bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-04-12: Both spliced and unspliced XBP1 regulates breast cancer cell fate response to antiestrogen via NFkappaB signaling
Authors: Clarke R , Hu R , Warri A , Jin L , Zwart A , Riggins R , Fang H-b 
Published: May 2019

Abstract
Unfolded protein response (UPR), a stress-induced survival mechanism, may be used by cancer cells to avoid cell death. Antiestrogen therapy, widely applied in the treatment of estrogen receptor-positive (ER+) breast cancer, induces endoplasmic reticulum stress (EnR stress) that leads to activation of each of the three arms of the UPR. One critical prosurvival activator that is regulated by two arms of the UPR is the transcription factor X-box binding protein 1 (XBP1). XBP1 exists in two isoforms, the transcriptionally inactive unspliced XBP1(U) and the spliced, active XBP1(S). Overexpression of XBP1(S) confers estrogen independence and antiestrogen resistance in ER+ breast cancer cells and XBP1(S) expression correlates with poor clinical responsiveness to Tamoxifen in ER+ breast tumors. However, the underlying signaling mechanisms regulated by XBP1, which may mediate its effects on antiestrogen resistance, are unknown. We show that depletion of endogenous XBP-1 by siRNA increases apoptosis, decreases autophagy, requires down-regulation of p65/RelA, a component of the pro-survival NFκB complex. Using novel spliced and non-spliceable forms of XBP1, we show that XBP1(U) and XBP1(S) both regulate NFκB activity via ERα signaling in breast cancer cells. XBP1(S), but not XBP1(U), also can regulate p65/RelA expression independent of ERα. Antiestrogen resistance as conferred by XBP1 overexpression in MCF-7 cells requires the activation of NFκB signaling; inhibition of NFκB signaling by either the small molecule NFκB inhibitor Parthenolide or p65/RelA siRNA sensitizes XBP1 overexpressing cells to Tamoxifen. The activation of XBP1 and the downstream NFκB signaling is likely to contribute to the TMEM33 overepxression induced apoptosis, as both NFκB signaling and XBP1(S) are elevated in TMEM33 overexpressed MCF7 cells. Thus, we have identified a critical regulatory link between the UPR/XBP1 pathway and pro-survival NFκB signaling that is a major contributor to endocrine responsiveness in ER positive breast cancer.
Citation Format: Clarke R, Hu R, Warri A, Jin L, Zwart A, Riggins R, Fang H-b. Both spliced and unspliced XBP1 regulates breast cancer cell fate response to antiestrogen via NFkappaB signaling [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-04-12.
Abstract P3-04-13: Protein tyrosine kinase 6 (PTK6) promotes survival of endocrine therapy-resistant ER+ breast cancer cells
Authors: Irie HY , Park SH , Katsyv I , Zhang W , Nayak A 
Published: May 2019

Abstract
Background/Rationale: The non-receptor tyrosine kinase PTK6/Brk is highly expressed in the ER+/Luminal breast cancer subtypes. PTK6 expression has prognostic significance for patients with ER+ disease; higher transcript levels are associated with poorer survival. The functions of PTK6 in the context of ER+ breast cancer and sensitivity to endocrine therapy have not been explored. We sought to determine the functional roles of PTK6 in ER+ breast cancer cells, including those that are relatively resistant to current endocrine therapies. Methods/Results. We modulated the expression of PTK6 using both gain- and loss-of-function approaches. Enhanced expression of PTK6 in Tamoxifen-sensitive ER+ breast cancer cells was sufficient to confer relative Tamoxifen resistance. Furthermore, downregulation of PTK6 in ER+ breast cancer cells, including those that have acquired resistance to Tamoxifen, induced apoptosis, as evidenced by an increase in AnnexinV+ cells and increased levels of cleaved PARP. PTK6 downregulation impaired growth of Tamoxifen-resistant variants of ER+ MCF7 and T47D cells (MCF7TamR and T47DTamR) in 3D Matrigel culture, and virtually abrogated primary tumor growth of MCF7TamR xenografts. Mechanistically, p38MAPK activation is critical for PTK6 downregulation-induced apoptosis of ER+ breast cancer cells, as p38 inhibition partially rescues cells from PTK6 shRNA-associated apoptosis. Conclusions: Our studies highlight the critical role that PTK6 plays in the survival of ER+ breast cancer cells, including those that are resistant to endocrine therapy. Enhanced PTK6 expression in ER+ breast cancer cells is sufficient to promote endocrine therapy resistance, which could contribute to the poorer prognosis associated with higher PTK6 expression in ER+ patient tumors. As small molecule PTK6 inhibitors are becoming available, our studies support further evaluation of PTK6 as a candidate therapeutic target for endocrine therapy resistant ER+ breast cancers.
Citation Format: Irie HY, Park SH, Katsyv I, Zhang W, Nayak A. Protein tyrosine kinase 6 (PTK6) promotes survival of endocrine therapy-resistant ER+ breast cancer cells [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-04-13.
Abstract P4-03-11: Fibroblasts isolated from the “normal-like” tissue adjacent to breast tumours suppress healthy epithelial progenitor cell proliferation while supporting tumour cell growth
Authors: Chatterjee S , Berdnikov A , Lee-Wing V , Safneck J , Buchel E , Raouf A 
Published: May 2019

Abstract
The tissue adjacent to breast tumors has been referred to as “normal-like” tissue despite exhibiting many alterations at epigenetic and gene expression levels consistent with enhanced proliferation and wound healing signatures. However, the influence of such alterations on the proliferation and differentiation of healthy breast progenitors is currently unknown. Fibroblasts are a major component of microenvironment for the healthy and malignant breast cells. We therefore, isolate fibroblast from primary breast tumors, tissue adjacent to tumors (TAT) and the healthy breast tissue and examine their ability to support proliferation of healthy and malignant breast cells. To characterize the TAT samples we first utilized clonal co-culture assays using breast cells obtained from the healthy breast tissue (reduction mammoplasty sample, RM) and the healthy fibroblasts. Our results suggested that the TAT samples surprisingly contained significantly decreased pool of progenitors compared to the RM samples. In order to study the underlying mechanism, we characterized fibroblasts derived from either the breast tumours (TAFs) or the TAT samples (TATF) or the RM normal samples (NAFs) and assessed their role on breast progenitor cell functions. Fibroblasts were isolated from the ER+ and ER- breast tumours and their adjacent breast tissue. We observed that matrigel co-cultures consisting of RM samples and NAFs led to a 5.5-fold expansion of the progenitors, whereas the co-cultures of TAT or the RM samples with either TAFs or TATFs failed to show expansion of epithelial progenitors. The comparative secretome analysis of the NAFs and the TATFs identified TGFβ as a candidate molecule primarily secreted only by the TATFs and not by NAFs. Interestingly, blocking TGFβ signaling restored both TAFs' and TATFs' ability to support the expansion of healthy progenitors in matrigel cultures. Lastly, we found that TAFs were able to enhanced breast cancer cell proliferation in vivo and in vitro but to a lesser extent than the TAFs. Our observations suggest that the tissues adjacent to breast tumours are transformed into a TGFβ-enriched environment that is supportive of breast tumour growth while suppressing the proliferation and differentiation potentials of the healthy breast progenitors. Our data also suggest that the use of TGFβ blockers may be important in reducing risk of local breast tumour recurrence.
Citation Format: Chatterjee S, Berdnikov A, Lee-Wing V, Safneck J, Buchel E, Raouf A. Fibroblasts isolated from the “normal-like” tissue adjacent to breast tumours suppress healthy epithelial progenitor cell proliferation while supporting tumour cell growth [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-03-11.
Abstract P4-19-07: Fertility concerns in young women after diagnosis of breast cancer: Experience of a breast cancer unit in México
Authors: Campos-Gomez S , Campos-Gomez KA , Ovando-Trujillo A , Palacios-Gutierrez F 
Published: May 2019

Abstract
Background
Nearly 30% of all new breast cancer diagnoses occur in pre-menopausal women and about 7% of diagnoses occurring in women aged 40 years or less. Breast cancer treatment can increase the risk of early menopause and infertility. It is the major source of distress and concern form many young breast cancer patients who have no finished their families and have plans for childbearing.
Methods
As part of multidisciplinary approach in the Breast Cancer Unit at Centro Oncologico Estatal ISSEMYM an evaluation psychosocial aspects of sexuality, fertility and menopause after diagnosis of breast cancer has been implemented.
We conducted an exploratory study to better understand fertility concerns, the role of fertility in the treatment decisions and chemotherapy acceptance in a cohort of young women newly diagnose breast cancer evaluated in a Breast Cancer Unit. We invited eligible women to participate, fertility concerns was the primary end point
Results
A total of 52 women were evaluated. Of these, we exclude 2 patients they have stage IV disease at re staging. Thus 50 women were included in the analyses. Median age at diagnosis was 36 years (range 23 to 40 years). 86% had children already at the time of breast cancer diagnosis. Only 4 participants (8%) reported that before their breast cancer diagnosis, they wanted to have future or additional children. Whereas forty six (92 %) did not. Of these patients 85% don't want to have children because of prior decision and 20% because fear of cancer recurrence. Forty nine patients would agree to receive chemotherapy (98%) and 51% would accept a risk of infertility of 76-100%. This acceptance was dependent on already having children. 68% would accept it only for ≥20% gain in cure.
Conclusion
Our study represents one of the first prospective evaluations of fertility concern in young women with recently diagnosed breast cancer in a Public Hospital in México. For the majority of young patients with breast cancer, cure remains their first priority. Most of the women have child before diagnosis and only 8% want to have additional children.
Citation Format: Campos-Gomez S, Campos-Gomez KA, Ovando-Trujillo A, Palacios-Gutierrez F. Fertility concerns in young women after diagnosis of breast cancer: Experience of a breast cancer unit in México [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-19-07.
Abstract P4-21-40: In vitro and in vivo activity of HER2-targeted antibody-liposomal doxorubicin conjugate MM-302 in HER2-intermediate tumors
Authors: Geretti E , Espelin C , Adiwijaya B , Coma S , Koncki Z , Sumner P , Dumont N , Garcia G , Bloom T , Janovsky J , Reynolds J , Campbell K , Moyo V , Molnar I , LoRusso P , Krop I , Miller K , Ma C , Munster P , Wickham T 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Abstract P5-02-04: Study on over-diagnosis of high-precision breast cancer screening ∼ Consideration from epidemiological point of view
Authors: Takebe K , Arai T 
Published: May 2019

Abstract
&lt;Introduction&gt;
In breast cancer screening, it has been attempted to combine US with MMG. For relatively small breasts and dense breasts, there is the opinion that this combination is useful. On the other hand, the problem of over-diagnosis of breast cancer screening has been raised. We've been breast cancer screening with US/MMG combination method since 2005. The results were examined from the epidemiological point of view.
&lt;Subjects and Methods &gt;
Breast cancer discovery rate through US/MMG screening at our facility from 2005 to 2014 was considered. The medical examination was performed on 35,353 women.
Kagawa Prefecture, in which our facility is located has had 100 percent breast cancer registration for more than 10 years. We have compared the breast cancer registration of 2013 with our examination results.
&lt;Results&gt;
Asymptomatic breast cancer detection rate in our breast cancer screening was 0.6%. ４６% of the detected cancer was DCIS. Low-grade DCIS (Van Nuys 1 and 2) accounted for three-quarters of DCIS. In invasive carcinoma, 10 mm or less of luminal A type was 17%, other luminal types 19%, non-luminal types 5% and unclassified 6%. If our facility's highly precise breast cancer medical examination were performed throughout Kagawa Prefecture, DCIS would be found in 860 cases, 10 mm or less of luminal A type found in 276, other luminal type found in 320 and non-luminal type found in 70 cases per year.Compared to the Kagawa Prefecture breast cancer registered in 2013, DCIS was 6.6 times larger than the registered data, 10 mm or less of luminal A 2.9 times larger, other luminal types 1.1 times larger, and non-luminal types 1.2 times larger. The differences between the registered data and our findings for DCIS and 10mm or less of luminal A type are remarkable.
&lt;Conclusion&gt;
With the US/MMG combination method, the detection rate of DCIS and 10 mm or less of luminal A type have been excessive. Many type of DCIS and tiny luminal A type must exist latently. When performing a high-precision breast cancer screening, it is necessary to note such over-diagnosis. Furthermore, it is also necessary to re-examine the pathology diagnostic criteria of DCIS.
Citation Format: Takebe K, Arai T. Study on over-diagnosis of high-precision breast cancer screening ∼ Consideration from epidemiological point of view [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-02-04.
Abstract P5-14-09: Luminal A breast cancer: Is it really a “good prognosis” disease? Prelimary results of the GIM-13 - AMBRA study
Authors: Cazzaniga ME , Mustacchi G , De Laurentiis M , Garrone O , Donadio M , Del Mastro L , Latini L , Livi L , Michelotti A , Montemurro F , Natoli C , Riccardi N , Turletti A , Giordano M , De Placido S , Biganzoli L , Pronzato P , Marchetti P 
Published: May 2019

Abstract
This abstract was not presented at the symposium.
Abstract P6-07-19: An alteration of hormonal receptor status throughout tumor progression related to prognosis in breast cancer patients
Authors: Lee E-S , Kim J , Yoo T-K , Kim Y , Han J , Kang YJ , Choi J , Rhu J , Lee H-B , Han W , Noh D-Y , Moon H-G 
Published: May 2019

Abstract
Purpose
We aimed to identify whether hormonal receptors change throughout tumor progression, because this may influence management and influence prognosis in breast cancer patients.
Patients and Methods
From the institution's database, we collected data of 963 patients who developed relapse during their follow-ups. To determine estrogen receptor(ER) and progesterone receptor (PR), we retrospectively reviewed immunohistochemical(IHC) results in both primary and relapsed tumors.
Results
Among a total of 963 patients, 280 and 683 patients experienced locoregional relapse only and distant metastasis irrespective of locoreginal relapse, respectively. ER in 650 patients and PR in 590 patients from both primary tumor and relapse were identified, revealing a change in 157 (24.2%) and 154 (26.1%) patients, respectively. In patients with distant metastasis, assessment of ER and PR showed an alteration in 86 and 56 patients, respectively. The overall survival related to the change of ER and PR status in primary tumor and relapse was significantly different (log rank, P&lt;0.001 in both ER and PR status). In addition, women with hormone receptors negative primary tumors that changed to hormone receptors positive tumors who received anti-hormonal therapy after relapse showed a statistically significant good overall survival (p&lt;0.001) compared with women who had constant ER-negative tumors.(cox regression, hazard ratio 2.32 ; 95% CI, 1.91 to 3.01)
Conclusion
The breast cancer showed alterations of hormone receptor status throughout tumor progression, hat were related to the strategy of treatment and significantly influences survival. Therefore, investigations of hormone receptor at relapse are essential and helpful in breast cancer patient management.
Citation Format: Lee E-S, Kim J, Yoo T-K, Kim Y, Han J, Kang YJ, Choi J, Rhu J, Lee H-B, Han W, Noh D-Y, Moon H-G. An alteration of hormonal receptor status throughout tumor progression related to prognosis in breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-19.
Abstract P6-10-07: Long survival of patients with locally advanced breast cancer on combined neoadjuvant chemotherapy and immune potentiation: Modern lessons from an old study
Authors: Pohlmann PR , van Cruijsen H , Stam AGM , Lougheed SM , van den Eertwegh AJM , Hoekman K , Scheper R , Buter J , van der Hoeven JJM , van der Wall E , Pinedo HM , de Gruijl TD 
Published: May 2019

Abstract
This abstract was not presented at the symposium.
Abstract BS1-1: High resolution intravital imaging of the mechanism of how breast cancer initiates and sustains systemic dissemination
Authors: Condeelis J 
Published: May 2019

Abstract
Multiphoton microscopy of live animals (IVI) has revolutionized our understanding of cancer metastasis. IVI demonstrates that TMEM, the intravasation doorway, composed of a three cell complex: Mena-Hi tumor cell, endothelial cell and Tie2-Hi/VEGF-Hi macrophage, is the only site in breast tumors where tumor cell intravasation occurs1. During tumor progression, macrophage progenitor cells undergo unidirectional transition from migratory to TMEM-associated macrophages2. During and after this macrophage programming, tumor cells migrate with macrophages and chemotax with high persistence to blood vessels under the control of HGF gradients3 arriving at TMEM1. The TMEM structure itself, as well as the signaling pathways unique to tumor cells interacting with TMEM, have been validated as prognostic markers for predicting metastasis in breast cancer patients4-6. These were the first markers of metastasis in clinical use derived from multiphoton intravital imaging.
TMEM are found in both primary and metastatic tumor sites of breast cancer7 and in primary and metastatic sites of pancreatic ductal and neuro-endocrine tumors. Clinical trials of TMEM inhibitors, targeting TMEM in both primary and secondary sites8,9, are now underway in breast cancer patients (clinical trials study number NCT02824575). As tumor cells interact with TMEM, MenaINV. expression in the tumor cells occurs in response to macrophage-induced NOTCH signaling10, which drives invadopod assembly/ function, and metastatic seeding11,12. MenaINV expression is necessary for invadopod-mediated transendothelial migration during intravasation at TMEM13 and assures the efficient dissemination of seeding competent and non-dividing tumor cells which, after a delay, contribute to metastatic recurrence at multiple systemic sites. These findings support TMEM as a critical therapeutic target for inhibiting breast cancer metastasis.
1.Harney, A.S. et al. (2015) PMC4560669
2.Arwert, E.N. et al. (2018) PMC5946803
3.Leung, E. et al. (2017) PMC5426963
4.Karagiannis, G.S. et al (2016) PMC4893654
5.Rohan, T.E. et al. (2014) PMC4133559
6.Sparano, J.A. et al. (2017)PMC5678158
7.Entenberg, D. et al. (2018)PMC5755704
8.Harney, A.S. et al. (2017)PMC5669998
9.Karagiannis, G.S. et al. (2017) PMC5592784
10.Pignatelli, J. et al. (2016) PMC5129016
11.Eddy, R.J. et al (2017) PMC5524604
12.Linde, N. et al. (2018) PMC5750231
13.Pignatelli, J. et al.(2014) PMC4266931
Citation Format: Condeelis J. High resolution intravital imaging of the mechanism of how breast cancer initiates and sustains systemic dissemination [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 BS1-1.
Abstract BS1-2: Neutrophil extracellular traps promote breast cancer metastasis
Authors: Egeblad M 
Published: May 2019

Abstract
Cancer cells from a primary tumor can disseminate to other tissues, but remain dormant and clinically undetectable for many years. Little is known about the cues that cause these dormant cells to “awaken”, resume proliferation, and develop into metastases. Using mouse models, we have found that sustained lung inflammation caused by tobacco smoke exposure or nasal instillation of lipopolysaccharide converted disseminated, dormant cancer cells to aggressively growing metastases. Using intravital imaging techniques, which allow for long-term time-lapse imaging of cancer cells and surrounding host cells in living mice, we observed that sustained inflammation induced the formation of neutrophil extracellular traps (NETs). NETs are pathogen-trapping structures generated by expulsion of the neutrophil's DNA with associated proteolytic enzymes in response to e.g., infections. We confirmed that NETs were present in clinical samples of breast cancer lung metastases. Mechanistic analysis revealed that NETs were required for awakening dormant cancer and specifically that two NET-associated proteases, neutrophil elastase and matrix metalloproteinase 9, sequentially cleaved laminin. The proteolytically remodeled laminin induced proliferation of dormant cancer cells by activating integrin alpha-3 beta-1 signaling. We generated antibodies against NET-remodeled laminin and these prevented awakening of dormant cells in mice. In addition, pharmacological inhibition of NET formation or digestion of NETs with DNase I-coated nanoparticles also markedly reduced awakening and lung metastases in mice. Our data suggest that induction of NETs is an important host-mediated mechanism of promoting metastasis and a potential therapeutic target to prevent preventing dormant cell awakening and prolong the survival of cancer patients.
Citation Format: Egeblad M. Neutrophil extracellular traps promote breast cancer metastasis [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 BS1-2.