Breast Cancer : Basic and Clinical Research最新文献

{"title":"Evaluation of the Potential Diagnostic Role of the Lnc-MIAT, miR-29a-3p, and FOXO3a ceRNA Networks as Noninvasive Circulatory Bioindicator in Ductal Carcinoma Breast Cancer.","authors":"Shokufeh Razi,&nbsp;Hossein Mozdarani,&nbsp;Roudabeh Behzadi Andouhjerdi","doi":"10.1177/11782234231184378","DOIUrl":"https://doi.org/10.1177/11782234231184378","url":null,"abstract":"<p><strong>Background: </strong>Over the last few decades, tremendous progress has been achieved in the early detection and treatment of breast cancer (BC). However, the prognosis remains unsatisfactory, and the underlying processes of carcinogenesis are still unclear. The purpose of this research was to find out the relationship between myocardial infarction-associated transcript (<i>MIAT</i>), <i>FOXO3a</i>, and <i>miRNA29a-3p</i> and evaluated the expression levels in patients compare with control and their potential as a noninvasive bioindicator in whole blood in BC.</p><p><strong>Methods: </strong>Whole blood and BC tissue are taken from patients before radiotherapy and chemotherapy. Total RNA was extracted from BC tissue and whole blood to synthesize complementary DNA (cDNA). The expression of <i>MIAT, FOXO3a</i>, and <i>miRNA29a</i>-<i>3p</i> was analyzed by the quantitative reverse transcription-polymerase chain reaction (RT-qPCR) method and the sensitivity and specificity of them were determined by the receiver operating characteristic (ROC) curve. Bioinformatics analysis was used to understand the connections between <i>MIAT, FOXO3a</i>, and <i>miRNA29a</i>-<i>3p</i> in human BC to develop a ceRNA (competitive endogenous RNA) network.</p><p><strong>Results: </strong>We identified that in ductal carcinoma BC tissue and whole blood, <i>MIAT</i> and <i>FOXO3a</i> were more highly expressed, whereas <i>miRNA29a</i>-<i>3p</i> was lower compared with those in nontumor samples. There was a positive correlation between the expression levels of <i>MIAT, FOXO3a</i>, and <i>miRNA29a</i>-<i>3p</i> in BC tissues and whole blood. Our results also proposed <i>miRNA29a</i>-<i>3p</i> as a common target between <i>MIAT</i> and <i>FOXO3a</i>, and we showed them as a ceRNA network.</p><p><strong>Conclusions: </strong>This is the first study that indicates <i>MIAT, FOXO3a</i>, and <i>miRNA29a</i>-<i>3p</i> as a ceRNA network, and their expression was analyzed in both BC tissue and whole blood. As a preliminary assessment, our findings indicate that combined levels of <i>MIAT, FOXO3a</i>, and <i>miR29a</i>-<i>3p</i> may be considered as potential diagnostic bioindicator for BC.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"17 ","pages":"11782234231184378"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c1/e5/10.1177_11782234231184378.PMC10331106.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10300877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Side Effects and Its Management in Adjuvant Endocrine Therapy for Breast Cancer: A Matter of Communication and Counseling.","authors":"Aina Johnsson,&nbsp;Kerstin Fugl-Meyer,&nbsp;Pal Bordas,&nbsp;Janet Åhman,&nbsp;Anna Von Wachenfeldt","doi":"10.1177/11782234221145440","DOIUrl":"https://doi.org/10.1177/11782234221145440","url":null,"abstract":"<p><strong>Objective: </strong>Women with a newly diagnosed hormone receptor-positive breast cancer are offered adjuvant endocrine therapy (AET). Although the treatment reduces the risk of relapse and death not all women are adherent to it. Many factors, including the therapy's menopausal side effects, can adversely affect adherence to the treatment. This study explores the extent to which women treated with AET perceived that health care providers addressed their side effects.</p><p><strong>Methods: </strong>Ten focus groups were set up, containing between four to nine women. In total, 58 women participated in the study-45 from the Stockholm metropolitan region and 13 from the scarcely populated Norrbotten region. The interviews were analyzed using qualitative content analysis with an inductive approach.</p><p><strong>Results: </strong>The women were usually satisfied with the care they received from the health care providers. However, their experiences were more complex when it came to their satisfaction with the care in terms of the menopausal side effects of therapy, sexuality in particular. The participants reported that their healthcare providers rarely asked about sex life-related side effects of the treatment.</p><p><strong>Conclusions: </strong>Health care providers need to communicate and consult about issues related to their patients' sex lives following their breast cancer diagnosis and during their treatment.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"17 ","pages":"11782234221145440"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10623248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of Breast Cancer Progression after Treatment in the Western Region of Saudi Arabia.","authors":"Majed Ramadan,&nbsp;Rwiah Alsiary,&nbsp;Noor Alsaadoun,&nbsp;Noara Alhusseini,&nbsp;Muhammad Raihan Sajid,&nbsp;Noor Mohamed Hamed,&nbsp;Tarek Ziad Arabi,&nbsp;Belal Nedal Sabbah","doi":"10.1177/11782234231158270","DOIUrl":"https://doi.org/10.1177/11782234231158270","url":null,"abstract":"<p><strong>Background: </strong>The risk of breast cancer progression is one of the most difficult factors to predict as it is studied in different populations, patient groups, or time frames, resulting in conflicting estimates of incidence rates reported in the literature. The purpose of this study is to identify predictive factors for breast cancer recurrences in a sample of the Middle Eastern population.</p><p><strong>Methodology: </strong>A cohort retrospective study included all eligible breast cancer patients at the National Guard Health Affairs (NGHA) Hospital in Jeddah, Western region, from 2015 to 2021. Our primary outcome was the progression status of the patients; we adjusted for demographic, clinical, and molecule characteristics of the population. From 2015 to 2021, there were 319 patients diagnosed with breast cancer. Multiple logistic regression analysis was used to estimate predictors of breast cancer progression.</p><p><strong>Results: </strong>One of five breast cancer patients had breast cancer progression (20.83%), while 66.15% of the progression patients were between the ages of 41-65. In multivariate analysis, age, progesterone receptor (PR), family history, and tumor size were significant predictors of breast cancer progression. The age group of 20-40 years was a protective predictor of breast cancer progression, patients in the young age group were less likely to be diagnosed with progression (OR = 0.35; CI = 0.15, 0.81). While negative PRs and tumor size greater than 2 cm were significant predictor factors of breast cancer progression (OR = 2.07; CI = 1.09, 3.91, OR = 2.02; CI = 1.9, 3.78).</p><p><strong>Conclusion: </strong>Although the effect of young age as a protective factor for the progression of breast cancer remains controversial, our study revealed that patients between 41 and 60 years of age had a higher rate of progression. Future larger prospective studies are needed to delineate the role of age and PR hormone receptors in determining the best treatment options for women with breast cancer in the Saudi population.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"17 ","pages":"11782234231158270"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8f/af/10.1177_11782234231158270.PMC10061810.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9296643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Endocrine Agents should be the Dominant Systemic Therapies Prescribed in Luminal A Breast Cancer.","authors":"Matthew G Davey,&nbsp;Michael J Kerin","doi":"10.1177/11782234221145409","DOIUrl":"https://doi.org/10.1177/11782234221145409","url":null,"abstract":"outcomes for premenopausal women who develop metastatic LABC","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"17 ","pages":"11782234221145409"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/18/c7/10.1177_11782234221145409.PMC9841871.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10541946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Treatment Score Post-5 Years as a Tool for Risk Estimation of Late Recurrence in Thai Patients With Estrogen-Receptor-Positive, Early Breast Cancer: A Validation Study.","authors":"Thitiya Dejthevaporn,&nbsp;Panchanin Patanayindee","doi":"10.1177/11782234231186869","DOIUrl":"https://doi.org/10.1177/11782234231186869","url":null,"abstract":"<p><strong>Background: </strong>The risk of late distant recurrence (LDR) of estrogen receptor (ER)-positive breast cancer continues even after 5 years of endocrine treatment. Clinical Treatment Score after 5 years (CTS5) was developed and validated as a tool to assess the risk of LDR using data from Tamoxifen, Arimidex Alone or in Combinations (ATAC) and Breast International Group 1-98 (BIG1-98) trials. This study aimed to externally validate CTS5 in a real-world cohort of patients treated at an academic center in Thailand.</p><p><strong>Methods: </strong>The study was a retrospective analytical research study of early-stage, ER-positive breast cancer patients. The primary endpoint was LDR. The risk of LDR was determined using the CTS5 calculator. Cox regression model and Kaplan-Meier survival analysis were applied for prognostic validation of CTS5. Calibration was performed by comparing observed LDR to expected LDR using the Hosmer-Lemeshow (H-L) test.</p><p><strong>Results: </strong>A total of 323 women were included with a median follow-up period of 11.6 years. The rate of LDR was 10.8%. The CTS5 was prognostic for LDR. C-index of the area under the ROC curve was 0.672. There was no significant difference between actual and expected numbers of LDR with an observed (O) LDR events to expected (E) number of LDR events ratio of 0.99 (0.86-1.12) (H-L <i>P</i> = .79) indicating a proper calibration in this cohort.</p><p><strong>Conclusions: </strong>Our study validated that CTS5 is accurate in predicting the risk of LDR in ER-positive breast cancer cases in Thai patients. Its performance seemed to be better in postmenopausal patients. CTS5 could be applied in routine clinical practice to improve decisions regarding prolonged endocrine therapy, particularly in resource-limited countries where molecular profiling are inaccessible.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"17 ","pages":"11782234231186869"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8e/53/10.1177_11782234231186869.PMC10392218.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9932995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marking Techniques for Targeted Axillary Dissection Among Patients With Node-Positive Breast Cancer Treated With Neoadjuvant Chemotherapy.","authors":"Inês Gante,&nbsp;João Pedro Maldonado,&nbsp;Margarida Figueiredo Dias","doi":"10.1177/11782234231176159","DOIUrl":"https://doi.org/10.1177/11782234231176159","url":null,"abstract":"<p><p>Invasive breast cancer with axillary lymph node (LN) invasion is a continuing problem worldwide. The morbidity associated with axillary LN dissection along with the high rate of nodal downstaging after neoadjuvant chemotherapy (NACT) made the standard treatment shift towards less invasive surgery. Sentinel lymph node biopsy (SLNB) after NACT is associated with high false-negative rates (13%-14%). To overcome this problem, it was concluded that the positive nodes should first be indicated with image-detectable markers and then removed together with SLNB: targeted axillary dissection (TAD). This review aims to describe and evaluate the different marking techniques for TAD in patients with node-positive breast cancer treated with NACT, namely: clip placement and guidewire localization; clip placement and 125I-labelled radioactive seed localization; clip placement and skin mark; clip placement and intraoperative ultrasound; tattooing with a sterile black carbon suspension; magnetic seeds; radar and infrared light technology localization. Targeted axillary dissection techniques have shown false-negative rates below 9% and identification rates above 95%. The most studied technique is guidewire localization, as it is also the oldest one. However, according to data gathered from this review, some newer techniques have shown to be very promising due to their statistical results and management factors.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"17 ","pages":"11782234231176159"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/98/48/10.1177_11782234231176159.PMC10226338.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9553583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tendency to Breast Cancer Screening Among Rural Women in Southern Iran: A Structural Equation Modeling (SEM) Analysis of Theory of Planned Behavior.","authors":"Ameneh Keshavarzi,&nbsp;Saeedeh Asadi,&nbsp;Abdolrahim Asadollahi,&nbsp;Fatemeh Mohammadkhah,&nbsp;Ali Khani Jeihooni","doi":"10.1177/11782234221121001","DOIUrl":"https://doi.org/10.1177/11782234221121001","url":null,"abstract":"<p><strong>Background: </strong>Early detection of breast cancer is a crucial factor in surviving the disease. This study aimed to investigate the mammography screening based on the theory of planned behavior (TPB) among rural women in Fasa and Shiraz cities, Iran.</p><p><strong>Methods: </strong>This study is a cross-sectional study performed on 800 female clients referring to rural health centers in Fasa and Shiraz cities in southern Iran in early 2021. The authors decided to send and distribute the electronic questionnaire form through the WhatsApp application in collaboration with the health staff of rural health centers for the people covered by these centers. Data gathering tools were a questionnaire on demographic characteristics, a questionnaire based on constructs of TPB, and behavior of mammography screening. Using the structural equation model (SEM), the TPB constructs and demographic variables were entered into the model. Data analysis was executed employing SPSS software version 26 and Amos version 24 (IBM Co., Ann Arbor, MI, USA). Analyzing the data was carried out using the 1-way analysis of variance (ANOVA), logistic regression, and structural equation analysis. During data analysis, various model indicators such as the goodness of fit, including comparative fit index (CFI), goodness-of-fit index (GFI), root mean square error of approximation (RMSEA), and chi-square index/<i>df</i> were evaluated. The significance level in all tests was considered 0.05.</p><p><strong>Results: </strong>The knowledge, attitude, and perceived behavioral control were the predictors of intention and behavior of mammography screening among the women. Among demographic variables, age, literacy, being menopausal, cancer in family, city, and ethnicity contribute more to the variance variation in TPB constructs. In this study, 7.2% of Persians, 8% of Qashqai Turks, and 4.5% of Arabs are contemplating going to mammography screening. In total, 6.8% (54 people) of all individuals intended to go mammography screening, and 5.4% (43 people) had a history of mammography screening. Goodness-of-fit indices (χ² = 18.45, <i>df</i> = 10, n = 800, χ²/<i>df</i> = 1.845, RMSEA = 0.032, GFI = 0.90, non-normed fit index (NNFI) = 0.91) of conceptual model of this study indicate the suitability of the model.</p><p><strong>Conclusions: </strong>The results of the study indicated that the constructs of the TPB can predict mammography screening behaviors in rural women. It has also demonstrated that mammographic behavior can be improved in rural women using education based on the TPB model, emphasizing critical psychological factors of creating or changing behavior.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"16 ","pages":"11782234221121001"},"PeriodicalIF":2.9,"publicationDate":"2022-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3d/79/10.1177_11782234221121001.PMC9452820.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33460147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of Breast Cancer Cell FASN Expression by Obesity-Related Systemic Factors.","authors":"Bryan McClellan,&nbsp;Tommy Pham,&nbsp;Brittany Harlow,&nbsp;Gabby Lee,&nbsp;Duan Quach,&nbsp;Christopher Jolly,&nbsp;Andrew Brenner,&nbsp;Linda deGraffenried","doi":"10.1177/11782234221111374","DOIUrl":"https://doi.org/10.1177/11782234221111374","url":null,"abstract":"<p><strong>Purpose: </strong>The objective of this study is to determine the impact of exposure to obesity-related systemic factors on fatty acid synthase enzyme (FASN) expression in breast cancer cells.</p><p><strong>Methods: </strong>MCF-7 breast cancer cells were exposed to sera from patients having obesity or not having obesity and subjected to quantitative reverse transcription polymerase chain reaction (RT-qPCR). Subsequent MTT and colony-forming assays using both MCF-7 and T-47D cells exposed to sera and treated with or without FASN inhibitor, TVB-3166, were used. MCF-7 cells were then treated with insulin and the sterol regulatory element-binding protein (SREBP) processing inhibitor, betulin, prior to analysis of FASN expression by quantitative RT-qPCR and western blot. Insulin-induced SREBP-FASN promoter binding was analyzed by chromatin immunoprecipitation with an anti-SREBP antibody.</p><p><strong>Results: </strong>In response to sera exposure (body mass index [BMI] >30) there was an increase in FASN expression in breast cancer cells. Furthermore, treatment with the FASN inhibitor, TVB-3166, resulted in a decreased breast cancer cell survival and proliferation while increasing apoptosis upon sera exposure (BMI >30). Insulin-exposed MCF-7 cells exhibited an increased FASN messenger RNA and protein expression, which is abrogated upon SREBP inhibition. In addition, insulin exposure induced enhanced SREBP binding to the FASN promoter.</p><p><strong>Conclusions: </strong>Our results implicate FASN as a potential mediator of obesity-induced breast cancer aggression and a therapeutic target of patients with obesity-induced breast cancer.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"16 ","pages":"11782234221111374"},"PeriodicalIF":2.9,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/e4/10.1177_11782234221111374.PMC9400406.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33444770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Syndrome and Breast Cancer Molecular Subtypes: An Observational Patient Study","authors":"Dafina Ademi-Islami, S. Manxhuka-Kerliu, Dhurata Tarifa-Koroveshi, Rozafa Koliqi, B. Mujaj","doi":"10.1177/11782234221080555","DOIUrl":"https://doi.org/10.1177/11782234221080555","url":null,"abstract":"Background: Breast cancer molecular subtypes share various prognostic profiles, and luminal A molecular subtypes have a better prognosis compared with other molecular subtypes. However, whether metabolic syndrome or individual risk factors of metabolic syndrome influence on the development of molecular subtype remains elusive. We aimed to assess the association between metabolic syndrome risk factors and breast cancer molecular subtypes among patients with metabolic syndrome in a clinical setting. Methods: In total, 101 breast cancer patients with mean age, 58.4 ± 8.5 years, and overt metabolic syndrome prospectively were recruited. Immunohistochemistry procedure was used to determine molecular subtypes. Assessment of clinical, biochemical, and anthropometric parameters was performed. Logistic regression analysis was used to assess the relationship between risk factors and breast cancer molecular subtypes categories. A similar approach was used to assess the relation between breast cancer molecular subtypes and menopause. Results: Comparison of metabolic syndrome individual risk factors according to breast cancer molecular subtypes no statistical difference was found for systolic (P = .33) and diastolic blood pressure (P = .17), fasting glucose (P = .77), triglycerides (P = .62), high-density lipoprotein (P = .33), body mass index (P = .87), and waist circumference (P = .81). A positive trend was found between high-density lipoprotein and HER2+. No association was found with other risk factors. Moreover, an association was found between HER2+ categories and menopause. Conclusion: In breast cancer patients with metabolic syndrome, we observed an increased trend between high-density lipoprotein and HER2+ molecular subtype, suggesting that underlying dyslipidemia may favor poor prognosis. HER2+ was associated with menopause which may influence further expression of HER2+ .","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"27 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83316436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining Carbon-Ion Irradiation and PARP Inhibitor, Olaparib Efficiently Kills BRCA1-Mutated Triple-Negative Breast Cancer Cells","authors":"Miki Kawanishi, M. Fujita, K. Karasawa","doi":"10.1177/11782234221080553","DOIUrl":"https://doi.org/10.1177/11782234221080553","url":null,"abstract":"Background: Triple-negative breast cancer (TNBC) exhibits poor prognosis due to the lack of targets for hormonal or antibody-based therapies, thereby leading to limited success in the treatment of this cancer subtype. Poly (ADP-ribose) polymerase 1 (PARP1) is a critical factor for DNA repair, and using PARP inhibitor (PARPi) is one of the promising treatments for BRCA-mutated (BRCA mut) tumors where homologous recombination repair is impaired due to BRCA1 mutation. Carbon ion (C-ion) radiotherapy effectively induces DNA damages in cancer cells. Thus, the combination of C-ion radiation with PARPi would be an attractive treatment for BRCA mut TNBC, wherein DNA repair systems can be severely impaired on account of the BRCA mutation. Till date, the effectiveness of C-ion radiation with PARPi in BRCA mut TNBC cell killing remains unknown. Purpose: Triple-negative breast cancer cell lines carrying either wild type BRCA1, BRCA wt, (MDA-MB-231), or the BRCA1 mutation (HCC1937) were used, and the effectiveness of PARPi, olaparib, combined with C-ion beam or the conventional radiation, or X-ray, on TNBC cell killing were investigated. Methods: First, effective concentrations of olaparib for BRCA mut (HCC1937) cell killing were identified. Using these concentrations of olaparib, we then investigated their radio-sensitizing effects by examining the surviving fraction of MDA-MB-231 and HCC1937 upon X-ray or C-ion irradiation. In addition, the number of γH2AX (DSB marker) positive cells as well as their expression levels were determined by immunohistochemistry, and results were compared between X-ray irradiated or C-ion irradiated cells. Furthermore, PARP activities in these cells were also observed by performing immunohistochemistry staining for poly (ADP-ribose) polymer (marker for PARP activity), and their expression differences were determined. Results: Treatment of cells with 25 nM olaparib enhanced radio-sensitivity of X-ray irradiated HCC1937, whereas lower dose (5 nM) olaparib showed drastic effects on increasing radio-sensitivity of C-ion irradiated HCC1937. Similar effect was not observed in MDA-MB-231, not possessing the BRCA1 mutation. Results of immunohistochemistry showed that X-ray or C-ion irradiation induced similar number of γH2AX-positive HCC1937 cells, but these induction levels were higher in C-ion irradiated HCC1937 with increased PARP activity compared to that of X-ray irradiated HCC1937. Elevated induction of DSB in C-ion irradiated HCC937 may fully activate DSB repair pathways leading to downstream activation of PARP, subsequently enhancing the effectiveness of PARPi, olaparib, with lower doses of olaparib exerting noticeable effects in cell killing of C-ion irradiated HCC1937. Conclusions: From this study, we demonstrate that C-ion irradiation can exert significant DSB in BRCA mut TNBC, HCC1937, with high PARP activation. Thus, PARPi, olaparib, would be a promising candidate as a radio-sensitizer for BRCA mut TNBC treatment, especiall","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":"s1-1 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85968688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}