RESUMO
OBJECTIVE: The aim of this study was to investigate the predictive importance of the previously validated log(ER)*log(PgR)/Ki-67 predictive model in a larger patient population. METHODS: Patients with hormone receptor positive/HER-2 negative and clinical node positive before chemotherapy were included. Log(ER)*log(PgR)/Ki-67 values of the patients were determined, and the ideal cutoff value was calculated using a receiver operating characteristic curve analysis. It was analyzed with a logistic regression model along with other clinical and pathological characteristics. RESULTS: A total of 181 patients were included in the study. The ideal cutoff value for pathological response was 0.12 (area under the curve=0.585, p=0.032). In the univariate analysis, no statistical correlation was observed between luminal subtype (p=0.294), histological type (p=0.238), clinical t-stage (p=0.927), progesterone receptor level (p=0.261), Ki-67 cutoff value (p=0.425), and pathological complete response. There was a positive relationship between numerical increase in age and residual disease. As the grade of the patients increased, the probability of residual disease decreased. Patients with log(ER)*log(PgR)/Ki-67 above 0.12 had an approximately threefold increased risk of residual disease when compared to patients with 0.12 and below (odds ratio: 3.17, 95% confidence interval: 1.48-6.75, p=0.003). When age, grade, and logarithmic formula were assessed together, the logarithmic formula maintained its statistical significance (odds ratio: 2.47, 95% confidence interval: 1.07-5.69, p=0.034). CONCLUSION: In hormone receptor-positive breast cancer patients receiving neoadjuvant chemotherapy, the logarithmic model has been shown in a larger patient population to be an inexpensive, easy, and rapidly applicable predictive marker that can be used to predict response.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Biomarcadores Tumorais/análise , Antígeno Ki-67/análise , Receptor ErbB-2/uso terapêutico , Terapia Neoadjuvante , Receptores de Progesterona/análise , Receptores de Progesterona/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos RetrospectivosRESUMO
BACKGROUND: Breast cancer clinical management requires the assessment of hormone receptors (estrogen (ER) and progesterone receptor (PR)), human epidermal growth factor receptor 2 (HER2) and cellular proliferation index Ki67, by immunohistochemistry (IHC), in order to choose and guide therapy according to tumor biology. Many studies have reported contradictory results regarding changes in the biomarker profile after neoadjuvant therapy (NAT). Given its clinical implications for the disease management, we aimed to analyze changes in ER, PR, HER2, and Ki67 expression in paired core-needle biopsies and surgical samples in breast cancer patients that had either been treated or not with NAT. METHODS: We included 139 patients with confirmed diagnosis of invasive ductal breast carcinoma from the Colombian National Cancer Institute. Variation in biomarker profile were assessed according to NAT administration (NAT and no-NAT treated cases) and NAT scheme (hormonal, cytotoxic, cytotoxic + trastuzumab, combined). Chi-squared and Wilcoxon signed-rank test were used to identify changes in biomarker status and percentage expression, respectively, in the corresponding groups. RESULTS: We did not find any significant variations in biomarker status or expression values in the no-NAT group. In cases previously treated with NAT, we did find a statistically significant decrease in Ki67 (p < 0.001) and PR (p = 0.02605) expression. When changes were evaluated according to NAT scheme, we found a significant decrease in both Ki67 status (p = 0.02977) and its expression values (p < 0.001) in cases that received the cytotoxic treatment. CONCLUSIONS: Our results suggest that PR and Ki67 expression can be altered by NAT administration, whereas cases not previously treated with NAT do not present IHC biomarker profile variations. The re-evaluation of these two biomarkers after NAT could provide valuable information regarding treatment response and prognosis for breast cancer patients.
Assuntos
Antineoplásicos/administração & dosagem , Biomarcadores Tumorais/análise , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Terapia Neoadjuvante , Biomarcadores Tumorais/metabolismo , Biópsia com Agulha de Grande Calibre , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Mastectomia , Prognóstico , Receptor ErbB-2/análise , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/análise , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: Neutrophils are among the key cellular players in the inflammatory milieu produced in patients with breast cancer (BC), and strong evidence exists in terms of the prognostic value of assessing the neutrophil-to-lymphocyte ratio (NLR) in patients with BC. In this study we sought to determine whether the baseline NLR correlates with pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS) in patients with locally advanced BC in the neoadjuvant chemotherapy (NAC) setting. METHODS: We analyzed the pretreatment NLR from the first blood count of patients treated from 2007 to 2015 in terms of pCR, DFS, and OS in patients with locally advanced BC. Patients received standard medical care based on national guidelines. RESULTS: A total of 1519 patients were included in the study. Median age was 49 years (22-88). The cutoff point for NLR was 2.0. NLR was not associated with pCR or DFS. However, patients with high NLR had worse OS in the presence of triple-negative BC (105.9 months; 95% confidence interval [CI], 100.2-111.5] vs. 98.7 months; 95% CI, 91.1-106.3; P = .029), Her2 overexpression (114.0 months; 95% CI, 110.5-118.0 vs. 100.8 months; 95% CI 95.7-105.9; P = .019), and residual disease after NAC for both phenotypes. Multivariate analysis showed that NLR was independently associated with OS (hazard ratio, 1.4; 95% CI, 1.02-1.95; P = .037). CONCLUSIONS: Pretreatment NLR in patients with locally advanced BC correlates with OS as an independent prognostic factor. This influence depends on phenotype and residual disease. Routine assessment of this parameter could be an easy and affordable tool for defining prognosis.
Assuntos
Neoplasias da Mama/terapia , Linfócitos , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/epidemiologia , Neutrófilos , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/estatística & dados numéricos , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Contagem de Linfócitos , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante/estatística & dados numéricos , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Receptor ErbB-2/análise , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/análise , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The purpose of this study was to investigate whether combining pembrolizumab with palliative radiation therapy (RT) improves outcomes in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). PATIENTS AND METHODS: Eligible patients had HR+/human epidermal growth factor receptor 2-negative MBC; were candidates for RT to ≥ 1 bone, soft tissue, or lymph node lesion; and had ≥ 1 lesion outside the RT field. Patients received 200 mg pembrolizumab intravenously 2 to 7 days prior to RT and on day 1 of repeating 21-day cycles. RT was delivered to a previously unirradiated area in 5 treatments each of 4 Gy. The primary endpoint was objective response rate. The study used a 2-stage design: 8 women were enrolled into the first stage, and if at least 1 of 8 patients experienced an objective response, 19 more would be enrolled. Secondary endpoints included progression-free survival, overall survival, and safety. Exploratory endpoints included association of overall response rate with programmed death-ligand 1 status and tumor-infiltrating lymphocytes. RESULTS: Eight patients were enrolled in stage 1. The median age was 59 years, and the median prior lines of chemotherapy for metastatic disease was 2. There were no objective responses, and the study was closed to further accrual. The median progression-free survival was 1.4 months (95% confidence interval, 0.4-2.1 months), and the median overall survival was 2.9 months (95% confidence interval, 0.9-3.6 months). All-cause adverse events occurred in 87.5% of patients, including just 1 grade 3 event (elevation of aspartate aminotransferase). CONCLUSIONS: RT combined with pembrolizumab did not produce an objective response in patients with heavily pre-treated HR+ MBC. Future studies should consider alternative radiation dosing and fractionation in patients with less heavily pre-treated HR+ MBC.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Quimiorradioterapia/métodos , Cuidados Paliativos/métodos , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Mama/patologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Quimiorradioterapia/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Critérios de Avaliação de Resposta em Tumores SólidosRESUMO
PURPOSE: Breast cancer with positive hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) is a special subgroup with different clinical features and survival, especially the endocrine therapy resistance. The main purpose of the study is to find the potential markers to predict the survival and endocrine therapy resistance of patients with HR+ /HER2+ breast cancer. METHODS: Surveillance, Epidemiology, and End Results (SEER) database was used to collect patients' clinical information and tumor features including age, tumor size, grade, stage and long-term survival; the BioPortal for Cancer Genomics (https://cbioportal.org) was used to download the gene data for specific patient group; cluster analyses of gene expression were conducted through the DAVID Bioinformatics Resources 6.8 software. RESULTS: All of the included patients were diagnosed as HR positive breast cancer, but the PR positive rates were more common in HER2- group and also the ER+ /PR+ disease. Patients in HR+ /HER2+ group were more likely to present as stage III-IV and grade III disease. Among HR+ /HER2+ patients, 68.6% received chemotherapy, while only 28.9% in HR+ /HER2- group received chemotherapy (P < 0.0001). The survival of HR+ /HER2+ group was poorer. From TCGA database, series genes which were differed between HR+ /HER2+ and HR+ /HER2- were screened out that related to ERBB2 closely: IKZF3, LASP1, CDK12, MLLT6, and RARA. The first three candidate genes were associated with patients' survival, especially in patients who received hormone therapies. CONCLUSION: This study analyzed the clinical characteristics and survival of patients with HR+/HER2+ breast cancer as a special subgroup. ERBB2, IKZF3, LASP1, and CDK12 were the potential markers of the resistance of endocrine therapy, and they will provide new strategies for clinicians.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The prognostic and clinical significance of single hormone receptor expression in breast cancer has not been clearly established. The goal of this study was to conduct a meta-analysis to compare the clinical outcomes of patients with ER+PR- tumours and ER-PR+ tumours to those of patients with ER+PR+ tumours. METHODS: A systematic review of the literature was conducted to identify studies that compared the clinical outcome of patients with ER+PR- tumours or ER-PR+ tumours with those of patients with ER+PR+ tumours. A total of 18 studies met the inclusion criteria and included 217,485 women. Standard methods for meta-analysis were used, including fixed-effect models. RESULTS: Patients with ER+PR- tumours or ER-PR+ tumours had significantly worse DFS (HR 1.60, 95% CI 1.44-1.77 and HR 2.27, 95% CI 1.67-3.09), BCSS (HR 1.43, 95% CI 1.33-1.53 and HR 1.82, 95% CI 1.68-1.98) and OS (HR 1.38, 95% CI 1.28-1.47 and HR 1.48, 95% CI 1.17-1.89) than those of patients with ER+PR+ tumours. In subgroup analyses, patients who had ER+PR- tumours experienced a higher risk of recurrence than patients with ER+PR+ tumours in the HER2- (HR 1.57, 95% CI 1.32-1.87), LN - (HR 2.07, 95% CI 1.44-2.86) and endocrine therapy (HR 1.65, 95% CI 1.45-1.89) subgroup. Patients who had HER2- and ER-PR+ tumours had an increased risk of recurrence compared with patients who had HER2- and ER+PR+ tumours (HR 3.10, 95% CI 1.92-5.10). CONCLUSIONS: Among patients with hormone receptor-positive breast cancer, patients with either ER+PR- tumours or ER-PR+ tumours have a higher risk of recurrence and a shorter survival time than those with ER+PR+ tumours. Patients with both types of breast cancer need additional or better treatments.
Assuntos
Neoplasias da Mama/mortalidade , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Neoplasias da Mama/química , Feminino , Humanos , Recidiva Local de Neoplasia/etiologia , Receptor ErbB-2/análiseRESUMO
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.
Assuntos
Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Receptores ErbB/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Adulto , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
One of the promising tools to evaluate collagen in the extracellular matrix is the second-harmonic generation microscopy (SHG). This approach may shed light on the biological behavior of cancers and their taxonomy, but has not yet been applied to characterize collagen fibers in cases diagnosed as invasive breast carcinoma (BC) of histological special types (IBC-ST). Tissue sections from 99 patients with IBC-ST and 21 of invasive breast carcinoma of no special type (IBC-NST) were submitted to evaluation of collagen parameters by SHG. Tissue microarray was performed to evaluate immunohistochemical-based molecular subtype. In intratumoral areas, fSHG and bSHG (forward-SHG and backward-SHG) collagen parameters achieved their lowest values in mucinous, papillary and medullary carcinomas, whereas the highest values were found in classic invasive lobular and tubular carcinomas. Unsupervised hierarchical cluster analysis and minimal spanning tree using intratumoral collagen parameters allowed the identification of three main groups of breast cancer: group A (classic invasive lobular and tubular carcinomas); group B (IBC-NST, metaplastic, invasive apocrine and micropapillary carcinomas); and group C (medullary, mucinous and papillary carcinomas). Our findings provide further characterization of the tumor microenvironment of IBC-ST. This understanding may add information to build more consistent tumor categorization and to refine prognostication.
Assuntos
Neoplasias da Mama/ultraestrutura , Carcinoma/ultraestrutura , Colágeno/análise , Matriz Extracelular/ultraestrutura , Idoso , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Carcinoma/química , Carcinoma/classificação , Carcinoma/patologia , Estrogênios , Matriz Extracelular/química , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Hormônio-Dependentes/química , Neoplasias Hormônio-Dependentes/patologia , Neoplasias Hormônio-Dependentes/ultraestrutura , Progesterona , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Análise Serial de Tecidos , Neoplasias de Mama Triplo Negativas/química , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/ultraestruturaRESUMO
AIMS: In women, uterine alterations have been associated with sex steroid hormones. Sex hormones regulate the expression of thyroid hormone receptors (TRs) in the uterus, but an inverse link is unknown. We analyzed the impact of hypothyroidism on histological characteristics, vascular endothelial growth factor (VEGF-A), progesterone receptors (PR), estrogen receptors (ER), thyroid hormone receptors (TRs), perilipin (PLIN-A), and lipid content in the uterus of virgin rabbits. MAIN METHODS: Twelve Chinchilla-breed adult female rabbits were grouped into control (nâ¯=â¯6) and hypothyroid (nâ¯=â¯6; 0.02% of methimazole for 30â¯days). The thickness of endometrium and myometrium, number of uterine glands, and infiltration of immune cells were analyzed. The expression of VEGF-A, PR, ERα, and PLIN-A was determined by RT-PCR and western blot. The uterine content of triglycerides (TAG), total cholesterol (TC), and malondialdehyde (MDA) was quantified. KEY FINDINGS: Hypothyroidism promoted uterine hyperplasia and a high infiltration of immune cells into the endometrium, including macrophages CD163+. It also increased the expression of VEGF-A, TRA, and ERα-66 but reduced that of PR and ERα-46. The uterine content of PLIN-A, TAG, and TC was reduced, but that of MDA was augmented in hypothyroid rabbits. SIGNIFICANCE: Our results suggest that uterine hyperplasia and inflammation promoted by hypothyroidism should be related to changes in the VEGF-A, PR, ER, and TRs expression, as well as to modifications in the PLIN-A expression, lipid content, and oxidative status. These results suggest that hypothyroidism should affect the fertility of females.
Assuntos
Hormônios Esteroides Gonadais/metabolismo , Hiperplasia/etiologia , Hiperplasia/fisiopatologia , Hipotireoidismo/complicações , Animais , Endométrio/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Hormônios Esteroides Gonadais/análise , Hipotireoidismo/fisiopatologia , Inflamação , Lipídeos/análise , Miométrio/metabolismo , Perilipina-1/análise , Perilipina-1/metabolismo , Progesterona/farmacologia , Coelhos , Receptores de Estrogênio/análise , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Receptores dos Hormônios Tireóideos/análise , Receptores dos Hormônios Tireóideos/metabolismo , Útero/metabolismo , Útero/fisiologia , Fator A de Crescimento do Endotélio Vascular/análiseRESUMO
BACKGROUND: Data on breastfeeding and breast cancer risk are sparse and inconsistent for Hispanic women. METHODS: Pooling data for nearly 6,000 parous Hispanic women from four population-based studies conducted between 1995 and 2007 in the United States and Mexico, we examined the association of breastfeeding with risk of breast cancer overall and subtypes defined by estrogen receptor (ER) and progesterone receptor (PR) status, and the joint effects of breastfeeding, parity, and age at first birth. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. RESULTS: Among parous Hispanic women, older age at first birth was associated with increased breast cancer risk, whereas parity was associated with reduced risk. These associations were found for hormone receptor positive (HR+) breast cancer only and limited to premenopausal women. Age at first birth and parity were not associated with risk of ER- and PR- breast cancer. Increasing duration of breastfeeding was associated with decreasing breast cancer risk (≥25 vs. 0 months: OR = 0.73; 95% CI = 0.60, 0.89; Ptrend = 0.03), with no heterogeneity by menopausal status or subtype. At each parity level, breastfeeding further reduced HR+ breast cancer risk. Additionally, breastfeeding attenuated the increase in risk of HR+ breast cancer associated with older age at first birth. CONCLUSIONS: Our findings suggest that breastfeeding is associated with reduced risk of both HR+ and ER- and PR- breast cancer among Hispanic women, as reported for other populations, and may attenuate the increased risk in women with a first pregnancy at older ages.