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The Society of Surgeons of Pakistan and The Society of Surgical Oncology of Pakistan with factions from various major centres comprising of surgical oncology, medical and radiation oncology collaborated to reach consensus on breast cancer management guidelines and a framework of "good practice" minimum standards of care. The aim of the task force was to enhance treatment standards, which have a direct correlation with improving patient mortality and morbidity and long-term survival whilst taking into consideration economic limitations of access to leading centers of excellence as well as minimum expertise required in health care. These multidisciplinary guidelines, whilst not exhaustive, aim to provide an algorithm of care for breast cancer patients at tertiary care centres and district level hospitals to provide most appropriate treatment.
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Neoplasias de la Mama , Cirujanos , Oncología Quirúrgica , Humanos , Femenino , Neoplasias de la Mama/cirugía , Pakistán , ConsensoRESUMEN
AIM: The goal of this study was to determine whether a delay in starting treatment via surgery or neoadjuvant chemotherapy is related to a decrease in cancer-specific survival (CSS) in women with operable breast cancer (BrCr). BACKGROUND: Limited medical infrastructure and a lack of cancer prevention awareness in low- and middle-income countries have caused high BrCr incidence and mortality rates. METHODS: We analyzed a retrospective cohort of 720 women treated at a single center from 2005 to 2012. CSS estimates were obtained by the Kaplan-Meier method. A Cox model of proportional risks was performed to obtain the risk of dying from BrCr. We also obtained the risk according to the category of treatment initiation. RESULTS: Women with locally advanced stages and without hormone receptor expression were more likely to initiate treatment after 45 days. Patients in Stage IIIA had a 78.1% survival if treatment was initiated before 45 days (95% CI, 0.70-0.84) and 63.6% survival if treatment was started after 45 days (95% CI, 0.44-0.78; p < 0.001). Patients in Stage IIIB had a 62.9% survival if treatment was initiated before 45 days (95% CI, 0.53-0.72) and 57.4% survival if treatment started after 45 days (95% CI, 0.31-0.89; p < 0.001). Prognostic factors in which lower survival was recognized were Stage IIIA, Stage IIIB, treatment initiation after 45 days, and triple-negative tumors. CONCLUSIONS: The initiation of treatment within the first 45 days of diagnosis of BrCr in women portends better survival compared with those who began treatment longer than 45 days from diagnosis.
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Cancer treatments with cytotoxic drugs have been shown to cause bone loss. However, effects on bone are less clear for ErbB-targeting tyrosine kinase inhibitors or their combination use with cytotoxic drugs. This study examined the effects of individual or combination treatments with breast cancer drugs lapatinib (a dual ErbB1/ErbB2 inhibitor) and paclitaxel (a microtubule-stabilizing cytotoxic agent) on bone and bone marrow of rats. Wistar rats received lapatinib (240 mg/kg) daily, paclitaxel (12 mg/kg) weekly, or their combination for 4 weeks, and effects on bone/bone marrow were examined at the end of week 4. Microcomputed tomographical structural analyses showed a reduction in trabecular bone volume in tibia following the lapatinib, paclitaxel or their combination treatments ( P < 0.05). Histomorphometry analyses revealed marked increases in bone marrow adipocyte contents in all treatment groups. Reverse transcription polymerase chain reaction gene expression studies with bone samples and cell culture studies with isolated bone marrow stromal cells showed that the all treatment groups displayed significantly reduced levels of osterix expression and osteogenic differentiation potential but increased expression levels of adipogenesis transcription factor peroxisome proliferator-activated receptor γ. In addition, these treatments suppressed the expression of Wnt10b and/or increased expression of Wnt antagonists (secreted frizzled-related protein 1, Dickkopf-related protein 1 and/or sclerostin). Furthermore, all treatment groups showed increased numbers of bone-resorbing osteoclasts on trabecular bone surfaces, although only the lapatinib group displayed increased levels of osteoclastogenic signal (receptor activator of nuclear factor κΒ ligand/osteoclastogenesis inhibitor osteoprotegrin expression ratio) in the bones. Thus, inhibiting ErbB1 and ErbB2 by lapatinib or blocking cell division by paclitaxel or their combination causes significant trabecular bone loss and bone marrow adiposity involving a switch in osteogenesis/adipogenesis potential, altered expression of some major molecules of the Wnt/ß-catenin signalling pathway, and increased recruitment of bone-resorbing osteoclasts.
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Adiposidad/efectos de los fármacos , Médula Ósea/metabolismo , Resorción Ósea/inducido químicamente , Lapatinib/farmacología , Paclitaxel/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Moduladores de Tubulina/farmacología , Animales , Proteínas Morfogenéticas Óseas/genética , Quimioterapia Combinada , Expresión Génica/efectos de los fármacos , Marcadores Genéticos/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Lapatinib/administración & dosificación , Lapatinib/efectos adversos , Proteínas de la Membrana/genética , PPAR gamma/genética , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Ratas , Ratas Wistar , Survivin/genética , Factores de Transcripción/genética , Moduladores de Tubulina/administración & dosificación , Moduladores de Tubulina/efectos adversos , Proteínas Wnt/genética , Vía de Señalización Wnt/efectos de los fármacosRESUMEN
Although bone marrow and bone toxicities have been reported in breast cancer survivors, preventative strategies are yet to be developed. Clinical studies suggest consumption of long chain omega-3 polyunsaturated fatty acids (LCn3PUFA) can attenuate age-related bone loss, and recent animal studies also revealed benefits of LCn3PUFA in alleviating bone marrow and bone toxicities associated with methotrexate chemotherapy. Using a female rat model for one of the most commonly used anthracycline-containing breast cancer chemotherapy regimens (adriamycin + cyclophosphamide) (AC) chemotherapy, this study investigated potential effects of daily LCn3PUFA consumption in preserving bone marrow and bone microenvironment during chemotherapy. AC treatment for four cycles significantly reduced bone marrow cellularity and increased marrow adipocyte contents. It increased trabecular bone separation but no obvious changes in bone volume or bone cell densities. LCn3PUFA supplementation (375 mg/100 g/day) attenuated AC-induced bone marrow cell depletion and marrow adiposity. It also partially attenuated AC-induced increases in trabecular bone separation and the cell sizes and nuclear numbers of osteoclasts formed ex vivo from bone marrow cells isolated from AC-treated rats. This study suggests that LCn3PUFA supplementation may have beneficial effects in preventing bone marrow damage and partially protecting the bone during AC cancer chemotherapy.
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Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Ciclofosfamida/efectos adversos , Suplementos Dietéticos , Doxorrubicina/efectos adversos , Ácidos Grasos Omega-3/farmacología , Animales , Antineoplásicos/efectos adversos , Huesos/diagnóstico por imagen , Huesos/efectos de los fármacos , Huesos/metabolismo , Huesos/patología , Microambiente Celular/efectos de los fármacos , Femenino , Osteoclastos/metabolismo , Sustancias Protectoras/farmacología , Ratas , Factores Sexuales , Microtomografía por Rayos XRESUMEN
PURPOSE: Anthracyclines (including doxorubicin) are still the backbone of commonly used breast cancer chemotherapy regimens. Despite increasing use of doxorubicin and cyclophosphamide (AC) combinations for treating breast cancer, their potential to cause adverse skeletal effects remains unclear. METHODS: This study examined the effects of treatments with the AC regimen on bone and bone marrow in adult female rats. RESULTS: AC treatment for four cycles (weekly intravenous injection of 2 mg/kg doxorubicin and 20 mg/kg cyclophosphamide) resulted in a reduced volume of trabecular bone at the metaphysis, which was associated with reduced serum levels of 25-hydroxy vitamin D3 and alkaline phosphatase. Reductions in densities of osteocytes and bone lining cells were also observed. In addition, bone marrow was severely damaged, including a severe reduction in bone marrow cellularity and an increase in marrow adipocyte content. Accompanying these changes, there were increases in mRNA expression of adipogenesis regulatory genes (PPARγ and FABP4) and an inflammatory cytokine (TNFα) in metaphysis bone and bone marrow. CONCLUSIONS: This study indicates that AC chemotherapy may induce some bone loss, due to reduced bone formation, and bone marrow damage, due to increased marrow adiposity. Preventive strategies for preserving the bone and bone marrow microenvironment during anthracycline chemotherapy warrant further investigation.
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Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Médula Ósea/efectos de los fármacos , Ciclofosfamida/toxicidad , Doxorrubicina/toxicidad , Fémur/efectos de los fármacos , Tibia/efectos de los fármacos , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipocitos/patología , Fosfatasa Alcalina/sangre , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Médula Ósea/metabolismo , Médula Ósea/patología , Calcifediol/sangre , Células Cultivadas , Microambiente Celular , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Esquema de Medicación , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo , Femenino , Fémur/metabolismo , Fémur/patología , Inyecciones Intravenosas , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoclastos/patología , Osteocitos/efectos de los fármacos , Osteocitos/metabolismo , Osteocitos/patología , PPAR gamma/genética , PPAR gamma/metabolismo , Ratas Sprague-Dawley , Tibia/metabolismo , Tibia/patología , Factores de Tiempo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The introduction of anthracyclines to adjuvant chemotherapy has increased survival rates among breast cancer patients. Cyclophosphamide, epirubicin and 5-fluorouracil (CEF) combination therapy is now one of the preferred regimens for treating node-positive breast cancer due to better survival with less toxicity involved. Despite the increasing use of CEF, its potential in causing adverse skeletal effects remains unclear. Using a mature female rat model mimicking the clinical setting, this study examined the effects of CEF treatment on bone and bone marrow in long bones. Following six cycles of CEF treatment (weekly intravenous injections of cyclophosphamide at 10 mg/kg, epirubicin at 2.5 mg/kg and 5-flurouracil at 10 mg/kg), a significant reduction in trabecular bone volume was observed at the metaphysis, which was associated with a reduced serum level of bone formation marker alkaline phosphatase (ALP), increased trends of osteoclast density and osteoclast area at the metaphysis, as well as an increased size of osteoclasts being formed from the bone marrow cells ex vivo. Moreover, a severe reduction of bone marrow cellularity was observed following CEF treatment, which was accompanied by an increase in marrow adipose tissue volume. This increase in marrow adiposity was associated with an expansion in adipocyte size but not in marrow adipocyte density. Overall, this study indicates that six cycles of CEF chemotherapy may induce some bone loss and severe bone marrow damage. Mechanisms for CEF-induced bone/bone marrow pathologies and potential preventive strategies warrant further investigation.
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Adiposidad/efectos de los fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Células de la Médula Ósea/metabolismo , Médula Ósea/metabolismo , Osteoclastos/metabolismo , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Médula Ósea/patología , Células de la Médula Ósea/patología , Ciclofosfamida/efectos adversos , Ciclofosfamida/farmacología , Epirrubicina/efectos adversos , Epirrubicina/farmacología , Femenino , Fluorouracilo/efectos adversos , Fluorouracilo/farmacología , Osteoclastos/patología , Ratas , Ratas Sprague-DawleyRESUMEN
PURPOSE: To assess the efficacy of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-based textural analysis in predicting response to chemotherapy in a cohort of breast cancer patients. MATERIALS AND METHODS: In all, 100 patients were scanned on a 3.0T HDx scanner immediately prior to neoadjuvant chemotherapy treatment. A software application to use texture features based on co-occurrence matrices was developed. Texture analysis was performed on precontrast and 1-5 minutes postcontrast data. Patients were categorized according to their chemotherapeutic response: partial responders corresponding to a decrease in tumor diameter over 50% (40) and nonresponders corresponding to a decrease of less than 50% (4). Data were also split based on factors that influence response: triple receptor negative phenotype (TNBC) (22) vs. non-TNBC (49); node negative (45) vs. node positive (46); and biopsy grade 1 or 2 (38) vs. biopsy grade 3 (55). RESULTS: Parameters f2 (contrast), f4 (variance), f10 (difference in variance), f6 (sum average), f7 (sum variance), f8 (sum entropy), f15 (cluster shade), and f16 (cluster prominence) showed significant differences between responders and partial responders of chemotherapy. Differences were mainly seen at 1-3 minutes postcontrast administration. No significant differences were found precontrast administration. Node +ve, high grade, and TNBC are associated with poorer prognosis and appear to be more heterogeneous in appearance according to texture analysis. CONCLUSION: This work highlights that textural differences between groups (based on response, nodal status, and triple negative groupings) are apparent and appear to be most evident 1-3 minutes postcontrast administration. The fact that significant differences for certain texture parameters and groupings are consistently observed is encouraging.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/estadística & datos numéricos , Reconocimiento de Normas Patrones Automatizadas/estadística & datos numéricos , Adulto , Anciano , Neoplasias de la Mama/epidemiología , Estudios de Cohortes , Medios de Contraste , Femenino , Humanos , Aumento de la Imagen/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Reconocimiento de Normas Patrones Automatizadas/métodos , Prevalencia , Pronóstico , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y Especificidad , Resultado del Tratamiento , Reino UnidoRESUMEN
Chemoresistance has been a major challenge in the treatment of patients with breast cancer. The diverse omics platforms and small sample sizes reported in the current studies of chemoresistance in breast cancer limit the consensus regarding the underlying molecular mechanisms of chemoresistance and the applicability of these study findings. Therefore, we built two transcriptome datasets for patients with chemotherapy-resistant breast cancersone comprising paired transcriptome samples from 40 patients before and after chemotherapy and the second including unpaired samples from 690 patients before and 45 patients after chemotherapy. Subsequent conventional pathway analysis and new subpathway analysis using these cohorts uncovered 56 overlapping upregulated genes (false discovery rate [FDR], 0.018) and 36 downregulated genes (FDR, 0.016). Pathway analysis revealed the activation of several pathways in the chemotherapy-resistant tumors, including those of drug metabolism, MAPK, ErbB, calcium, cGMP-PKG, sphingolipid, and PI3K-Akt, as well as those activated by Cushing's syndrome, human papillomavirus (HPV) infection, and proteoglycans in cancers, and subpathway analysis identified the activation of several more, including fluid shear stress, Wnt, FoxO, ECM-receptor interaction, RAS signaling, Rap1, mTOR focal adhesion, and cellular senescence (FDR < 0.20). Among these pathways, those associated with Cushing's syndrome, HPV infection, proteoglycans in cancer, fluid shear stress, and focal adhesion have not yet been reported in breast cancer chemoresistance. Pathway and subpathway analysis of a subset of triple-negative breast cancers from the two cohorts revealed activation of the identical chemoresistance pathways.
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Purpose: Cancer is the leading challenge to human health since the dawn of early Egyptian manuscripts, where they found tumour from fossils in the modernized 20th century. Increasing rate of incidence and death from cancer in the past few years is thought provoking. Among all type of cancers, breast cancer is very common among women and diverse in character. Drug resistance is the challenging aspect for traditional chemotherapy. Methods: Data was collected from online platform without any time restriction. After screening and evaluation, 66 articles were considered for this study. This review is a summarized collection of information from published studies on human genes associated with drug resistance in breast cancer treatment. Results: Analysis of these findings highlights the importance of MAP kinase and ABC gene families in creating resistance barriers. Genes involved in cell cycle alteration, apoptosis, and hippo pathway were also linked with drug resistance particularly in breast cancer. Conclusion: The exact mechanism of chemotherapy resistance is still unresolved and unexplained the drug resistance seen in breast cancer patients were multifactorial. Drug induced up regulation or down regulation of genes contributes unusual protein expression and ultimately leads to resistance. The ultimate focus of this review is to identify the genes having pivotal role in chemotherapy resistance in breast cancer.
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The application of nanomedicine represents an innovative approach for the treatment in the modern field of cancer chemotherapy. In the present research work, tamoxifen citrate loaded nanolipid vesicles were prepared conjugated with phosphoethanolamine as the linker molecule, and the specific antibody was tagged with the linker molecule on the bilayer surface of the vesicles. The main objective of this study is to determine the efficacy and biological behavior of antibody conjugated nanoliposome in breast cancer cell lines. Percentage of drug loading and loading efficiency was done and their results were compared to theoretical drug loading. The average diameter of those vesicles was within the 100 nm range, which is revealed in FESEM and TEM images and their lamellarity was observed in cryo-TEM images. The hydrodynamic diameter was done by particle size analysis and the surface charge was determined by the zeta potential parameter. Predominant cellular uptake was observed for antibody conjugated nanolipid vesicles in MCF-7 and MDA-MB-453 human breast cancer cell lines. A cellular apoptosis assay was conducted by flow cytometer (FACS). All experimental data would be more beneficial for the treatment of breast cancer chemotherapy. Further studies are warranted to investigate the efficacy and safety of antibody conjugated nanolipid vesicles in vivo for breast cancer animal model.
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OBJECTIVE: To evaluate the clinical efficacy of Huangqi Sijunzi decoction (HQSJZD) for treating cancer-related fatigue (CRF) of spleen and stomach Qi deficiency type after chemotherapy in patients with breast cancer. METHODS: A total of 94 breast cancer patients who developed CRF of spleen and stomach Qi deficiency type after chemotherapy were randomized into chemotherapy group (n=47) and traditional Chinese medicine (TCM) + chemotherapy group (n=47). The patients in chemotherapy group received the AC or EC regimen and non-drug interventions including psychological counseling, and those in TCM + chemotherapy group received oral administration of HQSJZD in addition to chemotherapy for 21 days as a treatment cycle, after which improvement of fatigue was assessed using Modified Piper Fatigue Scale. The active ingredients and targets of HQSJZD were screened using the TCM System Pharmacology Analysis Platform (TCMSP); the CRF- and breast cancer-related disease targets were retrieved based on data from the GeneCards, NCBI gene and OMIM databases to construct the component-target network and the protein-protein interaction (PPI) network. GO functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes KEGG pathway enrichment analysis of the target genes were performed to construct the component-disease-pathway-target biological network. The binding strength of the major drug ingredients and CRF key targets were predicted using AutoDock software. RESULTS: The scores for somatic fatigue, emotional fatigue and cognitive fatigue, along with the overall fatigue score, showed more significant improvements in TCM+chemotherapy group than in chemotherapy group (P < 0.001), and the response rate reached 89.4% in the combined treatment group. We identified 250 targets for HQSJZD, 2653 CRF-related genes, 15 329 breast cancer-related genes and 161 prescription-disease intersected targets, from which topological analysis identified 66 potential key targets. GO and KEGG enrichment analyses predicted multiple pathways related with the disease. Molecular docking results suggested that the core ingredients of HQSJZD showed high affinities to the key targets AKT1, CASP3, IL6, JUN and VEGFA, among which AKT1 might be the most important target for HQSJZD to treat CRF. CONCLUSION: HQSJZD can obviously improve CRF symptoms in breast cancer patients possibly by regulating multiple signaling pathways including PI3K-Akt through AKT1.
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Neoplasias de la Mama , Medicamentos Herbarios Chinos , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Femenino , Humanos , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Farmacología en Red , Fosfatidilinositol 3-QuinasasRESUMEN
BACKGROUND: This study was conducted to determine the frequency of amenorrhea after chemotherapy among breast cancer patients". METHODS: Total 201 premenopausal females (having menstruation during the past 6 months at the time of diagnosis) of age 15-45 years and had confirmed diagnosis of breast cancer requiring chemotherapy were included in the study using non-probability consecutive sampling technique. Amenorrhea within 6 months after the completion of chemotherapy was labelled as chemotherapy induced amenorrhea. Data was entered and analysed using SPSS-23. RESULTS: The mean age of the patients was reported as 37.06±5.68 years. Majority of the females were married (86.6%) & multigravida (81.1%). Most of the patients (23.9%) received neoadjuvant chemotherapy followed by surgery and radiotherapy. A total of 129 patients received Adriamycin plus cyclophosphamide followed by paclitaxel as chemotherapy regimen. Out of 201 females, 184 (91.5%) experienced amenorrhea after start or completion of chemotherapy. CONCLUSIONS: The frequency of CIA was very high among breast cancer patients in our study, long term follow-up is needed to see input of CIA on future fertility.
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Amenorrea , Antineoplásicos , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Amenorrea/inducido químicamente , Amenorrea/epidemiología , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Femenino , Humanos , PremenopausiaRESUMEN
BACKGROUND: Better quality of life (QOL) is associated with longer survival in cancer patients. This study evaluated the QOL and relationship between functioning and symptoms among female breast cancer patients before chemotherapy. METHODS: Cross-sectional study was conducted by including 74 participants attending a cancer clinic. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(s)-Core30 was applied for assessing QOL. It was composed of three domains namely global health status/QOL, functioning (includes five categories) and symptoms (includes nine categories). Pearson correlation and multiple linear regression were performed to find the relationship between functioning and symptoms in participants. The study was approved by Institutional Review Board of Defence Services Medical Research Centre, Myanmar with approval number IRB/2018/34. RESULTS: Global health status/QOL score was fair (61.8±20.1). Among the five categories of functioning, cognitive functioning score (83.6±19.8) was the highest and role functioning score (66.4±29.3) was the lowest. Among symptoms, insomnia score (29.3±30.7) was the highest and diarrhoea score (0.9±5.4) was the lowest. When Pearson correlation was performed, functioning and symptoms were negatively correlated. Fatigue had significant (p<0.001) moderate negative correlation with physical functioning, role functioning and emotional functioning, whereas pain with role functioning (p<0.001). When linear regression was performed, nausea & vomiting was the strongest predictor for impaired global health status/QOL (p<0.05), while fatigue was the strongest predictor for impairment in all five categories of functioning (p<0.05). CONCLUSIONS: Functioning and symptoms were negatively correlated in breast cancer patients. Nausea & vomiting and fatigue were the strongest predictors for impaired QOL.
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Neoplasias de la Mama/complicaciones , Estado de Salud , Calidad de Vida , Neoplasias de la Mama/fisiopatología , Neoplasias de la Mama/psicología , Cognición , Estudios Transversales , Emociones , Fatiga/etiología , Fatiga/fisiopatología , Fatiga/psicología , Femenino , Humanos , Mianmar , Náusea/etiología , Dolor/etiología , Rendimiento Físico Funcional , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Encuestas y Cuestionarios , Vómitos/etiologíaRESUMEN
We report three cases of heart failure (HF) associated with the use of cytotoxic drugs such as anthracycline, cyclophosphamide, and 5-fluorouracil in the treatment of breast cancer in Nigerians. The patients had systolic and diastolic HF: HF with reduced ejection fraction and preserved ejection fraction. The prevalence of breast cancer is increasing across Africa, and cytotoxics are some of the most common and best drugs used during management. The cardiotoxicity caused by these drugs limits their use as chemotherapeutic agents. Cytotoxic-induced HF is a preventable and manageable cause of cardiovascular disease (CVD) in Nigeria and Africa. This article discusses the pathophysiology of cytotoxic-induced HF and presents the risk factors that impair cardiovascular function. The importance of proper assessment and the prophylactic and therapeutic measures in the management of cytotoxic-induced HF are emphasized. The peculiar challenges in the management of cytotoxic-induced HF in Nigeria were also discussed. The need for early involvement of cardiologists by oncologists to improve on the chemotherapeutic and cardiovascular outcome in the management of patients with breast cancer was stressed. Perhaps, it is time to birth a new discipline of cardiooncology in Nigeria.
Résumé Nous rapportons trois cas d'insuffisance cardiaque (IC) associés à l'utilisation de médicaments cytotoxiques tels que l'anthracycline, le cyclophosphamide et le 5-fluorouracile dans le traitement du cancer du sein chez les Nigérians. Les patients avaient une HF systolique et diastolique: HF avec une fraction d'éjection réduite et une fraction d'éjection préservée. La prévalence du cancer du sein augmente à travers l'Afrique et les cytotoxiques sont parmi les médicaments les plus courants et les meilleurs utilisés pendant la prise en charge. La cardiotoxicité causée par ces médicaments limite leur utilisation comme agents chimiothérapeutiques. L'IC induite par les cytotoxiques est une cause évitable et gérable de maladies cardiovasculaires (MCV) au Nigéria et en Afrique. Cet article traite de la physiopathologie de l'IC induite par cytotoxique et présente les facteurs de risque qui altèrent la fonction cardiovasculaire. L'importance d'une évaluation appropriée et des mesures prophylactiques et thérapeutiques dans la gestion de l'IC induite par les cytotoxiques est soulignée. Les défis particuliers de la gestion de l'IC induit par des cytotoxiques au Nigeria ont également été discutés. La nécessité d'une implication précoce des cardiologues par les oncologues pour améliorer les résultats chimiothérapeutiques et cardiovasculaires dans la prise en charge des patientes atteintes d'un cancer du sein a été soulignée. Peut-être est-il temps de donner naissance à une nouvelle discipline de cardiooncologie au Nigeria.
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Antraciclinas/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Ciclofosfamida/efectos adversos , Fluorouracilo/efectos adversos , Insuficiencia Cardíaca/inducido químicamente , Anciano , Antraciclinas/uso terapéutico , Cardiotoxicidad , Ciclofosfamida/uso terapéutico , Femenino , Fluorouracilo/uso terapéutico , Humanos , Persona de Mediana EdadRESUMEN
Tumor-targeting nanomaterial-based chemotherapeutic drug delivery systems have been shown to represent an efficacious approach for the treatment of cancer because of their stability in blood circulation and predictable delivery patterns, enhanced tumor-selective drug accumulation, and decreased toxicity to normal tissues. The cell-surface transmembrane glycoprotein CD44 binds to the extracellular domain of hyaluronic acid (HA), and is overexpressed in breast, ovarian, lung, and stomach cancer. In this study, an HA-based nano-carrier incorporating doxorubicin (DOX) and cisplatin (CDDP) was synthesized as a CD44-targeting anti-cancer drug delivery system, and its tumor inhibition effects against CD44+ breast cancer cells were evaluated in vitro and in vivo. These dual drug-loaded HA micelles (HA-DOX-CDDP) exhibited significantly enhanced drug release under acidic conditions, and showed higher cellular uptake and stronger cellular growth inhibition than free drugs against 4T1 (CD44+) breast cancer cells. In contrast, no significant differences in growth inhibition and cellular uptake were observed between HA-DOX-CDDP and free drugs in NIH-3T3 (CD44-) control cells. Furthermore, HA-DOX-CDDP micelles exhibited stronger inhibitory effects and lower systemic toxicity than free drugs in a 4T1 mammary cancer-bearing mouse model, as determined using immunofluorescence and histological analyses. Therefore, HA-DOX-CDDP micelles represent a promising drug delivery system that exhibits acid-sensitive drug release, CD44-targeted delivery, and excellent biocompatibility and biodegradation. These properties resulted in excellent tumor accumulation and reduced adverse effects, indicating that HA-DOX-CDDP micelles have promising potential applications in chemotherapy for breast cancer.
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OBJECTIVE: To evaluate the clinical efficacy and partial action mechanism of mild moxibustion combined with salt-separated moxibustion for gastrointestinal discomfort caused by chemotherapy for breast cancer. METHODS: A total of 48 patients were randomly divided into an observation group and a control group, 24 cases in each group. The patients in the control group were treated with intravenous infusion of tropisetron hydrochloride (5 mg), once a day for three days; the patients in the observation group were additionally treated with mild moxibustion at Zusanli (ST 36), Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6) and salt-separated moxibustion at Shenque (CV 8), 15 min per treatment, once a day for 7 days. Before treatment and on the 7th day of chemotherapy, the levels of pepsinogenâ (PGâ ), pepsinogenâ ¡ (PGâ ¡), the ratio of PGâ to PGâ ¡ (PGR) and gastrin 17 (G-17) in serum were measured. Before treatment and on the 3rd, 5th, 7th day of chemotherapy, the gastrointestinal reactions (nausea, vomiting, constipation, diarrhea) were compared between the two groups. RESULTS: On the 7th day of chemotherapy, the serum levels of PGâ , PGâ ¡and G-17 in the observation group were lower than those in the control group (P<0.05), and the difference in the level of PGR in serum between the observation group and the control group was not statistically significant (P>0.05). The total scores of nausea, vomiting and constipation during chemotherapy in the observation group were significantly lower than those in the control group (all P<0.05). CONCLUSION: The mild moxibustion combined with salt-separated moxibustion could effectively improve the symptoms of nausea, vomiting and constipation caused by chemotherapy in patients with breast cancer, and its mechanism may be related to the down-regulation of the levels of PGâ , PGâ ¡ and G-17 in serum.
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Neoplasias de la Mama , Moxibustión , Puntos de Acupuntura , Neoplasias de la Mama/terapia , Humanos , Náusea , Resultado del TratamientoRESUMEN
OBJECTIVES: The communication patterns between clinician and patient, described as the patient centeredness of care (PCC), may be a critically important etiology of breast cancer (BC) racial disparity. The purpose of this prospective, comparative pilot study was to qualitatively explore and code for PCC during the clinical visit of women undergoing BC chemotherapy and compare by race. METHODS: Age-matched Black and White women were recruited. Audio recordings of clinical visits conducted prior to any cycle (except first) chemotherapy infusion were obtained and transcribed. Transcripts were blindly reviewed by three independent coders assigning PCC scores, ranging from 1 to 5, with lower scores indicating better PCC. Consensus was reached among reviewers via discussion. RESULTS: Dyads consisted of five Black (mean age 47) and five White (mean age 45) women undergoing BC chemotherapy. Twenty-four recordings were analyzed, 13 White and 11 Black. For all 22 PCC items, the mean scores were worse for Black women with significant differences (compared by chi-square analysis) noted for 6/22 items (27%). CONCLUSIONS: Qualitatively exploring clinician and patient communication patterns during the chemotherapy clinical visits informs the understanding of racial differences for symptom assessment, reporting, and management. These pilot findings inform future research exploring racial disparity in cancer treatment dose intensity.
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Negro o Afroamericano/psicología , Neoplasias de la Mama/etnología , Comunicación , Disparidades en Atención de Salud/etnología , Atención Dirigida al Paciente , Relaciones Médico-Paciente , Población Blanca/psicología , Adulto , Negro o Afroamericano/estadística & datos numéricos , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Investigación Cualitativa , Población Blanca/estadística & datos numéricosRESUMEN
Micelles are promising a nano drug carrier for cancer therapy. However, their application is often limited due to the instability of them in vivo. Herein, we reported the development of stereocomplex micelle (SCM) based on amphiphilic dextran-block-polylactide (Dex-b-PLA) that could improve the stability of micelles, reduce the early release of loaded drugs and target the breast cancer through the enhanced permeability and retention (EPR) effect for enhanced breast cancer therapy. The SCM were fabricated from the equimolar mixture of the enantiomeric Dex-b-PLA copolymers. Paclitaxel (PTX) as a model anti breast cancer drug was loaded in the SCM, noted as SCM/PTX. Transmission electron microscopy (TEM) and dynamic laser scattering (DLS) showed the diameter of SCM/PTX was below100 nm, which was suitable sizes for the EPR effect. The release kinetics of SCM/PTX exhibited that the release of PTX was obviously slow down and showed constant release. In the in vitro antitumor test, the SCM/PTX could effectively suppress the viability of 4T1 cells, which was demonstrated by the MTT assay. Moreover, the SCM/PTX could reduce the distribution of PTX at normal organs and obviously increase the accumulation of PTX at tumor sites. The circulation time of SCM/PTX was also obviously enhanced compared to free PTX. In the in vivo antitumor test, the SCM/PTX effectively inhibited the progression of 4T1 breast cancer in the orthotopic mouse model, as demonstrated by decreased tumor growth and increased apoptosis and necrosis areas within tumor tissues. In addition, the toxic side effects of PTX was also alleviated in the SCM/PTX group. This study introduced a stable micelle system that passive targeted the tumor for enhanced breast cancer therapy.
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Antineoplásicos Fitogénicos/química , Neoplasias de la Mama/tratamiento farmacológico , Dextranos/química , Portadores de Fármacos/química , Paclitaxel/química , Poliésteres/química , Animales , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacología , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Micelas , Paclitaxel/farmacología , Tamaño de la Partícula , Propiedades de Superficie , Distribución TisularRESUMEN
MICROABSTRACT: Women treated with chest radiation for Hodgkin lymphoma (HL) have significantly higher risk of developing breast cancer, and little is known about how these patients tolerate chemotherapy for breast cancer. This small retrospective study identified 15 patients, noting that these patients tolerate proposed chemotherapy regimens for breast cancer in rates similar to those without prior HL and therapeutic radiation. PURPOSE: Women treated for Hodgkin lymphoma (HL) with chest radiation have significantly higher risk of developing breast cancer, and little is known about how these patients tolerate chemotherapy for breast cancer. METHODS: Women with breast cancer diagnosed from 1986-2015 after radiation for HL were identified from hospitals and clinics in St. Paul and Minneapolis, Minnesota. Patient, tumor and treatment characteristics, and clinical outcomes were abstracted from medical records and summarized using descriptive statistics. Chemotherapy was defined as tolerated if all scheduled doses and cycles were completed without deviation from the initial plan, with lack of grade 3 or higher toxicity attributable to chemotherapy in categories including blood, cardiac, gastrointestinal, fatigue and pain. RESULTS: Forty-two patients with breast cancer and prior radiation for HL were identified, 15 of which received chemotherapy for breast cancer. We noted 75% tolerability of taxane-based and 100% tolerability of anthracycline-based chemotherapy, suggesting that most patients with prior radiation for HL tolerate chemotherapy for breast cancer. A subset of patients (N = 7) in this study were also treated with chemotherapy for HL prior to breast cancer diagnosis, and 86% (6 of 7) also tolerated chemotherapy for breast cancer. CONCLUSIONS: Treatment of breast cancer is strongly influenced by prior treatment of HL. Although this study was small and did not meet statistical significance, the data suggest that these patients tolerate proposed chemotherapy regimens for breast cancer in rates similar to those without prior HL and therapeutic radiation. Larger studies comparing specific chemotherapy dosing schedules are needed to address this complicated population.
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Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Neoplasias de la Mama/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Neoplasias Inducidas por Radiación/tratamiento farmacológico , Neoplasias Primarias Secundarias/tratamiento farmacológico , Adulto , Antraciclinas/administración & dosificación , Antraciclinas/uso terapéutico , Antraciclinas/toxicidad , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Antineoplásicos/toxicidad , Neoplasias de la Mama/etiología , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Hidrocarburos Aromáticos con Puentes/toxicidad , Supervivientes de Cáncer/estadística & datos numéricos , Estudios de Cohortes , Femenino , Humanos , Minnesota , Neoplasias Inducidas por Radiación/etiología , Neoplasias Primarias Secundarias/etiología , Proyectos Piloto , Radioterapia/efectos adversos , Estudios Retrospectivos , Taxoides/administración & dosificación , Taxoides/uso terapéutico , Taxoides/toxicidadRESUMEN
In the areas of chemotherapy, targeted therapy and immunotherapy, several interesting and clinically relevant data were presented at the 2017 San Antonio Breast Cancer Symposium (SABCS). This short review focuses on dose-dense and/or sequential administration of adjuvant chemotherapy, provides an update on targeted therapies for HER2-positive and triple-negative breast cancer and summarizes new results in the field of immunotherapy.