Therapy In Treatment Of Breast Cancer Research Articles

Optimisation of dispersive liquid-liquid microextraction for plasma sample preparation in bioanalysis of CDK4/6 inhibitors in therapeutic combinations for breast cancer treatment

Cyclin D dependent kinase 4 and 6 (CDK 4/6) inhibitors are novel anticancer drugs used in therapeutic combinations with endocrine therapy for breast cancer treatment. Their determination in patient plasma is of high interest as a prerequisite for possible therapeutic drug monitoring. Dispersive liquid-liquid microextraction (DLLME) shows great potential in bioanalytical sample preparation. Its simplicity and speed, along with the suitability for using small amounts of sample and hazardous solvents are some of its main advantages. However, its application on plasma samples is scarce and requires further development. The aim of this work was to explore the applicability of DLLME in the simultaneous extraction of six drugs of interest from human plasma, with an emphasis placed on achieving high extraction recoveries with low sample and solvent consumption. To tackle the low availability and amount of the plasma sample, as well as the complexity of the biological matrix, three novel DLLME modes are proposed: organic sample DLLME (OrS-DLLME), aqueous sample DLLME (AqS-DLLME), and a modified air-assisted DLLME (AA-DLLME). The extractant and disperser type and volume, volume ratios of all the components in the ternary system, effect of pH and salting out were optimised for all three proposed modes of DLLME. Optimised representative DLLME-HPLC-DAD-FLD method was validated and shown to be linear (R > 0.994), precise (RSD ≤13.8%, interday), accurate (bias −13.1–13.1%, interday) and robust (relative effect −3.34–6.08%). Simultaneous extraction of all six drugs with high recoveries (81.65–95.58%) was achieved. Sample volumes used were as low as 50–100 μL, with necessary organic solvent volumes in μL ranges. Greenness scores obtained using the AGREE software were between 0.63 and 0.66, demonstrating compliance with green analytical chemistry principles. Finally, the validated method was successfully applied on breast cancer patient plasma samples.

Abstract ED13-2: Radiation therapy and cardiovascular disease in breast cancer

Abstract This presentation will review the topic of radiation-induced cardiac dysfunction in patients with breast cancer. Specific areas of discussion include the a review of the cardiac-sparing techniques available for radiation therapy in breast cancer treatment; guidelines for the prevention, diagnosis, and treatment of cardiac dysfunction after radiation exposure in patients with breast cancer; and new areas of research in the field of radiation-induced cardiac disease in breast cancer. Emerging knowledge of how concurrent systemic therapies may interact with radiation to affect heart function will also be discussed. In addition, future directions in the field of radiation-induced heart dysfunction will be reviewed. Citation Format: Carmen Bergom. Radiation therapy and cardiovascular disease in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED13-2.

Preclinical In Vitro Investigation of MDM2 Inhibition in Combination with Antiangiogenic Therapy for Breast Cancer Treatment

Background: Combining antiangiogenic drugs with other chemotherapeutic drugs has been found to produce superior therapeutic outcomes and prevent drug resistance in a variety of cancers. Methods: Experimental assays such as the MTT assay, flow cytometry, western blotting, and qPCR have been used to evaluate the efficacy of combination therapy. Results: When compared to controls and monotherapies, the combination treatment of axitinib and idasanutlin demonstrated a substantial decrease in cell viability at lower doses, a significant decrease in migration, and a shift toward early and late apoptosis. This study examined major apoptotic, metastatic, and angiogenic factors, including MDM2, p21, BCL-2, BCL-XL, and MMP9, which have showed differential expressions at the protein and mRNA levels after combination. Axitinib and idasanutlin decreased tumorigenesis and migration in vitro in the MCF-7 cell line when compared to other chemotherapeutic medications. The suggested mechanisms of the antitumorigenic effect of the combination therapy may depend on its capacity to promote the production of apoptotic markers and reduce antiapoptotic markers. Conclusions: Treatments with axitinib and idasanutlin demonstrated effective therapeutic targeting of the primary angiogenic growth factor and, consequently, the pro-metastatic arbitrators. This will not only eliminate cancer cells but also stop other malignant processes and ultimately reduce the metastatic cascade.

A Review of Different Types of Liposomes and Their Advancements as a Form of Gene Therapy Treatment for Breast Cancer.

Breast cancer incidence and mortality rates have increased exponentially during the last decade, particularly among female patients. Current therapies, including surgery and chemotherapy, have significant negative physical and mental impacts on patients. As a safer alternative, gene therapy utilising a therapeutic gene with the potential to treat various ailments is being considered. Delivery of the gene generally utilises viral vectors. However, immunological reactions and even mortality have been recorded as side effects. As a result, non-viral vectors, such as liposomes, a system composed of lipid bilayers formed into nanoparticles, are being studied. Liposomes have demonstrated tremendous potential due to their limitless ability to combine many functions into a system with desirable characteristics and functionality. This article discusses cationic, anionic, and neutral liposomes with their stability, cytotoxicity, transfection ability, cellular uptake, and limitation as a gene carrier suitable for gene therapy specifically for cancer. Due to the more practical approach of employing electrostatic contact with the negatively charged nucleic acid and the cell membrane for absorption purposes, cationic liposomes appear to be more suited for formulation for gene delivery and therapy for breast cancer treatment. As the other alternatives have numerous complicated additional modifications, attachments need to be made to achieve a functional gene therapy system for breast cancer treatment, which were also discussed in this review. This review aimed to increase understanding and build a viable breast cancer gene therapy treatment strategy.

The Aryl Hydrocarbon Receptor Ligand 6-Formylindolo(3,2-b)carbazole Promotes Estrogen Receptor Alpha and c-Fos Protein Degradation and Inhibits MCF-7 Cell Proliferation and Migration

Introduction: Worldwide, breast cancer is the most common cancer in women and is the main cause of death among all neoplasia in this group. Luminal A breast cancer represents approximately 70% of all breast cancers and is treated with hormone therapies targeting estrogen receptor alpha (ERα). Unfortunately, patients develop drug resistance leading to recurrence of neoplasia due to estrogen-independent ERα reactivation. Therefore, it is crucial to identify new molecular targets downstream ERα signaling pathway that allows the implementation of better treatments to improve the outcome of breast cancer patients. Overexpression of c-Fos, an ERα gene target, has been associated with increased cell motility, malignancy, metastasis, and invasion while its neutralization results in decreased breast cancer tumorigenesis. The aryl hydrocarbon receptor (AHR) ligands halogenated and polycyclic aromatic hydrocarbons, highly toxic compounds, down regulate c-Fos and ERα levels. The present study aimed to evaluate whether 6-formylindolo(3,2-b)carbazole (FICZ), a no toxic AHR agonist, modifies c-Fos levels in MCF-7 mammary carcinoma cells as well as to determine its effects on cell proliferation and migration. In addition, the possible mechanism through which FICZ mediates c-Fos levels in MCF-7 cells was investigated. Methods: Initially, the effect of FICZ on c-Fos mRNA and protein levels in MCF-7 cells, untreated or treated with estradiol, was evaluated by qPCR and Western blot. 2,3,7,8-Tetrachloro-dibenzo-p-dioxin, an AHR prototype agonist, was used as a positive control. Next, we examined the effect of FICZ on MCF-7 cell proliferation and migration by cell counting, MTT, 3H-thymidine incorporation, and scratch-wound assays. Finally, the involvement of proteasome 26S on ERα and c-Fos protein degradation was investigated by the use of MG132 and Western blot. Results: The data show that FICZ treatment downregulates c-Fos mRNA and protein levels, most likely by promoting ERα proteasome degradation, blocking MCF-7 cell proliferation and migration. The results also demonstrate that liganded ERα was required for FICZ-mediated ERα degradation. Conclusions: Activation of AHR results in a decreased MCF-7 cell proliferation and migration by ERα and c-Fos down regulation. Targeting AHR might be a promising therapy for breast cancer treatment, particularly when estrogen-independent ERα reactivation presents.

T-type Ca2+ channels and their relationship with pre-neoplastic and neoplastic lesions in the human breast.

The expression of T-type voltage-dependent Ca2+ channels (Cav3) has been previously observed in breast cancer, but their expression and subcellular localization were not evaluated in pre-neoplastic lesions. Therefore, this work aimed to evaluate protein expression and subcellular localization of T-type channel isoforms in human breast tissue samples. Protein expressions of CaV3.1, CaV3.2, and CaV3.3 were evaluated by immunohistochemistry in breast without alteration, in proliferative non-neoplastic lesions, and in neoplastic ductal epithelial lesions of the human breast. CaV3.1, CaV3.2, and CaV3.3 nuclear expressions were decreased in advanced stages of neoplastic transformation, whereas CaV3.1 and CaV3.2 cytoplasmic expression increased. Also, the decrease in nuclear expression was correlated with an increase in cytoplasmic expression for CaV3.1 isoform. The change in CaV3 protein expression and subcellular localization are consistent with the neoplastic transformation stages of mammary epithelial cells, evident in early neoplastic lesions, such as ductal carcinomas in situ. These results suggest a possible involvement of CaV3 in the carcinogenic processes and could be considered as a potential pharmacological target in new therapies for breast cancer treatment.

Photodynamic therapy in breast cancer treatment.

Breast cancer is a serious public problem in modern society. Photodynamic therapy (PDT) is increasingly used in modern medicine. Currently, PDT is an innovative method of treating breast cancer. Irreversible damage to neoplastic tissues is associated with the use of physicochemical processes. Generating cytotoxic reactive oxygen species [singlet oxygen (1O2)] is leading to tumor cell death. At the same time, valuable information can be extracted from breast cancer cells. Photogenerated 1O2 is the major factor responsible for cell necrosis during PDT. 1O2 can react rapidly intracellularly with all organic substances. The use of photodynamic therapy on tissues in vitro creates conditions for testing various types of solutions and implementing them in in vivo treatment. This article is a review of recent advances in PDT for treatment of breast cancer. PDT is a novel cancer diagnostic and cancer treatment therapy. Therefore, an understanding of the possibility to generate a toxic form of 1O2 is necessary. The knowledge gained from the basics of PDT in vitro can be useful in biomedical applications in vivo. The current literature mentions PDT in the treatment of cancers located very deep within the human body. Therefore, the development of agents used to deliver 1O2 to the deep cancerous tissue is a new challenge which can have an efficient impact on this discipline. This review covers the literature between 2000-2022.

The Combination Therapy in Breast Cancer Treatment

Breast cancer (BC) is the cancer that most commonly diagnosed worldwide, which result in the cause of cancer-related deaths. The majority of BC diagnoses were HR+ and HER2- (71%) and HER2+BC accounts for 10-20% of all breast tumors. There is no magic drug for the treatment of breast cancer at present. Endocrine therapy is the preferable treatment for HR+/HER2- metastatic breast cancer. However, long-term use may produce certain drug resistance. Tucatinib, as a HER2 inhibitor, can be combined with chemotherapy to treat HER2+BC.Combination therapy can offers patients the opportunity to derive the maximum benefit from treatment, at the same time, it can minimize or eliminate relapse, drug resistance and toxic effects and thus the BC patients can have a good quality of life. This paper discussed the combination therapy of endocrine therapy or tucatinib with other drugs and compared their advantages and disadvantages in breast cancer therapy, providing better choice for clinical treatment of BC.

Treatment of chest wall osteoradionecrosis with a contralateral breast Y-V flap: a case report

Chest wall osteoradionecrosis, one of the most serious complications of radiation therapy for breast cancer treatment, is usually treated by wide debridement followed by coverage with a well-vascularized flap. However, the extent of radiation-induced injury and limits in performing wide resection of the injured bones often present challenges in treatment. Herein, we present our experience treating chest wall osteoradionecrosis with a contralateral breast Y-V flap in an 81-year-old woman. She was diagnosed with chest wall osteoradionecrosis and had grade 3 ptotic breasts. Redundant contralateral breast tissue was used for reconstruction to cover the wound. The flap was elevated in the subfascial plane after an inverted-T incision was made in the lower pole and inframammary fold of the contralateral breast, while preserving the perforators of the left lateral thoracic artery. The flap was spread using the Y-V advancement fashion to cover the wound. The patient was discharged 2 weeks after surgery. At 19 months postoperation, there were no complications or recurrence. The patient was satisfied with the short recovery time and surgical results. The contralateral breast Y-V flap allows simple and quick reconstruction, potentially expanding the available treatment options and therefore increasing flexibility in choosing a treatment plan for patients.

Nanoparticles-based Chemo-Phototherapy Synergistic Effects for Breast Cancer Treatment: A Systematic Review

Despite the promising outcomes, conventional therapies for breast cancer treatment suffer from apparent limitations, including systemic toxicity, adverse reactions, and tumor recurrence. In light of that, therapy that combines chemo-phototherapy with nanoparticles is of immense value as it provides an alternative that hope exerts better outcomes. This review systematically assesses publications between 2010 and 2022, focusing on the application of nanoparticles in chemo-phototherapy for breast cancer. A detailed search was conducted in Scopus, PubMed, and WoS, and relevant studies within the 11 years were selected. Final 18 out of 40 initial papers were selected, including studies on in vivo analysis. Detailed information on chemo-phototherapy effects, drug cargo design, the toxicity of nanomaterials, and immunomodulatory effects were extracted and discussed. This review demonstrates the promising anticancer activity of combined synergistic effects for breast cancer management.

Solubility Enhancement and Characterization of Tamoxifen Citrate Using Co-crystallization

Tamoxifen citrate (TC) is one of the anti-estrogen agents which has low solubility in the water. As TC is still used as the main therapy in breast cancer treatment, modifications are still being made to increase the solubility of TC for a successful treatment. In this research, co-crystallization of TC was performed using Nicotinamide (NIC), Isonicotinamide (ISO), Saccharin (SAC), Aspartame (ASP), and Benzoic Acid (BNZ) as a coformer with the molar ratio of 1:1, 1:2, and 2:1. Co-crystal was prepared by solvent drop grinding (SDG) and solvent evaporation (SE) methods using methanol. The results of the solubility test showed that TC-NIC and TC-ISO co-crystals with a 1:2 molar ratio made using the SDG and SE methods gave the best results. Meanwhile, the best dissolution test results were shown by TC-ISO co-crystals with a ratio of 1:2. Based on the characterization of physical stability, the SDG method resulted in more stable TC co-crystals than the SE method. Therefore, in this case, the SDG method could be more advantageous to be used for development in the field of co-crystallization.

Abstract P4-11-16: Feasibility and patient satisfaction with a smartphone application to improve medication adherence among patients with breast cancer

Abstract Introduction: Low medication adherence is associated with worse outcomes among patients with breast cancer (BC). Retrospective studies have shown decreased survival in patients with BC who are non-adherent to endocrine therapy, but less is known about newer oral cancer therapies and the impact on adherence to medications for chronic non-cancer conditions. New strategies to improve global medication adherence are needed. We assessed the feasibility and patient satisfaction of the Medisafe smartphone application in the initial phase of a trial to increase global medication adherence. Methods: Patients treated with oral anti-neoplastic therapy for treatment of BC were eligible. Enrolled patients received individualized instruction on Medisafe app installation and use. The Medisafe app sends patients push notification reminders at the times specified for each of their standing oral medications. Patients self-report whether each medication dose was taken or missed directly in the app. Patients were followed for 12 weeks. The primary endpoint was feasibility, defined as completion of the 12-week study intervention. uMARS (end-user Mobile Application Rating Scale) questionnaires were used to assess patient satisfaction with the Medisafe app at week 12. The objective feedback component of the uMARS contains 16 questions and includes 4 objective quality subscales: engagement, functionality, aesthetics, and information quality. Each question is answered on a 1-5 scale (5 indicates highest satisfaction), and mean responses were used to calculate an overall satisfaction score and a satisfaction score for each subsection. Results: Between July 2020 and July 2021, 58 patients were enrolled. The mean participant age was 58 years (range 31 - 87). As of June 30,2020 20 patients reached the 12-week endpoint. Of these patients, 18 (90%) completed the 12-week intervention. Of the 17 patients who completed the uMARS questionnaire, the mean overall uMARS score of the Medisafe app was 3.8 (SD 0.6). Table 1 displays the results for the uMARS subscales, which include a mean functionality score of 4.0 (SD 0.7) and mean information quality score of 4.1 (SD 0.7). Notably, 70.6% of participants reported that the app was easy to use and clearly designed, and 76.5% reported that the app’s content was appropriately designed for its specific target audience. Of the 13 patients who reported viewing educational information within the app, 84.6% reported that the information seemed credible. Almost half of patients (43.8%) reported that the app increased their awareness of the importance of addressing health behavior. Conclusions: Our early findings suggest that the use of a smartphone application to improve medication adherence among patients with cancer is feasible, with a high rate of participant completion. Furthermore, high patient-reported satisfaction with the Medisafe app suggests acceptability to promote long-term behavior change. Table 1: Patient Reported Satisfaction with the Medisafe App Evaluated Assessed by the Objective Feedback Component of the uMARS (end-user Mobile Application Rating Scale) Questionnaire at Week 12 (n=17) uMARS Objective ScoreMean± SDOverall3.8± 0.6 Engagement3.2± 0.8 Functionality4.0± 0.7 Performance4.2± 0.8 Ease of use4.1± 1.0 Aesthetics4.0± 0.6 Information Quality4.1± 0.7 Quality of info3.8± 0.8 Visual info4.3± 0.9 Credibility4.5± 0.8 Citation Format: Melissa K Accordino, Sophie Ulene, Erin Honan, Meghna S Trivedi, Katherine D Crew, Erik Harden, Cynthia Law, Dawn L Hershman. Feasibility and patient satisfaction with a smartphone application to improve medication adherence among patients with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-16.

TRAIL Therapy for Breast Cancer Treatment by Employing Lipopolymer mRNA Delivery

Promising improvements in synthesis of stable and nonimmunogenic messenger RNA (mRNA) have enhanced the potential for mRNA in in situ production of therapeutic proteins. In this study, we explored the delivery of an mRNA expressing the tumor necrosis factor-related apoptosis-inducing ligand protein (mTRAIL) into breast cancer cells and human bone marrow stromal cells (hBMSCs) by using aliphatic lipid-modified small molecular weight polyethylenimine (PEI) carriers. The duration and extent of TRAIL secretion after mRNA delivery were dependent on the cell type, but mRNA delivery consistently showed earlier and higher protein expression compared with plasmid DNA delivery. Higher TRAIL-induced cytotoxicity and apoptosis induction were evident in breast cancer cells after mTRAIL transfection. In addition, hBMSCs transfected with mTRAIL were able to effectively kill breast cancer cells after coculture. mTRAIL delivery with the lipopolymers resulted in significant inhibition of breast cancer tumor growth in a xenograft model in mice. We conclude that an mRNA-based approach to TRAIL expression is a highly promising approach to retard the growth of breast cancer cells.

Anhydroicaritin Inhibits EMT in Breast Cancer by Enhancing GPX1 Expression: A Research Based on Sequencing Technologies and Bioinformatics Analysis.

Background: Breast cancer (BC) is the leading cause of cancer-related deaths among women worldwide. The application of advanced technology has promoted accurate diagnosis and treatment of cancer. Anhydroicaritin (AHI) is a flavonoid with therapeutic potential in BC treatment. The current study aimed to determine AHI’s mechanism in BC treatment via RNA sequencing, comprehensive bioinformatics analysis, and experimental verification. Methods: Network pharmacology and MTT (3-(4,5)-dimethylthiazolyl-3,5- diphenyltetrazolium bromide) experiments were conducted to first confirm AHI’s anti-BC effect. RNA sequencing was performed to identify the genes affected by AHI. Differential expression analysis, survival analysis, gene set enrichment analysis, and immune infiltration analysis were performed via bioinformatics analysis. Western blot analysis, reverse transcription–polymerase chain reaction (RT-PCR) experiment, molecular docking, and drug affinity responsive target stability (DARTS) experiments were also performed to confirm AHI’s direct effect on glutathione peroxidase 1 (GPX1) expression. Confocal immunofluorescence analysis was conducted to verify AHI’s effect on the occurrence and development of epithelial–mesenchymal transition (EMT). Finally, BC nude mouse xenografts were established, and AHI’s molecular mechanism on BC was explored. Results: Network pharmacology results demonstrated that AHI’s therapeutic targets on BC were related to the proliferation, invasion, and metastasis of BC cells. AHI significantly inhibited the proliferation of 4T1 and MDA-MB-231 BC cells in the MTT experiments. RNA sequencing results showed that AHI upregulated the GPX1 expression in the 4T1 and MDA-MB-231 BC cells. Next, bioinformatics analysis revealed that GPX1 is less expressed in BC than in normal breast tissues. Patients with high GPX1 expression levels tended to have prolonged overall survival and disease-free survival than patients with low GPX1 expression levels in BC. Western blot and RT-PCR experiments revealed that AHI increased the protein and mRNA levels of GPX1. Molecular docking and DARTS experiments confirmed the direct binding combination between AHI and GPX1. After the evaluation of the EMT scores of 1,078 patients with BC, we found a potential anti-BC role of GPX1 possibly via suppression of the malignant EMT. The confocal immunofluorescence analysis showed that AHI increased E-cadherin expression levels and reduced vimentin expression levels in BC cells. Animal experiments showed that AHI significantly inhibited tumor growth. AHI also inhibited EMT by enhancing GPX1 and caspase3 cleavage, hence inhibiting EMT markers (i.e., N-cadherin and vimentin) and Ki-67. Conclusion: GPX1 plays a critical role in BC, which may be a biomarker for the prognosis. In addition, AHI suppressed EMT by increasing GPX1 expression, which may serve as a potential therapy for BC treatment.

Baicalin; a promising chemopreventive agent, enhances the antitumor effect of 5-FU against breast cancer and inhibits tumor growth and angiogenesis in Ehrlich solid tumor

Despite considerable advances in cancer treatment, chemotherapy remains a cornerstone in breast cancer therapy. Therefore, reducing chemoresistance and adverse effects of chemotherapy is a priority. In this regard, Baicalin (BA) is the dominant natural flavonoid extracted from the roots of Scutellaria baicalensis showed fascinating antitumor activity in many types of cancers, including breast cancer. The present study aimed to explore the chemopreventive and antitumor action of baicalin alone and in combination with 5-FU in addition to its ability to enhance the antitumor effect of 5-FU on breast cancer using the Ehrlich solid tumor-mice model. Materials and methodsA total of 70 female mice were divided into seven groups (1st group, saline group; 2nd group, DMSO group; 3rd group, BA+EST group; 4th group, EST group; 5th group, EST+5-FU; 6th group, EST+BA group; 7th group, EST+5-FU+BA).tumors were assessed by weight and histopathological examination. Inflammation, angiogenesis, and apoptosis were examined by ELISA, qRT-PCR, and immunohistochemical examinations. Resultsshowed that pre-treatment with baicalin and treatment with baicalin and/or 5-FU significantly reduced inflammation and angiogenesis indicated by suppression of NF-kB/ IL-1β and VEGF amplification loop with marked elevation in apoptosis indicated by up-regulation of apoptotic caspase-3, pro-apoptotic p53, Bax and downregulation of anti-apoptotic Bcl-2. ConclusionBA is a promising preventive or adjuvant therapy in breast cancer treatment with 5-FU mainly via cooperative inhibition of inflammation, angiogenesis, and triggering apoptotic cell death.

The Present and Future of Neoadjuvant Endocrine Therapy for Breast Cancer Treatment.

Simple SummaryThe treatment of breast cancer has evolved considerably over the last two decades, leading toward individualized disease management. Hormone-sensitive breast cancers constitute the vast majority of cases and endocrine therapy is the mainstay of their treatment. On the other hand, neoadjuvant or pre-surgical treatments provide a number of advantages for tumor management. In this review we will discuss the existing evidence on neoadjuvant endocrine therapy, as well as its possible future indications.Endocrine therapy (ET) has established itself as an efficacious treatment for estrogen receptor-positive (ER+) breast cancers, with a reduction in recurrence rates and increased survival rates. The pre-surgical approach with chemotherapy (NCT) has become a common form of management for large, locally advanced, or high-risk tumors. However, a good response to NCT is not usually expected in ER+ tumors. Good results with primary ET, mainly in elderly women, have encouraged studies in other stages of life, and nowadays neoadjuvant endocrine treatment (NET) has become a useful approach to many ER+ breast cancers. The aim of this review is to provide an update on the current state of art regarding the present and the future role of NET.

Cardiac substructure exposure in breast radiotherapy: a comparison between intensity modulated proton therapy and volumetric modulated arc therapy

Introduction Proton therapy for breast cancer treatment reduces cardiac radiation exposure. Left-sided breast cancer patients with indication for internal mammary chain (IMC) irradiation are most at risk of radiation-induced cardiotoxicity. This study aims to evaluate in this situation the potential dosimetric benefit of intensity modulated proton therapy (IMPT) over volumetric modulated arc therapy (VMAT) at the cardiac substructure level. Materials and methods Cardiac substructures were retrospectively delineated according to ESTRO guidelines on the simulation CT scans of fourteen left-sided breast cancer patients having undergone conserving surgery and adjuvant locoregional free-breathing (FB-) or deep inspiration breath-hold (DIBH-) VMAT with internal mammary chain irradiation. IMPT treatment was re-planned on the simulation CT scans. Mean doses to cardiac substructures were retrieved and compared between VMAT treatment plans and IMPT simulation plans. Pearson correlation coefficients were calculated between mean doses delivered to cardiac substructures using these two techniques. Results Mean doses to all cardiac substructures were significantly lower with IMPT than with VMAT. Regardless of the irradiation technique, the most exposed cardiac substructure was the mid segment of the left anterior descending coronary artery (LADCA). Pearson correlation coefficients between mean doses to cardiac substructures were usually weak and statistically non-significant for IMPT; mean heart dose (MHD) only correlated with mean doses delivered to the right ventricle, to the mid segment of the right coronary artery (RCA) and, to a lesser extent, to the LADCA. Conclusion The dosimetric benefit of IMPT over conformal photon therapy was consistently observed for all cardiac substructures. MHD may not be a reliable dosimetric parameter for precise cardiac exposure evaluation when planning IMPT.

Angiosarcoma associated with radiation therapy after treatment of breast cancer. Retrospective study on ten years

PurposeThe breast sarcoma induced by radiation therapy is rare but increasing, given the increased long-term survival of patients receiving radiation therapy. Fibrosarcoma, histiocytofibroma and angiosarcoma are the most common breast sarcoma. Angiosarcoma is the most common after breast cancer treated by radiation therapy, often diagnosed too late, with a severe prognosis and a high rate of recurrence. However, because of the low incidence of angiosarcoma associated with radiation therapy (AAR), the benefit of radiation therapy in breast cancer treatment outweighs the risk to develop angiosarcoma. The aim of this study is to evaluate these rare cases of AAR diagnosed in eastern Belgium in comparison to the data from the literature. Patients and methodsNine cases of AAR after radiation for breast ductal carcinoma were included in this retrospective study. AAR was diagnosed according to Cahan criteria between January 2007 and December 2016. Latency, incidence, management and prognosis are comparable to the literature. Results, conclusionThe median latency was 10 (4–24) years, the incidence of AAR in the East Belgian area was 0.09% of the patients irradiated on the same period. Patients were treated by surgery with wide local excision with or without reconstructive surgery, without radiotherapy and chemotherapy treatment. Kaplan-Meier analysis showed median overall survival of 61.8 months, patient survival of 55.6% at one year and 29.6% at five years. With the constant progress of medicine and its technologies, it would be possible to limit the occurrence of AAR or to diagnose it at an earlier stage.

Gold Nanoparticles Mediated Drug-Gene Combinational Therapy for Breast Cancer Treatment.

BackgroundCancer is a complex heterogeneous disease to which singular modes of treatment mostly fail to produce a desired therapeutic efficacy. Targeting different cellular pathways using combinational therapies has been gaining popularity in cancer treatment, with the added benefit of reducing dosage and side effects.MethodsA gold nanoparticle-mediated drug delivery nanoplatform was developed for co-delivery of doxorubicin and polo-like kinase 1 (PLK1) siRNA. Gold nanoparticles were coated with polyethyleneimine to facilitate assembly of PLK1 on the surface. Doxorubicin was loaded on nanoparticles through a pH-sensitive linker with a thiol group at one terminal end for controlled release.ResultsThe therapeutic efficiency of this co-delivery system was evaluated in 2D and 3D cultured systems. The reduced IC50 value clearly demonstrated the synergistic effect of combined drug and gene delivery over their individual delivery in a cancer treatment model.ConclusionThis study may provide an adaptable, facile platform to investigate drug-siRNA combinations for cancer inhibition.

Efek Sitotoksik Ekstrak dan Fraksi Umbi Paku Atai Merah (Angiopteris ferox Copel) Terhadap Sel Kanker Payudara T47D

The use of natural products has been widely used as a resource of new bioactive chemical compounds. One of them is the Paku Atai Merah (Angiopteris ferox Copel) tuber which has long been used empirically by the Dayak tribe of East Kalimantan as an anti-cancer. The purpose of this study was to determine the anticancer cytotoxic activity of the extract and fractions of Paku Atai Merah tuber against T47D breast cancer cells in vitro. Extract of Paku Atai Merah tubers was obtained by maceration method using ethanol solvent until obtained the ethanolic extract then fractionated using various solvents to obtain n-hexane, ethyl acetate, and aqueous-ethanol fractions. The cytotoxic effect was carried out based on the MTT assay. Phytochemical screening tests showed positive results for the presence of flavonoid, phenolic, tannin, saponin and steroid compounds. The results of the cytotoxic activity study showed that the ethyl acetate fraction had moderate cytotoxic activity in T47D cancer cells with an IC50 value of 84.8 µg/ml. Ethanol extract (513.06 µg/ml) and n-Hexane frsction (881.97 µg/ ml) were also included in the weak category. This study indicates that ethyl acetate fraction can be developed as a supportive therapy for breast cancer treatment.