RESUMEN
BACKGROUND: Associations of body shape with breast cancer risk, independent of body size, are unclear because waist and hip circumferences are correlated strongly positively with body mass index (BMI). METHODS: We evaluated body shape with the allometric "a body shape index" (ABSI) and hip index (HI), which compare waist and hip circumferences, correspondingly, among individuals with the same weight and height. We examined associations of ABSI, HI, and BMI (per one standard deviation increment) with breast cancer overall, and according to menopausal status at baseline, age at diagnosis, and oestrogen and progesterone receptor status (ER+/-PR+/-) in multivariable Cox proportional hazards models using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. RESULTS: During a mean follow-up of 14.0 years, 9011 incident breast cancers were diagnosed among 218,276 women. Although there was little evidence for association of ABSI with breast cancer overall (hazard ratio HR = 0.984; 95% confidence interval: 0.961-1.007), we found borderline inverse associations for post-menopausal women (HR = 0.971; 0.942-1.000; n = 5268 cases) and breast cancers diagnosed at age ≥ 55 years (HR = 0.976; 0.951-1.002; n = 7043) and clear inverse associations for ER + PR- subtypes (HR = 0.894; 0.822-0.971; n = 726) and ER-PR- subtypes (HR = 0.906; 0.835-0.983 n = 759). There were no material associations with HI. BMI was associated strongly positively with breast cancer overall (HR = 1.074; 1.049-1.098), for post-menopausal women (HR = 1.117; 1.085-1.150), for cancers diagnosed at age ≥ 55 years (HR = 1.104; 1.076-1.132), and for ER + PR + subtypes (HR = 1.122; 1.080-1.165; n = 3101), but not for PR- subtypes. CONCLUSIONS: In the EPIC cohort, abdominal obesity evaluated with ABSI was not associated with breast cancer risk overall but was associated inversely with the risk of post-menopausal PR- breast cancer. Our findings require validation in other cohorts and with a larger number of PR- breast cancer cases.
Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Femenino , Humanos , Persona de Mediana Edad , Índice de Masa Corporal , Neoplasias de la Mama/complicaciones , Factores de Riesgo , Progesterona , Estudios Prospectivos , Neoplasias de la Mama Triple Negativas/complicaciones , Posmenopausia , SomatotiposRESUMEN
BACKGROUND: Serum vitamin D (Vit-D) has been linked to the development of breast cancer (BC); however, their effect on pathological features and outcomes is undetermined. The purpose of this study was to examine the prognostic significance of baseline Vit-D levels and their effect on clinical outcomes. METHODS: We evaluated baseline serum Vit-D levels and baseline clinic-pathological features of female patients with non-metastatic BC between October 2018 and December 2019. A low Vit-D level was described as less than 30 nanogram per liter (ng/l). Patients were observed for a median of 24 months. To evaluate relationships between qualitative variables, the chi-square test was used. The Kaplan-Meier technique was used for survival analysis, and the log-rank test was used to compare the two survival curves. Correlation analysis was also used to examine the link between Vit-D levels and clinical outcomes. RESULTS: The eligibility criteria were fulfilled by 221 patients. The median age of onset was (50.7). The median Vit-D level was (23.1 ng/l) with a range of (4-46 ng/l). Approximately half of the patients (56.5%) had Vit-D levels < 30 ng/l, with HER2 positive and triple negative (TNBC) patients having a greater proportion of low Vit-D levels (p = <0.001). Patients with low baseline Vit-D levels had a larger tumor size, more positive lymph nodes, and were diagnosed at a later stage. Following follow-up, Vit-D deficiency was associated with a significantly increased risk of bone metastases (HR 3.37, 95% CI 1.32-8.59, p = 0.006), and Vit-D levels were significantly correlated with disease-free survival (DFS) and overall survival (OS) (r = 0.850, r = 0.573, p < 0.00, p < 0.001, respectively). CONCLUSIONS: Low serum Vit-D is associated with advanced stage and adverse characteristics. It is more prevalent in HER-2 positive and TNBC patients; it increases the chance of bone metastases, and has a significant correlation with DFS and OS.
Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Deficiencia de Vitamina D , Humanos , Femenino , Estudios de Cohortes , Neoplasias de la Mama/patología , Neoplasias de la Mama Triple Negativas/complicaciones , Neoplasias de la Mama Triple Negativas/patología , Vitamina D , Pronóstico , Deficiencia de Vitamina D/complicacionesRESUMEN
BACKGROUND: The risk factors for breast cancer (BC) among women in Brazilian populations are poorly understood. To date, few Brazilian studies have addressed the potential association between risk factors and molecular BC subtypes. This case-control study aimed to identify risk factors for BC in a population of Northeast Brazil. METHODS: Data from 313 patients with invasive BC and 321 healthy controls were obtained from medical records from two cancer treatment centres and personal interviews. Of the 313 BC patients, 224 (71.6%) had reached menopause. The following distribution of subtypes was found among 301 patients: (1) Luminal A: 54 (17.9%); (2) Luminal B: 175 (58.1%); (3) HER2/neu: 29 (9.7%); and (4) triple-negative breast cancer (TNBC): 43 (14.3%). Odds ratios (ORs) and confidence intervals (CIs) were determined using regression analysis. RESULTS: Regression modelling indicated that family history, obesity (≥ 30.0 kg/m2), alcohol consumption and contraceptive use increased the overall risk of BC 1.78 (95% CI: 1.22-2.59), 1.69 (95% CI: 1.08-2.63), 2.21 (95% CI: 1.44-3.39) and 2.99 (95% CI: 2.09-4.28) times, respectively. After stratification for menopausal status, alcohol consumption increased the risk of BC 4.15 (95% CI: 2.13-8.11) times, and obesity, as a single variable, increased the risk of BC 2.02 (95% CI: 1.22-3.37) times, only among postmenopausal women. In a case-control analysis, the risk of TNBC and Luminal B breast cancer were 4.06 (95% CI: 1.58-10.42) and 1.87 times (95% CI: 1.13-3.11) higher, respectively, in obese women than in non-obese women. Furthermore, alcohol consumption increased the risk of Luminal A and B subtypes 7.08 (3.40-14.73) and 1.77 (1.07-2.92) times, respectively. CONCLUSION: Family history, contraceptive use, obesity and alcohol consumption increased the risk of BC. Obesity and alcohol consumption differentially increased risk of TNBC and Luminal molecular subtypes.
Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Brasil/epidemiología , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/etiología , Estudios de Casos y Controles , Femenino , Humanos , Obesidad/complicaciones , Obesidad/epidemiología , Receptor ErbB-2 , Receptores de Progesterona , Factores de Riesgo , Neoplasias de la Mama Triple Negativas/complicaciones , Neoplasias de la Mama Triple Negativas/etiologíaRESUMEN
Reduced age-related terminal duct lobular unit (TDLU) involution has been linked to increased breast cancer risk and triple-negative breast cancer. Associations of TDLU involution levels with race and ethnicity remain incompletely explored. Herein, we examined the association between genetic ancestry and TDLU involution in normal breast tissue donated by 2014 healthy women in the United States. Women of African ancestry were more likely than European women to have increased TDLU counts (odds ratio [OR]trend = 1.36, 95% confidence interval [CI] = 1.07 to 1.74), acini counts per TDLU (OR = 1.47, 95% CI = 1.06 to 2.03), and median TDLU span (ORtrend = 1.44, 95% CI = 1.08 to 1.91), indicating lower involution, whereas East Asian descendants were associated with decreased TDLU counts (ORtrend = 0.52, 95% CI = 0.35 to 0.78) after controlling for potential confounders. These associations are consistent with the racial variations in incidence rates of triple-negative breast cancer in the United States and suggest opportunities for future work examining whether TDLU involution may mediate the racial differences in subtype-specific breast cancer risk.
Asunto(s)
Neoplasias de la Mama , Glándulas Mamarias Humanas , Neoplasias de la Mama Triple Negativas , Mama , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Femenino , Humanos , Incidencia , Riesgo , Neoplasias de la Mama Triple Negativas/complicaciones , Neoplasias de la Mama Triple Negativas/epidemiología , Neoplasias de la Mama Triple Negativas/genética , Estados Unidos/epidemiologíaRESUMEN
Triple-negative breast cancer (TNBC) is an aggressive, molecularly heterogeneous subtype of breast cancer. Obesity is associated with increased incidence and worse prognosis in TNBC through various potential mechanisms. Recent evidence suggests that the gut microbiome plays a central role in the progression of cancer, and that imbalances or dysbiosis in the population of commensal microbiota can lead to inflammation and contribute to tumor progression. Obesity is characterized by low-grade inflammation, and gut dysbiosis is associated with obesity, chronic inflammation, and failure of cancer immunotherapy. However, the debate on what constitutes a "healthy" gut microbiome is ongoing, and the connection among the gut microbiome, obesity, and TNBC has not yet been addressed. This study aims to characterize the role of obesity in modulating the gut microbiome in a syngeneic mouse model of TNBC. 16S rRNA sequencing and metagenomic analyses were performed to analyze and annotate genus and taxonomic profiles. Our results suggest that obesity decreases alpha diversity in the gut microbiome. Metagenomic analysis revealed that obesity was the only significant factor explaining the similarity of the bacterial communities according to their taxonomic profiles. In contrast to the analysis of taxonomic profiles, the analysis of variation of functional profiles suggested that obesity status, tumor presence, and the obesity-tumor interaction were significant in explaining the variation of profiles, with obesity having the strongest correlation. The presence of tumor modified the profiles to a greater extent in obese than in lean animals. Further research is warranted to understand the impact of the gut microbiome on TNBC progression and immunotherapy.
Asunto(s)
Microbioma Gastrointestinal , Obesidad/complicaciones , Obesidad/microbiología , Neoplasias de la Mama Triple Negativas/complicaciones , Neoplasias de la Mama Triple Negativas/microbiología , Análisis de Varianza , Animales , Bacterias/genética , Microbioma Gastrointestinal/genética , Metagenómica , Ratones , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ARNRESUMEN
Background As breast epithelium is affected by vitamin D, it may have a direct effect on breast density and the risk of breast cancer. Our aim was to study the serum levels of vitamin D in patients with malignant and benign breast disease, and to study the association, if any, between vitamin D levels, mammographic breast density (MD) and molecular subtypes of breast cancer. Methods In this cross-sectional, observational study, we enrolled 162 consecutive adult women with benign and malignant breast masses subjected to mammography and core-needle biopsy. Serum levels of vitamin D were estimated and correlated with MD and with immunohistochemical subtyping of breast cancer. Results The mean vitamin D level in these 162 patients was 12.44 (5.88) ng/ml, with vitamin D deficiency seen in 98%. The mean (SD) vitamin D level in MD type 1 was 16.19 (4.62) ng/ml and it decreased to 7.54 (2.58) ng/ml in MD type 4. High MD was associated with significantly lower vitamin D levels. The mean vitamin D level in patients with benign breast disease (n=102) was 13.73 (5.68) ng/ml, while it was significantly lower in patients with breast cancer (n=60) at 10.26 (5.61) ng/ml. Among patients with breast cancer, the good prognosis luminal A molecular subtype had mean vitamin D level of 12.94 (6.16) ng/ml, whereas the poor prognosis triple-negative subtype had a significantly lower value of 7.68 (3.42) ng/ml. Conclusion Our study shows that vitamin D deficiency has a significant relationship with breast cancer (v. benign breast disease), high MD (showing increased breast cancer risk) and poor prognosis triple-negative breast cancer. Vitamin D deficiency could be an important, potentially modifiable, risk factor for the prevention of breast cancer in susceptible populations.
Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Deficiencia de Vitamina D , Adulto , Densidad de la Mama , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/epidemiología , Estudios Transversales , Femenino , Humanos , Neoplasias de la Mama Triple Negativas/complicaciones , Neoplasias de la Mama Triple Negativas/diagnóstico por imagen , Neoplasias de la Mama Triple Negativas/epidemiología , Vitamina D , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiologíaRESUMEN
BACKGROUND: High levels of stromal tumor-infiltrating lymphocytes (sTIL) are associated with increased pathological complete response (pCR) rate and longer survival after neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. Here, we evaluated the value of sTIL in predicting pCR and explored prognosis in TNBC patients treated with neoadjuvant chemotherapy according to body mass index (BMI). METHODS: sTIL were scored centrally on pretreatment biopsies from 2 retrospective series of nonunderweight TNBC patients (n = 445). sTIL and BMI were considered as binary (sTIL: <30.0% vs ≥30.0%; BMI: lean vs overweight and obese) and continuous variables. Associations with pCR (ypT0/isN0) were assessed using logistic regression, and associations with event-free survival and overall survival were assessed using Cox regressions. RESULTS: 236 (53.0%) patients were lean and 209 (47.0%) overweight and obese. pCR was achieved in 181 of 445 (41.7%) patients. Median sTIL was 11.0%, and 99 of 445 (22.2%) tumors had high sTIL. A statistically significant interaction between sTIL and BMI, considered as categorical or continuous variables, for predicting pCR was observed in the multivariable analysis (Pinteraction = .03 and .04, respectively). High sTIL were statistically significantly associated with pCR in lean (odds ratio [OR] = 4.24, 95% confidence interval [CI] = 2.10 to 8.56; P < .001) but not in heavier patients (OR = 1.48, 95% CI = 0.75 to 2.91; P = .26) in the multivariable analysis. High sTIL were further associated with increased event-free survival in lean (hazard ratio [HR] = 0.22, 95% CI = 0.08 to 0.62; P = .004) but not in heavier patients (HR = 0.53, 95% CI = 0.26 to 1.08; P = .08). Similar results were obtained for overall survival. CONCLUSION: BMI is modifying the effect of sTIL on pCR and prognosis in TNBC patients treated with neoadjuvant chemotherapy.
Asunto(s)
Índice de Masa Corporal , Linfocitos Infiltrantes de Tumor/patología , Obesidad/epidemiología , Neoplasias de la Mama Triple Negativas/epidemiología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Femenino , Humanos , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/patología , Obesidad/terapia , Supervivencia sin Progresión , Estudios Retrospectivos , Células del Estroma/patología , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/complicaciones , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/terapiaRESUMEN
CASE PRESENTATION: A 48-year-old female never smoker with hypothyroidism and no significant prior respiratory complaints presented with 1 month of gradually worsening dyspnea on exertion. She denied any associated fevers, chills, weight loss, chest pain, productive cough, hemoptysis, or sick contacts. She was recently diagnosed with stage IV triple negative adenocarcinoma of the breast and was yet to receive chemotherapy.
Asunto(s)
Células Neoplásicas Circulantes/patología , Circulación Pulmonar , Neoplasias de la Mama Triple Negativas , Cateterismo Cardíaco/métodos , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Diagnóstico Diferencial , Disnea/diagnóstico , Disnea/etiología , Femenino , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/patología , Humanos , Microvasos/patología , Persona de Mediana Edad , Manejo de Atención al Paciente/métodos , Tomografía Computarizada por Rayos X/métodos , Neoplasias de la Mama Triple Negativas/complicaciones , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/terapiaRESUMEN
A 59 year-old woman was treated with adjuvant chemotherapy for triple negative breast cancer (TNBC) stage IB. She received pegfilgrastrim as secondary prophylaxis of neutropenia. After administration of pegfilgrastrim on day 11, she was hospitalised because of carotidynia and myocarditis that improved with antibiotics and steroids as an infection was suspected. Once she was recovered, another cycle of chemotherapy with pegfilgrastrim was administrated. At this time, the patient presented to our hospital with fever, odynophagia and chest pain, with diagnosis of myocarditis coupled with cardiogenic shock. She received antibiotics and steroids, advanced life support and also a pericardial window was done, with recovery of her condition. After a complete evaluation and exclusion of other possible aetiologies, we concluded that pegfilgrastrim was responsible for inducing carotidynia and myocarditis. Few cases have been published about Granulocyte-Colony stimulating factor (G-CSF) induced carotidynia and aortitis. However, this is the first reported case about G-CSF induced myocarditis and carotidynia.
Asunto(s)
Aortitis/diagnóstico , Aortitis/etiología , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Miocarditis/diagnóstico , Miocarditis/etiología , Antibacterianos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Filgrastim/administración & dosificación , Filgrastim/efectos adversos , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Persona de Mediana Edad , Neutropenia/tratamiento farmacológico , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Esteroides/uso terapéutico , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/complicaciones , Neoplasias de la Mama Triple Negativas/tratamiento farmacológicoRESUMEN
The most challenging issue for breast cancer (BC) patients is metastasis to other organs because current therapies do not prevent or eliminate metastatic BC. Here, we show that SM-164, a small molecule inhibitor, which degrades inhibitor of apoptosis proteins (IAPs), eliminated early-stage metastases and reduced progression of advanced BC metastasis from MDA-MB-231 BC cells in bones and lungs of nude mice. Mechanistically, SM-164-induced BC cell death is TNFα-dependent, with TNFα produced by IL-4-polarized macrophages triggering MDA-MB-231 cell apoptosis in combination with SM-164. SM-164 also inhibited expression of RANKL, which mediates interactions between metastatic BC and host microenvironment cells and induces osteoclast-mediated osteolysis. SM-164 did not kill adriamycin-resistant BC cells, while adriamycin inhibited SM-164-resistant BC cell growth, similar to parental cells. We conclude that SM-164 is a promising therapeutic agent for early stage bone and lung metastasis from triple-negative breast cancer that should be given prior to conventional chemotherapy.
Asunto(s)
Neoplasias Óseas/prevención & control , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Proteínas Inhibidoras de la Apoptosis/antagonistas & inhibidores , Neoplasias Pulmonares/prevención & control , Triazoles/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Neoplasias Óseas/metabolismo , Neoplasias Óseas/secundario , Línea Celular Tumoral , Doxorrubicina/farmacología , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Ratones , Ratones Desnudos , Ligando RANK/metabolismo , Neoplasias de la Mama Triple Negativas/complicaciones , Neoplasias de la Mama Triple Negativas/metabolismoRESUMEN
PURPOSE: To evaluate fertility preservation outcomes in breast cancer women with different hormonal receptor profiles before oncological treatment. METHODS: The study population included women with a diagnosis of breast cancer who underwent fertility preservation from 2009 until 2018 at a university-affiliated tertiary hospital. Stimulation parameters and fertility preservation outcomes were compared among the following receptor-specific profile groups: (1) estrogen receptor positive (ER+) versus estrogen receptor negative (ER-), (2) triple-negative breast cancer (TNBC) versus estrogen and progesterone receptor positive (ER+/PR+), and (3) TNBC versus non-TNBC. Primary outcome was the total number of mature oocytes. Secondary outcomes included the number of retrieved oocytes, the peak estradiol level, and the number of follicles > 14 mm on the final oocyte maturation trigger day. RESULTS: A total of 155 cycles were included in the final analysis. These were divided into the exposure groups of ER+ (n = 97), ER- (n = 58), ER+/PR+ (n = 85), TNBC (n = 57), and non-TNBC (n = 98). Cycle outcomes revealed similar number of retrieved oocytes and follicles > 14 mm on the trigger day. Women with TNBC had significantly lower number of mature oocytes compared with those with ER + PR+ (7 (5-11) versus 9 (7-15); p = 0.02) and non-TNBC (7 (5-11) versus 9 (7-16); p = 0.01) status. Triple-negative breast cancer profile was associated with a significant reduction in the chance of developing over 10 mature oocytes (OR 0.41; 95% CI 0.19-0.92). CONCLUSION: Among the different hormonal receptor profiles in breast cancer, the TNBC subtype has a negative effect on fertility preservation outcomes.
Asunto(s)
Oocitos/crecimiento & desarrollo , Receptores de Estrógenos/genética , Receptores de Progesterona/genética , Neoplasias de la Mama Triple Negativas/genética , Adulto , Criopreservación , Estrógenos/genética , Femenino , Preservación de la Fertilidad , Humanos , Recuperación del Oocito/métodos , Oocitos/trasplante , Inducción de la Ovulación , Neoplasias de la Mama Triple Negativas/complicaciones , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) predicts decreased distant metastasis. However, most patients do not experience pCR, and other risk factors for distant metastasis after NAC are poorly characterized. This study investigated factors predictive of distant metastasis in TNBC without pCR after NAC. METHODS: Women with TNBC treated with NAC, surgery, and radiation therapy in 2000 through 2013 were reviewed. Freedom from distant metastasis (FFDM) was compared between patients with and without pCR using the Kaplan-Meier method. In patients without pCR, univariate and multivariable Cox analyses were used to determine factors predictive of distant metastasis. RESULTS: We identified 153 patients with median follow-up of 4.0 years (range, 0.5-14.0 years). After NAC, 108 had residual disease (pCR, 29%). Five-year FFDM was 98% and 55% in patients with and without pCR, respectively (P<.001). Factors independently predicting FFDM in patients without pCR were pathologic nodal positivity (hazard ratio, 3.08; 95% CI, 1.54-6.14; P=.001) and lymphovascular space invasion (hazard ratio, 1.91; 95% CI, 1.07-3.43; P=.030). Patients with a greater number of factors had worse FFDM; 5-year FFDM was 76.5% for patients with no factors (n=38) versus 54.9% and 27.5% for patients with 1 (n=44) and 2 factors (n=26), respectively (P<.001). CONCLUSIONS: Lack of pCR after NAC resulted in worse overall survival and FFDM, despite trimodality therapy. In patients with residual disease after NAC, pathologic lymph node positivity and lymphovascular space invasion predicted worse FFDM.
Asunto(s)
Terapia Neoadyuvante/métodos , Neoplasias de la Mama Triple Negativas/complicaciones , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the absence of estrogen and progesterone receptors (ER, PR) and lacking an overexpression of human epidermal growth factor receptor 2 (HER2). Apart from this lack of therapeutic targets, TNBC also shows an increased capacity for early metastasis and therapy resistance. Currently, many TNBC patients receive neoadjuvant chemotherapy (NACT) upon detection of the disease. With TNBC likely being driven at least in part by a cancer stem-like cell type, we wanted to evaluate the response of primary cancer stem cells (CSCs) to standard chemotherapeutics. Therefore, we set up a survival model using primary CSCs to mimic tumor cells in patients under chemotherapy. Breast cancer stem cells (BCSCs) were exposed to chemotherapeutics with a sublethal dose for six days. Surviving cells were allowed to recover in culture medium without chemotherapeutics. Surviving and recovered cells were examined in regard to proliferation, migratory capacity, sphere forming capacity, epithelial-mesenchymal transition (EMT) factor expression at the mRNA level, and cancer-related microRNA (miRNA) profile. Our results indicate that chemotherapeutic stress enhanced sphere forming capacity of BCSCs, and changed cell morphology and EMT-related gene expression at the mRNA level, whereas the migratory capacity was unaffected. Six miRNAs were identified as potential regulators in this process.
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Doxorrubicina/efectos adversos , Células Madre Neoplásicas/efectos de los fármacos , Paclitaxel/efectos adversos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Doxorrubicina/farmacología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Transición Epitelial-Mesenquimal , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células Madre Neoplásicas/patología , Paclitaxel/farmacología , Cultivo Primario de Células , Análisis de Supervivencia , Neoplasias de la Mama Triple Negativas/complicaciones , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
PURPOSE: Patients with triple-negative breast cancer experience high rates of recurrence after radiation, which may be facilitated by the recruitment of circulating tumor cells to proinflammatory microenvironments in the absence of lymphocytes. We hypothesized that patients with lymphopenia and elevated inflammatory hematologic markers after radiation therapy would have an increased risk of locoregional failure. METHODS AND MATERIALS: With approval, we retrospectively studied a cohort of women treated with adjuvant radiation therapy for stage II-III triple-negative breast cancer. We analyzed the relationship between post-radiation therapy neutrophil:lymphocyte ratio (NLR) and locoregional recurrence by using Cox regression. RESULTS: One-hundred thirty patients met inclusion criteria, and median follow-up time was 7.6 years. Patients with an NLR ≥3 had a higher rate of locoregional failure (P = .04) and lower overall survival (P = .04). After adjusting for stage (hazard ratio [HR], 5.5; P < .0001) and neoadjuvant chemotherapy (HR, 2.5; P = .0162), NLR was highly predictive of locoregional failure (HR, 1.4; P = .0009). NLR was also highly predictive of overall survival (HR, 1.3; P = .0007) after adjustment for stage and neoadjuvant chemotherapy. CONCLUSIONS: Innate peripheral inflammation after radiation therapy for triple-negative breast cancer in an immunocompromised setting may be a novel prognostic biomarker for locoregional recurrence, progression, and survival. This finding supports preclinical studies of post-radiation therapy inflammation-mediated tumor progression. Further studies are needed to confirm this finding and develop treatment strategies.
Asunto(s)
Progresión de la Enfermedad , Recurrencia Local de Neoplasia , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/radioterapia , Adulto , Anciano , Femenino , Humanos , Inflamación/complicaciones , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Riesgo , Neoplasias de la Mama Triple Negativas/complicaciones , Neoplasias de la Mama Triple Negativas/mortalidadRESUMEN
BACKGROUND: Metastatic breast cancer with obstructive jaundice due to para-aortic lymph node enlargement is an unusual case that poses a therapeutic challenge in determining a chemotherapy regimen. CASE REPORT: A 61-year-old woman presented with triple-negative left invasive ductal breast carcinoma with liver and pulmonary metastases. After receiving gemcitabine and carboplatin as the 4th-line treatment, chemotherapy was postponed due to an increased bilirubin level. Abdominal imaging revealed para-aortic lymph node metastases compressing the distal common hepatic duct. The patient then received capecitabine along with ursodeoxycholic acid. This relieved her jaundice after 8 cycles of chemotherapy, and radiologic evaluation revealed a complete resolution of the obstructive jaundice. CONCLUSION: This finding emphasizes the success of capecitabine regimen as a salvage therapy in a metastatic breast cancer patient with hyperbilirubinemia and opens up the possibility of optimizing systemic chemotherapy for metastatic obstructive jaundice in the setting of limited facility resources.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Capecitabina/uso terapéutico , Ictericia Obstructiva/etiología , Neoplasias de la Mama Triple Negativas/complicaciones , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Capecitabina/administración & dosificación , Capecitabina/efectos adversos , Femenino , Humanos , Ictericia Obstructiva/diagnóstico , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Radiografía , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/diagnósticoRESUMEN
BACKGROUND: An increasing number of cancer patients die of cardiovascular diseases. The cardiotoxicity of chemotherapy is particularly important in triple-negative breast cancer (TNBC) with limited therapeutic options. Cardiac autophagy is an important mechanism of cardiotoxicity. This research was aimed to investigate the cardiotoxicity of chemotherapy in TNBC, screen the susceptible population, and determine the relationship between cardiotoxicity and autophagy-related polymorphisms. METHODS: From a total of 2450 stage I-III TNBC patients, 147 met the inclusion criteria and finally recruited. Electrocardiography (ECG) was performed before most chemotherapy cycles, and echocardiography (UCG) was performed according to clinical needs. All ECG and UCG records were re-interpreted by cardiologists at the National Center for Cardiovascular Disease, Fuwai Hospital. According to the National Center for Biotechnology Information and the Catalog of Somatic Mutations in Cancer database, we selected 25 single nucleotide polymorphisms (SNPs) related to autophagy and genotyped the 147 TNBC patients. Paired-sample T tests, Chi squared tests, and logistic regression models were employed for the analysis. RESULTS: Only 46 (31.3%) patients had normal ECG records after every chemotherapy cycle. Among the 16 patients who underwent UCG, 2 (12.5%) had a reversible decrease of left ventricular ejection fraction. The use of anthracyclines and excessive alcohol consumption were risk factors of ECG abnormalities. With the continuation of chemotherapy, heart rate gradually increased. Anthracyclines were associated with QRS duration abnormalities (P = 0.043). After genotyping for 25 autophagy-related SNPs, we found that the G allele of autophagy-related 13 (ATG13) rs10838611 was significantly associated with ECG abnormalities (odds ratio = 2.258, 95% confidence interval = 1.318-3.869; P = 0.003). CONCLUSION: ECG abnormalities caused by chemotherapy are common in the real world. Autophagy-related SNPs are associated with chemotherapy-induced cardiotoxicity, thereby providing new evidence for autophagy as a cause of chemotherapy-induced cardiac damage.
Asunto(s)
Cardiotoxicidad/etiología , Quimioterapia Adyuvante/efectos adversos , ADN/genética , Genómica/métodos , Terapia Neoadyuvante/efectos adversos , Polimorfismo Genético/genética , Polimorfismo de Nucleótido Simple/genética , Neoplasias de la Mama Triple Negativas/complicaciones , Adulto , Anciano , Autofagia , Cardiotoxicidad/patología , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
Most triple negative breast cancers (TNBCs) are aggressively metastatic with a high degree of intra-tumoral heterogeneity (ITH), but how ITH contributes to metastasis is unclear. Here, clonal dynamics during metastasis were studied in vivo using two patient-derived xenograft (PDX) models established from the treatment-naive primary breast tumors of TNBC patients diagnosed with synchronous metastasis. Genomic sequencing and high-complexity barcode-mediated clonal tracking reveal robust alterations in clonal architecture between primary tumors and corresponding metastases. Polyclonal seeding and maintenance of heterogeneous populations of low-abundance subclones is observed in each metastasis. However, lung, liver, and brain metastases are enriched for an identical population of high-abundance subclones, demonstrating that primary tumor clones harbor properties enabling them to seed and thrive in multiple organ sites. Further, clones that dominate multi-organ metastases share a genomic lineage. Thus, intrinsic properties of rare primary tumor subclones enable the seeding and colonization of metastases in secondary organs in these models.
Asunto(s)
Metástasis de la Neoplasia/genética , Neoplasias de la Mama Triple Negativas/complicaciones , Neoplasias de la Mama Triple Negativas/genética , Animales , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Modelos Animales de Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Ratones , Ratones SCID , Metástasis de la Neoplasia/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To investigate the relationship between obesity and disease-free survival (DFS) and overall survival (OS) of triple-negative breast cancer. METHODS: Citations were searched in PubMed, Cochrane Library, and Web of Science. Random effect model meta-analysis was conducted by using Revman software version 5.0, and publication bias was evaluated by creating Egger regression with STATA software version 12. RESULTS: Nine studies (4412 patients) were included for DFS meta-analysis, 8 studies (4392 patients) include for OS meta-analysis. There were no statistical significances between obesity with DFS (Pâ=â.60) and OS (Pâ=â.71) in triple-negative breast cancer (TNBC) patients. CONCLUSION: Obesity has no impact on DFS and OS in patients with TNBC.