bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P1-19-07: Real-world characteristics, treatment patterns, and overall survival in patients with metastatic breast cancer (mBC) and CNS metastases
Authors: Alvarado-Miranda A , Cabrera-Galeana P , Muñoz-Montaño WR , Lara-Medina F , Bargallo-Rocha E , Arrieta-Rodriguez O , Perez M , Porras-Reyes F , Mohar-Betancourt A , Gamboa C
Published: May 2019

Background:

CNS metastases are reported in about 10 to 15%. Knowledge about the management of these patients are limited because they are excluded from clinical trials due to its poor prognosis and morbidity. In these study, we aim to describe characteristics, treatment patterns, and overall survival (OS) of patients of mBC with CNS metastases at Instituto Nacional de Cancerología de Mexico (INCan) from january 2007 to december 2015.

Methods:

We include patients with histological diagnosis of mBC and tumoral activity in the CNS (at diagnosis or during de follow-up). mBC subtype was defined using HER2 and hormone receptor (HR) status by immunohistochemistry; systemic treatment, and mortality data were used to characterize mBC with CNS involment.

Results:

During the study period, we found 1272 patients diagnosed with metastatic disease, of whom 408 had CNS disease (novo/recurrence) the median follow up was 52 months. Table 1 describes the percentage of CNS metastases by subtype, clinical characteristics at diagnosis and median OS. Almost all patients (85.6%) were candidate to holocranial radiotherapy; after that, systemic treatment varied according to the subtype of mBC; 69.1% of TN received CT (26% based on platinum); 75.3% of HER2+ received systemic treatment, all included antiher2 therapy; luminal subtype, no one were treated with endocrine therapy.

Table 1.- characteristics and Overall suvival by subtype of mBC all mBC 1272 n(%)her2 positive 339 (26.6) n (%)triple negative 298 (23.4) n(%)luminal 636 (50) n(%)CNS metastasis at dianosis44 (3.5)12 (3.5)13 (4.4)19 (2.9)CNS mets after prog to systemic tx205(16.1)63(18.6)50(16.7)92(14.5)CNS as first place of recurrence159(12.5)75(22.2)34(11.4)50(7.8)prevalence on CNS mets408(10.7)150(14.7)97(10.8)161(8.4)median age at diagnosis of CNS mets50(28-84)50(29-84)48(28-80)51(28-80)median OS after CNS mets (months)14.927.29.3316.3

Conclusions:

HER2 positive breast cancer patients have the highest prevalence of CNS metastases, whereas luminal has the lowest. Patients with HER2+ and CNS metastases commonly receive treatment based on anti-HER2 therapy, maybe this target treatment contribute to the better survival achieved than patients with luminal or TN subtype. mBC with CNS metastases continues in the real world to be an unmet medical need.

Citation Format: Alvarado-Miranda A, Cabrera-Galeana P, Muñoz-Montaño WR, Lara-Medina F, Bargallo-Rocha E, Arrieta-Rodriguez O, Perez M, Porras-Reyes F, Mohar-Betancourt A, Gamboa C. Real-world characteristics, treatment patterns, and overall survival in patients with metastatic breast cancer (mBC) and CNS metastases [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 P1-19-07.
Abstract P2-01-15: Inflammatory breast cancer cells are characterized by attenuated SMAD dependent TGFβ signaling leading to impaired cell motility responses
Authors: Rypens C , Van Berckelaer C , Billet C , Hauspy J , Bertucci F , Peter V , Dirix L , Van Laere S
Published: May 2019

Introduction.Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer with elevated metastatic potential, characterized by the frequent presence of tumor emboli in dermal and parenchymal lymph vessels. In the past, evidence was provided that TGFβ signaling is part of the molecular biology of this disease. In this study, this relation was further examined.

Materials and methods. TGFβ1 induced cell motility (i.e. XCELLigence, wound healing assays), gene expression (RNA-sequencing) and peptide phosphorylation (i.e. PAMGene technology) patterns were investigated in a panel of 3 IBC and 3 subtype-matched nIBC cell lines. In addition, a series of tissue samples from 75 and 135patients with and without IBC was investigated for nuclear expression of total SMAD2, SMAD3 and SMAD4 using immunohistochemistry. Finally, SMAD protein expression data were related to gene expression data from patients with available Affymetrix HGU133plus2 profiles.

Results. The cell motility inducing capacity of TGFβ1 was strongly abrogated in all IBC cells independent of their molecular subtype (P=0.003). Genes differentially expressed between IBC and nIBC cells post 4 hours of TGFβ1 revealed attenuated expression of SMAD3 transcriptional regulators with concomitant overexpression of MYC target genes in IBC. Assessment of SMAD expression in patient samples demonstrated a near absence of nuclear SMAD3 expression in the primary tumors from patients with IBC (P<0.001) and a further reduction of SMAD3 staining intensity was observed in tumor emboli (P=0.019). Integrated analysis of gene and protein expression data revealed that a substantial fraction of the IBC signature genes correlated with SMAD3 and these genes (i.e. 21/24; P<0.001) carry evidence in favor of attenuated SMAD3 signaling in IBC.

Discussion. It is demonstrated that IBC cells are characterized by attenuated SMAD3 protein expression and transcriptional activity that obliterates the cell motility inducing capacity of TGFβ1. Recent studies revealed that SMAD3 is essential for TGFβ1 induced cell motility through induction of epithelial to mesenchymal transition (EMT). In the absence of SMAD3 expression, a partial EMT is induced leading to collectively invading cancer cells that are gifted with a high metastatic potential and favor lymphatic dissemination, thereby providing an intriguing explanatory model of the biology of tumor emboli in IBC.

Citation Format: Rypens C, Van Berckelaer C, Billet C, Hauspy J, Bertucci F, Peter V, Dirix L, Van Laere S. Inflammatory breast cancer cells are characterized by attenuated SMAD dependent TGFβ signaling leading to impaired cell motility responses [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 P2-01-15.
Abstract P2-01-17: Not presented
Authors: Dravis CP , Chung C-Y , Wahl GM
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Dravis CP, Chung C-Y, Wahl GM. Not presented [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 P2-01-17.
Abstract P2-01-25: Not presented
Authors: Xing W , Li Q , Cao R , Sun G , Jiang C
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Xing W, Li Q, Cao R, Sun G, Jiang C. Not presented [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 P2-01-25.
Abstract P2-02-14: Metabolic regulation and drug resistance in c-Src activated triple negative breast cancer
Authors: Jung KH , Park JH , Sirupangi T , Jia D , Gandhi N , Pudakalakatti S , Elswood J , Porter W , Putluri N , Zhang XH-F , Chen X , Bhattacharya PK , Creighton CJ , Lewis MT , Rosen JM , Wong L-JC , Das GM , Osborne CK , Rimawi MF , Kaipparettu BA
Published: May 2019

c-Src (Src) is a proto-oncogene involved in signaling that culminates in the control of multiple biological functions. Src is also one of the most frequently upregulated pathways in triple negative breast cancer (TNBC). Dysregulation of Src has been detected in TNBC and is strongly associated with tumor metastasis and poor prognosis. However, even after promising preclinical studies, Src inhibitors did not show major clinical advantage in unselected TNBC populations. We have previously published that metastatic TNBC has high energy-dependency to mitochondrial fatty acid beta-oxidation (FAO) and FAO activates Src by inducing autophosphorylation at Y419. However, our recent analysis suggests that as observed with the Src inhibitors, TNBC tumors treated with FAO inhibitors also develop drug-resistance and continue tumor growth. Evaluation of their drug resistance mechanism revealed that while short-term inhibition of FAO or Src induces autophagic and apoptotic cell deaths, long-term inhibition results in autophagy-mediated drug resistance and survival. Further analyses suggest that FAO and Src inhibitors activate mitogen-activated protein (MAP) kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway via the induction of cellular reactive oxygen species (ROS) in TNBC. Activated MEK/ERK then induces survival pathways for drug resistance and tumor survival. Validation of in vitro findings using in vivo TNBC models confirmed that combination of FAO/Src inhibitors with MEK/ERK inhibitors can provide significant benefit to overcome the therapeutic resistance of TNBC. These findings open-up new therapeutic opportunities to manage TNBC patients with currently non-targetable metastatic tumors.

Citation Format: Jung KH, Park JH, Sirupangi T, Jia D, Gandhi N, Pudakalakatti S, Elswood J, Porter W, Putluri N, Zhang XH-F, Chen X, Bhattacharya PK, Creighton CJ, Lewis MT, Rosen JM, Wong L-JC, Das GM, Osborne CK, Rimawi MF, Kaipparettu BA. Metabolic regulation and drug resistance in c-Src activated 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 P2-02-14.
Abstract P2-03-05: S100A7 enhances triple negative breast cancer growth and metastasis by cross-talk with resistin
Authors: Mishra S , Ahiwar DK , Shukla RK , Chatterjee N , Ganju R
Published: May 2019

Triple negative breast cancer (TNBC) represents ˜20% of all breast cancer cases and is highly refractory to existing therapies. Although, a number of putative functions have been proposed for S100A7, but its crosstalk with resistin in TNBC pathogenesis remains to be defined. S100A7/RAGE signaling has been shown to play an important role in inflammation-mediated breast cancer pathogenesis. S100A7/psoriasin, a member of the epidermal differentiation complex, is widely overexpressed in invasive estrogen receptor (ER)α-negative breast cancers. Thus, the objective of this study is to explore the cross-talk between S100A7 and resistin in TNBC cells. In this study, we observed that the treatment or overexpression of S100A7 increased the expression of resistin, cPLA2 and FASN expressions in TNBC cells. The overexpression/downregulation of S100A7 with exogenous resistin in TNBC cells also showed the marked changes in their migrating, sphere forming and colony forming abilities. The treatment of resistin also increases the effect of S100A7-mediated expansion of breast cancer stem cells (BCSCs) by increasing the ALDH activity and CD44+CD24- subpopulations. The in-vivo effects of resistin on breast tumor growth and metastasis were also analyzed by using MDA-MB-231 vector and S100A7 overexpressed MDA-MB-468 vector and S100A7 knock-down cells by using Xenograft NOD/SCID Il2rg null (NSG) mice model. Here, we have found that the treatment of resistin increased the tumor growth and metastases mediated by S100A7 by modulating the different myeloid cells populations. We have also shown that the S100A7 overexpressed MDA-MB-231 cells were much more sensitive to FASN and cPLA2 inhibitors as compared to vector control cells. The in-silico analyses also showed the clinical significance of S100A7 and resistin in TNBC pathogenesis. Collectively, these findings suggest the novel cross-talk in between S100A7 and resistin in TNBC pathogenesis and how resistin, cPLA2 and FASN could be used as potential therapeutic targets to inhibit the S100A7-mediated TNBC progression and metastasis.

Citation Format: Mishra S, Ahiwar DK, Shukla RK, Chatterjee N, Ganju R. S100A7 enhances triple negative breast cancer growth and metastasis by cross-talk with resistin [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 P2-03-05.
Abstract P2-03-12: Role of nucleus-specific intergenic long noncoding RNA-1476 in estrogen-dependent transcription in cancer
Authors: Choudhari R , Harrison AL , Carrillo CN , Gadad SS
Published: May 2019

Long noncoding RNAs (lncRNAs) are emerging as key regulators of diverse cellular processes, but their roles in cancer biology are just beginning to be elucidated. Previous work using Global Run-On sequencing (GRO-seq) to study the transcriptome of MCF-7 breast cancer cells identified a large number of unannotated noncoding RNAs. Integration of RNA-seq data from subcellular fractionated RNA (i.e., cytoplasm, nucleoplasm, and chromatin-associated) with GRO-seq data using a novel bioinformatics pipeline has yielded a comprehensive catalog of >1900 polyadenylated lncRNAs in MCF-7 cells, about half of which have not been annotated previously and about a quarter of which are estrogen-regulated. Analysis of RNA-seq data from hundreds of samples representing 13 different cancer and normal tissue types, revealed that many lncRNAs are differentially expressed in various cancers. Furthermore, a large number of lncRNAs show distinct expression patterns across molecular subtypes of cancer. In functional assays, Kaplan Meier analysis of selected lncRNA, such as lncRNA 1476, predicts clinical outcome in ER-positive cancer and is transcriptionally upregulated in MCF-7 cells upon estrogen treatment. LncRNA1476 has now been fully annotated (transcription start and stop site, 5' cap, polyA tail, and exon/intron structure), and cloned. Molecular analyses indicate that lncRNA1476 plays a critical role in ER-dependent pathway. Collectively, our results suggest that lncRNAs are essential in controlling biological processes.

Supported by a grant from the Cancer Prevention and Research Institute of Texas to S.S.G

Citation Format: Choudhari R, Harrison AL, Carrillo CN, Gadad SS. Role of nucleus-specific intergenic long noncoding RNA-1476 in estrogen-dependent transcription in 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 P2-03-12.
Abstract P2-06-16: New targets in triple negative breast cancer: Role of Oncostatin M receptor pathway
Authors: Alvarez I , Araujo A , Abaurrea A , Rezola R , Urruticoechea A , Lawrie C , Caffarel MM
Published: May 2019

BACKGROUND:Triple negative breast cancer (TNBC) has poor prognosis, lack of targeted therapies and are often refractory to conventional chemotherapy treatments. Therefore, finding new therapeutic targets for those tumours is an unmet need with high clinical impact. In this context, Oncostatin M receptor (OSMR) is a promising therapeutic target as it is over-expressed in this tumour subtype and its activation promotes invasiveness (Guo L, et al. 2013 Oncogene; West NR, et al.2014 Oncogene). We previously showed that OSMR is frequently copy-number gained and over-expressed in squamous cell carcinoma, where it induces migration, invasion and metastasis (Caffarel MM, et al 2013 Journal of Pathology; Caffarel MM, et al 2014 Journal of Pathology; Kucia-Tran JA, et al. 2016 Brit J Cancer; Kucia-Tran JA, et al 2018 Journal of Pathology). We now investigate the role of OSMR in breast cancer progression.

METHODS: To address this issue we use a wide array of tools including in vitro cell cultures and in vivo models. The expression of OSMR pathway was analysed in FFPE samples and large datasets of publicly available breast cancer samples (METABRIC, n=1462; and TCGA, n=547).

RESULTS: OSMR and its ligand Oncostatin M (OSM) are over-expressed in basal tumours, where they associate with shorter overall survival (p=0.015). While OSMR is expressed by breast cancer cells and cancer associated fibroblasts, the main source of OSM seems to be primarily macrophages. OSM treatment of breast cancer cells induces the expression of important mediators of angiogenesis and invasion. Importantly, OSMR activation accelerates tumour onset, tumour growth and metastasis in orthotopic xenografts in nude mice.

CONCLUSIONS: Our results support that OSMR pathway may have an important role in the initiation and progression of breast cancer and that it could be a promising candidate for therapeutic targeting in TNBC. OSMR could be blocked by antibody based inhibition, strategy that has had a major impact on breast cancer.

Citation Format: Alvarez I, Araujo A, Abaurrea A, Rezola R, Urruticoechea A, Lawrie C, Caffarel MM. New targets in triple negative breast cancer: Role of Oncostatin M receptor pathway [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 P2-06-16.
Abstract P2-06-24: Cannabinoid receptors agonist induces lysosome-mediated cell death in TNBC
Authors: Chatterjee N , Das S , Ahiwar D , Mishra S , Kaul K , Ganju R
Published: May 2019

Breast cancer is one of the leading causes of death among women in the United States. Among all the breast cancer subtypes, triple-negative breast cancer (TNBC) is denoted as having the highest rate of mortality due to inefficacious therapy, drug resistance, and high recurrences rate. Despite many therapeutic advances over the past decades, novel therapeutic approaches are required to treat TNBC. Although lysosomes have recently been identified as novel targets in a variety of cancers, not much known about their role in breast cancer especially in TNBC. Due to the altered features of lysosomes in cancerous cells, its functional ability affects cell proliferation, metabolism, adaptation, and autophagy in tumor cells. Thus, the induction of lysosomal membrane permeabilization (LMP) may be used as a novel approach in controlling the aberrant cellular functions in TNBC. Cannabinoid receptor 2 (CB2) is expressed in breast cancer and its agonist JWH-015 has been shown to inhibit TNBC growth and metastasis. However, not much is known about the mechanisms by which JWH015 inhibit growth and metastasis. To investigate JWH015-mediated therapeutic mechanisms, we examined the lysosome-mediated cell death in TNBC cells. We found that JWH015 induces cell death in TNBC cells through lysosomal disruption mechanism. We also showed that JWH-015 treatment increases releases of lysosomal proteins, cathepsin D/B, and autophagy marker LC3B and that leads to activation of apoptotic cell death signaling in TNBC. These alterations result in the formation of autolysosomes to promote LMP. Our findings elucidate the mechanism by which JWH-015 promotes LMP induced autophagy and regulates TNBC cell proliferation. These studies elucidate novel lysosomal-mediated cell death mechanisms through activation of CB2 receptors in TNBC.

Citation Format: Chatterjee N, Das S, Ahiwar D, Mishra S, Kaul K, Ganju R. Cannabinoid receptors agonist induces lysosome-mediated cell death in TNBC [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 P2-06-24.
Abstract P2-07-10: Not presented
Authors: Lee H-B , Kim KE , Ju YW , Jung J-G , Ryu H-S , Lee SB , Lee JW , Lee HJ , Kim M-S , Kwon S , Kim J , Kim C , Moon H-G , Noh D-Y , Ahn S-H , Park I-A , Kim S , Yoon S , Kim A , Han W
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Lee H-B, Kim KE, Ju YW, Jung J-G, Ryu H-S, Lee SB, Lee JW, Lee HJ, Kim M-S, Kwon S, Kim J, Kim C, Moon H-G, Noh D-Y, Ahn S-H, Park I-A, Kim S, Yoon S, Kim A, Han W. Not presented [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 P2-07-10.
Abstract P2-08-08: Isolated ipsilateral local recurrence of breast cancer: Predictive factors and prognostic impact
Authors: Houvenaeghel G , de Nonneville A , Cohen M , Classe J-M , Reyal F , Mazouni C , Chopin N , Martinez A , Daraï E , Coutant C , Colombo P-E , Gimbergues P , Chauvet M-P , Azuar A-S , Rouzier R , Tunon de Lara C , Murraciole X , Agostini A , Gonçalves A , Lambaudie E
Published: May 2019

Background

Tumour features associated with isolated invasive breast cancer ipsilateral local recurrence (ILR) after breast conservative treatment (BCT) and consequences on overall survival (OS) are still debated. The aim of our study was to examine predictive factors of isolated ILR after BCT with in sano resection and whole breast irradiation as well as the impact of such an ILR on overall survival in a large multi-institutional cohort.

Methods

Patients were retrospectively identified from a large cohort of 23,375 consecutive patients who underwent BCT for invasive breast cancer in 16 cancer centres. End-points were ILR rate and OS. The impact of ILR on OS was assessed through multivariate analysis by logistic regression and Cox model, adjusted on ERs/Grade status (ERs+/Grade 1, ERs+/Grade 2, ERs+/Grade 3 and ERs-) and then on tumour subtypes.

Results

Of 15,570 patients, ILR rate was 3.1%. Cumulative ILR rates differed according to ERs/grade (ERs+/Grade2: HR=1.42, p=0.010; ERs+/Grade3: HR=1.41, p=0.067; ERs-: HR=2.14, p<0.0001), endocrine therapy (HR=2.05, p<0.0001) and age<40-years old (HR=2.28, p=0.005) in multivariate analysis. When multivariate analysis was adjusted on tumour subtype, the latter was the only independent factor. OS-after-ILR was significantly different according to ILR-free intervals (HR=4.96 for ILR-free interval between 2-5-years and HR=9.00 when <2-years, in comparison with ≥5-years).

Impact of free interval time on OS among patients with ILR and among all patients  p-valueHRInfSupILRno ILR 1   <2 years0.0172.2551.1594.388 2-5 years0.0012.451.423.89 ≥5 years0.1030.5550.2741.126Tumor subtypesLuminal A G1 1   Luminal A G20.0031.4311.1321.810 Triple negative<0.00012.6992.0553.544 Luminal B ER-<0.00013.1952.4144.229 Luminal B ER+0.021.6081.0762.401 HER2+<0.00012.2791.4523.579

Conclusion

ERs/Grade status, lack of endocrine therapy and tumour subtypes predict isolated ILR risk in patients treated with BCT. Short ILR-free-intervals represent a strong pejorative factor for OS. These results may help selecting initial treatment as well as tailoring ILR systemic chemotherapy.

Citation Format: Houvenaeghel G, de Nonneville A, Cohen M, Classe J-M, Reyal F, Mazouni C, Chopin N, Martinez A, Daraï E, Coutant C, Colombo P-E, Gimbergues P, Chauvet M-P, Azuar A-S, Rouzier R, Tunon de Lara C, Murraciole X, Agostini A, Gonçalves A, Lambaudie E. Isolated ipsilateral local recurrence of breast cancer: Predictive factors and prognostic impact [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 P2-08-08.
Abstract P2-08-30: Vitamin D as a prognostic factor in triple negative early breast cancer
Authors: Morales Murillo S , Gasol Cudos A , Veas Rodriguez J , Santacana M , Canosa Morales C , Mele Olivé J
Published: May 2019

Background: Triple negative breast cancer is a special phenotype where the pathological complete response (pCR) remains the most important factor but only around a 40% of patients achieve this response. We analyze if the vitamin D receptors (VDR) could be a prognostic factor not related with the histological response.

Methods: A series of 160 patients with early or locally advanced triple negative breast cancer that received neoadjuvant chemotherapy were retrospectively reviewed from 2007 to 2017. Clinicopathological and vitamin D receptors analysis were correlated to pCR.

Results: Median age was 53, median tumor size 30mm, 48% had nodal involvement, and median ki67 expression was of 70%. Androgen receptor was expressed in 28% of tumors analyzed, EGFR in 89%, CK5/6 in 63%. VDR (cytoplasmatic and nuclear) expression was determined in 56 patients, finding in 45 (80%) an expression that was considered as high. We achieved a total of 73/160 pCR (45%) with a significant median disease free survival of 178 months (log rank p: 0,0001). In the univariate analysis, the initial tumoral size, initial nodal involvement and expression of VDR was significant; and in the mutivariate model the expression of VDR maintains the level of significance ( HR: 0,138 IC 95% 0,039-0,493 p:0,002).

Conclusions: The expression of VDR in the initial tumor before starting neoadjuvant chemotherapy is a strong predictor of recurrence independently of histological response with a median disease free survival of 149 months in patients with high expression versus 62 month. Furthermore, in patients without histological response, progression-free median survival is 86 months for patients with high expression versus 35 months.

Citation Format: Morales Murillo S, Gasol Cudos A, Veas Rodriguez J, Santacana M, Canosa Morales C, Mele Olivé J. Vitamin D as a prognostic factor in triple negative early 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 P2-08-30.
Abstract P2-08-32: Withdrawn
Authors: Perimbeti SP , Shrivastav R , Ward K , Styler M
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Perimbeti SP, Shrivastav R, Ward K, Styler M. 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 P2-08-32.
Abstract P2-14-21: Not presented
Authors: Lee S , Ahn SH , Lee JW , Chung IY , Ko BS , Kim HJ , Kim J , Shon G , Son BH
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Lee S, Ahn SH, Lee JW, Chung IY, Ko BS, Kim HJ, Kim J, Shon G, Son BH. Not presented [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 P2-14-21.
Abstract P3-03-05: Not presented
Authors: Jung S-Y , Han JH , Park SJ , Lee E-G , Lee MH , Lee ES , Kang H-S , Lee KS , Park IH , Sim SH , Jeong HJ , Kwon Y , Lee D-E , Joo J , Kim S-K , Lee S
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Jung S-Y, Han JH, Park SJ, Lee E-G, Lee MH, Lee ES, Kang H-S, Lee KS, Park IH, Sim SH, Jeong HJ, Kwon Y, Lee D-E, Joo J, Kim S-K, Lee S. Not presented [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 P3-03-05.
Abstract P3-03-24: ABCSG 33 - A multi center registry to evaluate the affect of macro metastasis in sentinel lymph node on survival
Authors: Strobl SA , Dubsky P , Exner R , Gnant M , Jakesz R , Tausch C , Wette V , Heck D , Luisser I , Bjelic-Radisic V , Schrenk P , Poyssl C , Mathis J , Fitzal F
Published: May 2019

Background:

Sentinel lymph node dissection identifies nodal positivity in early breast cancer. Trials like the ACOSOG Z0011 trial tried to show that the waiver of axillary dissection in nodal positive breast cancer (BC) has no effect on the oncologic outome, however real world data are rare and the role of adjuvant regional radiotherapy is still disputed in this respect.

Objective:

We initiated a multicenter observational registry to investigate omission of axillary lymph node dissection in nodal positive early BC.

Design and Setting:

The 18 sites participating in Austria and Switzerland included from 2014 to 2017 178 patients in this trail.

Patients:

Women with unilateral invasive lymph node positive BC with one or two sentinel lymph node makrometastases, who did not undergo axillary lymph node dissection were included.

Results:

We had a median follow up time of 3.1 years (range between 0.5 and 10.5 years), the median patient age is 63.6 years (range between 33 – 93 years). In 16.9% women had a G1 Grading, 53.1% had G2 tumor and 29.9% had a G3 tumor. Multifocality was seen in 18.1% of the patients. Luminal A tumors were seen in 16 (8.9%) and Luminal B in 82 (46.1%). Fourteen (7.8%) patients in this cohort had HER2 positive BC. In one (0.5%) local recurrence of the axilla occurred. Three (1.7%) of 178 patients died due to BC recurrence.

Conclusion:

Patients with macro metastasis in the sentinel lymph node, treated with breast conserving surgery and whole breast radiation did not have an increased risk of BC recurrence.

Therefore the authors assume that axillary dissection in patients with early stage BC and macro metastasis is not necessary in this patient cohort.

Citation Format: Strobl SA, Dubsky P, Exner R, Gnant M, Jakesz R, Tausch C, Wette V, Heck D, Luisser I, Bjelic-Radisic V, Schrenk P, Poyssl C, Mathis J, Fitzal F. ABCSG 33 - A multi center registry to evaluate the affect of macro metastasis in sentinel lymph node on survival [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 P3-03-24.
Abstract P3-03-42: Withdrawn
Authors: Bundred NJ , Foden P , Riches K , Morris J , Evans A , Todd C , Bramley M , Skene A , Purushotham A , Keeley V
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Bundred NJ, Foden P, Riches K, Morris J, Evans A, Todd C, Bramley M, Skene A, Purushotham A, Keeley V. 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 P3-03-42.
Abstract P3-04-02: Not presented
Authors: Chen X , Tong Y , Chen W , Li Y , Shen K
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Chen X, Tong Y, Chen W, Li Y, Shen K. Not presented [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 P3-04-02.
Abstract P3-06-02: Imprint of parity and age at first pregnancy on the genomic landscape of subsequent breast cancer
Authors: Nguyen B , Venet D , Lambertini M , Desmedt C , Salgado R , Horlings HM , Rothe F , Sotiriou C
Published: May 2019

Background: Although parity and age at first pregnancy are among the most known extrinsic factors that modulates breast cancer risk, their impact on the biology of subsequent breast cancer has never been explored in depth. In this study, we investigated the imprint of parity and age at first pregnancy on the pattern of somatic mutations, somatic copy number alterations (SCNAs), transcriptomic profiles, and tumor immune microenvironment by assessing infiltrating lymphocytes (TILs) levels of subsequent breast cancer.

Methods: A total of 313 patients with primary breast cancer with available whole genome, RNA sequencing and TILs data were included in this study. We used a multivariate analysis adjusted for age at diagnosis, pathological stage, molecular subtypes and histological subtypes. We compared nulliparous vs. parous, late parous vs. early parous, and nulliparous vs. pregnancy associated breast cancer (PABC) patients. Late and early parous patients were grouped by using the median age at first pregnancy as a cut-off value. PABC was defined as patients diagnosed up to 10 years postpartum.

Results: Genomic alterations of breast cancer were associated with age at first pregnancy but not with parity status alone. Independently of clinicopathological features, early parous patients developed tumors characterized by a higher number of Indels (Padj = 0.002), a lower frequency of CDH1 mutations (1.2% vs. 12.7%; Padj = 0.013), a higher frequency of TP53 mutations (50% vs. 22.5%; Padj = 0.010), MYC amplification (28% vs. 7%; Padj = 0.008), and a lower prevalence of mutational signature 2, putatively associated with APOBEC activity. PABC were associated with increased TILs infiltration (Padj = 0.0495).

Conclusions: These findings highlight an unprecedented link between reproductive history and the genomic landscape of subsequent breast cancer. This work advocates that reproductive history should be routinely collected in future large scale genomic studies addressing the biology of female cancers.

Citation Format: Nguyen B, Venet D, Lambertini M, Desmedt C, Salgado R, Horlings HM, Rothe F, Sotiriou C. Imprint of parity and age at first pregnancy on the genomic landscape of subsequent 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 P3-06-02.
Abstract P3-06-20: Druggable genomic landscape of primary and metastatic breast cancers
Authors: Sun SQ
Published: May 2019

Background: Several studies (e.g. The Pan-Cancer Atlas) have examined the druggable genomic landscape of breast cancers and other malignancies using The Cancer Genome Atlas (TCGA). However, TCGA is representative of newly-diagnosed, treatment-naïve breast cancers, whereas genomic profiling is typically used to inform therapy for metastatic and/or pre-treated breast cancers. Here, we characterize the druggable genomic landscape of breast cancers using AACR Genomics Evidence Neoplasia Information Exchange (GENIE), a multi-institutional pragmatic cancer genomics registry.

Methods: We obtained mutation, copy-number amplification (CNA), and fusion data from GENIE, which contains de-identified genomic records from 4506 breast carcinoma and carcinoma-in-situ (CIS) tumors. We used Clinical Interpretation of Variants in Cancer (CIViC) to label the potential druggability of these mutations, CNAs, and fusions. Further, we plan to assess variations in the druggable genomic landscape of breast tumors as a function of tumor characteristics (e.g. histology, tumor mutation burden), patient characteristics (age, sex, ethnicity), and genomics assay characteristics (e.g. PCR vs. hybridization capture).

Results: In GENIE, we identified 19932 mutations, 9334 copy number amplifications (CNA), and 987 fusions in 4506 breast tumors. CNAs suggesting potential druggability were relatively common (e.g. ERBB2 amplifications in 9.9% of tumors), whereas fusions suggesting potential druggability were relatively rare (e.g. NTRK fusions in 0.1% of tumors). Mutations suggesting potential druggability were identified in ERBB2 (3.5% of tumors) and mismatch repair genes [MLH1, MSH2, MSH3, MSH6, PMS1, PMS2] (3.7% of tumors).

Conclusion: GENIE can be used to infer druggability across a cohort of breast tumors likely to be considered for approved systemic therapy at tertiary academic centers. This may inform use of genomic assays and/or design of clinical trials for patients with breast tumors.

*The author would like to acknowledge the American Association for Cancer Research and its financial and material support in the development of the AACR Project GENIE registry, as well as members of the consortium for their commitment to data sharing. Interpretations are the responsibility of study authors.

Citation Format: Sun SQ. Druggable genomic landscape of primary and metastatic 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 P3-06-20.
Abstract P3-07-01: Towards a therapeutically relevant subtyping scheme for triple-negative breast cancer (TNBC), profiling results from A Randomized, TNBC Enrolling trial to confirm Molecular profiling Improves Survival (ARTEMIS)
Authors: Seth S , Huo L , Rauch G , Lau R , Gilcrease M , Adrada B , Piwnica-Worms H , Symmans WF , Draetta G , Futreal AP , Moulder S , Chang JT
Published: May 2019

Triple-negative breast cancer is a highly diverse group of cancers, with poor prognosis, and currently, there are no targeted drugs available in the clinic. In TNBC around 50% percent of the patients respond to chemotherapy, while, the other 50% percent relapse with poor prognosis. There is a need to understand better the targetable mechanisms driving TNBC via integrative analysis of gene-expression, copy-number, and mutational data.

Samples from 220 triple-negative breast cancer (TNBC) pts treated with NACT were prioritized for transcriptomic and genomic profiling. Non-negative matrix factorization was used on array-based profiling to identify six robust (ARTEMIS) subtypes. Comparing ARTEMIS subtypes with Vanderbilt subtypes, revealed significant overlap with 4/6 clusters while identifying two new clusters. Logistic regression on ssGSEA scores vs. subtypes revealed several pathways, selectively enriched specific subtypes. CL1/IM (Immune subtype), was enriched in INFg and INFa, while CL2 (MYC/mTOR), showed enrichment of several proliferation-related pathways. In addition, LAR and M (Mesenchymal) pts formed overlapping clusters, using either method.

Two new subtypes did not associate significantly with any of the previous subtypes. The majority of the tumors from the Vanderbilt BL2 and MSL were reclassified into a CL5 (ANGIO) cluster, which was enriched in angiogenesis geneset, including targetable genes like VEGF and FGFR. Also, an MYO (CL3) subtype was identified, with myogenesis-related genes. Of note, TIL (tumor infiltrating lymphocytes) and LAR quantification using IHC were associated with respective ARTEMIS subtypes. Finally, the IM subtype was significantly associated with higher rates of RCB 0-I and the M (CL4) subtype was associated with higher rates of RCB II-III, irrespective of the neoadjuvant treatment regimen.

ARTEMIS subtypes are a novel classification system for TNBC that is focused on therapeutic translation. Further, we show a possibility to classify previously un-classified (UNS) tumors, which will be validated using additional cohorts (TCGA/METABRIC).

Citation Format: Seth S, Huo L, Rauch G, Lau R, Gilcrease M, Adrada B, Piwnica-Worms H, Symmans WF, Draetta G, Futreal AP, Moulder S, Chang JT. Towards a therapeutically relevant subtyping scheme for triple-negative breast cancer (TNBC), profiling results from A Randomized, TNBC Enrolling trial to confirm Molecular profiling Improves Survival (ARTEMIS) [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 P3-07-01.
Abstract P3-07-05: Not presented
Authors: Hardeman A , Grushko T , Clayton W , Hurley I , Khramtsova G , Parker J , Perou C , Olopade O
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Hardeman A, Grushko T, Clayton W, Hurley I, Khramtsova G, Parker J, Perou C, Olopade O. Not presented [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 P3-07-05.
Abstract P3-07-11: Withdrawn
Authors: Jackson HW , Fischer JR , Zanotelli VR , Soysal SD , Simone M , Weber WP , Bodenmiller B
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Jackson HW, Fischer JR, Zanotelli VR, Soysal SD, Simone M, Weber WP, Bodenmiller B. 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 P3-07-11.
Abstract P3-08-22: Oncotype Dx recurrence score risk groups according to Ki67, a predictor to be considered
Authors: Namuche F , Ruiz R , Morante Z , Aguilar A , Gomez H
Published: May 2019

Background

The gene expression profiling assay OncotypeDx (ODx) prognosticates the risk of estrogen receptor positive (ER+) breast cancer (BC) recurrence and assesses the likely benefit from adjuvant chemotherapy in addition to endocrine therapy. There have been several attempts to develop algorithms that provide similar outcome prediction to the ODx assay with the use of routine clinicopathological characteristics. Ki67 is frequently incorporated into these assessments, although there is no standard cut-off for its use.

Methods

We retrospectively reviewed the electronic medical records of 330 patients with early stage ER+ BC for whom ODx recurrence score (RS) was available. Patients were diagnosed and treated at two specialized cancer centers between 2014 and 2017.

Our objective was to determine the ki67's median differences between ODx risk groups.

We used Spearman rho for the correlation between Ki67 and ODx score and used Kruskal-Wallis test for compare medians, pairwaise comparison for the intergroup relations.

Results

Mean age at diagnosis was 57.42 years (range 28-89). Mean tumor diameter was 15.67 mm. 78.9% were intermediate histologic grade and 9.7% patients had lymph node involvement. Median expression of ER and PR were 90% (5-100) and 70% (0-100), respectively. We assessed the correlation between Ki67 and ODx score, with a pearson r:0.31, p<0.001. The data showed a directly proportional trend between Ki67 and ODx score.

Median Ki67 was 20 (1-100). According to ODX RS, 61.5% of tumors were low risk, 30.3% were intermediate risk and, 8.2% were high risk. Median Ki67 within each category group is as follows: low: 15 (IQR:15), intermediate: 20 (IQR:18) and high: 40 (IQR:35), with a statistically significant difference between medians (p<0.001). In the Pairwise comparison intergroup the data showed: Low-Intermediate (p<0.05), Low-High (p<0.001), Intermediate-High (p<0.001).

Conclusions

The data showed directly proportional trend between Ki67 and ODx score. In our population there is a statistically significant difference between Ki67 medians according to ODx risk groups.

Citation Format: Namuche F, Ruiz R, Morante Z, Aguilar A, Gomez H. Oncotype Dx recurrence score risk groups according to Ki67, a predictor to be considered [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 P3-08-22.
Abstract P3-12-06: TOxicities of Locoregional Radiotherapy Associated with Bevacizumab in patients with non-metastatic breast cancer (TOLERAB): Final long-term evaluation
Authors: Clément-Zhao A , Tanguy M-L , Cottu P , De La Lande B , Bontemps P , Lemanski C , Baumann P , Levy C , Peignaux K , Reynaud-Bougnoux A , Gobillion A , Kirova Y
Published: May 2019

Background and Purpose: Recent phase 3 clinical trials have evaluated the addition of bevacizumab (B) to standard chemotherapy in the treatment of patients with non-metastatic breast cancer. But few data are available about the tolerance of B with locoregional radiation therapy (RT). The objective was to evaluate the 5 years late toxicities of the concurrent B and RT in non-metastatic breast cancer.

Material and methods: This is a multicenter prospective study including non-metastatic breast cancer patients enrolled in phase 3 clinical trials evaluating B with concurrent RT (BEATRICE, BETH, BEVERLY 1, BERVERLY 2) versus RT alone. All patients received neo-adjuvant or adjuvant chemotherapy and normo-fractionated breast or chest wall RT, with or without regional lymph nodes RT. B was administrated as an equivalent of 5 mg/kg every week for 1 year. The safety profile (using the Common Terminology Criteria for Adverse Events version 3.0) was evaluated at 1, 3 and 5 years after the completion of radiotherapy.

Results: From October 2007 to January 2012, 151 patients totally included. Median follow-up was 60 months (36-84) and 5 years late toxicities were available for 104 patients (46 with B and RT, 58 with RT alone). Median age was 51 (22-81). 61% of patients received regional lymph nodes RT. The majority of tumor was triple negative (65.6%), tumor size <2cm (50%) and nodal status negative (63.8%). Median total dose of B was 15000 mg (13200 – 18550) and median duration was 11.2 months (11-12.6). No grade ≥3 toxicity was observed. Only 16 patients had grade 1-2 toxicities (8 treated with B and RT, 8 with RT alone): n=4 (3.8%) had grade 1 pain, n=5 (4.8%) had grade 1-2 fibrosis, n=1 (1%) had grade 2 telangiectasia and n=5 (4.8%) had grade 1-2 lymphoedema. No significant difference between the 2 arms was observed. One patient of 46 evaluated had Left Ventricular Ejection Fraction inferior to 50%. At 5 years, overall survival was 93.8%, disease free-survival 89% and locoregional free-survival 93.1 %.

Conclusion: Concurrent B and locoregional RT provides acceptable 5-years toxicities in patients with non-metastatic breast cancer. No grade ≥3 toxicity was observed.

Citation Format: Clément-Zhao A, Tanguy M-L, Cottu P, De La Lande B, Bontemps P, Lemanski C, Baumann P, Levy C, Peignaux K, Reynaud-Bougnoux A, Gobillion A, Kirova Y. TOxicities of Locoregional Radiotherapy Associated with Bevacizumab in patients with non-metastatic breast cancer (TOLERAB): Final long-term evaluation [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 P3-12-06.
Abstract P3-12-11: Prophylactic application of SkinSafe film strips to the inframammary fold prevents moist desquamation during irradiation for breast cancer in a prospective trial
Authors: Garren D , Le B , Vasireddy R , Flynn L , Forster K , Malina L , Dorfman Y
Published: May 2019

Purpose: To investigate the effect of prophylactic use of SafeSkin films strips applied to the inframammary fold during whole breast or reconstructed breast irradiation to avoid moist desquamation to the inframammary fold.

Materials and Methods: Between November 15, 2016 and April 17, 2018, a total of 30 patients were recruited, with 29 patients contributing to analysis, and one patient with bilateral breast cancer. Areas of the breast treatment field not covered by the film were treated with physician's choice of cream, (80% Jean's Cream, 13% Aquafor, and 7% with no topical therapy). The treatment field was photographed weekly. SkinSafe strips were reapplied as needed, but were not applied if erythema was already observed in the inframammary fold. Severity of skin reaction was assessed using the RTOG scale.

Results: There was only one treatment interruption, against medical advice, due to axillary discomfort. One patient refused further trial participation after the first day. No short or long term side effects of film use were noted. Inframammary desquamation developed in only one patient, who tried to replicate the increased comfort of her inframammary tape with adhesive bandages when her tape came off. There was no moist desquamation under the SkinSafe film in the inframammary field in any patient. Axillary moist desquamation, where no film, but rather physician's choice of topical cream was applied, remained at 35%. Areas of skin adjacent to the SkinSafe film showed desquamation in 9.7% of patients, 0.5-1 cm in maximal diameter, all of which had resolved at time of completion.

Conclusions: Prophylactic use of SkinSafe film strips applied to the inframammary fold substantially reduces or eliminates the risk of inframammary desquamation during breast radiation.

Citation Format: Garren D, Le B, Vasireddy R, Flynn L, Forster K, Malina L, Dorfman Y. Prophylactic application of SkinSafe film strips to the inframammary fold prevents moist desquamation during irradiation for breast cancer in a prospective trial [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 P3-12-11.
Abstract P3-12-15: Withdrawn
Authors: Yap J , Tamimi M , Griffin M , Stanley T , Steinman J , Chen W , Catalfamo F
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Yap J, Tamimi M, Griffin M, Stanley T, Steinman J, Chen W, Catalfamo F. 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 P3-12-15.