bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation and cardiotoxicity: A retrospective analysis of a midwest population.
Authors: Tandan Nitin , Koester Cameron , Parajuli Priyanka , Lara Garcia Odalys Estefania , Regmi Manjari Rani , Cheema Asad , Maini Ruby , Abedrabo Sabree , Sahib Hamsa , Mirihagalle Noupama , Niaz Zurain , Bhandari Bishal , Johnson Alexander , Ibrahim Abdisamad M. , Delfino Kristin , Robinson Kathy , Desai Meghna R. , Kulkarni Abhishek 
Published: May 2020

e12616 Background: The most common female malignancy diagnosed in the US is breast cancer. Early breast cancer therapy is often treated with radiation therapy; one of the unfortunate side effects of radiotherapy in the past has been cardiotoxicity, especially coronary artery disease. Recent usage of dose reduction techniques have helped reduce these effects. Here, we present our analysis of breast cancer patients that received radiation therapy and the likelihood of cardiotoxicity. Methods: An IRB-approved retrospective study was performed utilizing ICD codes to analyze patients diagnosed with biopsy-confirmed breast cancer between January 1, 2014 and December 31, 2017. 478 of 1618 de-identified patients qualified for this study. Statistical analysis was performed with SAS v9.4. Descriptive statistics were computed for all study variables. Continuous variables were described with measures of central tendency (mean, median) and dispersion (range, standard deviation). Categorical variables were summarized as frequencies and percentages. Comparisons between categorical variables were compared with the Chi-Square test (or Fisher’s Exact) where appropriate. Survival curves were estimated using Kaplan-Meier methodology and analyzed with a log rank test. Predictors of survival were assessed with Cox proportional hazards regression analyses. All significance is assumed at the p < 0.05 level. Results: Of the 478 eligible patients, heart failure (HF), HF hospitalizations, acute coronary syndrome and overall cardiac events were compared among breast cancer patients. Patients who received radiation experienced HF 6.02% compared to 4.61% without radiation (p = 0.574). HF hospitalization was recorded as 2.27% in radiotherapy compared to 1.23% in non-radiotherapy patients (p = 0.686). Patients who radiation experienced ACS 2.27% of the time as compared to 1.21% in patients who were not treated with radiation. Of note, 9.25% receiving radiation experienced cardiac events compared to 4.24% in patients without radiation (p = 0.068). While results were not statistically significant, the trend of elevated cardiac events in breast cancer patients receiving radiation is noteworthy. Conclusions: Per our study, although statistically insignificant, radiation therapy may result in higher incidence of cardiac events in breast cancer patients. Further large-scale, prospective studies should be performed to confirm the aforementioned trends with respect to survival outcomes in urban and rural populations.
Identification of CCN1 transferred by extracellular vesicles derived from breast cancer cells responsible for doxorubicin-resistance.
Authors: Yang Sujin , Tang Jinhai 
Published: May 2020

e12623 Background: The anthracycline drug, doxorubicin, is one of the most frequently used chemotherapeutic drugs for breast cancer. However, not all patients respond to doxorubicin-containing combination chemotherapy due to chemo-resistance (natural or acquired). Preceding researches have shown that extracellular vesicles (EVs) can be readily harvested from peripheral blood for further biological analysis and thus perform an attractive source of tumor derived materials for identification of chemo-resistance factors. This study aims to provide a theoretical basis to use CCN1-containing EVs as new biomarkers and therapeutic targets for doxorubicin-resistance in breast cancer. Methods: A strategy combining RNA-sequencing technique and bioinformatic analysis was used to determine the level of differential expressed mRNAs in EVs samples from cellular supernatant (n = 4) and blood serum (n = 8) from chemo-resistant and chemo-sensitive patients. Serial gene expression analysis in patients (n = 203) who treated with neoadjuvant (GSE32603) were also employed to identified drug-resistance-related proteins. The expression of CCN1 was detected in doxorubicin-resistant cell lines (MCF-7/DOX),MCF-7 and their EVs by RT-qPCR and western blot. Then, we used cell apoptosis and immunofluorescence stain to confirm the ability of CCN1-containing EVs in conferring drug resistance. Immunohistochemistry stain and RT-qPCR were used to prove the expression level of CCN1 in tumor tissues from breast cancer patients (n = 80) and in serum EVs from patients treated with the whole neoadjuvant chemotherapy. Results: We combined the differentially expressed mRNAs from three datasets and found identified CCN1 as a drug-resistance-related factor in breast cancer. The expression level of CCN1 is much higher in MCF-7/DOX cells and their EVs compared with MCF-7 cells and their EVs. The addition of CCN1-containing EVs has been found significantly increase the resistance to doxorubicin in sensitive cells. Moreover, a higher expression level of CCN1 was detected in the progressive disease (PD)/stable disease (SD) group than in the partial response (PR)/complete response (CR) group both in tissues and serum EVs. Conclusions: All These findings demonstrate that CCN1-containing EVs appear to be essential in conferring resistance to doxorubicin. More importantly, we exhibit the potential applications of CCN1-containing EVs for predicting the efficiency and outcome of patients treated with doxorubicin-based chemotherapy.
Biodynamic response prediction in breast cancer patients receiving neoadjuvant chemotherapy.
Authors: Morgan Travis , Whitacre Eric , Burak William , Manahan Eric , Goedde Timothy , Greenspan Andrew , Woods John , Nolte David , Turek John , Loesch David M. , An Ran 
Published: May 2020

e12643 Background: Biodynamic signatures (temporal patterns of microscopic motion within a three-dimensional tumor explant) offer a phenomic biomarker that is highly predictive for therapeutic response. The purpose of this study is to evaluate predictive accuracy of a biodynamic drug response classifier in breast cancer patients receiving neoadjuvant chemotherapy (NAC). Methods: Consecutive breast cancer patients from 4 institutions were screened for enrollment in a prospective observational study (NCT03164863). Treatment-naïve needle biopsies were delivered to a central laboratory where biodynamic signatures were measured in living tumor fragments challenged by standard-of-care cytotoxins. Patients received NAC per institutional guidelines and were followed through surgical intervention. A four-point classifier was trained to predict pathologic complete response (CR) then prospectively validated. Results: Among patients completing neoadjuvant treatment and surgical intervention, 33% (24 of 72) achieved CR. The biodynamic classifier predicted CR with 96% sensitivity and 97% negative predictive value. Biodynamically “favored” (scoring ≥ 3) and “strongly favored” (scoring 4) regimens produced CR at rates of 56% (23 of 41) and 73% (19 of 26), respectively. Only 3% of patients (1 of 31) achieved CR from regimens scoring 1 or 2. Area under the receiver operating curve (AUC) was 87% (95% CI: 75% to 93%, p < .0001), with similar performance across all subtypes and therapy cohorts (range: 84% to 89%). Performance of the classifier on training and validation patients was statistically equivalent. Conclusions: Biodynamic scoring accurately predicts response in breast cancer patients receiving NAC and holds promise to substantially improve management of these patients. [Table: see text]
Risk of recurrence in patients with HER2+ breast cancer who achieved a pathological complete response (pCR) after neoadjuvant pertuzumab and trastuzumab (nPT), and received adjuvant trastuzumab (aT): Real-world evidence.
Authors: Robert Nicholas J. , O'Shaughnessy Joyce , Annavarapu Srinivas , Zhou Jie , Sussell Jesse , Cheng Anna , Fung Anita 
Published: May 2020

e12648 Background: The real-world risk of disease recurrence in patients with HER2+ early breast cancer who achieved pCR after receipt of nPT-based regimens and aT is unclear. Methods: Women with HER2+ breast cancer who achieved pCR after nPT-based regimens and received aT were identified in the US Oncology Network (USON). Patients initiated nPT between 2013 –2015 and were followed until recurrence of invasive disease or censoring. Data was sourced from structured fields and review of USON patient charts. Recurrence of invasive disease was defined as any of: recurrence of ipsilateral locoregional invasive breast cancer, contralateral breast cancer, distant disease recurrence, or death. Descriptive analyses were used to assess baseline demographic and clinical characteristics and the Kaplan-Meier method was used to assess invasive disease-free survival (iDFS), with stratification by nodal status. Results: A total of 238 pCR patients’ charts were reviewed. Median patient age was 52 (range: 23-88) years and a majority were White (77%). Most patients had stage IIA (39%) or IIB (24%) disease at diagnosis, ECOG score < 1 (85%), and tumor size > 2 cm (68%). At diagnosis, the majority of patients (57%) were node positive (N+) and negative for estrogen or progesterone receptor expression (51%). Median durations of therapy for nPT and aT were 4 (range: 1-8) and 7 (range: 0.03-53) months, respectively. The median duration of follow up was 47 (range: 1-70) months. Four-year iDFS probabilities are shown in the Table. Conclusions: Consistent with previously reported clinical trial data and several pooled analyses, results from this real-world study indicate that despite achieving pCR after nPT-based regimens, patients with HER2+ BC remain at risk for disease recurrence; in addition, node+ status appears to increase that risk. Therefore, patients should receive standard pertuzumab, trastuzumab adjuvant therapy to optimize treatment outcomes. [Table: see text]
Discordance between molecular subtyping from pre- and post-neoadjuvant chemotherapy (NACT) biopsy specimens in a Brazilian breast cancer cohort.
Authors: Tavares Monique Celeste , Leite Luciana de Moura , Cesca Marcelle Goldner , de Andrade Poliana , Pirolli Rafaela , Xerfan Mariana Pinheiro , Oliveira Fernanda A. , Silva Sinara Figueiredo , Zanco Fogassa Camilla Albina , Mattos Bruna Raphaeli Silva , Campos Fernando Augusto Batista , Sanches Solange Moraes , Cordeiro De Lima Vladmir Claudio 
Published: May 2020

e12649 Background: Discordance between immunohistochemistry (IHC) and molecular subtyping from pre and post neoadjuvant chemotherapy (NACT) biopsy specimens in breast cancer (BC) patients (pts) varies in the literature. This information could have prognostic and treatment implications. To evaluate the clinicopathologic characteristics and prognostic factors in pts with localized breast cancer treated with NACT who had IHC repeated in the post treatment biopsies. Methods: We retrospectively reviewed all BC pts treated with NACT at our service (2007 – 2018). Descriptive statistics were used to describe the population. Survival curves were estimated by Kaplan-Maier method, prognostic factors adjusted by Cox regression model. Results: 607 consecutive pts were treated with NACT at our service. From those, 178 (29.3%) had a pathological complete response, 420 (69.2%) had residual disease and 9 (1.5%) had an unknown status. For 95 pts, the IHC was repeated in the pathological specimen, with a change in the molecular subtype in 26 (27.3%) cases. 10 luminal pts lost the hormonal receptor expression and changed to triple negative, 6 luminal B became luminal A, 3 luminal A became luminal B, 6 pts lost the her2 amplification and 1 pt gained a her2 amplification. This 95 pts cohort had a median desease free survival (DFS) of 71 months (m) and an overall survival (OS) of 137m. Pts who had a change in their molecular subtype after NACT had a DFS of 52 m vs 71m (p .26) and OS 86m, not significantly different from those who maintained the same status (p .23). Conclusions: A little more than one quarter of the pts that had repeated post NACT IHC had a change in the molecular subtype, especially with loss of hormonal receptors of luminal tumors, that became triple negative. That did not translated into significantly worse survivals.
Metabolic profile in Mexican young women breast cancer (YWBC) to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC).
Authors: Cruz-Ramos Marlid , Nambo-Venegas Rafel , Campos-Salgado Jose Yair , Ruíz-Godoy Luz , Enríquez-Carcamo Victoria , Mohar Alejandro , Villarreal-Garza Cynthia 
Published: May 2020

e12652 Background: YWBC is associated with aggressive biology with a higher mortality rate and recurrence risk. Similar to older patients, pCR after NAC is a surrogate marker of disease-free survival and overall survival in YWBC. However, YWBC who did not achieve pCR did significantly worse. Metabolic profile (MP) has been used for biomarker discovery to monitor chemotherapy response. Few studies focus on using metabolomics to predict pCR in BC. The study aimed to identify MP in YWBC, before NAC to predict response to chemotherapy. Methods: A targeted metabolomics approach was employed to determine the concentration of 11 AAs, free carnitine, and 30 ACCs using electrospray tandem mass spectrometry in plasma of 30 YWBC patients, before NAC to select plasma biomarkers with the most predictive power to identify pCR in YWBC. Patients were classified in responders (R) and non-responders (NR), based on pCR or not-pCR reported by the pathologist department. The differences between R and NR groups were evaluated using an analysis of Random Forest decision trees according to the distribution of the variables. To evaluate the diagnostic power of each biomarker alone, we performed univariate receiver operating characteristics (ROC) analysis on each biomarker to obtain its ROC curve, ROC area under the curve (AUC), and standard error (SE) of the AUC. Results: We observed differences in MP between R and NR YWBC. Ten metabolites contributed most to differentiating between both groups. We developed a model that included two short-chain acyl-carnitines (AC4 and AC5:1) that allowed an AUC of 0.851 (0.767-0.921) and AUC of 0.737 (0.806-0.844) respectively, and ornithine with AUC of 0.723 (0.6-0.626). Conclusions: There are different MP among Mexican YWBC patients classified as R and NR to NAC. To our understanding, this is one of the first studies that evaluate MP in YWBC in Mexico. Further studies are needed to validate a metabolic signature to predict pCR in this patient group.
Need for systematic de-escalation of care in HER2+ breast cancer patients.
Authors: Pandey Tushar , Earnest Tyler M , Cole John A , Braun Eduardo 
Published: May 2020

e12657 Background: Over the last decade, there has been incredible progress in HER2-positive breast cancer patients with the adoption of targeted therapies like Trastuzumab and Pertuzumab to complement existing chemotherapies. Increasingly neoadjuvant therapy is the preferred method of therapy as it is better able to predict prognosis via pCR as well as guide adjuvant therapeutic strategy in cases with residual tumor. There are now a variety of combination therapies recommended for HER2-positive patients. As new therapies are developed, the standard-of-care shifts towards the regimen with highest pCR rate. The latest regimen being TCHP which produced pCR rates over 60% in clinical trials. While the improvement in pCR rates at a population level is encouraging, there is a growing sentiment among physicians that we may be over treating patients impacting both costs and resulting toxicity. Methods: We performed an analysis of Breast Cancer trials with pCR as the primary end point and stratification available based on HER2+ status. The cost (median insurance reimbursement) was also referenced from a recent ASCO observational study as a proxy for direct costs of drugs. Toxicities were referenced and each regimen scored (TS) from NCCN Evidence Blocks and adverse events from clinical trials. Potential savings were evaluated if a clinician had the ability to individualize regimen choice by patient. We utilized the SimBioSys TumorScope platform to perform in silico simulations to predict response to alternate therapies as it had previously used to analyze potential deescalate between AC-T vs TC in a HER2- cohort. Results: The following regimens were evaluated HP (pCR:17%,TS:1), TH (pCR: 29%,TS: 2) THP (pCR: 46%, TS: 3), TCH (pCR: 43%, TS: 4), TCHP (pCR: 64%, TS: 5), AC-TH (pCR: 43%, TS: 6), AC-THP(pCR: 55%, TS: 7). Based on an in-silico analysis and selection (where pCR was likely with multiple regimens), the lowest cost & toxicity regimen was selected. The estimated average saving per case of over $100,000 for the overall treatment plan . The calculated toxicity score was also reduced by this method to under 4 from the TCHP(5) standard of care. Conclusions: While the results above are estimates and perfection in such individualization may not be possible, an in-silico approach provides a promising solution.
Assisting decision making on the use of carboplatin for metastatic breast cancer.
Authors: Gomez Marti Juan Luis , Rosenzweig Margaret Q. , Brufsky Adam 
Published: May 2020

e13008 Background: Metastatic breast cancer (MBC) is currently treated with chemotherapy, often in combination with targeted or hormonal therapies. Current guidelines indicate the use of paclitaxel in combination with HER2-targeted therapy for HER2+ disease. Platins are often used in combination with taxanes for HER2+, and rarely for HER2(-), metastatic disease. While some studies reported no benefit from carboplatin (Carbo), others showed an additive effect in combination with a taxane (Txn). At this time, it is not clear if platins are an effective course of treatment for HER2+bone only disease. Therefore, this study investigates in a real-world clinical setting the utility of Carbo after the diagnosis of a first metastasis. Methods: Clinical information was obtained using a database with MBC patients seen at Magee Women’s Hospital from 1999-2019. After a chart review, patients were initially classified according to their molecular status and first metastatic location. Overall survival (OS) and time to next therapy (TTNT) were measured (months) and compared between those who received Txn and those who received Carbo in combination with a Txn after first metastatic diagnosis. Treatment response was investigated in either bone or visceral (lung or liver) MBC. Log ranks were used to estimate survival. Results: From 1,723 patients, 36.15% developed first metastasis to bone, 8.7% to lung, 12.63% to lymph node, 9.46% to liver, 4.17% to brain, and 23.33% to other sites. We found that HER2+ patients firstly diagnosed with visceral metastasis benefited from Carbo+Txn vs Txn only (OS 53.27 vs 38.17, P = 0.034), but not those who were HER2(-) (OS 23.20 vs 25.03, P = 0.307), or with bone metastasis, regardless of HER2 status (OS 38.57 vs 37.13, P = 0.718). However, patients with bone metastasis showed an increased TTNT with Carbo+Txn vs Txn alone (13.68 vs 8.167, P = 0.007). Finally, patients with liver metastasis who received Carbo+Txn had an increased OS (51.7 vs 20.4, P = 0.01) and TTNT (17.33 vs 8.63, P = 0.02) compared to Txn only. Looking separately at HER2 status, we found a nonsignificant trend towards Carbo+Txn efficacy in both subtypes. No differences in OS were found when looking at lung as the first metastatic location (Carbo+Txn vs Txn, 30.67 vs 27.03, P = 0.75). Conclusions: Patients whose first metastasis is to the liver, and those who are HER2+ and develop visceral metastasis, might benefit from carboplatin in combination with a taxane and HER2-targeted therapies. There is no benefit from adding carboplatin for bone metastasis. Further studies with larger datasets could validate these results.
Real-word incidence and management of durable complete response in de novo metastatic HER2-positive breast cancer.
Authors: Smith Claire Elizabeth Powers , Marcom Paul Kelly , Mitri Zahi Ibrahim 
Published: May 2020

e13017 Background: HER2-directed therapies enable a small number of patients with de novo HER2+ metastatic breast cancer (MBC) to achieve long term durable responses (DR). However, clinic-pathologic factors that correlate with DRs in de novo HER2+ MBC are unknown. Expert opinion dictates indefinite HER2-directed therapies for patients who achieve DRs, but real-world examples of this practice, especially the effect on cardiotoxicity, are lacking in the literature. Methods: This is a retrospective case control study of patients with de novo HER2+ MBC who received treatment with trastuzumab at two NCI designated cancer centers between the years 2012-2017. Patients were included if ≥2 years of follow up data were available or if patients were deceased. DRs are defined as radiographic complete or partial response without progression or death at any point after diagnosis. Controls are patients with evidence of radiographic progression or death any point after diagnosis. Age at diagnosis, ER/PR status, site of metastasis, and initial treatment were analyzed. An un-paired T test for age and fisher exact test for categorical variables were used. Results: A total of 96 patients with de novo HER2+ MBC, 28 with DRs and 68 with progression, were identified. Average follow up length for patients with DR was 90 months (range 27-224 months). Patients who progressed had a mPFS of 17.5 months and a mOS of 60 months. Results are shown in Table. Additionally, six patients (6.3%) developed reduced ejection fraction, one with DR, five with progression. Nine patients have been receiving trastuzumab for over ten years with no evidence of disease. Only one patient opted to discontinue this therapy a year after complete response and is disease free five years from diagnosis. Conclusions: Nearly a third of patients with de novo metastatic HER2+ MBC in our dataset achieved DR. Factors that predict DRs include single organ involved by metastatic disease and more intensive upfront chemotherapy including trastuzumab and pertuzumab. The majority of patients with DR continued HER2 directed therapy indefinitely with minimal cardiotoxicity. In the absence of predictive biomarkers of DRs, indefinite trastuzumab administration is common practice for these patients. [Table: see text]
Cardiac complications of CDK4/6 inhibitors for breast cancer.
Authors: Master Samip R. 
Published: May 2020

e13038 Background: Cardiac toxicity has largely been underestimated toxicity of CDK4/6 inhibitors. We did a retrospective analysis of data made available to public by the FDA regarding the cardiac adverse effects of CDK 4/6 inhibitors. We used data from trastuumab for comparison purpose. Methods: The FDA has made the data on adverse effects of various treatments available to general public through the FDA Adverse Events Reports System (FAERS) public dashboard. We investigated the cardiac toxicities of CDK 4/6 inhibitor therapies available at FDERS for the years 2018-2019. Results: A total of 27,079 advere events(AE) from CDK4/6 inhibitors namely, ribociclib, palbociclib and abemaciclib were reported during the year 2018-2019. Out the total, 805 i.e. 2.9% were cardiac AEs. The most common reported cardiac AE were atrial fibrillation (121), myocardial infarction (190), cardiac failure (85) and pericardial effusion (70). As shown in the table, percentage of cardiac AE compared to total AE reported were 2.2%, 5.4%, 7.9% and 7.2% respectively for Palbociclib, Abemaciclib, Ribociclib and trastuzumab. Conclusions: Out of the reported cases of adverse reaction to CDK4/6 inhibitors, 2.9 % were cardio toxicities. The incidence of cardiac complications was higher in ribociclib, compared to Palbociclib and Abemaciclib. [Table: see text]