5-65), 42 (13.7-67.7) and 26 (11-78), respectively, for a 3.7 hazard ratio of death (95% Confidence Interval [CI]: 1.3-10.3) for the triple negative group as compared to the HR(+)/HER2(-) group (p = 0.01). Conclusions: HR positive subtypes by immunohistochemistry where most frequent and showed a greater overall survival compared to the triple negative subtype.


Subject(s)
Humans , Female , Adult , Middle Aged , Breast Neoplasms/classification , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms/chemistry , Immunohistochemistry , Survival Rate , Retrospective Studies , Cohort Studies , Receptor, ErbB-2/analysis
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