bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-09-24: Combination treatment with bromodomain and extra-terminal motif inhibitors in triple-negative breast cancer
Authors: Schafer JM , Lehmann BD , Redman LN , Liu P , Stubbs M , Ruggeri B , Scherle P , Pietenpol JA 
Published: February 2018

Abstract
Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer. TNBC affects younger women and is characterized by earlier rates of relapse, higher frequency of visceral metastases, and shorter survival outcomes when compared to ER+ or HER2+ disease. Although the disease only represents ˜15% of all breast cancer cases, it accounts for 25% of all breast cancer deaths – with treatment options currently limited to chemotherapy. Development of targeted therapies for TNBC is challenging due to molecular heterogeneity and lack of high-frequency “driver” alterations amenable to therapeutic intervention. Recent studies have demonstrated increased sensitivity of TNBC to the anti-proliferative effects of Bromodomain and Extra-Terminal motif inhibitor (BETi) compared to the other breast cancer subtypes. To determine mechanisms of sensitivity to BETi, we analyzed the effect of a BETi across a panel of TNBC cell line models and identified cell lines that were both sensitive and insensitive to BETi. With the intent of identifying biomarkers of sensitivity, we performed RNA-seq and precision nuclear run-on and sequencing (PRO-seq) on both sensitive and insensitive cell line models and data generated identified significant differences in key growth regulatory and apoptotic signaling pathways, including notable differences in Myc-dependent signaling. Our data suggest potential biomarkers of BETi-sensitivity that may be of value in further pre-clinical studies. Further, our results provide mechanistic rationale for combinations of BETi with select, targeted therapies in a disease that is in need of new therapeutic intervention.
Citation Format: Schafer JM, Lehmann BD, Redman LN, Liu P, Stubbs M, Ruggeri B, Scherle P, Pietenpol JA. Combination treatment with bromodomain and extra-terminal motif inhibitors in triple-negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-09-24.
Abstract P2-11-06: Analysis of cardiac events among node positive breast cancer (NPBC) patients treated with three-dimensional conformal radiation therapy (3D-CRT)
Authors: Bradley JA , Sparks I , Prior P , Bergom C , Walker A , Wilson JF , Li XA , White J 
Published: February 2018

Abstract
Background: Regional nodal irradiation (RNI) in addition to the chest wall and/or breast can maximize local regional control and improve overall survival, but has been associated with late cardiac morbidity. We examined NPBC patients treated with RNI using 3D-CT based radiation therapy (RT) to evaluate incidence and type of cardiac events.
Methods: Between 2000 and 2007, 156 NPBC patients were treated with RNI following lumpectomy or mastectomy using 3D-CRT. In all cases, treatment target and normal tissue volumes were delineated on treatment CT scans. The heart contour included the left ventricle and the atria. Prescription dose was typically 50Gy in 25 fractions (range 44-54 Gy) to the chest wall and/or breast PTVeval. 37% received a boost to the chest wall and 73% to the lumpectomy cavity. The mean prescription dose to the axilla and supraclavicular lymph nodes was 47.6 Gy (range 43.2 – 54 Gy) and 46.8 Gy to the IMN (range 35.3 – 50.4 Gy). The dose-volume cardiac data and incidence of cardiac events is reported.
Results: Median follow-up of surviving patients was 7 years (range, 0.3-10.6). Median patient age was 50 (range, 27-91), 52% were premenopausal, 76% estrogen receptor positive, and 18% were HER-2 positive. The IMN received &gt; 40 Gy in 66%. Chemotherapy was used in 94% of patients, and it was anthracycline-based in 82.3%. At the time of RT, 12.5% smoked, 9% had diabetes, 33% with HTN, and 4.4% had a history of CAD.
Average mean heart dose for the cohort was 5.2 Gy (range, 0.2 - 25.3 Gy). Mean cardiac V25 was 5.4% (range, 0-20%), mean cardiac V45 was 1.7% (range, 0-13.3%), and mean maximum cardiac point dose was 45.4 Gy.
There was 1 (0.7% of cohort) right sided patient with cardiac events and 8 (5.1% of cohort) left experiencing cardiac events. A total of 18 cardiac diagnoses were experienced among the 9 patients: Coronary artery disease with or without myocardial infarction (4), congestive heart failure (6), cardiomyopathy (3), and arrhythmia (5).
Conclusions: The cardiac event rate among these NPBC patients treated with RNI and anthracycline-based chemotherapy was low, but more common in women with left-sided breast cancer compared to right. Additional analysis using 3DCRT volumes are important to validate these findings and better define the dose-volume parameters for cardiac toxicity.
Citation Format: Bradley JA, Sparks I, Prior P, Bergom C, Walker A, Wilson JF, Li XA, White J. Analysis of cardiac events among node positive breast cancer (NPBC) patients treated with three-dimensional conformal radiation therapy (3D-CRT) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-06.
Abstract P2-12-13: Withdrawn
Authors: Kotani H , Terada M , Mori M , Horisawa N , Sugino K , Iwase M , Oonishi S , Kataoka A , Adachi Y , Gondou N , Yoshimura A , Hattori M , Sawaki M , Iwata H 
Published: February 2018

Abstract
This abstract was withdrawn by the authors.
Abstract P2-13-03: Statin use and breast cancer survival – a Swedish nationwide study
Authors: Borgquist S , Broberg P , Olsson H 
Published: February 2018

Abstract
Background: A sizeable body of evidence shows that statins can cease proliferation of breast cancer and prevent breast cancer recurrence. Given the epidemiological findings from other Scandinavian populations, we hypothesized that statins may have anticancer effects and therefore reduce cancer-related mortality in a Swedish population. This study investigates the association between both pre- and post diagnostic statin use and breast cancer outcome.
Methods: A Swedish nation-wide retrospective cohort study of 20,559 Swedish women diagnosed with breast cancer (July 1st, 2005 through 2008). Dispensed statin medication was identified through the Swedish Prescription Registry. Breast cancer-specific death information was obtained from the national cause-of-death registry until December 31st, 2012. Cox regression models yielded hazard ratios (HR) and 95% confidence intervals (CI) regarding associations between statin use and breast cancer-specific and overall mortality.
Results: During follow-up, a total of 4,678 patients died, whereof 2,669 were considered breast cancer-specific deaths. Compared to non- or irregular use, regular pre-diagnostic statin use was associated with lower risk of breast cancer-specific death (HR=0.77 (95%CI 0.63-0.95), P=0.014). When evaluating diabetes patients only (N=545), this association was strengthened (HR=0.63 (95%CI 0.40-0.98), P=0.044). Post diagnostic statin use was in similarity associated with lower risk of breast cancer–related death compared to non-use (HR=0.83 (95%CI 0.75-0.93), P=0.001).
Conclusion: This study supports the notion that statin use is protective regarding breast cancer-specific mortality in agreement with previous Scandinavian studies, although less so with British studies. These disparities should be investigated further.
Citation Format: Borgquist S, Broberg P, Olsson H. Statin use and breast cancer survival – a Swedish nationwide study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-13-03.
Abstract P3-05-11: Immune and basal signature correlation to targeted therapies and race in QNBC patients
Authors: Hughley RW , Colomb WD , Shweta T , Yates C 
Published: February 2018

Abstract
Background: African American women have worse prognosis and poor survival rates due to lack of Androgen Receptor expression. These subtypes, the Quadruple Negative Breast Cancers (QNBC), currently have no treatments. Previously, we found that AA TNBC have 28% more chance of being QNBC and have 25% higher rate of progression vs the Caucasian Americans (CA). Also, these QNBC patients have a unique immune and basal signature. Here, we explore individual genes and their correlation to race and immune therapies. Methods: We analyzed AR mRNA expression in 925 tumors from CA or AA women from The Cancer Genome Atlas and independently validated AR protein levels by immunohistochemistry in 197 primary tumors. Samples were dichotomized as AR positive or negative using mean gene expression cutoff. Gene expression comparisons among groups were determined using standard t-tests, ANOVA, and odds ratios with a significance threshold alpha of 0.05. a of 0.05. Therapy targets were selected from the list of significantly differentiated genes. Boxplots and heatmaps were made using R packages. Cumulative Incidence plots for time to progression were constructed using XLStats and Grays test for significance. Results: QNBC CA have higher expression of PDCD4 (p &lt;.001), CD46 (p &lt;.001), CD3EAP (p =.04) and CD84 (p =.07) compared to QNBC AA. CD47 (p = .63) and PD1 (p =.96) express no significant differences in race[CY1]. QNBC AA show higher expression of NFKB (p &lt;.001), CCL2 (p &lt;.001), and IL12 (p &lt;.001) compared to QNBC CAs. Interestingly, QNBCs with high expressions of CD47 (p = .04) have poor prognosis[L2]. Thus, QNBC patients with low expression of CD46 (p =.025), PDCD4 (p &lt; .001), and CD3EAP (p &lt; .001) have poor prognosis and overall survival. Conclusions: Current immune targeted therapies like CD47 and PD1 looks favorable for treatment in some QNBC patients. Race appears to effect other major therapy target gene expressions in the QNBC immune basal signature as well. This may imply that QNBC AA and CA have different immune response which may explain racial progression differences. Assessment of immune markers may contribute to more accurate prognosis.
Citation Format: Hughley RW, Colomb WD, Shweta T, Yates C. Immune and basal signature correlation to targeted therapies and race in QNBC patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-11.
Abstract P3-05-12: VISTA expression on tumor-infiltrating lymphocytes in breast cancer: Clinical correlates and association with PD-1
Authors: Burugu S , Gao D , Nielsen TO 
Published: February 2018

Abstract
Background: The V-domain containing Ig Suppressor of T Cell Activation (VISTA) is a recently discovered immune checkpoint receptor with homology to PD-1. VISTA expression on tumor-infiltrating lymphocytes (TILs) blocks their proliferation and effector functions. Recent pre-clinical data in cancer mouse models treated with anti-VISTA and anti-PD-L1 combinations showed promising results and non-redundant functions of VISTA and PD-L1 blockade. However, the expression and prognostic value of VISTA+ TILs in primary breast tumors has not been investigated in detail. Here we assess expression, prognostic value, and associations of VISTA+TILs with other immune checkpoint markers (PD-1/PD-L1, LAG-3, and IDO-1) and with H&E TIL counts.
Methods: A tissue microarray consisting of breast carcinoma primary excision specimens (n=330) from the University of British Columbia hospital, linked to detailed clinicopathological data and outcomes, was used in this study. Patients from this cohort did not receive neoadjuvant treatment. A VISTA antibody (Clone D1L2G) was applied on a 4μm section of the tissue microarray by immunohistochemistry using a Ventana automated stainer. VISTA+TILs in direct contact with tumor nest were scored and reported as absolute count per 0.6mm core. Positive cases were defined as cases with VISTA+TILs≥1. All descriptive and survival analyses were conducted using SPSS software.
Results: VISTA+TILs were present in 30% of cases and were significantly (p&lt;0.05) associated with younger age (&lt;50 years old), larger tumors (&gt;2cm), hormone receptor negativity (ER/PR) and high Ki67proliferation index (≥13.25%). Almost half (48%) of basal-like breast cancers were positive for VISTA expressing TILs. No significant prognostic associations were observed in this cohort. Among the immune checkpoint receptors analyzed, VISTA+TILs were highly associated with PD-1+ TILs: 79% of cases positive for PD-1+TILs were also infiltrated by VISTA+TILs. Interestingly, we found that VISTA+TILs and PD-1+TILs were enriched in cases with otherwise low levels (&lt;10%) of H&E TILs.
Conclusions: Our study identifies the presence of VISTA+TILs in breast cancer patients and its strong association with PD-1+TILs. These results suggest that VISTA blockade could be a good candidate for combination therapy with other immune checkpoint inhibitors, a concept being tested in early phase clinical trials. Validation of these findings in a larger independent cohort powered for multivariate analysis is currently ongoing.
Citation Format: Burugu S, Gao D, Nielsen TO. VISTA expression on tumor-infiltrating lymphocytes in breast cancer: Clinical correlates and association with PD-1 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-12.
Abstract P3-05-18: The complex landscape of breast cancer immune evasion and its implications to personalized and combined immunotherapy
Authors: Bou-Dargham MJ , Liu Y , Sang Q-XA , Zhang J 
Published: February 2018

Abstract
Cancer immunotherapy activates the patient's immune system to recognize and kill cancer cells. The efficacy of immunotherapy in human breast cancer (BRCA) is hindered by the poor understanding of the immune system's anti-tumor response and tumor evasive mechanisms, and the lack of optimized treatment regimens for each BRCA patient. There are 6 known evasion mechanisms (M) by which tumors can escape immune surveillance. M1: immunosuppression via interleukin 10 (IL-10) and tumor growth factor beta (TGF-β); M2: induction of tolerance by cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and its ligands (PD-L1/PD-L2), and interferon gamma (IFN-γ); M3: apoptosis resistance via the expression of anti-apoptotic molecules, namely baculoviral IAP repeat-containing protein 3 (BIRC3), TNF receptor associated factor 1 (TRAF1), and TNF alpha induced protein 3 (TNFAIP3); M4: counterattack via decoy death receptors; M5: impaired antigen presentation by decreasing beta 2 microglobulin (B2M) and human leukocyte antigens A and B expression (HLA-A and HLA-B); and M6: ignorance caused by the absence of a danger signal or an antigen. Yet, which mechanisms or combination of mechanisms BRCA tumors utilize is unknown. Moreover, the currently used biomarkers for the choice of immunotherapy are not ideal, as for example, not all PD-L1+ patients respond to anti-PD-L1 treatment, and certain PD-L1- patients respond. Thus, there is a need for more precise biomarkers. Using the sequential biclustering method on the RNA-sequenced data of BRCA from The Cancer Genome Atlas (TCGA), eighty-one percent of BRCA patients were grouped into 7 different clusters (CL) of immune evasion subtypes. We found that the majority of breast cancer tumors utilize multiple immune evasion mechanisms. Tumors may use from 1 up to 4 combinatorial mechanisms simultaneously. We also identified classifier genes that would help sort patients based on their evasion mechanisms, and guide the choice of immunotherapy. This is especially important since the immune evasion molecules may not be the ideal biomarkers for the best choice of immunotherapy. Moreover, we showed that triple negative breast cancer (TNBC) patients were significantly associated with CL2 (M5).
Citation Format: Bou-Dargham MJ, Liu Y, Sang Q-XA, Zhang J. The complex landscape of breast cancer immune evasion and its implications to personalized and combined immunotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-18.
Abstract P3-10-09: The association age-related parity and HER2 over-expression in breast cancer
Authors: Bae SY , Kim J , You JY , Jung SP , Bae JW 
Published: February 2018

Abstract
Backgrounds
Reproductive factors, such as age at menarche, parity, age at first birth, and breast feeding, are known to be associated with risk of breast cancer. Recent studies show the association between the reproductive factors and the molecular subtypes of breast cancer, especially in luminal-like subtypes. Nulliparity is known a risk factor of breast cancer, multiparity is considered a protective factor. However, pregnancy associated breast cancers show the high expression of HER2, Therefore, we hypothesized the number of birth (multiparity) is correlated with the over-expression of HER2.
Methods
We reviewed the database of 2,594 breast cancer patients were over 20 years of age, diagnosed between January 2000 and April 2017 at Korea University of Anam Hospital, Seoul, Korea. According the number of birth, nulliparous (the number of birth = 0; 271 patients), primiparous (the number of birth = 1; 420 patients) and multiparous (the number of birth≥2; 1,903 patients) groups were classified.
Results
The median age (range) of nulliparous, primiparous and multiparous groups was 43 (22-77), 48 (27-87) and 51 (26-86) years (P&lt;0.001). In univariate analysis, the number of birth was associated with the expression of ER and HER2, nulliparous patients showed higher ER positivity (P=0.013) and multiparous patients showed higher HER2 overexpression (P=0.048). There was no association with PR and Ki-67 level. In logistic regression with age, the parity was negative correlation with ER positivity (OR 0.83, 95% CI 0.72-0.95, P=0.010) and positive correlation with HER2 overexpression (OR1.18, 95% CI 1.02-1.36, P=0.021) P=0.009) and multiparity was higher HER2 overexpression (OR 1.41, 95% CI 1.02-1.94, P=0.033). By subgroup analysis with menopausal status, there was statistically significance in only premenopausal women, not in postmenopausal women. In premenopausal women, the parity was negatively associated with ER positivity (OR 0.78, 95%CI 0.64-0.94, P=0.010) and multiparity was associated with HER2 overexpression (OR 1.72, 95%CI 1.12-2.63, P=0.013), there was no difference in HER2 overexpression between nulliparous and primiparous patients.
Conclusion
Parity was associated with ER and HER2 expression, multiparous patients were associated with ER negativity and HER2 overexpression, especially in premenopausal women. This suggests that pregnancy could affect risk of breast cancer, especially in HER2 positive breast cancer subtype (ER- HER2+ tumors), before menopause. We need further investigation and evaluation.
Citation Format: Bae SY, Kim J, You JY, Jung SP, Bae JW. The association age-related parity and HER2 over-expression in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-10-09.
Abstract P3-10-13: Bilateral breast cancer in China: A 10-year single-center retrospective study
Authors: Li H , Jiang H , Zhang R , Shao B , Yan Y , Ran R , Di L 
Published: February 2018

Abstract
BACKGROUD: Women with unilateral breast cancer are at increased risk for developing contralateral disease. The objective of the single-center retrospective study was to evaluate the incidence of bilateral breast cancer (BBC) and to analyze the clinicopathological characteristics for BBC in China.
METHODS: We retrospectively reviewed the electronic medical records of 3924 female patients with breast cancer consecutively treated at the department of Breast Oncology in the Peking University Cancer Hospital between 2006 and 2016. BBC was categorized as synchronous (within 6 months) or metachronous bilateral breast cancer (after 6 months of a first tumor). Patients with BBC were identified according to the criteria described by Chaudary et al. Patients with stage IV first breast cancer, and those who were found to have distant metastases between the first and second primary breast cancer were excluded. Analyses of demographic, clinicopathologic, and treatment characteristics were done between sBBC and mBBC.
RESULTS: The incidence of BBC in our population was 3.2% (127 of 3924). Of those, 2.5 % ( 99 of 3924) were metachronous bilateral breast cancer ( mBBC ), and 0.71 % (28 of 3924) were synchronous bilateral breast cancer ( sBBC ). The overall median age of the patients at first diagnosis was 45 years (range, 27-81 years). The age of onset of the first mBBC was significantly younger than that of sBBC ( p = 0.027). In mBBC subgroups, the median time interval between first and second tumors was 68 months (range, 7-342 months), and 80.8% of the second tumor were diagnosed within 10 years of the diagnosis of the first tumor. A positive family history of breast cancer was found in 25% of sBBC and 9.1% of mBBC ( p = 0.025). In ER-negative first tumor of mBBC, 56.1% of the second tumor were ER-positive. Mastectomy was the commonest surgery performed in these patients.
CONCLUSIONS: Our results confirmed the necessity of screening contralateral breast at the diagnosis of unilateral breast cancer and following-up for Chinese patients with breast cancer.
Citation Format: Li H, Jiang H, Zhang R, Shao B, Yan Y, Ran R, Di L. Bilateral breast cancer in China: A 10-year single-center retrospective study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-10-13.