bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are there inequities in reconstruction after mastectomy in breast cancer patients related to race or insurance status?
Authors: Chuba Paul J. , Vlachaki Maria T. , Koerner Sean , Stefani William , Falk Jeffrey 
Published: May 2020

e12615 Background: Patients with invasive or in-situ breast cancers may increasingly be offered bilateral mastectomy with reconstruction with a view towards achieving symmetry and risk reduction. We investigated whether this treatment option was offered equally based on race and insurance status. Methods: Rates of mastectomy and reconstruction were studied among 4703 patients diagnosed or treated at Ascension St John Hospital, Ascension Macomb Oakland Hospital, and Ascension Providence Hospital between 2005 and 2015. Data collected included demographics, tumor characteristics, insurance (primary payer), first course of surgical treatment, vital status, and cause of death. Cases coded as contralateral mastectomy and reconstruction were considered as representative of “bilateral mastectomy” and reconstruction. Results: Insurance status could be definitively categorized as HMO/PPO, fee for service (FFS), Medicare, or Medicaid in 2375 breast cancer patients. Medicaid HMO was categorized as Medicaid and Medicare with or without supplemental insurance was categorized as Medicare. For simplicity, cases coded as uninsured, other, and NOS were not analyzed further. A total of 406 of 2375 (17.0%) were coded as contralateral mastectomy with reconstruction. Smaller numbers of Medicare cases had contralateral mastectomy and reconstruction (7.3%) compared to 23.3% for HMO/PPO, 26.3% for FFS, and 16% for Medicaid, presumably related to older age. Within each insurance category, similar proportions of Caucasian and African American women were treated with contralateral mastectomy (Table) compared to all patients (Table). Conclusions: Patients having Medicaid insurance had lower rates of contralateral mastectomy and reconstruction compared to HMO/PPO and FFS cases. African American race did not appear to be associated with lower rates of this surgery within the Ascension St John, Ascension Macomb Oakland, and Ascension Providence hospitals. [Table: see text]
Prognostic and predictive value of neutrophil/lymphocyte ratio in patients with triple-negative and HER2-positive breast cancer undergoing neoadjuvant systemic therapy.
Authors: Jagiello-Gruszfeld Agnieszka I. , Jodkiewicz Magdalena , Kowalska Maria , Michalski Wojciech , Olszewski Wojciech P , Niwinska Anna , Gorniak Anna , Pogoda Katarzyna , Dubianski Roman , Gorska Katarzyna , Glinka Ewa , Pienkowski Tadeusz , Nowecki Zbigniew 
Published: May 2020

e12620 Background: Preoperative neutrophil-lymphocyte ratio (NLR) have been suggested to be correlated with the prognosis of patients with breast cancer (BC). However, the results still remain controversial. The goal of our study was to evaluate the predictive and prognostic value of NLR in early stage triple negative and HER2-pos breast cancer patients undergoing NAC. Methods: 96 female patients (pts) with histologically proven breast cancer (51 TNBC, and 45 HER2 pos) were analysed in this retrospective analysis. The NLR before the initiation of NAC was documented. Histopathological response in surgically removed specimens was evaluated using the Residual Cancer Burden (RCB) Calculator (by MD Anderson Cancer Center). The pCR was defined as no invasive tumor in primary tumor bed and lymph nodes. The NLR variable was analyzed as both continuous and categorical. The impact on pCR and RCB was tested using Mann-Whitney, Kruskal-Willis or the Chi-2 test, respectively. Results: Only 4 categories of NAC were used: in TNBC 4 x ACdd followed by 12 x PCL (38 pts) or 4 x ACdd followed by 12 x PCL+ carboplatin AUC 1.0-2 (13 pts), in HER2-pos 39 pts received 6 x TCH (docetaxel + tratuzumab + carboplatin AUC 6) and 6 pts 4 x ACdd followed by 12 x PCL iv + 4 x trastuzumab. In 27 pts (53%) with TNBC and 24 pts (53%) with HER2-pos breast cancer pCR was obtained after NAC. RCB distribution was: 0-53.1%, 1-22%, 2-17.6%, 3-7.3%. No association with NLR and pCR could be observed (p > 0.26). No association with NLR and RCB could be observed (p > 0.18). Conclusions: In our retrospective analysis we could not demonstrate predictive or prognostic value of NLR in the cohort of early stage triple negative and HER2-positive breast cancer patients treated with NAC. Further studies are planned in a group of patients with Luminal B, HER2 – negative breast cancer, who received NAC.
Clinical value of kinase Aurora-A serum level determination in patients with breast cancer qualified for neoadjuvant chemotherapy: Pilot study.
Authors: Kotowicz Beata , Winter Pawel , Fuksiewicz Małgorzata , Jagiello-Gruszfeld Agnieszka I. , Pogoda Katarzyna , Nowecki Zbigniew , Kowalska Maria 
Published: May 2020

e12627 Background: Aurora A (AURKA) is serine/threonine kinase that plays a regulatory role in mitosis and multiple signaling pathways. Overexpression of AURKA has been found in many solid tumors including breast cancer. It also has been found to be a prognostic marker indicating resistance to taxane treatment and poor prognosis in ER positive breast cancer. The aim of this study is to assess clinical value of Aurora-A serum level determination in patients with breast cancer qualified for neoadjuvant chemotherapy. Methods: 60 patients with confirmed breast cancer before treatment were qualified for the study, aged 31-77 (median 52 years), including 30 premnopausal and 30 pomenopausal. The control group consisted of 30 healthy women aged 20-80 (median 53 years). Clinical and pathological features were determined in a selected group of patients with breast cancer who subsequently underwent preoperative chemotherapy, i.e. tumor size (T), lymph node status (N), presence of distant metastases (M), estrogen receptor status (ER) and progesterone (PgR), HER2 receptors and Ki 67 proliferative index. The blood serum of the examined patients and healthy women was determined by the enzyme-linked ELISA method in doublets of the AURKA biomarker concentration. Mann-Whitney test and ROC curve analysis were used for statistical calculations. Results: No significant differences were found between the concentrations of AURKA in breast cancer patients and in the control group. In both analyzed groups there were no significant differences in biomarker levels depending on the menopausal status. When assessing the relationship between AURKA concentrations and clinical-pathological features, significant differences were found depending on the state of the lymph nodes (N0 vs N1 + N2) (p = 0.006). There was no correlation between the concentrations of the tested biomarker and the tumor size (T), the state of receptors and the Ki67 index. In patients with a lack of receptors (triple negative vs others), higher levels of Aurora A (p = 0.06) in the blood serum were observed at the level of the statistical trend. Conclusions: The preliminary results obtained indicate the potential usefulness of determining the concentration of the new biomarker Aurora A in the blood serum of patients with breast cancer. The research is continuing.
Neoadjuvant chemotherapy regimens for triple-negative breast cancer: Insights from network meta-analysis.
Authors: Miyashita Hirotaka , Cruz Christina , Malamud Stephen C. 
Published: May 2020

e12635 Background: The best regimen for neoadjuvant chemotherapy for triple-negative breast cancer (TNBC) is unknown. Recent studies have shown promising data that adding carboplatin improves the rate of pathological complete response (pCR) in TNBC). Therefore, we performed a network meta-analysis to define the overall most effective neoadjuvant systemic therapy for TNBC. Methods: We searched MEDLINE, Cochrane Library, and EMBASE from inception to December 2019 for studies comparing the efficacy of different neoadjuvant regimens in patients with TNBC. We performed a network meta-analysis comparing the regimens in the selected studies using the random-effects model. We focused on anthracycline (A), bevacizumab (B), everolimus (E), and platinum salts (Pl) because these are the medications commonly added to taxane based regimens. All studies contained a taxane regimen. We analyzed the rate of pCR (ypT0/is, N0) and the incidence of grade 3-4 neutropenia, thrombocytopenia, nausea/vomiting, and diarrhea. Results: We identified a total of 13 randomized control trials for this analysis. We compared eight different classes of regimens. We found that regimens containing Pl were significantly superior to Pl non-containing regimens for the rate of pCR. (risk ratio (RR) for pCR [95% confidence interval (CI)]: 1.66 [1.19-2.31], 1.37 [1.14-1.64], and 1.36 [1.14-1.62] for no medications of special interest vs Pl, A vs A+Pl, and A+B vs A+B+Pl, respectively). Regimens containing B were associated with a significantly better rate of pCR. (RR for pCR [95% CI]: 1.24 [1.06-1.46] and 1.23 [1.01-1.51] for A vs A+B and A+Pl vs A+B+Pl, respectively) In contrast, adding A into the regimen did not improve the rate of pCR. In the safety analysis, regimens containing Pl were associated with a significantly higher incidence of grade 3-4 neutropenia and thrombocytopenia. Regimens containing B showed a higher incidence of grade 3-4 nausea/vomiting, and diarrhea. Conclusions: For TNBC, adding Pl or B into the neoadjuvant therapy regimen brings about a higher pCR rate, though they are associated with an increase in hematologic or gastrointestinal complications. The benefit of adding A to the neoadjuvant chemotherapy regimen for TNBC is not apparent.
Comprehensive analysis of long noncoding RNA expression in circulation of breast cancer patients on neoadjuvant therapy.
Authors: Krastev Boris , Timcheva Constanta , Valev Spartak , Zhbantov Georgi , Stoykov Ivaylo , Stamenov Georgi 
Published: May 2020

e12644 Background: Though long considered “nonfunctional”, recent evidence is growing that non-coding RNAs, including long non-coding RNAs (lncRNAs), have an active role in tumor biology, mainly as gene expression regulators. Breast cancer is heterogeneous in nature and locally advanced cases are distinct entity in terms of curability. Being borderline between early and metastatic disease, long-term outcome here strongly depends on the efficacy of systemic therapy. To the best of our knowledge, no study has yet investigated global changes of circulating lncRNAs in this patient population during preoperative (neoadjuvant) treatment. Methods: We conducted a small transcriptomic trial on 10 locally advanced breast cancer patients, assessing lncRNA and messenger RNA (mRNA) expression in plasma samples before (S1) and after (S2) initiation of neoadjuvant therapy. Next-generation sequencing was performed with differential gene expression analysis between S1 and S2 groups. We assessed co-expression between lncRNAs and mRNAs, identifying mRNAs whose transcription was potentially regulated by lncRNAs, i.e. “lncRNA target genes”. In order to elucidate biological roles of these target mRNAs, we performed gene ontology (GO) and pathway analysis (Kyoto Encyclopedia of Genes and Genomes, KEGG). Results: 394 lncRNAs and 1085 mRNAs demonstrated statistically significant difference in expression between pretreatment and posttreatment samples. Co-expression analysis revealed positive correlation between 25 lncRNAs and 25 mRNAs located in cis, while potential trans interactions exceeded 105. GO evaluation of lncRNA target genes was significant for 44 terms: 28 for biological process (BP), 9 for cellular component (CC) and 7 for molecular function (MF). The most annotated terms for BP, MF and CC were respectively biosynthetic process, DNA-binding transcription factor activity and nucleus. KEGG analysis showed that 105 of 201 analyzed pathways were statistically significant with most prominent being pathways in cancer and transcriptional misregulation in cancer. Conclusions: Despite limited in size, present study provides broad view on transcriptional landscape in blood circulation, interrogating in vivo dynamics of systemic gene expression during neoadjuvant breast cancer treatment. It demonstrates that substantial number of circulating lncRNAs could be up- or downregulated in the course of therapy and this has the potential to control protein-coding genes that are tightly implicated in cancer biology.
SimBioSys TumorScope: Spatio-temporal modeling of the tumor microenvironment to predict chemotherapeutic response.
Authors: Cole John A , Peterson Joseph R , Earnest Tyler M , Hallock Micahel J , Pfeiffer John R , Pandey Tushar , Braun Eduardo 
Published: May 2020

e12650 Background: One of the most important sources of variability affecting each patient’s response to neoadjuvant chemotherapy (NACT) is drug and nutrient perfusion, The SimBioSys TumorScope is a computational decision-support system that is designed to predict the flow of drugs and nutrients throughout the tumor microenvironment, and the subsequent response of the tumor to treatment. By enabling healthcare providers to simulate a range of different standard-of-care treatment regimens in a realistic 3D model of each patient’s tumor, providers can predict which treatments are most effective, and provide the best possible care for their patients. Methods: SimBioSys TumorScope implements a multi-scale simulation technology that couples several biophysical and biochemical models in order to predict how individual patients' tumors respond to NACT. The simulations explicitly track the 3D morphology of the tumor and surrounding tissues (based on MRI images), as well as the concentrations of key nutrients and drugs as they change over time. At each location within the 3D model, these concentrations are used to predict cell growth and death rates. As different regions of the tumor grow or die, its macroscopic shape changes. Results: SimBioSys TumorScope was retrospectively applied to over 300 breast cancer patients that received NACT. Simulations were initialized with pre-treatment MRI data, and run through the entirety of each patient's specified treatment regimen. Predicted changes in tumor volume and longest dimension were then compared against measured values at several time-points after initiation of therapy, yielding Pearson correlations of over 0.93 for both. Work is underway to extend the technology to lung tumors; early results show very different metabolic behaviors from those of breast tumors, and significantly less response to treatment overall. Conclusions: Through accurate spatio-temporal modeling of drug and nutrient perfusion, metabolic behavior, and the physico-chemical interactions that arise between tissues, the SimBioSys TumorScope for Breast Cancer can accurately predict the response of patients treated with NACT.
Impact of malnutrition and anemia at diagnosis in both: Pathological response and tumor-infiltrating-lymphocytes post neoadjuvant chemotherapy.
Authors: Roque Katia MERCEDES , Galvez Nino Marco , Castaneda Altamirano Carlos Arturo , Castillo Garcia Miluska , Sanchez Joselyn , Bernabe Luis A. , Fuentes Hugo Alejandro , Sandival Gustavo , Cotrina José M. , Dunstan Jorge Antonio , Abugattas Julio , Mantilla Raúl , De La Cruz Miguel , Gomez Henry Leonidas 
Published: May 2020

e12654 Background: The response after neoadjuvant chemotherapy (NAC) is the main prognostic factor in breast cancer (BC), likewise, malnutrition, anemia and systemic inflammation have also been associated to prognosis in breast cancer. We evaluated the association between pathological response (PR) and tumor infiltrating lymphocytes (TILs) post NAC with nutritional predictors as body mass index (BMI), prognostic nutritional index (PNI), anemia and neutrophil/lymphocyte index (N/L). Methods: This is a retrospective analysis of women diagnosed with BC between 2006 to 2017 at Instituto Nacional de Enfermedades (INEN) who received NAC. Pathological response was classified through residual cancer burden (RCB) and TILs post NAC which were prospectively evaluated by a pathologist. Clinical and pathological features as well as survival status were obtained from patient files. Results: We identified 439 women with BC who received NAC. Median age was 49 years, histological grade 3 was found in 245 patients (55.8%) and stage IIIB was the most frequent at diagnosis with 257 patients (58.5%). Luminal B subtype was the most frequent (43.7%). Rate of pCR was 10.5% and median TILs post NAC was 20%. About nutritional predictors, we use the median as a cutoff to discriminate between high and low values, for BMI was 27.5, for PNI was 56, for hemoglobin was 13.2 and for NLR was 1.84. There was no association for TILs post NAC with BMI (p = 0.38), PNI (p = 0.057) and hemoglobin (p = 0.43). We found a positive association between ILN and TILs post NAC (p = 0.001). On the other hand, we don’t found association for RCB with BMI (p = 0.45), PNI (p = 0.641), ILN (p = 0.2) and hemoglobin (p = 0.15). In the multivariate analysis, only RCB was an independent predictor for DFS (95 % CI, 87-100.5; p = 0.00001) and OS (95 % CI, 101.8-114.1; p = 0.00001). There was no association between BMI, PNI, ILN and anemia with OS and DFS. For the TILs post NAC there was a tendency to association with DFS (p = 0.07) and OS (p = 0.07). Conclusions: There are association between neutrophil/lymphocyte index with TILs after NAC. There was no association between nutritional and systemic predictors with long-term outcomes. The pathologic response is a biomarker for predicting the long-term outcomes of breast cancer patients.
Neoadjuvant chemotherapy in locally advanced breast cancer: Clinicopathological characteristics and correlation with pathological complete response.
Authors: Choudhary Priyanshu , Gogia Ajay , Deo Svs , Mathur Sandeep , Sharma Dayanand 
Published: May 2020

e12658 Background: The data regarding incidence, response rates to neoadjuvant chemotherapy (NACT) and factors affecting pathological complete response (pCR) rate in locally advanced breast cancer (LABC) patients are lacking from India. Methods: This ambispective study was carried out at B.R.A., I.R.C.H, AIIMS, New Delhi, in between period of January 2013 to December 2019. We screened 1500 cases of breast cancer who presented to our institute and found 600 cases to be LABC,425 patients were started on NACT, 284 had undergone surgery and were included in our analysis. Results: The median age of diagnosis was 46 years (range 24-72years). Fifty four percent cases were postmenopausal, 54% had a left sided cancer,45 % right sided cancer,1 % had bilateral breast cancer. The median duration of symptoms was 5 months. The clinical stage according to AJCC staging system was Stage IIB – 11%(32), IIIA -21 % (58), IIIB- 60%(169) and IIIC- 8%(24) .Sixty five percent(186) cases presented with clinical skin involvement and 80% (228) patients has clinical node positivity.In our cohort 52% (148) cases were hormone positive (ER/PR positive), 42 %(119) cases were HER2/neu positive, 30%(84) were triple negative breast cancer (TNBC), 23 % (67) were positive for ER/PR and HER2/neu. Ninety percent of the cases were able to receive the planned neoadjuvant treatment before surgery. Post NACT 83% cases had a modified radical mastectomy (MRM) and 17% were able to undergo breast conserving surgery (BCS).Overall pCR was achieved in 59(21%) cases, 17% in hormone positive cases, 25% in HER2/neu positive cases (30% in cases receiving HER2/neu directed therapy vs 20% in cases who didn’t receive HER2 /neu directed therapy) and 27% in TNBC cases. During the study period 54 cases (19%) had relapsed,8 cases (3%) had a local relapse and a 46 cases (16%) had a systemic relapse. Grade ¾ toxicity occurred in 25 % cases, the most common were diarrhea, neutropenia, CINV, oral mucositis and thrombocytopenia and other rare toxicities (DVT, hand foot syndrome,myalgia). Febrile neutropenia was recorded in 2.5 % cases. There were 2 induction deaths. Stage II, absence of ER/PR expression showed statistically significant correlation with path CR rates. Conclusions: Locally advanced breast cancer constitutes around 40% cases at our institute. Post NACT pCR was achieved in 21% of cases, HER2/neu positive cases and TNBC showed higher pCR rates. The factors affecting pCR rate were absence of ER/PR expression and stage II disease.
Acquired immune deficiency of cancer: Evaluation of NK cell number as a predictor of overall survival in breast cancer.
Authors: Williams R. Michael , Yunis Edmond J 
Published: May 2020

e13003 Background: Cancer specialists, be they molecular geneticists or oncology clinicians, now accept the fact that a cancer results after a deleterious mutation in the apoptosis program AND failure of the immune system, innate (non-specific) and adaptive (specific), to eliminate the now abnormal transformed cell and it's progeny. Just as the acquired immune deficiency syndrome existed as a syndrome BEFORE the HIV virus was described, the disease AIDS/HIV was designated because the virus explained the syndrome and made HIV/AIDS a disease. We believe cancer works the same way. Cancer is a failure of surveillance by the immune system which leads to a disease, one we have described as AIDS/cancer (J Immunol May 1, 2019, 202, 1S, 182.79). Methods: Commercially available laboratory analysis of peripheral blood (Quest Diagnostics) and standard treatment protocols for breast cancer. Results: The immune system can be evaluated with samples of peripheral blood where cell subsets, antibody levels, etc. are measurable. Here we present results from over 200 unselected breast cancer patients, independent of Stage. All patients were treated with standard protocols. The initial number of NK cells in peripheral blood, but not other cell subsets or immunoglobulin levels, are a, and likely the, most significant predictor for survival. Kaplan Meier survival analysis, done when 20% of the entire population had died, showed that none of the patients in the upper quartile for NK cell number had died. Survival differences, comparing the top 50% vs. bottom 50% in initial NK number. were also highly significant (P < 0.05). Conclusions: We conclude that the innate immune system, reflected as numbers of NK cells in the blood are the most significant predictor of survival.