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1.
Rev. senol. patol. mamar. (Ed. impr.) ; 36(1): 1-8, ene.-mar. 2023. tab
Artigo em Espanhol | IBECS | ID: ibc-EMG-475

RESUMO

Introducción: el tratamiento conservador de la mama junto con la radioterapia es de elección en las pacientes con cáncer de mama precoz. Gracias a un mayor conocimiento de la radiobiología tumoral, la tendencia actual consiste en utilizar técnicas de irradiación parcial acelerada, entre las que destaca la radioterapia intraoperatoria (RIO). Métodos: estudio prospectivo multicéntrico dividido en 2 grupos comparativos con casos consecutivos de las pacientes a que han recibido una cirugía conservadora por cáncer de mama asociada o no a RIO. Se valora la relación de esta terapia con los valores de las proteínas involucradas en la respuesta biológica (IL6, IL8, CXCL10, IL1β y TNF- α) en muestras de suero preoperatorio y a las 24 h desde la cirugía, y de drenaje quirúrgico a las 6 y 24 h desde la cirugía. Resultados: se ha objetivado en las pacientes tratadas con RIO una disminución significativa de IL6 e IL8, así como un aumento de CXCL10 favorable para la lucha contra la progresión del tumor (p valor < 0,05). Las alteraciones del sistema inmunológico se manifiestan tanto en suero como en débito del drenaje quirúrgico a las 6 y 24 h desde la cirugía. Conclusiones: la RIO modifica la respuesta biológica en las pacientes con cáncer de mama. A pesar de que se deben desarrollar más líneas de investigación, la comprensión de los mecanismos de desarrollo del tumor, abre una nueva etapa en el desarrollo de tratamientos perioperatorios dirigidos a dianas concretas que compensen las consecuencias dañinas de la cirugía. (AU)


Introduction: Breast conserving surgery with radiotherapy is the treatment of choice in patients with early breast cancer. Due to a better understanding of tumour radiobiology, the current trend is to use accelerated partial irradiation techniques, among which intraoperative radiotherapy (RIO) stands out. Methods: Prospective multicentre study divided into two comparative groups with consecutive cases of patients who have undergone conservative surgery for breast cancer associated or not with RIO. The relation of this therapy with the values of proteins involved in the biological response (IL6, IL8, CXCL10, IL1β y TNF- α) is assessed in serum samples preoperative and 24 hours after surgery, and surgical drainage samples at 6 and 24 hours after surgery. Results: A significant decrease in IL6 and IL8, as well as an increase in CXCL10 favourable for the fight against tumour progression (p-value < 0.05) was observed in patients treated with RIO. Immune system alterations are manifested in both serum and surgical drainage debit at 6 and 24 hours after surgery. Conclusions: RIO modifies the biological response in breast cancer patients. Although more lines of research need to be developed, the understanding of the mechanisms of tumour development opens a new stage in the development of perioperative treatments directed at specific targets that compensate for the harmful consequences of surgery. (AU)


Assuntos
Humanos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Estudos Prospectivos , Radiobiologia , Proteômica , Interleucinas
2.
Rev. senol. patol. mamar. (Ed. impr.) ; 36(1): 1-8, ene.-mar. 2023.
Artigo em Espanhol | IBECS | ID: ibc-EMG-480

RESUMO

Presentamos la visión futurista que de su especialidad tienen 7 líderes de opinión estrechamente comprometidos con la patología mamaria. Las especialidades incluidas fueron radiología, patología, cirugía, cirugía plástica, medicina nuclear, oncología médica y oncología radioterápica. Los autores plasman, en este artículo, sus opiniones y criterios respecto a los avances que vislumbran en su futuro profesional.Conceptos clave como sistemas de cribado sin radiación, transcriptómica clínica, diagnóstico funcional del tumor, inteligencia artificial, navegación intraoperatoria, biopsia líquida, ADN tumoral circulante, reconstrucción con técnicas microquirúrgicas avanzadas, hipofraccionamiento extremo o teragnosis, son algunos de los conceptos presentados y discutidos.Los autores justifican sus puntos de vista, abriendo líneas de trabajo a tener en cuenta para optimizar esfuerzos y el conocimiento futuro. (AU)


We present the futuristic vision of their specialty of seven opinion leaders closely involved in breast pathology. The specialties were radiology, pathology, surgery, plastic surgery, nuclear medicine, medical oncology, and radiation oncology. In this article, the authors express their opinions and criteria regarding the advances they foresee for their professional future.Key concepts such as radiation-free screening systems, clinical transcriptomics, functional tumor diagnosis, artificial intelligence, intraoperative navigation, liquid biopsy, circulating tumor DNA, reconstruction with advanced microsurgical techniques, extreme hypofractionation or theragnosis are some of the concepts presented and discussed.The authors justify their points of view, suggesting lines of work to optimize efforts and future knowledge. (AU)


Assuntos
Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Radioterapia (Especialidade) , Inteligência Artificial , Tolerância a Radiação , Medicina Nuclear
3.
JCO Clin Cancer Inform ; 7: e2200099, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36724402

RESUMO

PURPOSE: Arkansas is one of only four known states that have linked All-Payer Claims Database (APCD) to state's cancer registry (Arkansas Cancer Registry [ACR]). We evaluated the reporting consistency of radiation therapy (RT) between the two sources. METHODS: Women age ≥ 18 years diagnosed in 2013-2017 with early-stage hormone receptor-positive breast cancer who received breast-conserving surgery were identified. Patients must have continuous insurance coverage (any private plans, Medicaid, and Medicare) in the 13 months (month of diagnosis and 12 months after). Receipt of RT was identified independently from ACR and APCD. We calculated sensitivity, specificity, positive predictive value, and negative predictive value for receipt of RT coded by the registry compared with APCD billing claims as the gold standard. We assessed the degree of concordance between the data sources by Cohen's kappa statistics. RESULTS: The final sample included 2,695 patients who were in both databases and satisfied our inclusion/exclusion criteria. Using APCD as the gold standard, there were high sensitivity (88.1%) and positive predictive value (87.7%) and moderate specificity (71.1%) and negative predictive value (71.8%). The overall agreement between the two sources was 83.0%, with a kappa statistic of 0.59 (95% CI, 0.56 to 0.63). Consistency measures varied by age, stage, and insurance type with Medicare fee-for-service coverage only having the best and private insurance only the worse consistency. CONCLUSION: In patients with early-stage hormone receptor-positive breast cancer who received breast-conserving surgery, recording of RT receipt was moderately consistent between Arkansas APCD and ACR. Future studies are needed to identify factors affecting reporting consistency to better use this unique resource in addressing population health problems.


Assuntos
Neoplasias da Mama , Medicare , Humanos , Estados Unidos/epidemiologia , Feminino , Idoso , Adolescente , Medicaid , Sistema de Registros , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Gerenciamento de Dados
5.
BMC Cancer ; 23(1): 9, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597031

RESUMO

BACKGROUND: In this study, we aim to evaluate the cosmetic outcome differences between Intraoperative electron beam radiation therapy (IOERT) and whole breast radiotherapy (WBR) with further investigation of boosted IOERT. METHODS: This retrospective cohort study was conducted in two referral centers in Tehran, Iran. 116 women aged 30 to 79 with early-stage breast cancer (T0-2N0-1M0) eligible for breast conservation were divided into two groups of 58 based on the intervention they received, and further subgroups were defined based on receiving boosted IOERT. Patients in both groups underwent breast conservation surgery and those in the IOERT group received either a 21 Gy radical dose (radical IOERT) or 12 Gy boosted electron beam radiotherapy and a routine fractionated dose of 50 Gy in 25 sessions of WBR (boosted IOERT). Those in the WBR group were administered 50Gy in 32 sessions. Physician-assessed cosmetic outcome was defined as the primary result and incidence of fat necrosis and fibrosis and post-operative chronic pain were secondary outcomes. RESULTS: Post-operative cosmetic outcome scores and chronic pain, showed no significant difference between the two groups. The median cosmetic score in both groups was 9. Fat necrosis and fibrosis had significantly higher rates in the IOERT group (P. VALUE: 0.001). However, the majority (21/34 or 61.8%) of this complication was observed in the boosted IOERT subgroup and no statistical significance was recorded between the radical IOERT subgroup and the WBR group. CONCLUSIONS: In early-stage breast cancer treatment, radical IOERT has noninferiority compared to WBR in terms of cosmesis. Regarding fat necrosis and fibrosis, boosted IOERT was associated with higher rates in comparison to other groups. Therefore, radical IOERT seems to be a better treatment option for selected patients.


Assuntos
Neoplasias da Mama , Dor Crônica , Necrose Gordurosa , Humanos , Feminino , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Estudos Retrospectivos , Irã (Geográfico) , Fibrose , Recidiva Local de Neoplasia/radioterapia
8.
PLoS One ; 18(1): e0280456, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36693073

RESUMO

BACKGROUND: Volumetric modulated arc therapy (VMAT) with varied bolus thicknesses has been employed in postmastectomy radiotherapy (PMRT) of breast cancer to improve superficial target coverage. However, impact of bolus thickness on plan robustness remains unclear. METHODS: The study enrolled ten patients with left-sided breast cancer who received radiotherapy using VMAT with 5 mm and 10 mm bolus (VMAT-5B and VMAT-10B). Inter-fractional setup errors were simulated by introducing a 3 mm shift to isocenter of the original plans in the anterior-posterior, left-right, and inferior-superior directions. The plans (perturbed plans) were recalculated without changing other parameters. Dose volume histograms (DVH) were collected for plan evaluation. Absolute dose differences in DVH endpoints for the clinical target volume (CTV), heart, and left lung between the perturbed plans and the original ones were used for robustness analysis. RESULTS: VMAT-10B showed better target coverage, while VMAT-5B was superior in organs-at-risk (OARs) sparing. As expected, small setup errors of 3 mm could induce dose fluctuations in CTV and OARs. The differences in CTV were small in VMAT-5B, with a maximum difference of -1.05 Gy for the posterior shifts. For VMAT-10B, isocenter shifts in the posterior and right directions significantly decreased CTV coverage. The differences were -1.69 Gy, -1.48 Gy and -1.99 Gy, -1.69 Gy for ΔD95% and ΔD98%, respectively. Regarding the OARs, only isocenter shifts in the posterior, right, and inferior directions increased dose to the left lung and the heart. Differences in VMAT-10B were milder than those in VMAT-5B. Specifically, mean heart dose were increased by 0.42 Gy (range 0.10 ~ 0.95 Gy) and 0.20 Gy (range -0.11 ~ 0.72 Gy), and mean dose for the left lung were increased by 1.02 Gy (range 0.79 ~ 1.18 Gy) and 0.68 Gy (range 0.47 ~ 0.84 Gy) in VMAT-5B and VMAT-10B, respectively. High-dose volumes in the organs were increased by approximate 0 ~ 2 and 1 ~ 3 percentage points, respectively. Nevertheless, most of the dosimetric parameters in the perturbed plans were still clinically acceptable. CONCLUSIONS: VMAT-5B appears to be more robust to 3 mm setup errors than VMAT-10B. VMAT-5B also resulted in better OARs sparing with acceptable target coverage and dose homogeneity. Therefore 5 mm bolus is recommended for PMRT of left-sided breast cancer using VMAT.


Assuntos
Neoplasias da Mama , Radioterapia de Intensidade Modulada , Neoplasias Unilaterais da Mama , Humanos , Feminino , Radioterapia de Intensidade Modulada/métodos , Neoplasias Unilaterais da Mama/radioterapia , Neoplasias Unilaterais da Mama/cirurgia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Órgãos em Risco
9.
Curr Oncol ; 30(1): 1151-1163, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36661737

RESUMO

Breast re-irradiation (reRT) after breast-conserving surgery (BCS) using external beam radiation is an increasingly used salvage approach for women presenting with recurrent or new primary breast cancer. However, radiation technique, dose and fractionation as well as eligibility criteria differ between studies. There is also limited data on efficacy and safety of external beam hypofractionation and accelerated partial-breast irradiation (APBI) regimens. This paper reviews existing retrospective and prospective data for breast reRT after BCS, APBI reRT outcomes and delivery at our institution and the need for a randomized controlled trial using shorter courses of radiation to better define patient selection for different reRT fractionation regimens.


Assuntos
Neoplasias da Mama , Reirradiação , Feminino , Humanos , Mastectomia Segmentar/métodos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Estudos Prospectivos , Estudos Retrospectivos
10.
Clin Nutr ESPEN ; 53: 268-273, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36657923

RESUMO

AIM: This study aims to evaluate the effect of early nutritional intervention on adverse clinical events in women with breast cancer undergoing neoadjuvant chemotherapy. DESIGN AND SETTINGS: This is a randomized clinical trial performed at the beginning of neoadjuvant chemotherapy for women with breast cancer treated at an oncology referral center (Brazil) and followed until the end of radiotherapy period, at least. Registered under ClinicalTrials.gov Identifier no. RBR-3SHHXS. METHODS: Participants were allocated to a control group - CG (nutritional guidance on healthy eating practices) or an intervention group - IC (nutritional guidance and individualized food plan). Chemotherapy toxicity (primary endpoint) was considered a precocious adverse clinical event and it was evaluated by self-reported gastrointestinal symptoms observed at any time during the first three cycles of treatment. Post-surgical complications, radiotherapy toxicity, and weight change were considered long-term adverse events. RESULTS: 34 women (19 in the IG and 15 in the CG) were evaluated. The early nutritional intervention was associated with low gastrointestinal chemotoxicity (nausea, vomiting, and constipation, p < 0.001, p < 0.048, and p < 0.024, respectively). However, there were no statically significant differences between both groups in the presence of long-term adverse events (radiotherapy toxicity-88.2% vs 76.9%, weight loss-21.1% vs 26.7% for IC and CG respectively, p > 0.05 for both). CONCLUSION: The early nutritional intervention was associated with a low frequency of precocious events, but not with long-term adverse events in women with breast cancer during treatment.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Projetos Piloto , Brasil
11.
Breast Cancer Res Treat ; 198(1): 43-51, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36604352

RESUMO

PURPOSE: Breast reirradiation (reRT) after breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy for women presenting with recurrent or new primary breast cancer. There are limited data on safety of different fractionation regimens. This study reports safety and efficacy among women treated with repeat BCS and reRT. METHODS AND MATERIALS: Patients who underwent repeat BCS followed by RT from 2015 to 2021 at 2 institutions were analyzed. Univariate logistic regression models were used to identify predictors of acute and late toxicities. Kaplan-Meier estimates were used to evaluate overall survival (OS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LR-RFS). RESULTS: Sixty-six patients were reviewed with median follow-up of 16 months (range: 3-60 months). At time of first recurrence, 41% had invasive carcinoma with a ductal carcinoma in situ (DCIS) component, 41% had invasive carcinoma alone and 18% had DCIS alone. All were clinically node negative. For the reirradiation course, 95% received partial breast irradiation (PBI) (57.5% with 1.5 Gy BID; 27% with 1.8 Gy daily; 10.5% with hypofractionation), and 5% received whole breast irradiation (1.8-2 Gy/fx), all of whom had received PBI for initial course. One patient experienced grade 3 fibrosis, and one patient experienced grade 3 telangiectasia. None had grade 4 or higher late adverse events. We found no association between the fractionation of the second course of RT or the cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%. CONCLUSION: In this series of patients with recurrent or new primary breast cancer, a second breast conservation surgery followed by reirradiation was effective with no local recurrences and an acceptable toxicity profile across a range of available fractionation regimens at a median follow up of 16 months. Longer follow up is required.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Reirradiação , Humanos , Feminino , Mastectomia Segmentar/métodos , Carcinoma Intraductal não Infiltrante/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/etiologia , Mastectomia , Reirradiação/efeitos adversos , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico
12.
JCO Glob Oncol ; 9: e2200127, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36706350

RESUMO

PURPOSE: Hypofractionated breast radiotherapy has been found to be equivalent to conventional fractionation in many clinical trials. Using data from the European Society for Radiotherapy and Oncology Global Impact of Radiotherapy in Oncology survey, we identified preferences for hypofractionation in breast cancer across World Bank income groups and the perceived facilitators and barriers to its use. MATERIALS AND METHODS: An international, electronic survey was administered to radiation oncologists from 2018 to 2019. Demographics, practice characteristics, preferred hypofractionation regimen for specific breast cancer scenarios, and facilitators and barriers to hypofractionation were reported and stratified by World Bank income groups. Variables associated with hypofractionation were assessed using multivariate logistic regression models. RESULTS: One thousand four hundred thirty-four physicians responded: 890 (62%) from high-income countries (HICs), 361 (25%) from upper-middle-income countries (UMICs), 183 (13%) from low- and lower-middle-income countries (LLMICs). Hypofractionation was preferred most frequently in node-negative disease after breast-conserving surgery, with the strongest preference reported in HICs (78% from HICs, 54% from UMICs, and 51% from LLMICs, P < .001). Hypofractionation for node-positive disease postmastectomy was more frequently preferred in LLMICs (28% from HICs, 15% from UMICs, and 35% from LLMICs, P < .001). Curative doses of 2.1 to < 2.5 Gy in 15-16 fractions were most frequently reported, with limited preference for ultra-hypofractionation, but significant variability in palliative dosing. In adjusted analyses, UMICs were significantly less likely than LLMICs to prefer hypofractionation across all curative clinical scenarios, whereas respondents with > 1 million population catchments and with intensity-modulated radiotherapy were more likely to prefer hypofractionation. The most frequently cited facilitators and barriers were published evidence and fear of late toxicity, respectively. CONCLUSION: Preference for hypofractionation varied for curative indications, with greater acceptance in earlier-stage disease in HICs and in later-stage disease in LLMICs. Targeted educational interventions and greater inclusivity in radiation oncology clinical trials may support greater uptake.


Assuntos
Neoplasias da Mama , Hipofracionamento da Dose de Radiação , Humanos , Feminino , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia , Fracionamento da Dose de Radiação , Inquéritos e Questionários
13.
Sci Rep ; 13(1): 1530, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707535

RESUMO

Tumour cells exhibit altered metabolic pathways that lead to radiation resistance and disease progression. Raman spectroscopy (RS) is a label-free optical modality that can monitor post-irradiation biomolecular signatures in tumour cells and tissues. Convolutional Neural Networks (CNN) perform automated feature extraction directly from data, with classification accuracy exceeding that of traditional machine learning, in cases where data is abundant and feature extraction is challenging. We are interested in developing a CNN-based predictive model to characterize clinical tumour response to radiation therapy based on their degree of radiosensitivity or radioresistance. In this work, a CNN architecture is built for identifying post-irradiation spectral changes in Raman spectra of tumour tissue. The model was trained to classify irradiated versus non-irradiated tissue using Raman spectra of breast tumour xenografts. The CNN effectively classified the tissue spectra, with accuracies exceeding 92.1% for data collected 3 days post-irradiation, and 85.0% at day 1 post-irradiation. Furthermore, the CNN was evaluated using a leave-one-out- (mouse, section or Raman map) validation approach to investigate its generalization to new test subjects. The CNN retained good predictive accuracy (average accuracies 83.7%, 91.4%, and 92.7%, respectively) when little to no information for a specific subject was given during training. Finally, the classification performance of the CNN was compared to that of a previously developed model based on group and basis restricted non-negative matrix factorization and random forest (GBR-NMF-RF) classification. We found that CNN yielded higher classification accuracy, sensitivity, and specificity in mice assessed 3 days post-irradiation, as compared with the GBR-NMF-RF approach. Overall, the CNN can detect biochemical spectral changes in tumour tissue at an early time point following irradiation, without the need for previous manual feature extraction. This study lays the foundation for developing a predictive framework for patient radiation response monitoring.


Assuntos
Neoplasias da Mama , Análise Espectral Raman , Humanos , Animais , Camundongos , Feminino , Xenoenxertos , Redes Neurais de Computação , Algoritmos , Neoplasias da Mama/radioterapia
14.
Anticancer Res ; 43(2): 733-739, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36697057

RESUMO

BACKGROUND/AIM: Mastectomy is the standard treatment of in-breast-recurrence of breast cancer after breast conserving surgery (BCS) and external beam radiation therapy (EBRT). In selected cases, it is possible to preserve the breast if targeted intraoperative radiotherapy (TARGIT-IORT) can be given during the second lumpectomy. This is a comparative analysis of overall survival and quality of life (QoL). PATIENTS AND METHODS: Patients in our database with in-breast-recurrence and either mastectomy or BCS and TARGIT-IORT were included. Identified patients were offered participation in a prospective QoL-analysis using the BREAST-Q questionnaire. The cohorts were compared for confounding parameters, overall survival, and QoL. RESULTS: Thirty-six patients treated for in-breast-recurrence were included, 21 had received a mastectomy and 16 patients had received BCS with TARGIT-IORT. Mean follow-up was 12.8 years since primary diagnosis and 4.2 years since recurrence. Both groups were balanced regarding prognostic parameters. Overall survival was numerically longer for BCS and TARGIT-IORT, but the numbers were too small for formal statistical analysis. No patient had further in-breast-recurrence. Psychosocial and sexual wellbeing did not differ between both groups. Physical wellbeing was significantly superior for those whose breast could be preserved (p-value=0.021). Patient-reported incidence and severity of lymphedema of the arm was significantly worse in the mastectomy group (p=0.007). CONCLUSION: Preserving the breast by use of TARGIT-IORT was safe with no re-recurrence and no detriment to overall survival in our analysis and led to a statistically significant improvement in physical wellbeing and incidence of lymphedema. These data should increase the confidence in offering breast preservation after in-breast-recurrence of breast cancer.


Assuntos
Neoplasias da Mama , Linfedema , Neoplasias Mamárias Animais , Humanos , Animais , Feminino , Mastectomia , Mastectomia Segmentar/efeitos adversos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Qualidade de Vida , Estudos Prospectivos , Recidiva Local de Neoplasia/cirurgia , Cuidados Intraoperatórios , Radioterapia
15.
Eur Rev Med Pharmacol Sci ; 27(1): 256-274, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36647876

RESUMO

OBJECTIVE: In addition to significantly reducing breast cancer recurrence risk, radiotherapy also prolongs patients' lives. However, radiotherapy-related genes and biomarkers still remain poorly understood. The present study aimed to identify radiation-associated genes in breast cancer. MATERIALS AND METHODS: Breast cancer data were downloaded from Gene Expression Omnibus (GEO) and UCSC Xena database. The gene ontology (GO) enrichment and gene set enrichment analysis (GSEA) were performed for annotation and integrated discovery. Protein-protein interaction (PPI) network was constructed by STRING database and hub genes were identified. Then, immunohistochemistry and tissue expression of key genes was analyzed by using the Human Protein Atlas (HPA) and GEPIA database. Genes associated with prognosis were identified by performing univariate cox analysis. RESULTS: We identified 341 differentially expressed genes related to radiotherapy in breast cancer patients. PPI analysis revealed a total of 129 nodes and 516 interactions and identified five hub genes (EGFR, FOS, ESR1, JUN, and IL6). In addition, 11 SDEGs THBS1, SERPINA11, NFIL3, METTL7A, KCTD12, HSPA6, EGR1, DDIT4, CCDC3, C11orf96, and BCL2A1 candidate genes can be used as potential diagnostic markers. The calibration curve and ROC indicate good probability consistencies of 3-years and 5-year survival rates of patients between estimation and observation. CONCLUSIONS: Our findings provide novel insight into the functional characteristics of breast cancer through integrative analysis of GEO data and suggest potential biomarkers and therapeutic targets for breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/radioterapia , Perfilação da Expressão Gênica , Biomarcadores Tumorais/genética , Mapas de Interação de Proteínas/genética , Prognóstico , Biologia Computacional , Regulação Neoplásica da Expressão Gênica
16.
Eur J Med Res ; 28(1): 27, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36642742

RESUMO

Radiotherapy and targeted therapy are essential treatments for patients with brain metastases from human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, the combination of radiotherapy and targeted therapy still needs to be investigated, and neurotoxicity induced by radiotherapy for brain metastases has also become an important issue of clinical concern. It remained unclear how to achieve the balance of efficacy and toxicity with the application of new radiotherapy techniques and new targeted therapy drugs. This article reviews the benefits and potential risk of combining radiotherapy and targeted therapy for HER2-positive breast cancer with brain metastases.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Feminino , Humanos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias da Mama/genética , Neoplasias da Mama/radioterapia
17.
Strahlenther Onkol ; 199(1): 67-77, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36515701

RESUMO

PURPOSE: A major complication of sequential and concomitant chemoradiation in breast cancer treatment is interstitial pneumonitis induced by radiation therapy (RT), systemic therapy, or a combination of both. Dose and volume of co-irradiated lung tissue directly correlate with the risk of radiation pneumonitis. Especially in case of combined treatment, it is often unclear which of the used therapeutic agents promote pneumonitis. METHODS: This was a prospective monocentric study including 396 breast cancer patients. A systematic analysis of single and combined therapeutic measures was performed in order to identify treatment-related factors enhancing the risk of pneumonitis post RT. RESULTS: Overall incidence of pneumonitis of any grade was 38%; 28% were asymptomatic (grade 1) and 10% were symptomatic (> grade 1). Pneumonitis > grade 2 did not occur. Beside age, smoking status, and mean lung dose, the combined treatment with goserelin and tamoxifen significantly enhanced the risk of pneumonitis in a supra-additive pattern (odds ratio [OR] 4.38), whereas each agent alone or combined with other drugs only nonsignificantly contributed to a higher pneumonitis incidence post RT (OR 1.52 and OR 1.16, respectively). None of the other systemic treatments, including taxanes, increased radiation pneumonitis risk in sequential chemoradiation. CONCLUSION: Common treatment schedules in sequential chemoradiation following breast-conserving surgery only moderately increase lung toxicity, mainly as an asymptomatic complication, or to a minor extent, as transient pneumonitis ≤ grade 2. However, combined treatment with tamoxifen and the LHRH analog goserelin significantly increased the risk of pneumonitis in breast cancer patients after chemoradiation. Thus, closer surveillance of involved patients is advisable.


Assuntos
Neoplasias da Mama , Pneumonite por Radiação , Feminino , Humanos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/tratamento farmacológico , Gosserrelina/uso terapêutico , Estudos Prospectivos , Pneumonite por Radiação/epidemiologia , Pneumonite por Radiação/etiologia , Medição de Risco , Tamoxifeno/uso terapêutico
18.
Neoplasia ; 35: 100862, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36508876

RESUMO

Intrinsic or acquired radioresistance often limits the efficacy of radiation therapy (RT), thereby leading to local control failure. Cancerous cells have abnormal pH dynamics due to high metabolic demands, but it is unclear how pH dynamics contribute to radioresistance. In this study, we investigated the role of Na-H exchange 1 (NHE1), the major intracellular pH (pHi) regulator, in RT response. We observed that RT increased NHE1 expression and modulated pHi in MDA-MB-231 human breast cancer cells. When combined with RT, pharmacological NHE1 inhibition by 5-(N-Ethyl-N-isopropyl)amiloride (EIPA) reduced pHi and clonogenic survival. EIPA attenuated radiation-damaged DNA repair, increasing G2/M cell cycle arrest. The combination of EIPA and RT increased apoptotic cell death while decreasing phosphorylation of NF-κB p65. Similarly, the knockdown of NHE1 increased radiosensitivity with lower pHi and increased apoptosis. Consistent with in vitro data, the EIPA plus RT inhibited the growth of MDA-MB-231 xenograft tumors in mice to a greater extent than either EIPA or RT alone. EIPA abrogated the RT-induced increase in NHE1 and phospho-NF-κB p65 expression in tumor tissues. Such coincidence of increased NHE1 level, pHi, and NF-κB activation was also found in radioresistant MDA-MB-231 cells, which were reversed by EIPA treatment. Bioinformatics analysis of RNA sequencing data revealed that inhibiting NHE1 reversed three core gene networks that were up-regulated in radioresistant cells and correlated with high NHE1 expression in patient samples: NF-κB, senescence, and extracellular matrix. Taken together, our findings suggest that NHE1 contributes to RT resistance via NF-κB-mediated signaling networks, and NHE1 may be a promising target for improving RT outcomes.


Assuntos
Neoplasias da Mama , NF-kappa B , Humanos , Camundongos , Animais , Feminino , NF-kappa B/metabolismo , Trocadores de Sódio-Hidrogênio/genética , Trocadores de Sódio-Hidrogênio/metabolismo , Trocador 1 de Sódio-Hidrogênio/genética , Trocador 1 de Sódio-Hidrogênio/metabolismo , Amilorida/farmacologia , Apoptose , Neoplasias da Mama/genética , Neoplasias da Mama/radioterapia , Concentração de Íons de Hidrogênio
19.
J Plast Reconstr Aesthet Surg ; 76: 18-26, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36512998

RESUMO

BACKGROUND: Capsular contracture following post-mastectomy radiotherapy (PMRT) is commonly seen in patients undergoing implant-based immediate breast reconstruction (IBR). Further understanding of the underlying biology is needed for the development of preventive or therapeutic strategies. Therefore, we conducted a comparative study of gene expression patterns in capsular tissue from breast cancer patients who had received versus those who had not received PMRT after implant-based IBR. METHODS: Biopsies from irradiated and healthy non-irradiated capsular tissue were harvested during implant exchange following IBR. Biopsies from irradiated (n = 13) and non-irradiated (n = 12) capsules were compared using Affymetrix microarrays to identify the most differentially regulated genes. Further analysis using immunohistochemistry was performed in a subset of materials to compare the presence of T cells, B cells, and macrophages. RESULTS: Enrichment testing using Gene Ontology (GO) analysis revealed that the 227 most differentially expressed genes were mainly involved in an inflammatory response. Twenty-one GO biological processes were identified [p < 0.05, false discovery rate (FDR) < 5%], several with B-cell-associated inflammation. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) analysis identified macrophages as the most common inflammatory cell type in both groups, further supported by immunostaining of CD68. Radiation remarkably increased B-cell infiltration in the capsular region of biopsies, as quantified by immunostaining of CD20 (p = 0.016). CONCLUSIONS: Transcript analysis and immunohistochemistry revealed inflammatory responses in capsular biopsies regardless of radiotherapy. However, the radiation response specifically involved B-cell-associated inflammatory responses.


Assuntos
Implante Mamário , Implantes de Mama , Neoplasias da Mama , Mamoplastia , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia , Implantes de Mama/efeitos adversos , Radioterapia Adjuvante/efeitos adversos , Mamoplastia/efeitos adversos , Inflamação , Expressão Gênica
20.
J Plast Reconstr Aesthet Surg ; 76: 76-87, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36513014

RESUMO

BACKGROUND: Approximately 80% of patients undergoing total mastectomy in the US opt for implant-based breast reconstruction (IBBR). A two-stage reconstruction with tissue expander (TE) remains the most common technique. Since the implementation of ADMs, a prepectoral approach has gained popularity and is becoming the standard of care. Herein, we compared the surgical and postoperative outcomes of prepectoral versus subpectoral two-stage IBBR. METHODS: A retrospective chart review was performed between January 2011 and December 2020. We included female patients undergoing immediate two-stage IBBR. The primary outcomes of this study were to compare the 30-day morbidity and the overall rate of complications during the first and second stages of reconstruction, and to compare the time to initiate postmastectomy radiotherapy (PMRT). Propensity score matching was implemented. RESULTS: After matching, 154 reconstructions were analyzed, 77 in each group. The two matched groups exhibited comparable (p > 0.05) characteristics for all analyzed demographic and intraoperative independent variables. Reconstructions in the prepectoral group had a shortened median time for drain removal (13-days vs. 15-days, p = 0.001). The intraoperative expansion volumes were higher in the prepectoral group (300 ml versus 200 ml, p = 0.025). The 30-day morbidity and first- and second-stage complication rates were not significantly different between groups. The time to start postmastectomy radiation therapy (PMRT) was not significantly different between groups (134-days versus 126.5-days, p = 0.58). CONCLUSION: Prepectoral and subpectoral TE placement had comparable complication rates during the first and second stages of IBBR. Timing for TE-to-Implant exchange and initiation of PMRT were comparable between the two approaches.


Assuntos
Implante Mamário , Implantes de Mama , Neoplasias da Mama , Mamoplastia , Humanos , Feminino , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/complicações , Implante Mamário/métodos , Implantes de Mama/efeitos adversos , Estudos Retrospectivos , Pontuação de Propensão , Mastectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Mamoplastia/métodos , Morbidade
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