bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-12-15: Triple-negative breast cancers (TNBCs) rich in infiltrating stromal plasma cells have improved disease-free survival and overall survival
Authors: McIntire PJ , Cui X , Ginter PS , Irshaid L , Chen Z , Shin SJ 
Published: March 2017

Abstract
Background Tumor-infiltrating lymphocytes (TILs) have emerged as a prognostic indicator in patients with TNBC. Furthermore, lymphocyte-predominant breast cancer (LPBC), defined as those containing ≥50% stromal TILs has been shown to be associated with better prognosis. While cell-mediated immunity has received much of the credit for anti-tumor responses, the International TILs Working Group recommends that the assessment of stromal density of TILs should incorporate all mononuclear cells including plasma cells. Very little is known about the role of humoral immunity, particularly the role of plasma cells in the anti-tumoral response in breast cancer. We sought to evaluate the prognostic value of plasma cells in the setting of stromal TIL assessment of TNBC. Design Morphologic assessment of TILs was performed on a representative H&E slide of 76 cases of primary TNBC. For each case, the stromal density of TILs was estimated and then classified as LPBC or non-LPBC using a cutoff of ≥50% for the former. Also, the plasma cell intensity defined as the mean percentage of stromal plasma cells of five 40x high power microscopic fields of TILs was recorded at 5% increments. Statistical analyses were performed using disease-free survival (DFS) and overall survival (OS) (range: 16 to 196 months, mean: 110 months) as primary endpoints. Results Plasma cell intensity was dichotomized at 12.5% and predictive of OS [.21, 95% confidence interval (CI) .05-.93, P = 0.0401)]. A positive dose related response trended toward significance for each 5% increase in plasma cell intensity (.97, 95% CI .93-1.01, P = 0.1168). Disease-free survival also trended positively towards significance (.39, 95% CI .13-1.20, P = 0.0991). When comparing LPBC, tumors rich in plasma cells (&gt;12.5% of TILs) trended towards longer DFS (.17, 95% CI .02-1.62, P = 0.1226) when compared to plasma cell poor LPBC. Conclusion In addition to the cell-mediated immune response in TNBC, our findings suggest that humoral immunity may also play a role in predicting recurrence and survival in these patients. Our findings suggest that inclusion of an additional parameter of plasma cell intensity may be prognostically valuable in TIL assessment of TNBC.
Citation Format: McIntire PJ, Cui X, Ginter PS, Irshaid L, Chen Z, Shin SJ. Triple-negative breast cancers (TNBCs) rich in infiltrating stromal plasma cells have improved disease-free survival and overall survival [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 P4-12-15.
Abstract P4-21-33: HER2 activity regulates the pro-trastuzumab immune tumor microenvironment
Authors: Tagliabue E , Forte L , Regondi V , Ghirelli C , Aiello P , Triulzi T 
Published: March 2017

Abstract
It is well know that trastuzumab activity against HER2-positive breast carcinomas (BCs) depends also on immune cells. Our genomic analysis of 53 HER2-positive BCs indicated that those exquisitely sensitive to treatment are addicted to this oncoprotein and are enriched in immune pathways and T-cells infiltration, raising the hypothesis that HER2 regulates immune cells recruitment. The aim of this study was to investigate how HER2 activity contributes to mold tumor microenvironment.
Gene expression profile analysis of 53 HER2-pos BCs showed that trastuzumab-sensitive tumors express significantly higher levels of chemokines involved in immune cells recruitment (IFNγ-related CXCLs and CCLs) and higher levels of immune checkpoint ligands (PD-L1, PD-L2) than tumors that do not benefit from trastuzumab. Immunohistochemistry analysis on FFPE tumor specimens showed a significant positive association between tumor cell positivity for CXCL9, CXCL10 and CCL2 and trastuzumab sensitivity. In vitro analysis in HER2-positive BC cell lines revealed that while IFNγ-related chemokines (CXCL9 and CXCL10) are not directly regulated by HER2 signaling, CCL2 was significantly up-regulated both at mRNA and protein levels by HER2 stimulation with EGF/HRG and down-modulated by HER2 inhibition with trastuzumab. The EGF-induced increase in CCL2 expression was abrogated by the concomitant treatment with PI3K inhibitor but not with MEK inhibitor, indicating that HER2 regulates CCL2 expression via the PI3K pathway. HER2 signals derived from cell stimulation with EGF/HRG caused also the upmodulation of PD-L1/PD-L2 both at mRNA and protein levels while their inhibition with trastuzumab reduced their levels.
Overall, our results support the notion that the activated HER2 oncogene concomitantly induces the expression of CCL2 and PD-L1/PD-L2 regulating infiltration of pro-trastuzumab immune cells and their suppression. Thus, it is likely that activity of trastuzumab in therapy-responsive tumors derives from its ability in relieving suppression of recruited antitumor effector immunity.
Supported by Italian Association for Cancer Research (AIRC).
Citation Format: Tagliabue E, Forte L, Regondi V, Ghirelli C, Aiello P, Triulzi T. HER2 activity regulates the pro-trastuzumab immune tumor microenvironment [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 P4-21-33.
Abstract P5-10-09: Prospective cross-sectional-study on participation in mammography screening according to immigration background and education status
Authors: Kuehnle E , Oeztuerk T , Siggelkow W , Luebbe K , Moser A , Noeding S , John J , Noesselt T , Busch C , Arfsten M , Lemster S , Hillemans P , Doerk T , Park-Simon T-W 
Published: March 2017

Abstract
Introduction
Although the health of immigrants is an important issue in national health care policy there is a serious shortage of data in many countries. Most studies lack information on educational status which is a major limitation. In this prospective cross-sectional-study we analyzed the influence of immigration background and educational status on the participation in mammography screening programs in Lower-Saxony, Germany.
Material and methods
Data collection was conducted from 2012-2016 in six certified breast cancer centers using a personal questionnaire and data from the patients' medical records. Stratification into subgroups was carried out according to first and second generation immigrants and country of origin.
Results
1547/2129 primary breast cancer cases were analyzed. The percentage of patients with a history of immigration in our study cohort was 17.7%. The majority of them were citizens of EU27 Member states. First generation immigrants (n= 146), second generation immigrants (n=129), natives (n= 1272). No significant difference was seen in sex, age, tumor stage, histology, grading, Ki-67, Her2/neu-status, and hormone receptor status. A 100% participation rate in the mammography screening program was seen in patients with no school graduation. The lowest participation rate (85.5%) was seen in the group of native Germans with a college graduation and in first generation immigrants with a high school graduation (86.7%). Detailed statistical analysis will be presented on the poster.
Conclusion
No difference was seen between immigrants and native Germans with regard to tumor biology. In first-generation immigrants mammography screening was well accepted despite cultural and linguistic differences. Participation rate decreased with higher education level in all groups. High school graduates with immigrant background participated more frequently in breast cancer screening than native high school graduates. These findings mainly relate to immigrants from EU27 Member states rather than immigrants from non EU countries.
Citation Format: Kuehnle E, Oeztuerk T, Siggelkow W, Luebbe K, Moser A, Noeding S, John J, Noesselt T, Busch C, Arfsten M, Lemster S, Hillemans P, Doerk T, Park-Simon T-W. Prospective cross-sectional-study on participation in mammography screening according to immigration background and education status [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 P5-10-09.
Abstract P5-13-01: Sociodemographic and economic factors are essential determinants of weight gain between before and after cancer diagnosis: Results from the prospective population-based NutriNet-Santé cohort
Authors: Fassier P , Zelek L , Partula V , Lecuyer L , Srour B , Bachmann P , Touillaud M , Druesne-Pecollo N , Galan P , Hercberg S , Cohen P , Hoarau H , Latino-Martel P , Gonzalez R , Deschasaux M , Touvier M 
Published: March 2017

Abstract
Background: While many cancer patients are affected by weight loss, others tend to gain weight, which may impact prognosis and risk of recurrence and of second cancer. The aim of this prospective study was to investigate weight variation between before and after cancer diagnosis and socio-demographic, economic, lifestyle and clinical factors associated with moderate-to-severe weight gain.
Methods: 1051 incident cases of first primary cancer were diagnosed in the NutriNet-Santé cohort between 2009 and 2015. Weight was prospectively collected every 6 months since subjects' inclusion (i.e. an average of 2y before diagnosis). Mean weights before and after cancer diagnosis were compared with paired Student's t-test. Factors associated with moderate-to-severe weight gain (≥5% of initial weight) were investigated by multivariable logistic regression.
Results: Weight loss was observed in men (-3.54kg in those who lost weight, p=0.0002) and in colorectal cancer patients (-3.94kg, p=0.0012). Weight gain was observed in breast and skin cancers (2.83kg, p=0.047, and 2.96kg, p=0.03 respectively). Women (OR=1.99[1.18-3.35]), younger patients (OR=1.78[1.05-3.03]), those with lower education (OR=2.17[1.07-4.37]), those with excess weight before diagnosis (OR=1.53[1.02-2.30]) and those who stopped smoking after diagnosis (OR=4.60[2.06-10.25]) were more likely to experience moderate-to-severe weight gain. In breast cancer patients, induced menopause was associated with weight gain (OR=4.12[1.76-9.67]), but no association was detected for tumor characteristics or treatments.
Conclusion: This large prospective cohort provided original results on weight variation between before and after cancer diagnosis, highlighting different weight trajectories. Socio-demographic and economic factors appeared to strongly influence the risk of weight gain, illustrating social inequalities in health.
Citation Format: Fassier P, Zelek L, Partula V, Lecuyer L, Srour B, Bachmann P, Touillaud M, Druesne-Pecollo N, Galan P, Hercberg S, Cohen P, Hoarau H, Latino-Martel P, Gonzalez R, Deschasaux M, Touvier M. Sociodemographic and economic factors are essential determinants of weight gain between before and after cancer diagnosis: Results from the prospective population-based NutriNet-Santé cohort [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 P5-13-01.
Abstract P5-14-05: Capecitabine in early breast cancer: A meta-analysis of randomized controlled trials
Authors: Natori A , Ethier J-L , Amir E , Cescon DW 
Published: March 2017

Abstract
Background
Capecitabine is an effective therapy for metastatic breast cancer. Its role in early breast cancer is uncertain due to conflicting data from randomized controlled trials (RCTs).
Methods
PubMed and major conference proceedings were searched to identify RCTs comparing standard chemotherapy (defined as cyclophosphamide/methotrexate/5-fluorouracil, anthracycline-based regimens or anthracycline/taxane combinations) with or without capecitabine in the neo-adjuvant or adjuvant setting. Hazard ratios (HR) for disease-free (DFS) and overall survival (OS), as well as odds ratios (ORs) for safety and tolerability were extracted or calculated and pooled in a meta-analysis. Subgroup analysis compared triple negative breast cancer (TNBC) to non-TNBC and whether capecitabine was given in addition to or in place of standard chemotherapy. Meta-regression was used to explore the influence of TNBC on OS.
Results
Eight studies comprising 9302 patients were included. In unselected patients, capecitabine did not influence DFS (HR 0.99, p=0.93) or OS (HR 0.90, p=0.36). There was a significant difference in DFS when capecitabine was given in addition to, compared to in place of standard treatment (HR 0.92 vs. 1.62, interaction p=0.002). Addition of capecitabine to standard chemotherapy was associated with significantly improved DFS in TNBC vs non-TNBC (HR 0.72 vs. 1.01, interaction p=0.02). Meta-regression confirmed this association with OS (R=-0.967, p=0.007). Capecitabine increased Grade 3/4 diarrhea (OR 2.33, p&lt;0.001) and hand foot syndrome (OR 8.08, p&lt;0.001), and resulted in more frequent treatment discontinuation (OR 3.80, p&lt;0.001).
Conclusion
Adding capecitabine to standard chemotherapy appears to improve DFS and OS in TNBC, but increases adverse events in keeping with its known toxicity profile. Consideration of this treatment is warranted, especially in high-risk patients.
Citation Format: Natori A, Ethier J-L, Amir E, Cescon DW. Capecitabine in early breast cancer: A meta-analysis of randomized controlled trials [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 P5-14-05.
Abstract P5-14-10: Weekly doxorubicin and daily oral cyclophosphamide followed by nab-paclitaxel for adjuvant therapy of high-risk localized breast cancer
Authors: Cho E , Wu Q , Rubinstein L , Linden H , Gralow J , Specht J , Gadi V , Ellis G 
Published: March 2017

Abstract
BACKGROUND: The addition of taxanes to anthracycline-based adjuvant chemotherapy has improved disease free survival (DFS) in women with high-risk early-stage breast cancer. Many studies have sought to optimize the dose intensity and density of these agents to produce improvements in outcome and tolerability. The purpose of this study was to assess the use of metronomic doxorubicin plus daily oral cyclophosphamide (AC) for 12 weeks followed by nab-paclitaxel (nP) for 12 weeks in this population. Those patients with Her2 positive disease were also given adjuvant trastuzumab.
METHODS: A non-randomized phase II clinical trial was designed to (1) test the DFS at 2 years compared to historical controls, (2) assess dose intensity delivered, (3) assess use of nP in the adjuvant setting, and (4) evaluate toxicities associated with the regimen. Overall survival (OS) was a secondary outcome. The dosing of A was 24mg/m2 IV qweek and C was 60mg/m2 oral daily; nP, 100mg/m2 IV qweek.
RESULTS: Sixty patients were enrolled on the study with a median follow-up of 6 years and a median age of 50 (range 30-69). 58% of patients had node positive disease. Receptor categories included hormone receptor positive (ER positive or PR positive) and HER2 negative (n=24; 40%); ER negative, PR negative, and HER2 negative (triple negative; n=19; 32%); or HER2 positive (n=17; 28%). DFS at 2 years was 93% (1 death, 3 recurrence) and at 6 years was 82%, comparable to historical controls. OS at 2 years and 6 years was 98% and 88%, respectively. Mean dose intensity was greater than 90% for AC and 88% for nP. Treatment was well-tolerated with the most common grade ≥3 toxicity being neutropenia and a 2% incidence of febrile neutropenia.
Disease-free survival and overall survival at 2 and 6 years 2 year 6 year DFS %OS %DFS %OS %All patients93988288ER+ or PR+, HER2-921007979Triple negative89957989HER2+10010088100
CONCLUSSIONS: Patients achieved similar DFS to that seen in historical controls with similar rates of adverse events. Since nP dosing was 100 mg/m2, even with 88% dose intensity, the delivered taxane dose is greater than standard weekly paclitaxel. Notably disease control was particularly impressive in the triple negative subtype, which has been shown to benefit from nP over standard paclitaxel in the neoadjuvant setting in the GeparSepto (GBG 69) trial. Metronomic AC followed by nP is a safe, effective option for delivery of adjuvant chemotherapy for high-risk patients.
Citation Format: Cho E, Wu Q, Rubinstein L, Linden H, Gralow J, Specht J, Gadi V, Ellis G. Weekly doxorubicin and daily oral cyclophosphamide followed by nab-paclitaxel for adjuvant therapy of high-risk localized breast cancer [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 P5-14-10.
Abstract P5-16-27: Variation in the use of neoadjuvant chemotherapy for breast cancer in the Netherlands. A lack of consensus
Authors: Spronk PER , Bommel van ACM , Siesling S , Vrancken Peeters M-JT , Smorenburg CM 
Published: March 2017

Abstract
Introduction
Neoadjuvant chemotherapy (NAC) is an important initial strategy in the management of stage III locally advanced breast cancer (LABC) as being advised in our national guidelines. Furthermore, NAC is increasingly being used in stage II BC for downsizing the tumour in order to enable breast conservation therapy (BST). The aim of this study was to examine which patient-, tumour- and hospital related factors influence its use in clinical daily practice. In addition, we investigated the preferences of the surgical- and medical- oncologist as well as the patients'.
Methods
(1) All operated women [aged 18-70] from January 2011 to September 2015 were selected from the multidisciplinary NABON Breast Cancer Audit (NBCA). Multivariable logistic regression was used to assess significant independent predictors of NAC use. (2) Both specialists and ex-patients were provided with a survey about decision-making.
Results
Overall, 21% of stage II (N=18011) and 70% of stage III patients (N=1715) received NAC. Factors associated with NAC utilization included young age, a diagnostic MRI, histology, large tumour size, more advanced nodal disease, hormone-receptor negative tumours and participation in neoadjuvant trials.After case mix correction variation between hospitals remained (range 10% – 90%). Evidenced by additional survey research, reasons for indication of NAC vary widely among specialists (response rate of 24%; N=100). From the patient survey (response rate of 52%; N=390) it appears that in patients where chemotherapy is recommended, 50% was not informed about the option of NAC.
Conclusion
There is considerable variation in the use of NAC for BC in the Netherlands. Although various patient, tumor and institutional factors are associated with the use of NAC, these can only explain part of the observed variation in treatment patterns between hospitals. Survey research shows a need for uniformity of selection criteria in the use of NAC between specialists. Also, the information necessary for patients to decide on which treatment option they prefer seems far from complete in clinical practice.
Citation Format: Spronk PER, Bommel van ACM, Siesling S, Vrancken Peeters M-JT, Smorenburg CM. Variation in the use of neoadjuvant chemotherapy for breast cancer in the Netherlands. A lack of consensus [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 P5-16-27.
Abstract P6-01-10: Estrogen receptor β2 and β5 increase expression of ABCG2 and drug resistance of the triple- negative breast cancer cell line SUM159
Authors: Faria M , Gustafsson J-A , Strom A 
Published: March 2017

Abstract
Recent clinical studies indicate that estrogen receptor β2 (ERβ2) and β5 (ERβ5) expression in TNBC correlates to worse prognosis. We have expressed ERβ2 and ERβ5 in the triple negative cell line SUM159. Estrogen receptors β2 and β5 are highly similar to estrogen receptor β1, except for a truncated C-terminus making the remaining ligand -binding domain incapable of binding to estrogen. In addition, at the C-terminus, ER β2 and β5 have a unique peptide each of 27 and 4 amino acids in length respectively. Stably expressing ERβ2 and ERβ5 using a transposon integrated, tetracycline- regulated expression system increases expression of the drug resistance gene, ABCG2 in the triple negative SUM159 cells. Furthermore, we also find that the cells become more resistant to treatments with paclitaxel. We find that ERβ2 and ERβ5 interact with HIF-1α and HIF-2α and are recruited to HIF response elements (HRE's) in chromatin. In agreement with this, we find that ERβ2 and ERβ5 are recruited to the ABCG2 promoter, which contains HRE's and is known to be a target of HIF signaling. We propose that ERβ2 and ERβ5 play a role in chemo - resistance of TNBC and that targeting these factors may reduce chemo resistance thus preventing tumor-relapses and their associated mortalities.
Citation Format: Faria M, Gustafsson J-A, Strom A. Estrogen receptor β2 and β5 increase expression of ABCG2 and drug resistance of the triple- negative breast cancer cell line SUM159 [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 P6-01-10.