bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bevacizumab, etoposide, and cisplatin (BEEP) in brain metastases of breast cancer progressing from radiotherapy: Results of the first stage of a multicenter phase II study.
Authors: Lu Yen-Shen , Chen Wei-Wu , Lin Ching-Hung , Tseng Ling-Ming , Yeh Dah-Cherng , Wu Pei-Fang , Chen Bang-Bin , Chao Ta-Chung , Tsai Yi-Fang , Huang Shu-Min , Shih Tiffany Ting-Fang , Cheng Ann-Lii 
Published: March 2020

1079 Background: With a general prolongation of survival, brain metastasis (BM) has become a common complication of breast cancer. However, management of BM remains a severe challenge. We hypothesized that bevacizumab (BE) could significantly enhance drug delivery of etoposide (E) and cisplatin (P), two of the cytotoxic agents that have moderate activity in BM of breast cancer, to brain tumors and thereby improve the efficacy. Methods: Breast cancer patients (pts) with BM progression after whole brain radiotherapy (WBRT) were enrolled. Pts received BE 15 mg/kg day 1, and E 70 mg/m2/day, days 2-4, P 70 mg/m2/day, day 2, every 21 days for a maximum of 6 cycles. The primary endpoint was a centrally assessed CNS objective response (CNS-OR) defined as a ≥50% reduction in the volumetric sum of all measurable CNS lesions in the absence of increasing steroid use, development of new CNS lesion, or progressive neurologic symptoms. Using a Simon’s optimal two-stage design with 15% as a minimum interest in CNS-OR rate (by intent to treat analysis), 11 pts were needed at the first stage; and a total of 31 evaluable for the whole study. Results: Among 16 pts enrolled from Jan 2011 to Jan 2012, 12 pts were evaluable for treatment response at the time of abstract submission. Median age was 55 (range 34-66); 1 pt was ER+HER2-, 5 pts were HER2+, and 6 pts were ER-HER2-. The median treatment cycles were 4.5 (range 1-6). Nine of 12 pts (75%; 95%CI 42.8-94.5) achieved CNS-OR including 6 pts (50%) with ≥80% and 3 pts (25%) with 50-80% CNS volumetric reduction, respectively. Two pts had non-CNS disease progression while CNS tumors remained under control. The median CNS progression free survival was 6.6 months (95% CI 0.8-12.4). Grade 3 /4 toxicities included neutropenia, leukopenia, anemia, and platelet in 13 (25.5%), 6 (11.8%), 2 (3.9%), and 2 (3.9%) cycles, respectively. Seven pts (58.3%) had received dose reduction to E 60 mg/m2 and P 60 mg/m2. Early reporting of this study was approved by Data and Safety Monitoring Committeedue to an extremely promising result. Conclusions: BEEP regimen has a significant anti-tumor effect for BM of breast cancer which progresses after WBRT.
Validation of NAD(P)H quinone oxidoreductase (NQO1) expression as a predictive factor for adjuvant chemotherapy benefit in patients with early breast cancer.
Authors: Arnedos Monica , Goubar Aicha , Sprott Kam M. , Jiang Chunsheng , Suschak Jessica , Weaver David T. , Delaloge Suzette , Conforti Rosa , Andre Fabrice 
Published: March 2020

1091 Background: NAD(P)H:quinone oxidoreductase-1 (NQO1) has important antioxidant functions by stabilizing p53 from proteasomal degradation. NQO1 knockdown is associated with higher susceptibility to oxidative stress. Polymorphisms suppressing NQO1 are predictors of poor survival in patients with breast cancer (BC) treated with anthracyclines. BC cell lines with impaired NQO1 function showed resistance to epirubicin chemotherapy (CT) independently of p53 status suggesting NQO1 as predictive factor for anthracycline benefit. In this study we hypothesized that lack of NQO1 could predict resistance to anthracycline-containing CT in patients with early breast cancer (EBC). Methods: Patients were identified from two French multicentric trials that randomized patients with EBC to adjuvant anthracycline-based CT vs no CT between 1988 and 1995. NQO1 was determined in TMAs by automated quantitative assessment of immunofluorescence (On-Q-ity Inc, Waltham). Cut-off for positivity was the median value of NQO1 expression. Univariate and multivariate Cox regression models were performed. Treatment effect was assessed on long term overall survival (OS). Results: NQO1 expression was assessed in 600 patients. 75% were postmenopausal, had more often grade II (62%), LN-negative (58%) and ER-positive (67%) BC. Higher NQO1 expression was observed in postmenopausal (P=0.02) patients. No relation with other clinicopathological factors (grade, LN or ER) was observed. Effect of adjuvant CT on death rates was dependant on NQO1 level. Hazard ratio (HR) for treatment efficacy at the four quartiles of NQO1 were 1.07 (95%CI: 0.69-1.7), 0.87 (0.64-1.19), 0.66 (0.45-0.97), 0.46 (0.22-0.95) (interaction test: 0.1). Interaction test was statistically significant (0.02) when NQO1 expression was considered as binary variable with median value taken as cut-off. NQO1 remained predictive among ER+ patients only. HR for OS was 0.61 (0.36-1.02) and 1.25 (0.79-1.99) in patients with high and low NQO1 respectively. Conclusions: This study adds to the existing data suggesting NQO1 expression as an independent predictor of efficacy for adjuvant anthracycline-containing CT.
Analysis of pretreatment nonpharmacologic, pharmacologic factors, and yoga intervention on CINV outcomes in breast cancer patients undergoing adjuvant chemotherapy.
Authors: Usharani Malur R. , Raghavendra Rao M. , Gopinath Kodaganur Srinivasachar , S Ramesh Bilimagga , Diwakar Ravi B , Rao Nalini K , Ajaikumar Basavalinga S. , Nandini P K 
Published: March 2020

1093 Background: Chemotherapy induced nausea and vomiting (CINV) is affected by both pretreatment patient factors, chemotherapy and antiemetic regimen and psychological interventions. In this study we evaluated the effects of mind body intervention such as yoga in modulating CINV outcomes controlled for the above factors. Methods: Chemotherapy naïve breast cancer patients with stage II and III disease participating in a randomized controlled trial comparing yoga (n=45) vs. supportive therapy (n=53) were assessed for CINV outcomes during adjuvant chemotherapy. Morrows Assessment of nausea and emesis was used to asses CINV symptoms including their frequency, severity and anticipatory nature. We developed a multiple regression analyses to test the role of intervention on CINV beyond that explained by the independent prognostic factors [age (<50/≥50 years), stage of disease (II vs III), menopausal status (pre vs post), antiemetic regimen (5HT3 antagonists vs. antidopaminergics), administration of anxiolytics (yes/ no) and type of chemotherapy regimen (FAC vs. CMF)] that were included in model A. Model B includes these six variables plus intervention (yoga vs. supportive therapy) in predicting nausea and vomiting outcomes. Results: Intervention emerged as a primary predictor for nausea frequency (β= -0.38, p=0.002), intensity (β= -0.44, p=0.001 ), anticipatory nausea frequency (β=-0.26 , p= 0.04) and intensity (β=-0.38 , p=0.004 ). Age group emerged as a primary predictor for anticipatory vomiting frequency (β=-0.39 , p=0.01 ) and secondary predictor for nausea frequency (β=-0.41, p= 0.006). Administration of anxiolytics emerged as a primary predictor for vomiting intensity (β=-0.40, p= 0.001) and secondary predictor for anticipatory nausea frequency (β=-0.26 , p= 0.05). Conclusions: Yoga intervention influences CINV outcomes when controlled for pretreatment and pharmacological factors during chemotherapy in breast cancer patients poorly controlled for nausea and vomiting.
Prevention of chemotherapy-induced damage to ovarian reserve by sphingosine-1-phosphate
Authors: LI Fang , Ozkaya Enis , Akula Komala , Desutter Petra , Oktay Kutluk 
Published: March 2020

1097 Background: Chemotherapy agents such as cyclophosphamide (Cy) and doxorubicin (D) are known to compromise ovarian function. We have previously shown that these agents alter ovarian function by causing apoptotic death of primordial follicles and thereby causing diminishment of ovarian reserve (Cancer Research 2007; Aging 2011). While assisted reproduction techniques exist to preserve fertility there has been no proven approach to pharmacologic preservation of ovarian function. Sphingosine-1-Phosphate (S1P) is a naturally occurring ceramide-induced death pathway inhibitor. Here we investigated whether S1P can prevent Cy or D-induced apoptotic follicle death in mouse ovaries. Methods: Eight wk old NOD mice (n=23) were treated with Cy (75 mg/kg), Cy+S1P (200 μM), D (10 mg/kg), D+S1P or vehicle only (Control). S1P was administered via continuous infusion using a mini-osmotic pump beginning 3 hours prior to single dose chemotherapy injection for 72 hours. Ovaries were removed 72h later and serially sectioned, and stained with anti-caspase 3 (AC-3) antibody for the detection of apoptosis in primordial follicles. The ratio of apoptotic to total follicles was expressed as percentage in each group. Results: Both Cy and D resulted in significant increase in apoptotic follicle death compared to controls (48.2±11.6 vs. 28.2±8.9, p=0.016 and 46.4±5.4 vs. 24.8±5.2, p=0.004, respectively). Percentages of apoptotic follicles were similar between Cy and D-treated groups (48.2±11.6 vs. 46.4±5.4, P=NS) indicating that these agents were equally gonadotoxic. S1P treatment resulted in a significant decrease in the percentage of apoptotic follicles both in the Cy (25.6±3.5, P<0.011) and the D group (32.2±10.8, P< 0.013) compared to controls. In the S1P-treated groups, the percentages of apoptotic follicles were similar to those in untreated controls indicating that S1P completely blocked Cy and D-induced apoptotic follicle death. Conclusions: S1P can block apoptotic follicle death induced by highly cytotoxics agents. In addition, we showed that S1P can block follicle death by chemotherapy agents that act through different molecular mechanisms. If targeted delivery systems can be developed, S1P may hold significant promise in preserving fertility by pharmacological means.
Receipt of locoregional therapy among young women with breast cancer.
Authors: Freedman Rachel A. , Virgo Katherine S. , Labadie Julia , Partridge Ann H. , Keating Nancy Lynn 
Published: March 2020

1100 Background: Although younger women with breast cancer have the most to gain from receipt of optimal care, few data are available regarding their receipt of locoregional breast cancer treatments. Methods: We identified 318,083 women aged 18-64 who were diagnosed with invasive breast cancer at hospitals reporting to the National Cancer Data Base, a large national cancer registry, during 2004-2008. We used multivariable logistic regression to assess the association of patient age with mastectomy vs. breast-conserving surgery (BCS), radiation with BCS, and post-mastectomy radiation (PMRT) with varying indications, adjusting for patient and tumor characteristics, area-level socioeconomic status, and insurance. Results: Overall, 4% of women were aged ≤35 and 7% were aged 36-40. Women aged ≤35 were significantly more likely to have mastectomy than BCS compared with women aged 56-60 (57% vs. 35%, adjusted odds ratio [OR] 1.97; 95% Confidence Interval [CI] 1.87-2.07) but were less likely to receive radiation if BCS was performed (69% vs. 80%, OR 0.77; 95% CI 0.73-0.82). For those who underwent mastectomy, although overall rates of PMRT receipt were low, women aged ≤35 were more likely to receive postmastectomy radiation (PMRT) despite the presence or absence of clinical indications for PMRT (OR 1.11; 95% CI 1.01-1.22 for strong indications, OR 1.71; 95% CI 1.53-1.91 for borderline indications, and OR 1.49; 95% CI 1.28-1.73 for no indications [all vs. ages 56-60]). Conclusions: Young women with breast cancer may not be receiving optimal locoregional therapy. We observed lower odds of radiation after BCS but higher odds of PMRT for young women regardless of indications for PMRT. Efforts are needed to further understand and improve the receipt of appropriate adjuvant radiation therapy among young women to improve their disease-free and overall survival.
Primary tumor resection to improve survival and local disease control in stage IV inflammatory breast cancer.
Authors: Akay Catherine Liebig , Ueno Naoto T. , Chisholm Gary B. , Hortobagyi Gabriel N. , Woodward Wendy A. , Alvarez Ricardo H. , Lucci Anthony , Bedrosian Isabelle , Kuerer Henry Mark , Hunt Kelly , Huo Lei , Babiera Gildy 
Published: March 2020

1102 Background: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer typically presenting with early metastasis. Optimal outcomes are achieved with multimodality treatment strategies in the non-metastatic setting. Data is limited, however, on the benefit of surgery in patients with metastatic IBC. We evaluated the effect of primary tumor resection on outcomes in patients with newly diagnosed stage IV IBC. Methods: We reviewed records of 172 patients with metastatic IBC treated at our institution from 1994 - 2009. All patients received systemic therapy with or without locoregional therapy (LRT). Patient demographics, receptor (ER) and HER2-neu status, grade, histology, presence of lymphovascular invasion, margin status, number of distant disease sites, pathologic response of primary tumor and clinical response to systemic therapy (CRS) at distant disease sites were recorded. Overall survival (OS), distant progression-free survival (DPFS), and chest/skin involvement at last follow-up were evaluated. Kaplan-Meier survival analyses, univariate (UV) and multivariate (MV) logistic regression models were used. Chest/skin involvement was compared between groups using Kruskal-Wallis test. Results: Seventy-nine (45%) patients underwent primary tumor resection. Average age was 51 (22-78). Median live-patient follow-up was 33 months. OS and DPFS were significantly better for patients who underwent LRT versus none (p<0.0001). Factors associated significantly for improved DPFS on MV analysis were ER and HER2-neu status (HR 0.61,0.60 p=0.02,0.05 ,respectively), LRT (HR .38, p=0.002) and CRS (HR 0.62, p=0.03). ER status (HR .45, p<0.001), LRT (HR .30, p<0.001) and CRS (HR 0.54, p=0.02) were significant predictors for higher OS on MV analysis. At last follow up, chest/skin involvement was moderate/severe in 11% of patients in LRT group versus 35% of patients in no LRT group (p<0.0001). Conclusions: This latest retrospective study demonstrates metastatic IBC patients who undergo LRT in addition to systemic therapy may have improved survival and local control outcomes. CRS may be used to guide LRT. A prospective randomized trial is needed to validate these findings.
Can primary tumor markers of cancer-initiating cells predict lymph node positivity in breast cancer patients?
Authors: Chagpar Anees B. , Neumeister Veronique , Lannin Donald R. , Rimm David 
Published: March 2020

1121 Background: Cancer initiating cells, characterized by ALDH1 positivity and/or colocalization of ALDH1 and CD44, have been shown to be associated with poor prognosis in breast cancer patients. The prognostic value of these tumor markers with respect to prediction of lymph node (LN) status remains unclear. Methods: Tissue microarrays from a cohort of 223 breast cancer patients diagnosed between 2003 and 2007 were evaluated using the AQUA method for quantitative immunofluorescence for CD44 and ALDH1. These data, along with other clinicopathologic data, were correlated with LN positivity. Results: The median patient age of the cohort was 56 (range; 26-89), with a median tumor size of 1.5 cm. 72 (32.0%) patients were LN positive. The median number of LNs excised was 3 (range; 1-27). Of the LN positive patients, the median number of positive LNs was 1.5 (range; 1-24). Levels of CD44, ALDH1, and ALDH1 colocalizing with CD44 did not correlate with number of positive LNs (Spearman rho coefficients: -0.042, 0.131, and 0.058, respectively), nor overall LN status. Tumor size and lymphovascular invasion (LVI) were the only factors found to be significantly correlated with LN status. Conclusions: While ALDH1 colocalized with CD44 has been found to be associated with poor prognosis in breast cancer patients, these markers do not predict LN status. Given that the only factors that reliably predict LN status are tumor size and LVI, further work is required to find primary tumor markers that may predict LN status in order to spare patients axillary surgery. [Table: see text]
Clinical findings and outcomes from MRI staging of breast cancers in women.
Authors: Raghavendra Akshara , Ricker Charite Nicolette , Ji Lingyun , Church Terry , Tang Sujie , Larsen Linda , Sheth Pulin , Tripathy Debu 
Published: March 2020

1124 Background: For patients diagnosed with breast cancer, case series have shown that staging MRI can detect occult breast cancers in 1-10% of cases. Prevalence and risk factors in underserved populations remain unclear. Methods: We performed a retrospective analysis of all patients, newly diagnosed, with breast cancer who had a preoperative staging MRI seen at Norris Comprehensive Cancer Center and LAC +USC, that cares for an underserved and minority population, from 2006 to 2011. Demographic, clinicopathologic and imaging data were obtained through a review of electronic records. Non index lesions were defined as those not known to be malignant, not presenting with clinical, mammographic or ultrasound findings, in a different quadrant and given an MRI BIRADS score of 4 or 5. Results: A total of 718 patients were analyzed and 148 patients (21%) had a total of 187 non index lesions; 63% were ipsilateral, 26% contralateral and 11% bilateral. As initial evaluation of non-index ipsilateral lesions, 71 (38%) had biopsy, 24 (13%) had excision and 34 (18%) had mastectomy. For contralateral non-index lesions, 41 (22%) had contralateral biopsy, 6 (3%) had excision and 11(6%) had mastectomy. Among all non index lesions, 111 (59%) were benign, 14 (7%) DCIS and 62 (33%) invasive cancer. Occult ipsilateral cancer was detected in 50 (6.9%) of patients and contralateral in 10 (1.4%) and bilateral in 6 (0.8%). Conclusions: The occult cancer detection rate with staging MRI was in this 9.2% of this diverse population. No clear risk factors were identified, with detailed factors, including BRCA status to be updated and reanalyzed. [Table: see text]
Changes in glucose, insulin, and insulin resistance from presurgery to post adjuvant treatment for breast cancer.
Authors: Guinan Emer M. , Hussey Juliette M. , Healy Laura , Carroll Paul A. , Kennedy John , Connolly E. M. 
Published: March 2020

1511 Background: Elevated fasting insulin levels at breast cancer diagnosis are associated with increased risk of recurrence and reduced survival. (Goodwin PJ, et al. JCO. 2012;30:164-171) Weight gain related to adjuvant treatment coupled with sedentary activity habits may further alter insulin-related measures for breast cancer survivors. We present results from a prospective longitudinal study examining changes in insulin-related markers from pre breast cancer surgery to post adjuvant treatment. Methods: Subjects were recruited from St. James’s hospital, Dublin, Ireland at the time of breast cancer diagnosis (stage I-III). Fasting pre-surgery blood samples were drawn to measure insulin, glucose and glycosylated haemoglobin A1c (HBA1C). Insulin resistance was calculated using the homeostatic model assessment (HOMA). Subjects with no evidence of active cancer completed the same measurements 2-5 years later. Paired sample t-tests were used to measure changes from pre-surgery to post-adjuvant treatment. Statistical significance was set at P = .05. Results: Forty-four subjects (n = 22 postmenopausal) completed both measurements (mean ± SD age 54.1±8.6 years). Mean time since diagnosis to follow-up measures was 3.4±0.8 years. Adjuvant therapy included chemotherapy (n=37), radiotherapy (n=36), biological therapy (n=8) and concurrent hormonal therapy (n=37). There was a statistically significant increase in insulin (mean ± SD change 2.8±4.1mU/L, P=.000), insulin resistance (0.54±1.0, P=.001) and HBA1C (0.1±0.2 %, P= .003). Fasting glucose levels did not change (P = .06). Conclusions: Results indicate that patients with breast cancer experience significant increases in insulin, insulin resistance and HBA1C from pre-surgery to post adjuvant treatment. Elevated post-treatment insulin levels may further contribute to risk of breast cancer recurrence and mortality, while also predisposing to the development of cardiovascular disease and type 2 diabetes mellitus. Exercise and diet interventions are warranted in this population to improve markers of insulin resistance as a surrogate for improving breast cancer and overall health outcomes.
An alternative approach to identify women at risk for colorectal cancer.
Authors: Bruegl Amanda S. , Djordjevic Bojana , Westin Shannon Neville , Soliman Pamela T. , Brandt Amanda C. , Daniels Molly S , Lu Karen H. , Broaddus Russell 
Published: March 2020

1513 Background: Hereditary colorectal cancer (CRC) is preventable; however, identification of individuals at sufficiently high risk to warrant heightened surveillance is difficult. Lynch Syndrome (LS) is an inherited cancer syndrome due to germline mutation in a DNA mismatch repair gene. For women with LS, the lifetime risk of endometrial cancer (EC) is 64% and CRC is 54%. Fifty percent of women with LS will present with EC or ovarian cancer prior to CRC. Therefore, women with LS associated EC represent an ideal group for CRC prevention. The optimal method to identify women with LS associated EC is not known. The purpose of this study was to determine the utility of Amsterdam II and Society of Gynecologic Oncology (SGO) Criteria (modified Bethesda criteria that use EC as the sentinel cancer) in identifying women with LS associated EC. Our ultimate goal is to identify women at increased risk of CRC. Methods: Immunohistochemistry (IHC) for DNA mismatch repair proteins and MLH1 methylation analyses were used to identify LS associated EC among 388 women. EC was designated as LS if there was loss of mismatch repair protein expression. Absence of MLH1 methylation was required to confirm LS in tumors with MLH1 protein loss. Results: Fifty-nine (15.2%) of the EC patients tested had LS. These patients are summarized in the table. Conclusions: Clinical criteria to detect LS identify 17/59 (29%) - 44/59 (74%) of women who present with EC first. EC with MSH2 loss is most likely to occur in younger women and women with positive family history of EC and CRC, features classically associated with LS. In general, the MSH6 mutation is associated with older age at diagnosis and fewer familial CRCs, however, we found a large number of MLH1 (50%) and PMS2 (86%) cases diagnosed at greater than 50 years with no family history of CRC. Our data suggest that classic clinical screening criteria are inadequate to detect patients with LS who present with EC, potentially missing up to 25% of these patients. [Table: see text]