bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-15-25: Prognostic factors associated with pathological complete response in early breast cancer patients undergoing neoadjuvant chemotherapy. The importance of Ki-67 and molecular subtype
Authors: Rapoport BL , Barnard-Tide J , Smit T , Nayler S , Benn C-A 
Published: May 2019

Abstract
Background: Ki-67 immunohistochemical determination is a widely used biomarker of cell proliferation in patients (pts) undergoing endocrine treatment for breast BC. The role of Ki-67 in pts undergoing neoadjuvant chemotherapy (NAC) for early BC remains controversial.
Methods: We analyzed retrospectively data on 137 patients undergoing taxane and/or anthracycline, transtuzumab based NAC. Luminal A was documented in 6 pts, Luminal B in 29 pts, Her-2 positive in 30 pts and triple negative breast cancers (TNBC) in 72 pts. Pathological complete response (pCR) was defined as the complete disappearance of the invasive cancer in the breast and absence of tumor in the axillary lymph nodes examined by axillary clearance.
Results: The pCR rate of the entire cohort was 41.6%. At 2 years 92% of pts who attained a pCR were disease free compared to 80% of pts who did not attain a pCR (log rank test p &lt; 0.0147).
On univariate analysis factors associated with higher pCR included primary tumor size (T1 68% vs. T2 41% vs. T3 or T4 0%, Chi2=20.05, p&lt;0.00017), nodal disease (N0 49% vs. N1 39% vs. N2 8%, p&lt;0.02948), ER receptor status (negative 59% vs. positive 14%, p&lt;0.00000), PR receptor status (negative 53% vs. positive 17%, p&lt;0.00002), molecular subtype (TNBC 53.4%, Her2=50% and Luminal A + B was 8.5%, p&lt;0.00002), Ki67 (&gt;40=55% vs. 15-39=34% vs. &lt;15=0%, p&lt;0.00060) and Stage (I= 85% vs. IIA=49% vs. IIB=36% vs. III=5%, p&lt;0.00006). Factors not associated with a higher pCR included age, menopausal status, extranodal spread and lympho-vascular invasion. In a logistic regression model Ki-67 as a continuous variable (p&lt;0.01203) and molecular subtype (p&lt;0.02228) retained its significance; while tumor size, stage of disease, nodal status, ER and PR loss significance.
Conclusion: Ki67 and molecular subtype (Her-2 positive disease and TNBC) are independent prognostic factors of pCR in pts with early BC undergoing NAC.
Citation Format: Rapoport BL, Barnard-Tide J, Smit T, Nayler S, Benn C-A. Prognostic factors associated with pathological complete response in early breast cancer patients undergoing neoadjuvant chemotherapy. The importance of Ki-67 and molecular subtype [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 P1-15-25.
Abstract P1-17-04: Long-term safety follow-up of patients with early stage breast cancer treated with scalp cooling on the Dignitana scalp cooling trial
Authors: Rugo HS , Klein P , Melin SA , Hurvitz SA , Melisko ME , Moore A , D'Agostino RB , Deluca A , Cigler T 
Published: May 2019

Abstract
Background
Scalp cooling has demonstrated efficacy in preventing hair loss in women with early stage breast cancer receiving neo/adjuvant chemotherapy. Data from 2 prospective trials (Rugo et al, and Nangia et al, JAMA 2017) led to FDA clearance of 2 automated scalp-cooling devices to prevent chemotherapy induced alopecia (CIA). Although scalp metastases from breast cancer are rare, historical concerns about scalp cooling included a theoretical increase in risk of recurrence in scalp due to reduced delivery of chemotherapy to the scalp.
Methods
We conducted a multicenter prospective trial evaluating the efficacy and safety of the DigniCap in women with stage I-II breast cancer receiving neo/adjuvant chemotherapy excluding sequential or combination anthracycline/taxanes with concurrent matched controls. The primary endpoint was unblinded patient self-assessment of 5 photographs using the Dean scale to estimate hair loss 4 weeks following the last dose of chemotherapy, with success defined as a Dean score of 0-2 (≤ 50% hair loss); additional endpoints included quality of life (QOL) and both short and long-term safety.
Results
106 patients using the scalp cooling device and 16 concurrent controls were enrolled. As previously reported, the use of scalp cooling was associated with less alopecia and improvement in several measures of QOL (Rugo et al, JAMA 2017). 91 patients have follow-up (FU) out to 3 years; 73 with estrogen receptor (ER) positive and 18 with ER negative disease. 5 DigniCap patients have developed recurrent breast cancer in breast (n=1), liver (n=1), bone, liver and breast (n=1), bone, liver, lung, and nodes (1), and bone, breast, GI tract and bladder (n=1). Of 12 control patients with available FU, 1 developed metastases to liver. 2 patients have died of metastatic disease, one in the DigniCap arm and one in the control arm. No new safety signals have been detected.
Conclusion
Scalp cooling using the DigniCap system in patients with early stage breast cancer receiving taxane based neo/adjuvant chemotherapy is safe and effective. No scalp metastases have been reported 3 years following completion of study treatment. 4 year FU data will be presented.
The study was funded by The Lazlo Tauber Family Foundation (UCSF), the Anne Moore Breast Cancer Research Fund (Weil Cornell), and the Friedman Family Foundation (Mount Sinai Beth Israel), as well as partially by Dignitana.
Citation Format: Rugo HS, Klein P, Melin SA, Hurvitz SA, Melisko ME, Moore A, D'Agostino, Jr. RB, Deluca A, Cigler T. Long-term safety follow-up of patients with early stage breast cancer treated with scalp cooling on the Dignitana scalp cooling 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 P1-17-04.
Abstract P1-17-06: Breast cancer in elderly women: Ageism or primum non nocere?
Authors: Muzaffar M , Vohra N , Wong J 
Published: May 2019

Abstract
Background: The risk of breast cancer increases with advancing age. Routine use of screening mammogram in women after 75yrs and its impact on overall survival is controversial. Studies have also found that elderly breast cancer patients are underrepresented among clinical trials and a tendency for undertreatment may result in inferior outcome.
Method and Material:Female patients with breast cancer who were 75 years or older and diagnosed from 2000-2015 were identified from Surveillance, Epidemiology, and End Results (SEER) 18 database. We excluded patients with unknown stage and race. We performed multivariate and survival analysis using JMP pro 13.
Results: 186,682 women with breast cancer of ≥ 75 yrs. were identified from the SEER. 167,802 patients met the inclusion criteria. Mean age was 81.27 years (CI 95% 81.25-81.30). Most of the patients were white (88%), and had Stage I/II (83%) breast cancer.78% of patients had estrogen receptor positive cancer, while 66% had grade 1/2 disease. The 5-year overall survival was 74% for Stage I,60% for Stage II,38% for stage III and 11% for Stage IV cancer(p&lt;0.0001). The disease specific survival (DSS)for stage I (96%), Stage II (88%), Stage III (64%), and Stage IV (23%).Out of the patients who were deceased at the time of analysis only 24% of deaths were attributed to this cancer. Cox proportional hazards regression model of overall survival [Table:1]
Cox proportional hazards regression model of overall survivalVariableHazard ratio( 95% CI)p value75—79 80-84 85+1 1.22 1.7&lt;0.0001Race White Black Others1 1.14 0.95&lt;0.001ER Positive Negative unknown1 1.19 1.2&lt;0.001Stage I Stage II Stage III Stage IV1 1.17 1.66 3.7&lt;0.001
Conclusion: Early breast cancer continues to be the most common presentation for patients ≥75 yrs. of age. Historical prognostic factors of breast cancer like race, hormone receptor status, stage and grade continue to impact cancer outcome among elderly patients. Only 24% of deaths among the deceased were attributed to this breast cancer highlighting the concern for over diagnosis. Nonetheless once diagnoses is established a multidisciplinary comprehensive geriatric assessment should be the cornerstone of the management.
Citation Format: Muzaffar M, Vohra N, Wong J. Breast cancer in elderly women: Ageism or primum non nocere? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-17-06.
Abstract P1-18-06: First-line treatment for endocrine sensitive bone-only metastatic breast cancer: Is more always better?
Authors: Toss A , Venturelli M , Sperduti I , Isca C , Molinaro E , Barbieri E , Piacentini F , Omarini C , Cortesi L , Cascinu S , Moscetti L 
Published: May 2019

Abstract
The standard first-line for endocrine sensitive metastatic breast cancer (BC) is represented by endocrine therapy. Several phase III clinical trials searched for more effective endocrine strategies. Nevertheless, the use of combinations for the first-line treatment of bone-only disease (BoD) is widely discussed, due to its indolent course. Our meta-analysis aims to explore the role of new endocrine strategies in BoD.
A systematic review of electronic databases was conducted to identify the phase III clinical trials comparing the standard AI to novel experimental strategies. The hazard ratios (HR) for PFS were pooled in a meta-analysis. The heterogeneity of the data was evaluated by Chi-square Q test and I2 statistic.
8 studies were included in the analyses. 4 trials explored the role of CDK4/6 inhibitors (Monaleesa2 and 7, Monarch3 and Paloma2), 2 trials analyzed Fulvestrant + AI (SWOG and FACT), one trial studied Fulvestrant monotherapy (FALCON), while one trial evaluated the association between Bevacizumab and Letrozole (ALLIANCE). 6 trials reported data regarding the BoD, while 2 trials included the BoD in the non-visceral disease. Overall, the meta-analyses showed a PFS advantage for the experimental arms [HR 0.70 p 0.012], with a significant moderate/high heterogeneity [I2 66.48% p 0.004]. Only the FALCON and Paloma2 showed a significant improvement in PFS, respectively for Fulvestrant and Palbociclib + Letrozole. Considering only trials reporting data for BoD, the experimental arms significantly improved the PFS [HR 0.66 p 0.005], with a low/moderate non-significant heterogeneity [I2 44.95% p 0.106].
The novel strategies showed to be able to improve the PFS of BoD. Nonetheless, only Palbociclib + Letrozole provided statistically significant data of advantage in this setting. In clinical trials, BoD is often included in the non-visceral disease subgroup. Future clinical trials should take into account the differences in natural history and better prognosis of BoD, in order to define the best approach to these patients.
Citation Format: Toss A, Venturelli M, Sperduti I, Isca C, Molinaro E, Barbieri E, Piacentini F, Omarini C, Cortesi L, Cascinu S, Moscetti L. First-line treatment for endocrine sensitive bone-only metastatic breast cancer: Is more always better? [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 P1-18-06.
Abstract P1-19-06: The prognostic value of HER2, YKL-40 and IL-6 in cerebrospinal fluid in trastuzumab naïve breast cancer patients diagnosed with meningeal carcinomatosis
Authors: Ryberg M , Johansen JS , Grantzau TL , Dehlendorff C , Nielsen DL 
Published: May 2019

Abstract
Background
With the improvements in treatment of patients with metastatic HER2-positive breast cancer (BC) the development of CNS metastases has become a major limitation of life expectancy and quality of life for many patients. Meningeal carcinomatosis represents approximately 10-20% of CNS metastases. The prognosis of meningeal carcinomatosis remains extremely poor. In the present study, we analysed the prognostic value of HER2, YKL-40 and IL-6 in cerebrospinal fluid (CSF) of meningeal carcinomatosis.
Methods
Between June 1985 and August 1992 sixty-nine CSF samples were collected at Herlev Hospital from trastuzumab naïve BC patients suspected of meningeal carcinomatosis. The cohort was composed of BC patients from two previous studies. Meningeal carcinomatosis was confirmed by tumour cells in CSF (or autopsy/scans). The samples were centrifuged, frozen and kept at -80oC. The concentrations of YKL-40, IL-6 and HER2 in CSF were measured by commercial ELISA (Quidel and R&D) or Luminez (HER2 in second study). Overall survival in meningeal carcinomatosis was analysed with Kaplan-Meier curves and log rank tests using the median CSF value of HER2, YKL40 and IL-6 as cut off.
Results
20 patients (29%) had meningeal carcinomatosis (18 patients had tumour cells in CFS, one was diagnosed by autopsy and one by CT scan; 13 of these patients participated in the first study and 7 in the second).10 patients had concomitant brain metastasis. The median survival was 35 days (4-305 days).
The median [IQR] CSF concentration of YKL-40 was 284 ng/ml (187-597), IL-6 was15.9 pg/ml (6.5-51.0) and HER2 was 1.5 (0.36-8.70) in the patients with meningeal carcinomatosis. The survival was significantly shorter in patients with high levels of YKL-40 (p=0.03) and IL-6 (p=&lt;0.01). The CSF HER2 level (p=0.51) or presence of brain metastasis (p=0.77) were not associated with survival.
Conclusion
In this cohort high levels of YKL-40 and IL-6 in CSF were associated with short survival in patients with BC and meningeal carcinomatosis. This was not found for HER2 in CSF or concomitant brain metastasis.
Citation Format: Ryberg M, Johansen JS, Grantzau TL, Dehlendorff C, Nielsen DL. The prognostic value of HER2, YKL-40 and IL-6 in cerebrospinal fluid in trastuzumab naïve breast cancer patients diagnosed with meningeal carcinomatosis [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 P1-19-06.
Abstract P1-20-01: Intraoperative ketorolac in high-risk breast cancer patients with and without inflammation. A prospective, randomized, placebo-controlled clinical trial
Authors: Berliere M , Bouche G , Duhoux F , Coulie P , De Cloedt J , Dekleermaker A , Guillaume J-E , Ledent M , Machiels J-P , Mustin V , Swinnen W , Vander Essen L , Van Maanen A , Verougstraete J-C , De Kock M , Forget P 
Published: May 2019

Abstract
Introduction: Perioperative events may affect the risk of breast cancer recurrence after surgery. Ketorolac, a non-steroidal anti-inflammatory drug routinely used to improve pain control postoperatively has been associated with better breast cancer outcome in retrospective studies. However, it is still unknown whether a single dose of pre-incisional ketorolac may be sufficient to prolong recurrence-free survival.
Patients and methods: The KBCt trial (NCT01806259) is a national, multicenter, prospective, double-blind, placebo-controlled, randomized phase III trial in high risk breast cancer patients. Each patient was assigned to the ketorolac or the placebo group. Patients were given one dose of ketorolac tromethamine (Taradyl®, N.V. Roche S.A., Belgium) or a matching placebo 30 minutes before surgery. Eligible patients were ≥18 and ≤75 years old with histologically or cytologically confirmed, invasive ductal or lobular breast carcinoma planned for curative breast cancer surgery, and with at least one of these 3 criteria: a Neutrophil-to-Lymphocyte Ratio ≥4, node-positive disease (cN1-N3) or a triple-negative histology. The primary endpoint of the study was Disease-Free Survival (DFS). Secondary endpoints included safety, pain assessment and overall survival.
Results: Two hundred and three patients were assigned to ketorolac (n=96) or placebo (n=107). Baseline characteristics were similar between arms. Patients had a mean age of 55.7 (SD 14) years. Both intra- and post-operative blood losses were not different between groups and there was no difference in pain at day 1 after surgery. There was no difference between the 2 arms for DFS (p=0.52) nor for OS (p=0.88).
Discussion and conclusion: This study shows that a single administration of 30 mg of ketorolac tromethamine before surgery does not increase disease-free survival in high risk breast cancer patients. Overall survival is also comparable. No safety concerns were observed in this study.
Citation Format: Berliere M, Bouche G, Duhoux F, Coulie P, De Cloedt J, Dekleermaker A, Guillaume J-E, Ledent M, Machiels J-P, Mustin V, Swinnen W, Vander Essen L, Van Maanen A, Verougstraete J-C, De Kock M, Forget P. Intraoperative ketorolac in high-risk breast cancer patients with and without inflammation. A prospective, randomized, placebo-controlled clinical 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 P1-20-01.
Abstract P2-01-05: Targeting of casein kinase 1δ inhibits triple negative breast cancer metastasis
Authors: Bayle S , Lafitte M , Quereda V , Roush WR , Duckett DR 
Published: May 2019

Abstract
Metastasis is responsible for most breast cancer mortalities and 30% of the patients with breast cancer will develop metastases. Despite the establishment of efficient targeted therapies for breast cancer, there is no cure for metastatic disease. Our research team have developed a potent, highly selective, small molecule inhibitor of casein kinase-1 delta (CK1δ), a serine/threonine kinase. We have demonstrated that our lead molecule (SR-3029) provokes tumor specific cell death and tumor regression in pre-clinical orthotopic xenograft models of triple negative breast cancer (TNBC) including, basal-like patient derived (PDX) breast cancer models. Herein, we demonstrate that targeting CK1δ inhibits tumor cell invasion in cell based studies and markedly reduces both the number and size of metastasis lesions spreading from the breast to the lung in vivo. We show that invasion impairment is due to the inhibition of key effectors of the epithelial-mesenchymal transition. We have developed Lumifluor patient-derived xenograft models and assessed the effect of our inhibitors at various stages during the process of metastases. We have identified CK1δ as an efficacious therapeutic target with dual potential for triggering apoptosis of breast tumor cells and impairing metastatic spread from the primary tumor.
Citation Format: Bayle S, Lafitte M, Quereda V, Roush WR, Duckett DR. Targeting of casein kinase 1δ inhibits triple negative 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 P2-01-05.
Abstract P2-01-07: M2-like tumor-associated macrophages require Tartrate-resistant acid phosphatase as overall function to promote breast cancer metastasis
Authors: Dai M-S , Lo H-C , Chen L-C , Janckilla A , Tseng S-F 
Published: May 2019

Abstract
Tartrate-resistant acid phosphatase (TRAP) is a member of the purple acid phosphatase family and is also known as type 5 acid phosphatase. It is mainly expressed in cells of the monocyte lineage, including osteoclasts, macrophages, and dendritic cells (DCs). There are two isoforms of TRAP enzyme: TRAP-5a and TRAP5b, and TRAP-5b is produced by post-translational modification of TRAP-5a. TRAP-5b is the major isoform of TRAP secreted by osteoclasts and it has been shown that TRAP-5b activity correlates with the number of osteoclasts and serum activity in rat and human studies. In contrast, macrophages and DCs are thought to secrete TRAP-5a as the major subtype, whereas TRAP-5a is a non-specific marker of macrophage activation. The recent studies show that higher-grade proliferative tumors with much necrosis were associated with abundant macrophage expressing TRAP. Here we generate TRAP-/- knockout mice to study the function of TRAP in tumorigenesis. In vitro experiments have found that the expression of TRAP in macrophages is essential for the full promoting tumor function of M2-like tumor-associated macrophages (TAM) including tumor growth and metastasis. Marrow-derived macrophages (BMDM) extracted from the TRAP-/- mice lost promote tumor migration activity. The 4T1 tumor (murine breast cancer cell line) conditioned medium was used to induce TAM formation found M2-like TAM formation in wild type BMDM was promoted higher than that of TRAP-/- BMDM. In contrast, the TRAP-/- is much higher M1-like TAM formation than the wild type. Xenograft tumor formation assays were used to monitor tumor formation by combining 4T1 and different M2 polarized macrophages into BALB/c mice. M2-polarized macrophages with trap-defective BMDM showed reduced promoted neoplastic activity compared to wild type. In MMTV-PyMT transgenic mice, spontaneous tumor formation in knockout trap-/- significantly repressed tumor formation compared to TRAP+/+ wild type mice. Finally, we hypothesized that TRAP is essential for the full function of M2-like tumor-associated macrophages and promotes tumor metastasis.
Citation Format: Dai M-S, Lo H-C, Chen L-C, Janckilla A, Tseng S-F. M2-like tumor-associated macrophages require Tartrate-resistant acid phosphatase as overall function to 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 P2-01-07.
Abstract P2-01-10: Withdrawn
Authors: Hasan MK , Widhopf II GF , Zhang S , Shen Z , Briggs SP , Kipps TJ 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Hasan MK, Widhopf II GF, Zhang S, Shen Z, Briggs SP, Kipps TJ. 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 P2-01-10.