bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is there an additional health-related quality of life (HRQL) benefit with abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC) beyond that mediated by clinical endpoints?
Authors: Cella David , Molina Arturo , Gagnon Dennis D. , Espindle Derek , Hao Yanni , Basch Ethan M. 
Published: March 2020

9617 Background: HRQL was evaluated as part of COU-AA-301, a randomized phase 3 trial of AA + prednisone (P) vs placebo + P in mCRPC patients (pts) post-docetaxel, where AA + P demonstrated significant benefits over P in numerous HRQL measures. Here we report post hoc analyses investigating the role of disease progression (px) in mediating the HRQL benefits of AA. Methods: Intensity of pain and fatigue and their interference with daily activities were assessed with the BPI-SF and BFI questionnaires and multiple domains of HRQL with the FACT-P questionnaire. Mediation analyses were conducted using a series of 3 models (Baron & Kenny J Pers Soc Psychol 1986), to assess whether presence and timing of disease px mediated treatment effects of AA + P vs P on HRQL changes: in Model 1, HRQL (i.e. the outcome variable) is predicted by treatment, in Model 2, px (i.e. the mediator variable) is predicted by treatment, and in Model 3, HRQL is predicted by both treatment and px. Three different disease px indicators (ie, PSA px, radiographic px, and a composite px variable) were used. Results: Treatment predicted the change in FACT-P total score from baseline (Model 1; p = 0.011). Treatment (as sole predictor) was significantly (p ≤ 0.001) predictive of both PSA px and radiographic px (Model 2). Some of the treatment benefit of AA + P on the FACT-P total score was not explained as the result of the effect of treatment on PSA and radiographic px (Model 3; p = 0.030). In Model 3, pts with late (> 250 d post-randomization) or no px had better FACT-P scores than those with early px for PSA px (p = 0.019, no px; p = 0.008, late px) and radiographic px (p = 0.054, no px; p = 0.017, late px). Models evaluating the mediating role of the composite px variable showed the same pattern of results. Identical sets of mediation analyses conducted for the BPI and BFI also exhibited very similar outcomes. Conclusions: In post-docetaxel mCRPC pts, the benefits of AA to HRQL appear to be related to both treatment assignment and the mediating effects of disease px. HRQL end points expand understanding of treatment benefit beyond clinical disease px end points. Clinical trial information: NCT00638690.
N-telopeptide of type I collagen (NTX) dynamics over one year of determinations in patients with breast cancer (BC) with bone metastases (BM): Predictive factors of outcome.
Authors: Shan Ning , Alho Irina , Matias Margarida , Faria Mariana , Casimiro Sandra , Ferreira Arlindo , Leitzel Kim , Ali Suhail M. , Lipton Allan , Costa Luis 
Published: March 2020

9634 Background: The bone resorption marker NTX at baseline is a prognostic marker in BC patients with BM treated with zoledronic acid (ZOL), Coleman RE, JCO 2005. We investigate how the response of urinary NTX levels during ZOL therapy is related to patient outcome and disease characteristics. Methods: Consecutive BC patients with BM were prospectively included if they received monthly intravenous ZOL. Urinary NTX was determined at baseline and at following 1, 3, 6, 9 and 12 months from the initial ZOL treatment. NTX levels were considered elevated if > 50 nmol/mmol creatinine. The NTX changes were compared with patient and disease characteristics. Relative risks for negative clinical outcomes were estimated with Cox regression models. Results: Seventy-one BC patients with BM, mean aged 61.4 (29-87), were included. Mean survival was 34.1 months (3-131), with 21 patients alive after the last follow up (median 29 months). Thirty-nine patients also had extraskeletal metastases (BM-E+). Totally 329 urinary NTX samples were evaluated. At baseline, mean NTX was 153.0 (15.4 – 700.7) and 78.9% had elevated levels. Mean baseline NTX increased with age: 71.2 (<40); 139.3 (50-59); 241.8 (70-79). Among patients with normal NTX at 3 months, 89.5% continued to show normal NTX at 12 months. After ZOL treatments, 46.9%, 54.7%, and 61.0% of patients had normal NTX at 3, 6 and 12 months, respectively. NTX variance (1-12 months) was higher for BM-E+ patients compared with BM-only patients, p<0.001. Risk factor of death for patients with persistent elevated NTX at 3 months was 1.74 (p=0.074). Age and BM-E+ were also associated with risk of death. There was a trend to shorter survival in BC-E+ patients (p=0.056). Majority of patients (88.2%) with longer survival (> 36 months) and younger (age < 60) received endocrine therapy. Conclusions: Early (3 months) urinary NTX normalization to ZOL correlates with long-term NTX normalization and survival. BC-E+ patients have a reduced NTX normalization rate compared to BM-only patients and may deserve further investigation for a more adequate schedule of bone-targeting agents.
S0221: Comparison of two schedules of paclitaxel as adjuvant therapy for breast cancer.
Authors: Budd G. Thomas , Barlow William E. , Moore Halle C. F. , Hobday Timothy J. , Stewart James A. , Isaacs Claudine , Salim Muhammad , Cho Jonathan K. , Rinn Kristine , Albain Kathy S. , Chew Helen K. , Burton Gary Von , Moore Timothy David , Srkalovic Gordan , McGregor Bradley Alexander , Flaherty Lawrence E. , Livingston Robert B. , Lew Danika , Gralow Julie , Hortobagyi Gabriel N. 
Published: March 2020

CRA1008 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Evaluation of TOP2A and TIMP-1 as predictive markers of pathologic complete response to neoadjuvant anthracycline-based chemotherapy.
Authors: Maia Joyce Maria L. , Santos Elizabeth Santana , Lessa Rafael Costa , Costa Felipe D'Almeida , Bezerra Stephania , Rocha Rafael Malagoli , Benevides Carlos Frederico Lopes , Lima Vladmir C. , Ribeiro Adriana Regina G. , Fanelli Marcello Ferretti , da Costa Alexandre Andre Balieiro Anastacio , Mello Celso Abdon 
Published: March 2020

e11503 Background: Factors predictive of response to anthracyclines can help selecting patients who really benefit from its use. HER2 amplification, TOP2A aberrations, and changes in tissue inhibitor of metalloproteinase (TIMP-1) expression in breast carcinomas have been shown to be associated with incremental benefit from anthracycline chemotherapy. Methods: We retrospectively analyzed data on the outcome of patients undergoing neoadjuvant anthracycline-based chemotherapy. Evaluated nuclear TOP2A protein expression and cytoplasmatic TIMP-1 expression in tumor cells in breast cancer biopsies by immunohistochemistry (IHC) and reviewed the pathological responses after completion of neoadjuvant treatment. Results: From 2002 to 2012, data from 97 patients was reviewed. Sixty four patients had the paraffin blocks corresponding to the pre-treatment biopsy to analysis the TOP2A and forty nine to TIMP-1. Patients were considered positive for TOP2A if the level of expression in IHC was higher than 20% and graduated TIMP-1 as weak, moderate or strong expression. Thirty percent of the patients achieved pathologic complete response (pCR) in pos-treatment surgical specimens. There was an association between TOP2A IHC expression and tumor pathological complete response (pCR) with higher pCR in TOPO2A positive tumors (pCR 44% vs 14%; p=0.008). There was no association between TIMP-1 expression and pCR. A moderate or strong TIMP-1 expression was associated with higher disease-free survival in multivariate analysis (p=0,005). No difference in PFS and OS was observed between patients with pCR after a median follow-up of 36 months. Conclusions: The expression of TOP2A seems to be a promising predictive biomarker of pCR to antracycline-based neoadjuvant chemotherapy in HER2 breast cancer. The predictive value and form of assessment of TIMP-1 remain uncertain. These findings should be better evaluated in prospective neoadjuvant trials.
Validation of MSKCC nomogram for prediction of metastasis to nonsentinel lymph nodes in carcinoma breast in Indian patients.
Authors: Somashekhar S. P. , Rauthan Amit 
Published: March 2020

e11510 Background: Sentinel node biopsy has emerged as the standard of care in clinically node negative breast cancer (cT1,T2 N0). In cases where sentinel node is negative, ALND can be avoided. In nearly 30-50% cases, the sentinel lymph nodes is the only site of metastases, demonstrated in Indian population too. In ASCOG ZOO11 trial, patients who had metastases in sentinel node did not undergo ALND. Patients in the trial received radiation as part of breast conservation surgery. In Indian patients, this is not applicable as most of the patients undergo mastectomy. It would be highly beneficial to identify the subset of patients, where the sentinel node is the only site of metastasis. Various nomograms have been used to predict the risk of metastasis in non sentinel nodes. MSKCC nomogram has been validated in many studies in the USA and Netherlands. Methods: The records of 240 breast cancer patients between 2007 and 2011 who underwent SLN and / or ALND were selected. Serial hemotoxylin and eosin (HE) analysis and immunohistochemistry were routinely performed on each sentinel node. Various factors like T size, histology and grade, lymphovascular invasion, number of +ve and –ve sentinel nodes, hormonal status, multifocality were recorded. Risk of non sentinel node metastasis were calculated by nomogram. Results: 63 out of 240 patients had sentinel node positivity and underwent ALND 20 out of 63(31%) had metastasis in non sentinel nodes also. Mean predictive risk as per nomogram for SLN was 53% and non SLN mets was 68%. None of our patients had low risk of non sentinel node metastasis as per MSKCC nomogram. Conclusions: MSKCC nomogram is not validated for Indian Breast Cancer patients, in our study population as it could not differentiate between patients having metastasis in sentinel node only from those having non sentinel node metastasis based on risk stratification. Because in India, the mean Tumour (T) size is big and Grade is usually high grade and one of the reason the present MSKCC nomogram is not applicable to Indian Breast cancer patients. In Indian populations, a different nomogram is required to correctly predict the non sentinel node metastasis.
Retrast: Retreatment after adjuvant trastuzumab—Our regional southern Italy experience.
Authors: Caruso Michele , Adamo Vincenzo , Tralongo Paolo , Giuffrida Dario , Gebbia Vittorio , Leonardi Vita , Soto Parra Hector J. , Valenza Roberto , Borsellino Nicolo , Sanò Maria Vita , Priolo Domenico , Di Mari Anna Maria , Prestifilippo Angela , Ricciardi Giuseppina , Miano Eleonora , Zacchia Alessandra , Ferraú Francesco 
Published: March 2020

e11526 Background: Trastuzumab (T) is the standard of care for pts with HER2+ve BC. Relapse after adj T remains a rare event. Since the large use of T in adj setting, becomes crucial to evaluate advantages of retreatment with T for pts who relapsed after treatment in early stage. There is still lack of clinical evidence and poor data from CT to say that there is a benefit in T re-exposure after relapse following adj T. Methods: Since Jun 2006 and Dec 2011, we reviewed pts with early BC treated with T in adj therapy, relapsed and re-treated with T in first line therapy, in 10 departments of medical oncology in Sicily. We aimed to study feasibility, responses and treatment outcome. Results: 62 pts with HER2+ve fulfilled the criteria for this analysis and 47 were evaluated. Pts had a median age of 53 ys (29-79). ER/PgR-ve cases were 16 (34 %). Ki67 was > 20% in 34 pts (74%). 31 pts (64%) had >3 nodes+ve. All the pts received adj therapy with anthra+/-taxane. 55% of pts had >2 metastatic sites. 12 (25,5%) pts were revalued for HER2: 10 pts confirmed 3+ and two pts 2+ were FISH+. Median time from diagnosis to relapse was 25 mos (7 – 36). Median time from last dose of T to relapse was 10 ms (2 – 35). 33 (70,2%) pts and 14 pts (29,8%) had early (< 12 ms) and late progression (≥ 12 ms) respectively after adj T. First line of therapy was T in combination with mono/polychemotherapy in 42 pts (89,3%) and 5 pts (10,6%) respectively. 27 pts (57,4%) had objective responses (CR 5, PR 22) and 7 pts (14,8%) stable disease. 13 pts (27,6%) had progression: all of these pts had early progressive disease after adj T, 9 pts (69,2%) had Ki67>20%, 5 pts (38,4%) were ER/PgR-ve and 8 pts (61,5%) ER/PgR+ve. Median TTP was 4 mos (range 2-7). Median TTP for early and late relapses pts were respectively 3,7 and 4,8 mos, (p = 0,4). Median OS from relapse to death was 23 mos (r 12 – 37). LVSD G1 (EF < 60-50%) was observed only in 7 pts (14%). Conclusions: Our data confirm the feasibility and safety of treatment with T after adj T therapy and is active for a disease control rate in 72,4% of cases. These results demonstrate that relapses after adj T occurred early (<12 ms) in 70% of pts. However pts with primary resistance (27,6%) should be well categorized using biomolecular markers to receive up-front drugs that overcome the resistance to T.
Neoadjuvant trastuzumab and sequential chemotherapy with cisplatin, vinorelbine, and docetaxel for stage II-III breast cancer patients: Final results of a single institution phase II study.
Authors: Carillio Guido , Aiello Rosa Anna , Chiarenza Maurizio , Alì Marco , Mazzola Antonella , Di Marco Rosanna , Taibi Eleonora , Fallica Giuseppina , Casella Tiziana , Zacchia Alessandra , Castiglione Gaetano , Caruso Francesco , Caruso Michele ,   Humanitas Centro Catanese di Oncologia
Published: March 2020

e11527 Background: Several studies demonstrated the efficacy of neoadjuvant trastuzumab in breast cancer patients. However, cardiotoxicity intrinsic and increased by combining anthracyclines or chest wall radiotherapy remains a ticklish issue, mainly when is durable and occurs in potentially healable young patients. Methods: A phase II study of neoadjuvant trastuzumab and sequential chemotherapy was started in the late 2007 at Humanitas CCO and enrolled 42 patients with stage II-III HER2-positive breast cancer. Treatment consisted of 18 administrations of weekly trastuzumab combined with a sequential regimen including 3 courses of cisplatin 80 mg/m2 d1 + vinorelbine 25 mg/m2 d1 and d8 q3w followed by 3 courses of docetaxel 100 mg/m2d1 q3w. Peg-filgrastim was given in each course. Postoperative trastuzumab q3w was administered for one year. Radiant and endocrine therapy were delivered according to standard practice. Primary objective was the rate of pathologic complete response (pCR), now defined as no evidence of residual invasive cancer, both in breast and lymph nodes. A first report of the study was presented as poster at ASCO 2010. Results: With regard to real patient characteristics observed in the daily clinical practice, no restrictive sample selection was established and the eligible patients were accrued consecutively. Median age was 48 (range 23-71). Twenty-three patients (55%) had stage III tumors and 7 of them stage IIIB, including 4 cases of tumor spreading to skin (T4b) and 3 cases of inflammatory carcinoma (T4d). Seventeen patients (40%) had tumor with no expression of hormone receptors and 36 (86%) with ki67≥14%. The rate of pCR was 26% (11/42). Among 29 women initially candidate to radical mastectomy, 13 of them (45%) finally received breast-conserving surgery and 8 skin-sparing mastectomy. Treatment was well tolerated and produced only moderate alopecia and no case of significant LVEF decrease. Conclusions: Neoadjuvant trastuzumab combined with the above non-anthracycline-containing sequential chemotherapy may be considered a safe and effective regimen in HER2-positive breast cancer patients. Clinical trial information: 2006 000392 15.
Association of the neutrophil to lymphocyte ratio with survival patients with in metastatic breast cancer.
Authors: Unlu Ozan , Aygun Sevda , Petekkaya Hilbrahim , Gecmez Gizem , C. Roach Emir , Babacan Taner , Sahin Ugur , Keskin Özge , Kertmen Neyran , Aksoy Sercan , Altundag Kadri 
Published: March 2020

e11544 Background: Identification of simple and measurable prognostic factors is an important issue in treatment evaluation of breast cancer. Although various markers are considered while making a decision to treatment modality, clinicians investigate for new prognostic factors for reason of highly variable responses of individuals. Therefore, this study estimates the survival probability of the neutrophil to lymphocyte ratio (NLR) for patients with metastatic breast cancer. Methods: We included the patients with metastatic breast carcinoma who were treated for metastasis. NLR were calculated and patients were divided into four quartiles (25th, 50th and 75th NLR; the lowest being the 1st quartile, the highest being 4th quartile ). Survival status was retrieved from our cancer registry. Survival analysis, stratified by NLR quartiles, was used to evaluate the predictive value of NLR. Results: Eighty-one patients with metastatic breast cancer were included in this study. Median age of diagnosis of the patients was 47 (26-83), the majority of them had grade II (%37) and grade III (%29.6) tumors and were metastatic at the time of their initial diagnosis. ER (+), PR (+) and HER2 (+) percentages were confirmed as 82%, 73% and 24% ,respectively. Ten percent of the patients were triple negative. Median follow-up time was 26 months and 29 patients died during the follow up period. We analyzed the overall survival among NLR quartiles. When we compared the quartiles with the highest and lowest NLR values, the quartile with the lowest NLR values had longer median overall survival than the quartile with the highest NLR values (212 vs. 27 months; p=0.01). The second and third quartiles, however, showed no statistically significant difference of overall survival between four quartiles. Conclusions: NLR can be a prognostic factor for overall survival in metastatic breast cancer patients.
Impact of enriched environment on tumor growth and adipokines secretion in a mouse model of mammary cancer.
Authors: Basu Samar , Combe Kristell , Nachat-Kappes Rachida , Farges Marie-Chantal , Rossary Adrien , Goncalves-Mendes Nicolas , Vasson Marie-Paule 
Published: March 2020

e11552 Background: Enriched environment (EE) by promoting physical activity and social communication reduces development of tumors such as in colon cancer. It seems to act particularly through a decrease of leptin production which linked to breast cancer risk. Thus, the aim of this study was to investigate the effect of EE on the mammary tumor development and to identify the molecular pathways in relation to adipokines secretion. Methods: 3-week-old female C57BL/6 mice were housed in standard environment (SE) or in EE for 9 weeks. A half of EE and SE mice received either EO771 syngeneic cells injection into the inguinal mammary fat pad (EE and SE tumor) or vehicle (EE and SE control). After 3 weeks, the mice were sacrificed for blood and tumor analysis : expression of leptin, COX-2 (inflammation), Ki-67 (proliferation) and caspase 3 (apoptosis) were determined using immunostaining and western blotting. Plasma adipokines were quantified by immunoassay (ELISA, Luminex). Results: Tumor volume and weight were lower in EE mice vs SE tumor (-29% and -26% respectively). COX-2 and Ki67 expressions were decreased (20% and 40% of positive cells respectively) while caspase-3 levels were increased (450% of positive cells) relative to SE tumor (100%). EE control mice showed a significant increase in adiponectin levels but no change in those of leptin, IL-6, TNF-α, PAI-1, MCP-1 and resistin vs SE control. No significant difference between EE and SE tumor groups were observed for these inflammatory markers. Conclusions: These data showed for the first time that EE housing inhibits mammary tumor growth which results in a marked intratumoral COX-2 under-expression and an increase in the plasma adiponectin/leptin ratio without any change in inflammatory response. So, COX-2 and adipokines seem to be key regulating factors in breast carcinogenesis. [Table: see text]
Activation of P38MAP kinase in estrogen-positive invasive breast cancers: Relation with HER2 and downstream signaling phosphorylated proteins expression.
Authors: Merlin Jean-Louis , Harle Alexandre , Lion Maeva , Chrétien Anne-Sophie , Ramacci Carole , Leroux Agnès 
Published: March 2020

e11560 Background: P38 kinases are members of the mitogen-activated protein kinase (MAPK) family. In breast cancers MAPK, as well as PI3 kinase-AKT pathway signaling proteins have major implication in molecular oncogenesis and are extensively investigated as putative targets for therapy. The present study reports the investigation of the expression of P38MAPK and its phosphorylated form (p-P38MAPK) in clinical specimens of invasive breast carcinomas in relation with estrogen receptor and HER2 expression, as well as MAPK and PI3K signaling phosphorylated proteins. Methods: The expression of P38MAPK and p-P38MAPK as well as p-AKT, p-GSK3β, p-S6 kinase, p-MEK1, p-ERK1/2 were semi-quantitatively assessed using multiplex bead immuno-assay. The analyses were performed retrospectively in frozen specimens from 46 invasive breast tumors classified according to estrogen receptor (ER) and HER2 status. Results: All specimens were taken at diagnosis and validated for tumor content >50%. Twenty-nine were ER+, 17 were HER2+, 10 were triple negative (TN) tumors. Analyses were performed in triplicate from total protein extracts and were achievable in all specimens. P38MAPK was found to be expressed in all tumor specimen and significantly (P=0.002) overexpressed in ER+ tumors. P38MAPK was lower in TN tumors than in all others. The median expression of phosphorylated-P38MAPK was also higher in ER+ than in ER- tumors and lower in TN tumors than in all others. HER2 status had no influence on P38MAPK and p-P38MAPK expression. No variation in the phosphorylation rate of P38MAPK was observed in relation with ER, HER2 or TN status. Significantly higher (P=0.0048) expression of p-AKT tumors was observed in HER2+ tumors. No significant difference in p-MEK1, p-GSK3β and p-S6K expression was evidenced in any other comparisons based on ER and HER2 expression subtypes. Conclusions: Investigation of the expression of multiple phosphorylated signaling proteins can be used as molecular biomarkers for personalized targeted therapy. In ER+ invasive breast cancer, the overexpression of P38MAPK could serve as biomarker for evaluation of P38MAPK inhibitors.