The Effect of Intraoperative Radiotherapy on Breast Cancer: Focus on the Levels of Angiogenic Factors

Abstract Objective: Angiogenesis is one of the hallmarks of cancers that is involved in tumor progression. Angiogenic factors induce the formation of new blood vessels and tumor extension, and finally reduce the survival of patients. Intraoperative radiotherapy (IORT), in which radiation is delivered to the tumor bed can kill cells and change tumor microenvironment. Here, we compared the impact of IORT on the levels of angiogenic factors in the blood and surgical wound fluids (SWF) of the breast cancer patients. Patients and Methods: Blood and drained wound fluid (WF) samples were collected from the breast cancer patients before and after surgery, followed by quantification of the amounts of TGF-β, EGF, FGF, VEGF and DLL4 in the patients using ELISA.Results: Our results were indicative of significant differences between the pre-surgery and post-surgery serum levels of EGF, DLL4 and VEGF. In addition, linear regression analysis showed the significant impact of IORT, vascular invasion and lymph node (LN) involvement on the difference between TGF-β levels in the blood before and after surgery-IORT. According to the outcomes of multivariate analysis, IORT changed the levels of EGF and FGF in the blood and WF. Furthermore, logistic regression analyses showed that TGF-β and EGF can be used as predictor markers of the late-stage and LN involvement of the disease. Interestingly, IORT was able to reduce the risk of death and the recurrence rate of disease. Conclusions: In summary, IORT is a safe and effective treatment that can affect angiogenesis and improve the survival of breast cancer patients.

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Surgery for primary tumor benefits survival for breast cancer patients with bone metastases: a large cohort retrospective study

BMC Cancer ◽

10.1186/s12885-021-07964-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhangheng Huang ◽

Xin Zhou ◽

Yuexin Tong ◽

Lujian Zhu ◽

Ruhan Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factors ◽

Bone Metastases ◽

Cancer Patients ◽

Primary Tumor ◽

Predictive Accuracy ◽

Rank Test ◽

Breast Cancer Patients ◽

Risk Of Death ◽

The Impact

Abstract Background The role of surgery for the primary tumor in breast cancer patients with bone metastases (BM) remains unclear. The purpose of this study was to determine the impact of surgery for the primary tumor in breast cancer patients with BM and to develop prognostic nomograms to predict the overall survival (OS) of breast cancer patients with BM. Methods A total of 3956 breast cancer patients with BM from the Surveillance, Epidemiology, and End Results database between 2010 and 2016 were included. Propensity score matching (PSM) was used to eliminate the bias between the surgery and non-surgery groups. The Kaplan-Meier analysis and the log-rank test were performed to compare the OS between two groups. Cox proportional risk regression models were used to identify independent prognostic factors. Two nomograms were constructed for predicting the OS of patients in the surgery and non-surgery groups, respectively. In addition, calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the performance of nomograms. Result The survival analysis showed that the surgery of the primary tumor significantly improved the OS for breast cancer patients with BM. Based on independent prognostic factors, separate nomograms were constructed for the surgery and non-surgery groups. The calibration and ROC curves of these nomograms indicated that both two models have high predictive accuracy, with the area under the curve values ≥0.700 on both the training and validation cohorts. Moreover, DCA showed that nomograms have strong clinical utility. Based on the results of the X-tile analysis, all patients were classified in the low-risk-of-death subgroup had a better prognosis. Conclusion The surgery of the primary tumor may provide survival benefits for breast cancer patients with BM. Furthermore, these prognostic nomograms we constructed may be used as a tool to accurately assess the long-term prognosis of patients and help clinicians to develop individualized treatment strategies.

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Incidence of Venous Thromboembolism and the Impact on Survival in Breast Cancer Patients

Journal of Clinical Oncology ◽

10.1200/jco.2006.07.4393 ◽

2007 ◽

Vol 26 (1) ◽

pp. 70-76 ◽

Cited By ~ 156

Author(s):

Helen K. Chew ◽

Theodore Wun ◽

Danielle J. Harvey ◽

Hong Zhou ◽

Richard H. White

Keyword(s):

Breast Cancer ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Metastatic Disease ◽

Cancer Stage ◽

Breast Cancer Patients ◽

Data Set ◽

Discharge Data ◽

Risk Of Death ◽

The Impact

Purpose The incidence of venous thromboembolism (VTE) and the risk factors associated with development of VTE have not been reported in a large population-based study of breast cancer patients. Patients and Methods The California Cancer Registry was merged with the Patient Discharge Data Set, and the number of VTE events determined among patients diagnosed between 1993 and 1999. Results Among 108,255 patients with breast cancer, the 2-year cumulative VTE incidence was 1.2%, with a rate of 1.2 and 0.6 events/100 patient-years during the first and second half-year, respectively. The 1-year incidence of VTE was significantly increased compared with the general population (standardized incidence ratio of VTE, 4.2; 95% CI, 3.9 to 4.4). In a multivariate model, significant predictors of developing VTE within 2 years were: age (hazard ratio [HR], 2.0 if > 75 years v < 45; 95% CI, 1.6 to 2.6), the number of chronic medical comorbidities (HR, 2.9 if 3 v 0; 95% CI, 2.4 to 3.5), and advancing cancer stage (HR, 6.3; 95% CI, 5.3 to 7.5 for metastatic v local disease). In multivariate models, VTE was a significant predictor of decreased 2-year survival (HR, 2.3; 95% CI, 2.1 to 2.6) and when stratified by initial cancer stage, the effect was highest in patients with localized (HR, 5.1; 95% CI, 3.6 to 7.1) or regional stage (HR, 3.5; 95% CI, 2.5 to 4.8) cancer compared with patients with metastatic disease (HR, 1.9; 95% CI, 1.5 to 2.4). Conclusion Approximately 1% of breast cancer patients developed VTE within 2 years, with the highest incidence in the first 6 months after diagnosis. Metastatic disease and comorbidities were the strongest predictors. The diagnosis of VTE was associated with a higher risk of death within 2 years.

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Surgery for Primary Tumor Benefits Survival for Breast Cancer Patients With Bone Metastases: A Large Cohort Retrospective Study

10.21203/rs.3.rs-92765/v1 ◽

2020 ◽

Author(s):

Zhangheng Huang ◽

Xin Zhou ◽

Yuexin Tong ◽

Lujian Zhu ◽

Ruhan Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factors ◽

Bone Metastases ◽

Cancer Patients ◽

Primary Tumor ◽

Predictive Accuracy ◽

Rank Test ◽

Breast Cancer Patients ◽

Risk Of Death ◽

The Impact

Abstract Background: The role of surgery for the primary tumor in breast cancer patients with bone metastases (BM) remains unclear. The purpose of this study was to determine the impact of surgery for the primary tumor in breast cancer patients with BM and to develop prognostic nomograms to predict the overall survival (OS) of breast cancer patients with BM.Methods: A total of 3,956 breast cancer patients with BM from the Surveillance, Epidemiology, and End Results database between 2010 and 2016 were included. Propensity score matching (PSM) was used to eliminate the bias between the surgery and non-surgery groups. The Kaplan-Meier analysis and the log-rank test were performed to compare the OS between two groups. Cox proportional risk regression models were used to identify independent prognostic factors. Two nomograms were constructed for predicting the OS of patients in the surgery and non-surgery groups, respectively. In addition, calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the performance of nomograms.Result: The survival analysis showed that the surgery of the primary tumor significantly improved the OS for breast cancer patients with BM. Based on independent prognostic factors, separate nomograms were constructed for the surgery and non-surgery groups. The calibration and ROC curves of these nomograms indicated that both two models have high predictive accuracy, with the area under the curve values ≥0.700 on both the training and validation cohorts. Moreover, DCA showed that nomograms have strong clinical utility. Based on the results of the X-tile analysis, all patients were classified in the low-risk-of-death subgroup had a better prognosis.Conclusion: The surgery of the primary tumor can provide survival benefits for breast cancer patients with BM. Furthermore, these prognostic nomograms we constructed can be used as a tool to accurately assess the long-term prognosis of patients and help clinicians to develop individualized treatment strategies.

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Impact of timeliness of breast radiotherapy on health outcomes in early breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.6591 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 6591-6591

Author(s):

H. T. Gold ◽

H. T. Do

Keyword(s):

Breast Cancer ◽

Health Outcomes ◽

Cancer Patients ◽

Early Breast Cancer ◽

White Women ◽

Disease Free Survival ◽

Breast Cancer Patients ◽

Post Surgery ◽

Stage 1 ◽

The Impact

6591 Background: The objective of this study is to understand the impact of timely radiotherapy on disease-free survival (DFS) in early breast cancer patients ages 65 and above. Methods: The study population is women diagnosed from 1991–1999 in the linked SEER-Medicare database who underwent breast-conserving surgery and radiotherapy within 6 months of diagnosis. Median followup varies from 4 years for ductal carcinoma in situ (DCIS)(n=1,185) to 5 years for Stage 1 disease (n=7,481), and ranges from 0–11 years. Descriptive and proportional hazards analysis of this longitudinal cohort were conducted. Covariates include age, race, poverty, marital status, comorbidity, rurality, radiation completion and delay, elapsed time since diagnosis, comedo necrosis histology (DCIS only), and chemotherapy receipt (Stage 1 only). Subjects were censored at end of followup (including enrolling in Medicare managed care from Medicare fee-for-service) or death. Treatment delay is defined as radiotherapy beginning 8+ weeks post-surgery without chemotherapy or 4+ weeks after chemotherapy ends; other definitions also were explored. Radiotherapy is considered complete if the patient received greater than 16/22 of expected treatments, based on scientific literature. Results: DFS is negatively associated with radiation delay (OR=1.24, p=0.003 for Stage 1; OR=1.40, p=0.054 for DCIS) and Klabunde's inpatient comorbidity index (OR=1.32, p=0.004 for Stage 1; OR=1.66, p=0.065 for DCIS). Additional analyses suggest that a longer delay of 12+ weeks post-surgery (16+ weeks post-chemotherapy) further reduces DFS (OR=4.66, p<0.0001 for Stage 1; OR=12.4, p<0.0001 for DCIS). Non-white women with Stage 1 disease are more likely to delay radiotherapy (p<0.0001), but are not more likely to have worse outcomes (p>0.3). Conclusions: Delayed initiation of radiation therapy is associated with decreased DFS following radiotherapy for early breast cancer and DCIS. Non-white race is associated with delay, but not reduced DFS. Programs targeting referring physicians and patients should be developed to promote timely receipt of radiotherapy by early breast cancer patients, thereby reducing the risk of adverse health outcomes. No significant financial relationships to disclose.

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Association of Lifestyle Variables and Anthropometric Variables among Breast Cancer Patients at the University College Hospital, Ibadan

European Journal of Medical and Health Sciences ◽

10.24018/ejmed.2021.3.4.997 ◽

2021 ◽

Vol 3 (4) ◽

pp. 154-160

Author(s):

Emmanuel Olumide Adesuyi ◽

Samuel Adedapo Olawoore ◽

Adebayo Komolafe ◽

Oluwatobi Bamidele Kolawole

Keyword(s):

Breast Cancer ◽

Health Education ◽

Cancer Patients ◽

Anthropometric Measurements ◽

Breast Cancer Patients ◽

College Hospital ◽

University College ◽

Before And After ◽

The University ◽

The Impact

Globally, breast cancer is the commonest cause of cancer death and the most frequently diagnosed cancer among women. This study aim to assess lifestyle indices and anthropometric measurements among breast cancer patients at the University College Hospital, Ibadan. This was a descriptive cross-sectional study. 250 respondents were recruited for the study after anticipating a non-response rate of 10%. Simple random sampling technique was used to select participants for the study. A self-designed open-ended questionnaire was adopted. Two hundred and fifty copies were distributed and retrieved. Data collected were analyzed and descriptive statistics presented in tables and charts while hypothesis were tested using multinomial logistic regression at 0.05 level of significance. Majority 150 (60%) of the respondents were within the age range of 45-64 years and 137 (54.8%) of them had tertiary education. The mean: Age was 50 years, weight before, after diagnosis were 72.8kg and 69.2kg, BMI before, and after diagnosis were 28.65 and 27.21 respectively, waist hip ratio (WHR) was 0.91 and conicity index was 1.37. All the respondents 250 (100%) were involved in different type of exercise before diagnosis but only 100 (40%) continued after diagnosis. Out of about 20 (8%) respondents who were smoking before diagnosis, only 15 (6%) continued smoking after diagnosis and out of the 95 (38%) of those who consumed alcohol before diagnosis, only 90 (36%) continued after diagnosis. There were statistically significant associations between BMI, WHR, obesity and selected lifestyle variables before and after diagnosis at p≤0.05. Conclusively, lifestyle variables were found to have significant influence on the anthropometric measures of the body of breast cancer patients regardless of their morbid or pre-morbid state. This study further ratifies the obesity predictive capacity of the body’s anthropometric measurements, which is largely influenced by various lifestyle indices and perhaps other unknown variables such as genetics and environmental influence. Even though a little modification of certain lifestyles were recorded after respondents were being diagnosed with breast cancer, this undeniably could be as a result of fear of disease outcomes, personal effort to get knowledge or the impact of health education from care givers. It was recommended that caregivers should ensure proper health education of clients on lifestyle changes in order to have a safer life and exclude known factors that can predispose them to breast cancer.

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Overexpression of microRNA-21 in the Serum of Breast Cancer Patients

MicroRNA ◽

10.2174/2211536608666190318105757 ◽

2019 ◽

Vol 9 (1) ◽

pp. 58-63

Author(s):

Batool Savari ◽

Sohrab Boozarpour ◽

Maryam Tahmasebi-Birgani ◽

Hossein Sabouri ◽

Seyed Mohammad Hosseini

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Cancer Progression ◽

Tumor Resection ◽

Tumor Grade ◽

Healthy Controls ◽

Breast Cancer Patients ◽

Serum Samples ◽

Post Surgery ◽

Polymerase Chain

Background: Breast cancer is the most common cancer diagnosed in women worldwide. So it seems that there's a good chance of recovery if it's detected in its early stages even before the appearances of symptoms. Recent studies have shown that miRNAs play an important role during cancer progression. These transcripts can be tracked in liquid samples to reveal if cancer exists, for earlier treatment. MicroRNA-21 (miR-21) has been shown to be a key regulator of carcinogenesis, and breast tumor is no exception. Objective: The present study was aimed to track the miR-21 expression level in serum of the breast cancer patients in comparison with that of normal counterparts. Methods: Comparative real-time polymerase chain reaction was applied to determine the levels of expression of miR-21 in the serum samples of 57 participants from which, 42 were the patients with breast cancer including pre-surgery patients (n = 30) and post-surgery patients (n = 12), and the others were the healthy controls (n = 15). Results: MiR-21 was significantly over expressed in the serum of breast cancer patients as compared with healthy controls (P = 0.002). A significant decrease was also observed following tumor resection (P < 0.0001). Moreover, it was found that miR-21 overexpression level was significantly associated with tumor grade (P = 0.004). Conclusion: These findings suggest that miR-21 has the potential to be used as a novel breast cancer biomarker for early detection and prognosis, although further experiments are needed.

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CBR3 V244M is associated with LVEF reduction in breast cancer patients treated with doxorubicin

Cardio-Oncology ◽

10.1186/s40959-021-00103-0 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Jennifer K. Lang ◽

Badri Karthikeyan ◽

Adolfo Quiñones-Lombraña ◽

Rachael Hageman Blair ◽

Amy P. Early ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Care Center ◽

Left Ventricular ◽

The Body ◽

Left Ventricular Ejection ◽

Breast Cancer Patients ◽

Ventricular Ejection Fraction ◽

Echocardiographic Parameters ◽

The Impact

Abstract Background The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts. Objectives This study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment. Methods We recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson’s biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA). Results Breast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups. Conclusions CBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.

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PITX2 DNA-Methylation: Predictive versus Prognostic Value for Anthracycline-Based Chemotherapy in Triple-Negative Breast Cancer Patients

Breast Care ◽

10.1159/000510468 ◽

2020 ◽

pp. 1-9

Author(s):

Rudolf Napieralski ◽

Gabriele Schricker ◽

Gert Auer ◽

Michaela Aubele ◽

Jonathan Perkins ◽

...

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

Predictive Value ◽

Untreated Patient ◽

Triple Negative ◽

Statistical Significance ◽

Breast Cancer Patients ◽

The Impact

Background: PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. Material and Methods: The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. Results: The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; p = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR >2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; p = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; p = 0.014). Conclusion: In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.

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