Breast Cancer Management Consensus By The Society of Surgeons and Surgical Oncology Society of Pakistan.

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.

Chemotherapeutic Resistance Genes of Breast Cancer Patients - An Overview.

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.

Subpathway Analysis of Transcriptome Profiles Reveals New Molecular Mechanisms of Acquired Chemotherapy Resistance in Breast Cancer.

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.

[Huangqi Sijunzi decoction for treating cancer-related fatigue in breast cancer patients: a randomized trial and network pharmacology study].

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.

Mechanistic Approach of Nano Carriers for Targeted in Cancer Chemotherapy: A Newer Strategy for Novel Drug Delivery System.

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.

Huangqi Sijunzi decoction for treating cancer-related fatigue in breast cancer patients: a randomized trial and network pharmacology study / 南方医科大学学报

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.

Quality Of Life And Relationship Between Functioning And Symptoms Of Female Patients With Breast Cancer Before Chemotherapy In A Cancer Clinic At Yangon,Myanmar.

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.

Development of a Hyaluronic Acid-Based Nanocarrier Incorporating Doxorubicin and Cisplatin as a pH-Sensitive and CD44-Targeted Anti-Breast Cancer Drug Delivery System.

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.

Amenorrhea After Chemotherapy In Breast Cancer Patient.

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.

Cytotoxic-induced heart failure among breast cancer patients in Nigeria: A call to prevent today's cancer patients from being tomorrow's cardiac patients.

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.

Provider delay in treatment initiation and its influence on survival outcomes in women with operable breast cancer.

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.

[Clinical efficacy and action mechanism of mild moxibustion combined with salt-separated moxibustion for gastrointestinal response in breast-cancer chemotherapy patients].

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 pepsinogenⅠ(PGⅠ), pepsinogenⅡ (PGⅡ), the ratio of PGⅠto PGⅡ (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 PGⅠ, PGⅡand 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 PGⅠ, PGⅡ and G-17 in serum.

Clinical efficacy and action mechanism of mild moxibustion combined with salt-separated moxibustion for gastrointestinal response in breast-cancer chemotherapy patients / 中国针灸

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 pepsinogenⅠ(PGⅠ), pepsinogenⅡ (PGⅡ), the ratio of PGⅠto PGⅡ (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 PGⅠ, PGⅡand G-17 in the observation group were lower than those in the control group (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 <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 PGⅠ, PGⅡ and G-17 in serum.

Stereocomplex micelle loaded with paclitaxel for enhanced therapy of breast cancer in an orthotopic mouse model.

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.

Individual or combination treatments with lapatinib and paclitaxel cause potential bone loss and bone marrow adiposity in rats.

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.

Exploring Racial Differences in Patient Centeredness of Care (PCC) During Breast Cancer (BC) Chemotherapy Clinical Visits.

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.

Analysis of time interval between breast cancer diagnosis and treatment / Análise do tempo decorrido entre diagnóstico e tratamento do câncer de mama

Introduction: Breast cancer has a good prognosis when treated early. However, the mortality rate in Brazil is still high. The time interval between radiological suspicion and diagnosis/treatment impacts the survival. Methods: This is a retrospective crosssectional study that assessed patients treated at a reference center, with abnormal breast imaging findings and subsequent confirmation of breast cancer, from January 2011 to June 2015. We reviewed variables related to the dates of the abnormal test result, first mastology appointment, biopsy, surgery, and the start of chemotherapy ­ when indicated. Time intervals were compared using the Friedman and Kruskal-Wallis tests with the software SPSS® 23.0. Results: We analyzed 65 patients. The median time between the abnormal test result and first mastology appointment was 35 days; between first mastology appointment and biopsy, 31 days; between biopsy and surgery, 85 days; and between surgery and chemotherapy, 137 days. The last two intervals showed significant differences (p<0.001). Discussion: Breast cancer patients had a significant delay until surgery and the start of chemotherapy. Early integration of the multidisciplinary team involved in this process and internal audits are necessary to optimize time intervals.

Introdução: O câncer de mama apresenta bom prognóstico quando tratado precocemente, entretanto, a mortalidade no Brasil continua elevada. O tempo entre suspeita radiológica e diagnóstico e tratamento tem impacto na sobrevida. Métodos: Foi realizado um estudo transversal e retrospectivo que avaliou pacientes atendidas em centro de referência com imagem mamária alterada e posterior confirmação de câncer de mama de janeiro de 2011 a junho e 2015. Foram revisadas variáveis relacionadas às datas do exame alterado, da primeira consulta, da biópsia, da cirurgia e do início da quimioterapia, quando indicada. Os intervalos de tempo foram comparados pelos testes Friedman e Kruskal-Wallis, pelo programa SPSS® 23.0. Resultados: Foram analisadas 65 pacientes. A mediana de tempo entre exame alterado e primeira consulta foi 35 dias, entre consulta na mastologia e biópsia foi 31 dias, entre biópsia e cirurgia foi 85 dias e entre cirurgia e quimioterapia foi 137 dias. Foram observadas diferenças significativas nos dois últimos intervalos (p<0,001). Discussão: As pacientes com câncer de mama apresentaram atraso significativo até a cirurgia e até o início da quimioterapia. Há necessidade da integração precoce da equipe multidisciplinar implicada nesse processo e auditorias internas a fim de otimizar os intervalos de tempo

SABCS 2017: update on chemotherapy, targeted therapy, and immunotherapy.

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.

A pilot study evaluating chemotherapy tolerability for breast cancer patients who have received prior treatment and chest radiation for Hodgkin Lymphoma.

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.

Long Chain Omega-3 Polyunsaturated Fatty Acid Supplementation Protects Against Adriamycin and Cyclophosphamide Chemotherapy-Induced Bone Marrow Damage in Female Rats.

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.