Breast Cancer : Basic and Clinical Research最新文献

{"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":"Association of Mammary Gland Disease With Metabolic Syndrome Factors in Japanese Women-Case-Control Study Based on Health Screening Results.","authors":"Sakika Sumida,&nbsp;Tadayuki Iida,&nbsp;Masao Yoshikawa,&nbsp;Kaoru Nagaoka","doi":"10.1177/11782234221127652","DOIUrl":"https://doi.org/10.1177/11782234221127652","url":null,"abstract":"<p><strong>Background: </strong>The association of obesity with breast cancer is clear. Although body mass index (BMI) is used as an indicator of obesity, its accuracy remains questionable. Although, there factors for diagnosing metabolic syndrome are caused by obesity, the association with breast cancer has not been clarified.</p><p><strong>Methods: </strong>Women who underwent breast cancer screening with mammography and measurements of metabolic syndrome factors, including waist circumference, blood glucose, triglycerides, HDL (high-density lipoprotein) cholesterol levels, and systolic and diastolic pressure, twice within a 2-year period were enrolled (n = 314), with a final sample size of 256. To determine the presence of mammary gland disease, 2 expert physicians interpreted radiogram findings, with category 3 or higher shown by mammography considered to indicate an abnormality.</p><p><strong>Results and conclusions: </strong>Waist circumference at the initial measurement was marginally significant as a risk factor for onset of mammary gland disease (odds ratio [OR] = 1.036, <i>P</i> = .045) and thus was concluded to be a risk factor for disease onset. Although not significant, a 2-year increase in systolic and diastolic blood pressure has been presumed to be risk factors (systolic: OR = 1.020, <i>P</i> = .085, diastolic: OR = 1.040, <i>P</i> = .065), while high levels of HDL cholesterol have been presumed to protect against the disease (OR = 0.982, <i>P</i> = .064). Based on these results, waist circumference and blood pressure are speculated to be related to development of mammary gland disease.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":" ","pages":"11782234221127652"},"PeriodicalIF":2.9,"publicationDate":"2022-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a7/d6/10.1177_11782234221127652.PMC9638686.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40476788","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":"Determining Prognostic Factors of Disease-Free Survival in Breast Cancer Using Censored Quantile Regression.","authors":"Akram Yazdani,&nbsp;Shahpar Haghighat","doi":"10.1177/11782234221108058","DOIUrl":"https://doi.org/10.1177/11782234221108058","url":null,"abstract":"<p><strong>Background: </strong>The analysis of disease-free survival and related factors leads to a better understanding of the patient's condition and recurrence-related characteristics and provides a basis for more appropriate treatment guidance. In this study, we aimed to investigate the role of prognostic factors on disease-free survival in breast cancer with a quantile regression model.</p><p><strong>Methods: </strong>This retrospective study was conducted by reviewing data obtained from 2056 breast cancer patients. Age at diagnosis and education status, tumor size, lymph node ratio, tumor grade, estrogen receptor and progesterone receptor, type of surgery, use of radiotherapy, chemotherapy, and hormone therapy were the prognosis factors considered in this study. A quantile regression model was used to investigate prognostic factors of disease-free survival in breast cancer.</p><p><strong>Results: </strong>Disease recurrence was verified in 251 (13.9%) women, and 39 (0.02%) women died before experience recurrence. The 10th percentile of disease-free survival for patients with the hormone therapy was 23.85 months greater than patients who did not receive this treatment (<i>P</i> value < .001). In the examination of the tumor size, the 10th and 20th percentiles of disease-free survival for patients with tumor size > 5 cm were 31.06 and 27 months less than patients with the tumor size < 2 cm, respectively (<i>P</i> value = .006 and .021, respectively). Compared with grade 1 tumors, the 10th and 20th percentiles of disease-free survival for patients with grade 3 tumors decreased 30.11 and 38.32 months, respectively (<i>P</i> value < .001 and .038, respectively). The 10th and 20th percentiles of disease-free survival decreased 28.16 and 45.32 months with a 1 unit increase in lymph node ratio, respectively (<i>P</i> value = .032 and .032, respectively).</p><p><strong>Conclusions: </strong>Among the prognostic factors, tumor size, grade, and lymph node ratio showed a close relationship with disease-free survival in breast cancer. The findings indicated that developing public screening and educational programs through the health care system with more emphasis on low-educated women is needed among Iranian women.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":" ","pages":"11782234221108058"},"PeriodicalIF":2.9,"publicationDate":"2022-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/05/d8/10.1177_11782234221108058.PMC9251962.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40477074","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":"Evolving Evidence for the Optimization of Neoadjuvant Therapy in Triple-Negative Breast Cancer.","authors":"Diogo Silva,&nbsp;Alexandra Mesquita","doi":"10.1177/11782234221107580","DOIUrl":"https://doi.org/10.1177/11782234221107580","url":null,"abstract":"<p><p>Representing 15% to 20% of all invasive breast cancers, adjuvant systemic treatment for early-stage, high-risk triple-negative breast cancer (TNBC) is preferentially done in the neoadjuvant setting based on a chemotherapy backbone of anthracyclines and taxanes. Pathological complete response to neoadjuvant treatment constitutes the main objective, regarding its correlation with oncological outcomes. The optimal neoadjuvant regimen to achieve the highest rates of pathological complete response is still under investigation, with the increasing knowledge on the molecular pathways, genomic sequencing, and immunological profile of TNBC allowing for the development of a wide array of new therapeutic options. This review aims to summarize the current evidence and ongoing clinical trials of new therapeutic options for the neoadjuvant treatment of TNBC patients.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":" ","pages":"11782234221107580"},"PeriodicalIF":2.9,"publicationDate":"2022-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7e/8a/10.1177_11782234221107580.PMC9243491.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40468327","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":"Preoperative Breast Magnetic Resonance Imaging as a Predictor of Response to Neoadjuvant Chemotherapy.","authors":"Robert Browne,&nbsp;Peter McAnena,&nbsp;Niamh O'Halloran,&nbsp;Brian M Moloney,&nbsp;Emily Crilly,&nbsp;Michael J Kerin,&nbsp;Aoife J Lowery","doi":"10.1177/11782234221103504","DOIUrl":"https://doi.org/10.1177/11782234221103504","url":null,"abstract":"<p><strong>Introduction: </strong>The ability to accurately predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer would improve patient selection for specific treatment strategies, would provide important information for patients to aid in the treatment selection process, and could potentially avoid the need for more extensive surgery. The diagnostic performance of magnetic resonance imaging (MRI) in predicting pCR has previously been studied, with mixed results. Magnetic resonance imaging performance may also be influenced by tumour and patient factors.</p><p><strong>Methods: </strong>Eighty-seven breast cancer patients who underwent NAC were studied. Pre-NAC and post-NAC MRI findings were compared with pathologic findings postsurgical excision. The impact of patient and tumour characteristics on MRI accuracy was evaluated.</p><p><strong>Results: </strong>The mean (SD) age of participants was 48.7 (10.3) years. The rate of pCR based on post-NAC MRI was 19.5% overall (19/87). The sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy in predicting pCR were 52.9%, 77.1%, 36.0%, 87.1%, and 72.4%, respectively. Positive predictive value was the highest in nonluminal versus Luminal A disease (45.0% vs 25.0%, <i>P</i> < .001), with higher rates of false positivity in nonluminal subtypes (<i>P</i> = .002). Tumour grade, T category, and histological subtype were all independent predictors of MRI accuracy regarding post-NAC tumour size.</p><p><strong>Conclusion: </strong>Magnetic resonance imaging alone is insufficient to accurately predict pCR in breast cancer patients post-NAC. Magnetic resonance imaging predictions of pCR are more accurate in nonluminal subtypes. Tumour grade, T category, and histological subtype should be considered when evaluating post-NAC tumour sizes.</p>","PeriodicalId":9163,"journal":{"name":"Breast Cancer : Basic and Clinical Research","volume":" ","pages":"11782234221103504"},"PeriodicalIF":2.9,"publicationDate":"2022-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e4/94/10.1177_11782234221103504.PMC9234834.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40410169","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}