bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ES10-3: Blockade of estrogen signaling boosts antitumor immunity by inhibiting tumor-induced pathological myelopoiesis
Authors: Conejo-Garcia J 
Published: May 2019

Abstract
Although the role of estrogen signaling in the progression of a subset of breast tumors has been underscored by the clinical use of Estrogen Receptor antagonists, how estrogens impact protective anti-tumor immunity remains poorly investigated. Here we show that estrogen signaling accelerates the progression of different estrogen insensitive tumor models by contributing to tumor-promoting emergency myelopoiesis. This results in increased mobilization of myeloid-derived suppressor cells (MDSCs), and also increases their intrinsic immunosuppressive activity on a per cell basis, in vivo in the bone marrow of tumor-bearing hosts. Accordingly, estrogens have a profound effect on T-cell-dependent anti-tumor immunity and tumor-promoting inflammation, even independently of the sensitivity of tumor cells to estrogen signaling. Differences in tumor growth in the presence of estrogen-insensitive tumor cells are dependent on blunted anti-tumor immunity and, correspondingly, disappear in immunodeficient hosts and also upon MDSC depletion. Mechanistically, estrogen receptor alpha activates the STAT3 pathway in human and mouse bone marrow myeloid precursors by enhancing JAK2 and SRC activity. Consequently, selective antagonists of estrogen receptor alpha (but not estrogen receptor beta) could have significant effects in delaying the progression of estrogen-sensitive and estrogen-insensitive tumors, providing a rationale for blocking estrogen signals to boost the effectiveness of anti-cancer immunotherapies. Our data therefore provide novel mechanistic insight into how enhanced estrogenic activity contributes to malignant progression in established tumors by driving pathological, tumor-promoting myelopoiesis. Our work suggests that new anti-estrogen drugs without agonistic effects (different from tamoxifen) could have benefits to boost protective immunity in a wide range of cancers, while augmented estrogenic activity could contribute to tumor initiation and/or malignant progression.
Citation Format: Conejo-Garcia J. Blockade of estrogen signaling boosts antitumor immunity by inhibiting tumor-induced pathological myelopoiesis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES10-3.
Abstract OT3-02-05: CORALLEEN: A phase 2 clinical trial of chemotherapy or letrozole plus ribociclib as neoadjuvant treatment for postmenopausal patients with luminal B/HER2-negative breast cancer
Authors: Gavila J , Saura C , Oliveira M , Ciruelos E , Gonzalez X , de la Peña L , Bermejo de las Heras B , Muñoz M , Fernandez P , Villagrasa P , Ortega V , Lopez R , Celiz P , Pascual T , Prat A 
Published: May 2019

Abstract
Background: Dysregulation of cyclin D-CDK4/6-Rb pathway is associated with endocrine resistance in hormone receptor–positive (HR+) breast cancer. Recently, a CDK4/6 inhibitor has shown unprecedented efficacy in metastatic disease, leading to its regulatory approval. Several others are currently in clinical development for the management of HR+ breast cancer in the early and advanced settings. However, it is vital to gain insights into the molecular and biological effects of this class of agents and could identify patients who can benefit the most, delaying or avoiding the use of chemotherapy.The neoadjuvant setting provides an ideal scenario to carry out these investigations. Hence, we propose to conduct an exploratory study to evaluate the biological effects and the efficacy of ribociclib in patients with primary luminal B tumors. We hypothesize that the combination of ribociclib plus letrozole may offer clinical benefit in the preoperative setting. Methods: This is a parallel, multicenter, two-arm, randomized exploratory study in postmenopausal women with primary operable HR+/HER2-negative Luminal B breast cancer designed to evaluate the clinical benefit of ribociclib plus letrozole. Eligibility includes stage I-III operable breast cancer, Luminal B by PAM50, ECOG 0-1. They will be randomized 1:1 to receive either six 28-days cycles of ribociclib (600mg; 3-weeks-on/1-week-off) plus daily letrozole (2.5mg) or chemotherapy: four cycles of AC (doxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2 every 21 days) followed by weekly paclitaxel during 12 weeks. Baseline, Day 15 on-treatment, and surgical specimens will be collected for molecular characterization and evaluation of response (decrease in Ki67, change to ROR low disease) The primary endpoint is the rate of Residual Cancer Burden (RCB) per MD Anderson Cancer Center procedures. A rate of RCB 0 and 1 score at surgery, with a rank between 20% to 25% with 47 evaluable patients by group of treatment will offer a precision between 11.5% and 12.4%, respectively (95%CI). Ninety-four patients will be enrolled in 21 sites across Spain. The trial was activated in July 2017. As of June 2018, 78 patients have been recruited.
Citation Format: Gavila J, Saura C, Oliveira M, Ciruelos E, Gonzalez X, de la Peña L, Bermejo de las Heras B, Muñoz M, Fernandez P, Villagrasa P, Ortega V, Lopez R, Celiz P, Pascual T, Prat A. CORALLEEN: A phase 2 clinical trial of chemotherapy or letrozole plus ribociclib as neoadjuvant treatment for postmenopausal patients with luminal B/HER2-negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-02-05.
Abstract OT3-08-01: A phase Ib/II clinical trial investigating the efficacy of nitric oxide deprivation and docetaxel in triple negative breast cancer
Authors: Chung AW , Ensor JE , Darcourt J , Belcheva A , Patel T , Chang JC , Niravath PA 
Published: May 2019

Abstract
Triple negative breast cancer (TNBC) is an aggressive disease that currently lacks an efficacious form of therapy. Although chemotherapy is the current standard of care for metastatic TNBC, the 5-year prognosis remains grim with a high rate of disease recurrence. Cancer relapse is thought to be initiated by chemotherapy-resistant breast cancer stem cells (BCSCs). These BCSCs give rise to a diverse clonal population that results in a heterogeneous cancer, which complicates targeted therapeutic strategies. Our previous studies revealed that BCSCs utilize inducible nitric oxide synthase (iNOS)-derived nitric oxide to promote their proliferation, migration, and self-renewal capacity. In an effort to target the BCSC population, we found that iNOS inhibition with NG-monomethyl-L-arginine (L-NMMA) sensitized BCSCs to docetaxel in vivo in TNBC xenograft models, leading to decreased BCSC viability and tumor burden. These findings suggest that BCSC resist conventional therapy in a nitric oxide-dependent manner and that combination of L-NMMA with docetaxel will effectively target BCSCs to prevent further relapse. A phase Ib/II clinical trial was conducted to determine the maximum tolerated dose, recommended phase 2 dose (R2PD), dose-limiting toxicities (DLTs), and efficacy of the L-NMMA and docetaxel combination in TNBC patients with chemotherapy-refractory locally advanced or metastatic disease. For the phase Ib portion of the study, a standard Bayesian continual reassessment method is being used to investigate 7 dose levels of L-NMMA (5, 7.5, 10, 12.5, 15, 17.5, and 20 mg/kg) and two dose levels of docetaxel (75 and 100 mg/m2). Sixteen patients have been recruited to date, and based on current pharmacokinetics, pharmacodynamics, and safety data, the RP2D is expected to be docetaxel 100 mg/m2 (Day 1) and L-NMMA 20 mg/kg (Days 1-5) every 3 weeks. Two and three patients received 15 mg/kg L-NMMA + 75 mg/m2 docetaxel and 17.5 mg/kg L-NMMA + 100 mg/m2 docetaxel, respectively. Of these 5 patients, one partial responder completed 8 cycles before discontinuing treatment due to taxane-associated neuropathy. Among the five patients treated at the RP2D, only one taxane-associated DLT occurred. The overall response rate for patients treated at the higher doses was 22.2%. Early results of the phase Ib/II trial indicate the safety, tolerability, and promising activity of the first-in-class pan-NOS inhibitor L-NMMA in combination with chemotherapy in the treatment of chemotherapy-refractory TNBC.
Citation Format: Chung AW, Ensor JE, Darcourt J, Belcheva A, Patel T, Chang JC, Niravath PA. A phase Ib/II clinical trial investigating the efficacy of nitric oxide deprivation and docetaxel in triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-08-01.
Abstract P1-06-11: Microsatellite instability in triple negative breast cancers
Authors: Kurata K , Kubo M , Mori H , Kawaji H , Motoyama Y , Kuroki L , Yamada M , Kaneshiro K , Kai M , Nakamura M 
Published: May 2019

Abstract
Background:Microsatellite instability (MSI) is a phenotype resulting from defect in mismatch repair genes. The Food and Drug Administration approved anti-programmed death 1 (PD-1) immune checkpoint inhibitor for any solid tumor with MSI-high (MSI-H). Some tumors had good response to PD-1 blockade and it is a promising treatment for a part of refractory breast cancers. Our goal was to determine the frequency of MSI in triple negative breast cancer (TNBC), one of the most clinically aggressive subtypes.
Patients and Methods:This study included 228 patients with primary TNBC underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Genomic DNA was extracted from formalin-fixed and paraffin-embedded tissue. Tumor and control DNA were amplified by polymerase chain reaction at the following 5 microsatellite markers: NR-21, BAT-26, BAT-25, NR-24, MONO-27. We classified the tumors as microsatellite stable(MSS), MSI-low or MSI-H.
Results: The mean age of patients was 59 years (range: 30-89) and all were women. T1 tumors were 57.9% and N0 were 67.5%. Meanwhile, the tumors with nuclear grade 3 were 66.2% and high Ki-67 (&gt; 30%) were 66.7%. Among the 228 tumors, 222 tumors (97.4%) revealed MSS, of which 6 (2.6%) revealed MSI and 2 (0.9%) were MSI-H. Among the MSI tumors, T and N factor were showed as follows: T1: 2 tumors, T2: 3 tumors, T3: 1 tumor, N0: 5 tumors and N1: 1 tumor. Of two MSI-H tumors, one showed T1N0 and another showed T2N0. The both of them showed nuclear grade 3, high Ki-67 (&gt; 30%) and had common following instable markers: NR-21, BAT-26 and BAT-25.
Conclusions: Our results demonstrated that the frequency of MSI-H was 0.9% (2/228). MSI might not be useful as a biomarker for immune check point inhibitors. MSI should be combined with another biomarker such as tumor mutational burden in TNBC.
Citation Format: Kurata K, Kubo M, Mori H, Kawaji H, Motoyama Y, Kuroki L, Yamada M, Kaneshiro K, Kai M, Nakamura M. Microsatellite instability in triple negative breast cancers [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-06-11.
Abstract P1-07-02: Withdrawn
Authors: Di Nicola M , Volpari T , Fucà G , Romero Cordoba S , De Santis F , Rondinone O , Faraci S , Ferris F , Puricelli C , Castagnoli L , Marullo R , Cerchietti L , Pupa S 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Di Nicola M, Volpari T, Fucà G, Romero Cordoba S, De Santis F, Rondinone O, Faraci S, Ferris F, Puricelli C, Castagnoli L, Marullo R, Cerchietti L, Pupa S. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-07-02.
Abstract P1-08-19: 10-year conditional recurrence risks, overall and relative survival for breast cancer patients in the Netherlands: Taking account of event-free years
Authors: van Maaren MC , Strobbe LJ , Smidt ML , Moossdorff M , Poortmans PM , Siesling S 
Published: May 2019

Abstract
Background
Survival estimates valid at the time of diagnosis are of limited value for (ex-)breast cancer patients who survived several years, as it includes information on already deceased patients. This study analyzed the 10-year conditional risk of recurrent breast cancer in specific prognostic subgroups according to T and N stage and breast cancer subtypes. Secondly, we investigated 10-year conditional overall (OS) and relative survival (RS), adjusted for confounding.
Patients and methods
We selected all women diagnosed in 2005 with operated T1-2N0-1 breast cancer from the Netherlands Cancer Registry. Patients were classified into T1N0, T1N1, T2N0 and T2N1 stage. Ten-year conditional recurrence rates were calculated for every year from diagnosis for patients without an event (local (LR), regional recurrence (RR), distant metastasis (DM) or death). Ten-year conditional OS was calculated using multivariable Cox regression. RS was estimated by dividing patient survival rates by those of the general Dutch population.
Results
We included 7,969 patients: 52.3% had T1N0, 15.3% T1N1, 19.9% T2N0 and 12.5% T2N1 stage. For T1N0, 10-year LR rates changed from 4.6% at diagnosis to 0.5% in year 10. RR rates decreased from 2.3% to 0.2% and DM rates decreased from 7.8% to 0.6%. For T2N1 stage, the LR, RR and DM rates decreased from 6.2% to 0.8%, 5.2% to 0.4% and 19.6% to 1.5%, respectively. Of all patients, 1,702 patients (21.4%) had an unknown breast cancer subtype and were consequently excluded from the analyses according to subtype. Of the remaining 6,267 patients, 3,774 (60.2%) had luminal A, 1,465 (23.4%) had luminal B, 314 (5.0%) had HER2 positive and 714 (11.4%) had triple negative disease For the luminal A subtype, LR, RR and DM rates ranged from 3.9% to 0.4%, 1.7% to 0.5% and 7.3% to 1.1%, while for triple negative these rates ranged between 5.6% to 0.7%, 4.9% to 0.2% and 16.7% to 0%, respectively. Differences between subgroups attenuated over time and all recurrence rates became ≤1.5% in year 10. Ten-year OS and RS, adjusted for confounding, showed diminishing risk differences between subgroups over time.
Conclusion
Differences in recurrence rates, OS and RS between prognostic subgroups decreased as years passed by. These results highlight the importance of taking into account disease-free years to more accurately predict (ex-)breast cancer patients' prognosis over time.
Citation Format: van Maaren MC, Strobbe LJ, Smidt ML, Moossdorff M, Poortmans PM, Siesling S. 10-year conditional recurrence risks, overall and relative survival for breast cancer patients in the Netherlands: Taking account of event-free years [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-19.
Abstract P1-08-21: Association of depression and anxiety disorder with the risk of mortality in breast cancer: A national health insurance service study in South Korea
Authors: Kim YS , Shim E-J , Lee JW , Cho J , Jung HK , Kim NH , Lee JE , Min J , Noh WC , Park S-H 
Published: May 2019

Abstract
PURPOSE: To examine whether depression, anxiety disorder and their co-occurrence would increase the risk of mortality in patients with breast cancer, and whether antidepressant treatment would reduce the same.
PATIENTS AND METHODS: Data were retrieved from the database of the Korean National Health Insurance Service. Of 145,251 patients diagnosed with breast cancer between 2007 and 2014, 20,870 patients diagnosed with depression or anxiety disorder one year before breast cancer diagnosis were excluded. Thus, data of 124,381 patients were included in this study.
RESULTS: Anxiety disorder was more prevalent than depression in patients with breast cancer, and similar factors were associated with both depression and anxiety disorder. Overall, female sex, older age, residence in metropolitan areas, lower income, higher comorbidity, carcinoma in situ, and the receipt of any type of cancer therapies were associated with an increased risk of depression or anxiety disorder. Depression and anxiety disorder were associated with an increased risk of mortality (Hazard Ratio (HR) = 1.26, 95% CI=1.18–1.36; HR=1.14, 95% CI=1.08–1.22, respectively) and their co-occurrence further increased the risk (HR=1.38, 95% CI=1.24–1.54). Antidepressant treatment was related to a reduced risk of mortality. Compared to patients with no depression, among those with depression, the risk of mortality was 2.18 times higher (95% CI=1.69–2.81) in patients who did not receive antidepressant treatment and 1.25 times higher (95% CI =1.17–1.32) in those who received antidepressant treatment.
CONCLUSION: The current findings suggest that psychiatric comorbidities are markers of increased mortality risk in patients with breast cancer. This underscores the need for screening and treating depression and anxiety disorders to improve survival in breast cancer.
Citation Format: Kim YS, Shim E-J, Lee JW, Cho J, Jung HK, Kim NH, Lee JE, Min J, Noh WC, Park S-H. Association of depression and anxiety disorder with the risk of mortality in breast cancer: A national health insurance service study in South Korea [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-21.
Abstract P1-16-06: Improved survival of patients with metastatic breast cancer in routine care is restricted to tumors with positive hormone receptor and/or Her2-expression. Survival analysis of 1,321 patients treated between 1995 and 2017 in oncology group practices
Authors: Weide R , Rendenbach B , Laubenstein H-P , Braun U , Hünermund K , Burkhard O , Ehscheidt P , Feiten S , Chakupurakal G , Friesenhahn V , Kleboth K , Köppler H , Lutschkin J , Thomalla J , van Roye C , Heymanns J 
Published: May 2019

Abstract
Introduction: 18,000 women die due to metastatic breast cancer in Germany per year. Median survival is 20–28 months after diagnosis. The question we wanted to answer was whether survival has improved in routine care?
Methods: Retrospective analysis of all patients with metastatic breast cancer who were treated between 06/1995-12/2017 in 5 community-based oncology group practices in Germany.
Results: 1,321 patients were analyzed with a median age of 62 (23–100). Localizations of metastases were distributed as follows: 49% visceral, 33% bone, 6% CNS, 12% others. 79% were hormone-receptor-positive, 20% Her2-positive, 9% triple-negative. Median overall survival was 37 months (95% Confidence Interval: 34–40), survival probability after 5 years 32.5%. Survival was significantly correlated with localizations of metastases, number of metastasized organs, disease free survival since initial diagnosis, hormone- and Her2-receptor status and age. Patients with hormone-receptor-positive tumors had a median overall survival of 39 months, Her2-positive patients of 45 months and triple-negative patients of 20 months. 86% of hormone-receptor-positive patients received antihormonal therapy. 81% of Her2-positive patients received anti-Her2 therapy. Overall survival according to treatment period 1995-2000, 2001-2005, 2006-2011, 2012-2017 was 34, 35, 37 and 38 months respectively. OS of patients with hormone-positive tumors according to treatment period was 35, 43, 38, and 42 months respectively. OS of patients with Her2-positive tumors according to treatment period was 39, 29, 51, and 54 months respectively. OS of patients with triple-negative tumors according to treatment period was 7, 11, 16, and 25 months respectively.
Conclusions: Improved survival of patients with metastatic breast cancer in routine care is strongly restricted to hormone receptor- and Her2-positive tumors most likely due to improved targeted therapies directed against the estrogen-receptor and Her2.
Citation Format: Weide R, Rendenbach B, Laubenstein H-P, Braun U, Hünermund K, Burkhard O, Ehscheidt P, Feiten S, Chakupurakal G, Friesenhahn V, Kleboth K, Köppler H, Lutschkin J, Thomalla J, van Roye C, Heymanns J. Improved survival of patients with metastatic breast cancer in routine care is restricted to tumors with positive hormone receptor and/or Her2-expression. Survival analysis of 1,321 patients treated between 1995 and 2017 in oncology group practices [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-16-06.
Abstract P1-17-08: High-dose chemotherapy and immunotherapy in premenopausal breast cancer patients with more than 10 axillary nodes (PBC+10N). Long-term follow-up of a phase II study
Authors: Recchia F , Candeloro G , Rea S 
Published: May 2019

Abstract
Background: PBC+10N have a high risk of relapse. Experimental studies suggest that high expression of vascular endothelial growth factor (VEGF) promotes tumor progression through neoangiogenesis and that natural killer (NK) cells mediate lytic activity against cancer cell lines. In a phase I-II study, we have shown that low-dose interleukin-2 (IL-2) and 13-cis retinoic acid (RA) increased NK cells and decreased VEGF, in patients with advanced cancer and a clinical benefit from chemotherapy (Clin Cancer Res 7: 1251, 2001). We assumed that IL-2 and RA, increasing NK and decreasing VEGF, could improve disease-free survival (DFS) and overall survival (OS) in PBC+10N. Primary endpoint was the evaluation of NK cells and VEGF; secondary endpoints were DFS, OS and toxicity. Methods: 34 patients with PBC+10N, after high-dose chemotherapy and peripheral blood progenitor cell transplantation were entered into the study. They were given hormonal therapy if needed and subcutaneous IL-2, 1.8 X 106 IU and oral RA, 0.5 mg/Kg for 5 days/week, 3 weeks/month, until progression. NK cells, VEGF, response and toxicity were assessed every 4 months. Results: After a median follow-up of 120 months (range 69-209), a total of 41 courses of high-dose chemotherapy and 60 courses of immunotherapy were delivered. A statistically significant improvement of NK cells [from a mean of 302 ± 75/mm3 to a mean of 582 ± 72/mm3 (p &lt; 0.001)] and a decrease of VEGF [from a mean of 525 ± 68 pg/mm3 to a mean of 155 ± 13 pg/mm3, (p &lt; 0.001)], were observed. 18-years DFS and OS were 29% and 32%, respectively. A significant improvement, with respect to NCI SEER data (*), was observed in the 5-year OS rate: 55% vs. 6% No WHO grade 3 or 4 toxicity was observed, while grade 2 cutaneous toxicity and fever occurred in 20% and 13% of patients, respectively. Conclusions: Our data show that immunotherapy with IL-2/RA, may determine, with an acceptable toxicity profile, a statistically significant improvement of NK cells, a decrease of VEGF, and better 5-year survival rates with respect to NCI SEER data.
Citation Format: Recchia F, Candeloro G, Rea S. High-dose chemotherapy and immunotherapy in premenopausal breast cancer patients with more than 10 axillary nodes (PBC+10N). Long-term follow-up of a phase II study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-17-08.