scholarly journals The Planckian Distribution Equation As A Novel Method To Predict The Efficacy Of Breast Cancer Pharmacotherapy

2021 ◽  
Author(s):  
Shreshth Rajan
Keyword(s):  
Breast Cancer ◽  
Patient Specific ◽  
Mrna Levels ◽  
Breast Cancer Patients ◽  
Drug Induced ◽  
Doxorubicin Treatment ◽  
Rutgers University ◽  
Before And After ◽  
Novel Method ◽  
Distribution Equation

Chemotherapy-related deaths, the result of treatment with faulty medications, account for nearly 10% of all breast cancer deaths (Rashbass, 2016). Patient-specific, personalized medicine is evidently required to administer optimized therapeutics and prevent treatment-related mortality. In order to develop a predictive model for breast cancer therapy, the following study analyzed the mRNA data of 4,704 genes derived from 20 breast cancer patients before and after doxorubicin treatment for 16 weeks (O’brien et al., 2006; Perou et al., 2000). The genomic data of each patient was first stratified into 9 groups (corresponding to the 9 Mechanisms defined in Figure 4) based on mRNA expression in response to the tumor and to the doxorubicin treatment. The study then employed the Planckian Distribution Equation (PDE) discovered at Rutgers University to model the stratified samples by transforming each mechanism into a single long-tailed histogram fitted by the PDE. Our PDE model is based on 3 parameters - A, B, and C - of which 2 were extracted from each model to generate the plots seen in figures 5e and 5f. The drug-induced slopes of the A vs C plots were then determined for all 9 mechanisms of each patient. The study observed an increase in post-treatment mRNA levels for longer surviving patients in 6 mechanisms. Further analysis displayed how the drug treatment uniquely altered each of the mechanisms based on the length of patient survival. These results indicate that the PDE-based procedures described herein may provide a novel tool for discovering potential anti-breast cancer pharmaceuticals.

scholarly journals Towards integration of 64Cu-DOTA-trastuzumab PET-CT and MRI with mathematical modeling to predict response to neoadjuvant therapy in HER2 + breast cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Angela M. Jarrett ◽  
David A. Hormuth ◽  
Vikram Adhikarla ◽  
Prativa Sahoo ◽  
Daniel Abler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Treatment Response ◽  
Growth Factor Receptor ◽  
Patient Specific ◽  
Mathematical Framework ◽  
Breast Cancer Patients ◽  
Data Types ◽  
Her2 Breast Cancer ◽  
Mri Scans

AbstractWhile targeted therapies exist for human epidermal growth factor receptor 2 positive (HER2 +) breast cancer, HER2 + patients do not always respond to therapy. We present the results of utilizing a biophysical mathematical model to predict tumor response for two HER2 + breast cancer patients treated with the same therapeutic regimen but who achieved different treatment outcomes. Quantitative data from magnetic resonance imaging (MRI) and 64Cu-DOTA-trastuzumab positron emission tomography (PET) are used to estimate tumor density, perfusion, and distribution of HER2-targeted antibodies for each individual patient. MRI and PET data are collected prior to therapy, and follow-up MRI scans are acquired at a midpoint in therapy. Given these data types, we align the data sets to a common image space to enable model calibration. Once the model is parameterized with these data, we forecast treatment response with and without HER2-targeted therapy. By incorporating targeted therapy into the model, the resulting predictions are able to distinguish between the two different patient responses, increasing the difference in tumor volume change between the two patients by > 40%. This work provides a proof-of-concept strategy for processing and integrating PET and MRI modalities into a predictive, clinical-mathematical framework to provide patient-specific predictions of HER2 + treatment response.

scholarly journals Cognitive and Psychological Impact of BRCA Genetic Counseling in Before and After Definitive Surgery Breast Cancer Patients

2012 ◽  
Vol 19 (13) ◽  
pp. 4003-4011 ◽  
Author(s):  
Juliette Christie ◽  
Gwendolyn P. Quinn ◽  
Teri Malo ◽  
Ji-Hyun Lee ◽  
Xiuhua Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Counseling ◽  
Cancer Patients ◽  
Psychological Impact ◽  
Breast Cancer Patients ◽  
Before And After ◽  
Definitive Surgery

scholarly journals Breast Cancer: Preparing for Surgery

EDIS ◽  
2007 ◽  
Vol 2007 (15) ◽  
Author(s):  
Martha C. Monroe ◽  
Barbara F. Shea
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Medical Procedures ◽  
Breast Cancer Patients ◽  
Fact Sheet ◽  
Before And After ◽  
And Coping

FCS8829, a 4-page fact sheet by Martha C. Monroe and Barbara F. Shea, is intended for breast cancer patients who are preparing for their lumpectomy or mastectomy surgery. It helps patients understand what to expect before and after surgery. Includes information on understanding medical procedures and coping physically and psychologically. Also features quotes and experiences from other breast cancer patients. Published by the UF Department of Family, Youth and Community Sciences, April 2007.

scholarly journals Drug-Induced Resistance and Phenotypic Switch in Triple-Negative Breast Cancer Can Be Controlled via Resolution and Targeting of Individualized Signaling Signatures

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 5009
Author(s):  
Swetha Vasudevan ◽  
Ibukun A. Adejumobi ◽  
Heba Alkhatib ◽  
Sangita Roy Chowdhury ◽  
Shira Stefansky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Patient Specific ◽  
Network Structures ◽  
Breast Cancers ◽  
Drug Induced ◽  
Tcga Dataset

Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancers which is treated mainly with chemotherapy and radiotherapy. Epidermal growth factor receptor (EGFR) was considered to be frequently expressed in TNBC, and therefore was suggested as a therapeutic target. However, clinical trials of EGFR inhibitors have failed. In this study, we examine the relationship between the patient-specific TNBC network structures and possible mechanisms of resistance to anti-EGFR therapy. Using an information-theoretical analysis of 747 breast tumors from the TCGA dataset, we resolved individualized protein network structures, namely patient-specific signaling signatures (PaSSS) for each tumor. Each PaSSS was characterized by a set of 1–4 altered protein–protein subnetworks. Thirty-one percent of TNBC PaSSSs were found to harbor EGFR as a part of the network and were predicted to benefit from anti-EGFR therapy as long as it is combined with anti-estrogen receptor (ER) therapy. Using a series of single-cell experiments, followed by in vivo support, we show that drug combinations which are not tailored accurately to each PaSSS may generate evolutionary pressure in malignancies leading to an expansion of the previously undetected or untargeted subpopulations, such as ER+ populations. This corresponds to the PaSSS-based predictions suggesting to incorporate anti-ER drugs in certain anti-TNBC treatments. These findings highlight the need to tailor anti-TNBC targeted therapy to each PaSSS to prevent diverse evolutions of TNBC tumors and drug resistance development.

scholarly journals Concordance Between ER, PR, HER2 neu Receptors Before and After Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Heba F. Taha ◽  
Ola M. Elfarargy ◽  
Reham A. Salem ◽  
Doaa Mandour ◽  
Amira A. Salem ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Before And After ◽  
Tumor Phenotype

Abstract Background Introducing neoadjuvant chemotherapy (NCT) in a breast cancer patient may be associated with changes in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth hormone receptor 2 (HER2) status. Method In our prospective cohort study, we evaluated the impact of change in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth hormone receptor 2 (HER2) on the prognosis of breast cancer patients treated with neoadjuvant chemotherapy (NCT). We investigated 110 patients with locally advanced breast cancer for ER, PR and HER2 status of their lesions before and after NCT. Result For hormone receptor status (HR) (which include ER, PR) of the residual tumor of the patients after receiving NCT, 12 (10.9%) of them changed from HR (+) to HR (−) and 15 (13.6%) changed from HR (−) to HR (+). For HER2 status after NCT, 8 (7.3%) patients changed from HER2 (+) to HER2 (−) and 9 (8.2%) patients changed from HER2 (−) to HER2 (+). Triple negative (TN) tumor phenotype changes occurred in 17 (15.5%) patients. Patients for whom the HR status changed from positive to negative had poor prognosis for both disease-free survival (DFS) and overall survival (OS) in univariate survival analysis. Conclusion Changes in ER, PR, HER2 status and tumor phenotype in breast cancer patients after NCT had a negative prognostic impact and were associated with a poor prognosis.

scholarly journals Multiomics analysis of serial PARP inhibitor treated metastatic TNBC inform on rational combination therapies

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Marilyne Labrie ◽  
Allen Li ◽  
Allison Creason ◽  
Courtney Betts ◽  
Jamie Keck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
Parp Inhibition ◽  
Patient Specific ◽  
Combination Therapies ◽  
Breast Cancer Patients ◽  
Effector Cells ◽  
Basal Breast Cancer ◽  
Rational Combination

AbstractIn a pilot study, we evaluated the feasibility of real-time deep analysis of serial tumor samples from triple negative breast cancer patients to identify mechanisms of resistance and treatment opportunities as they emerge under therapeutic stress engendered by poly-ADP-ribose polymerase (PARP) inhibitors (PARPi). In a BRCA-mutant basal breast cancer exceptional long-term survivor, a striking tumor destruction was accompanied by a marked infiltration of immune cells containing CD8 effector cells, consistent with pre-clinical evidence for association between STING mediated immune activation and benefit from PARPi and immunotherapy. Tumor cells in the exceptional responder underwent extensive protein network rewiring in response to PARP inhibition. In contrast, there were minimal changes in the ecosystem of a luminal androgen receptor rapid progressor, likely due to indifference to the effects of PARP inhibition. Together, identification of PARPi-induced emergent changes could be used to select patient specific combination therapies, based on tumor and immune state changes.

scholarly journals Managing Cancer and Living Meaningfully (CALM) Intervention on Chemotherapy-Related Cognitive Impairment in Breast Cancer Survivors

2020 ◽  
Vol 19 ◽  
pp. 153473542093845
Author(s):  
Ke Ding ◽  
Xiuqing Zhang ◽  
Jingjing Zhao ◽  
He Zuo ◽  
Ziran Bi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cognitive Impairment ◽  
Psychological Distress ◽  
Cognitive Function ◽  
Cancer Therapy ◽  
Cancer Patients ◽  
Functional Assessment ◽  
Breast Cancer Survivors ◽  
Breast Cancer Patients ◽  
Before And After

Objective: To evaluate the effectiveness and feasibility of Managing Cancer and Living Meaningfully (CALM), which is used to reduce chemotherapy-related cognitive impairment (CRCI), relieve psychological distress, and improve quality of life (QOL) in Chinese breast cancer survivors (BCs). Methods: Seventy-four BCs were enrolled in this study. All patients were randomly assigned to either the CALM group or the care as usual (CAU) group. All patients were evaluated by the Functional Assessment of Cancer Therapy–Cognitive Function (FACT-Cog), Distress Thermometer (DT), and the Functional Assessment of Cancer Therapy–Breast (FACT-B) before and after CALM or CAU application to BCs with CRCI. We compared the differences in all these scores between the CALM group and the control group and analyzed the correlation between cognitive function and QOL. Results: Compared with the CAU group, the performance of the CALM group on the FACT-Cog, DT, and FACT-B showed significant differences before and after CALM ( t = −18.909, −5.180, −32.421, P = .000, .000, .000, respectively). Finally, there was a positive correlation between cognitive function and QOL in breast cancer patients before ( r = 0.579, P = .000) and after ( r = 0.797, P = .000) treatment. Conclusions: The present results indicated that CALM has salutary effects on the improvement of cognitive impairment and QOL and relieves psychological distress in breast cancer patients, which may be due to a positive correlation between psychological distress and cognitive function or QOL.

scholarly journals Myocardial infarction, ischaemic stroke and pulmonary embolism before and after breast cancer hospitalisation

2011 ◽  
Vol 106 (07) ◽  
pp. 149-155 ◽  
Author(s):  
Sumitra Shantakumar ◽  
Pieter W. Kamphuisen ◽  
Fernie J. A. Penning-van Beest ◽  
Ron M. C. Herings ◽  
Myrthe P. P. van Herk-Sukel
Keyword(s):  
Breast Cancer ◽  
Myocardial Infarction ◽  
Pulmonary Embolism ◽  
Ischaemic Stroke ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Increased Risk ◽  
Before And After ◽  
Receive Treatment ◽  
Free Women

SummaryWe studied the occurrence of myocardial infarction (MI), ischaemic stroke (IS) and pulmonary embolism (PE) before and after breast cancer hospitalisation compared with cancer-free controls. For this, women with a first breast cancer hospitalisation during 2000–2007 were selected from the PHARMO Record Linkage System, including drug use and hospitalisations of three million inhabitants in the Netherlands, and matched 1:10 by age to cancer-free women. The occurrence of MI, IS and PE were assessed in the 12 months before and after breast cancer hospitalisation. The study included 11,473 breast cancer patients, with a mean (± SD) age of 59 (± 14) years. Breast cancer patients were two to three times as likely as their cancer-free controls to have had a hospitalisation for PE, MI or IS in the 12 months before diagnosis, though prevalence was <1% in all groups. Breast cancer patients experienced an extreme high risk of PE in the first six months after diag- nosis (hazard ratio [HR] 23.5, 95% confidence interval [CI] 11.1–49.7 compared to controls), which declined gradually to a four times increased risk (HR 3.6, 95%CI 2.4–5.5) more than 12 months after breast cancer hospitalisation. However, incidence was low: less than five events per 1,000 person years during all time periods. For MI and IS we did not observe significant increased HRs after breast cancer hospitalisation compared to controls. Breast cancer patients seem to have a higher risk profile to develop MI and IS, and receive treatment that increases the risk of PE compared to cancer-free controls, although the frequency of hospitalisations was low.

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