bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene polimorphisms and biological factors as possible predictors for patients with pleural metastatic breast cancer
Authors: Montes-Worboys A. , Romero A. , Casas A. M. , Arellano E. , Juan J. M. , Moreno J. A. , Rodriguez Panadero F. 
Published: March 2020

10671 Background: Pronosis of breast cancer varies widely in patients with similar clinical features. Therefore, we investigated other factors with possible prognostic value. The CYP17 gene has a polimorphism related to a increased susceptibility to breast cancer (single T; A1 allele to C; A2 allele). ( Mitrunen et al. Cancer Epidemiol Biomarkers Prev 2000,9;12;1343–8). On the other hand, it has been found in the MTHFR gene a common C-T substitution at nucleotide 677 that is associated with reduced enzyme activity and increased risk of breast cancer (Capmbell et al., Breast Cancer Research 2002;4,6:R14). Other genes such as GSTT1 and GSTM1 variant genotypes have a controversial association to breast cancer. We have analyzed the genotype and biological factors in a group of patients with pleural metastatic cancer of the breast and compared it to a control group of women with no cancer. Methods: Forty-six patients with breast cancer and forty women as controls were includes in the study. Age at diagnosis of the primary tumor, TNM staging, interval free of disease, estrogen and progesteron receptors, Ki67, p53 and Her-2neu expression were recorded, as well as survival from the time of diagnosis and polimorphism of CYP17, MTHFR, GSTT1 and GSTM1 genes. Results: Mean survival differed significantly between patients having pleural effusion as the first site of relapse as compared to those with other sites of relapse (28’9 vs 11’9 months, p = 0’004). A high Ki67 expression correlated best with longer survival after talc pleurodesis. We detected a high frequency in the CYP17 A2 variant genotype in patients with metastatic breast cancer compared to the control group. As for MTFHR gene, we found a high frequency for the T/T genotypes variant in breast cancer group. No significant differences between control and cancer group were found in either GSTT1 and GSTM1 gene variations. Conclusions: Genotype and biological factors, such as factors investigated in this study, play an important role as predictors for patients with pleural metastatic breast cancer. No significant financial relationships to disclose.
The Head to Head trial: Letrozole vs anastrozole as adjuvant treatment of postmenopausal patients with node positive breast cancer
Authors: De Boer R. , Burris H. A. , Monnier A. , Mouridsen H. , O’Shaughnessy J. A. , McIntyre K. , Pritchard K. I. , Smith I. , Yardley D. 
Published: March 2020

10672 Introduction: Aromatase Inhibitors (AIs) have demonstrated both efficacy and safety advantages over tamoxifen (T) in all treatment settings in breast cancer (BC) and are becoming the new standard of care as endocrine therapy for postmenopausal patients (PM) with BC. Rationale: Cumulative evidence suggests that all AIs may not be the same, raising the question of whether there is a superior AI, and whether any specific patient populations derive differing degrees of benefit from a particular AI. In the ATAC trial, evaluating anastrozole (A) in PM patients with early breast cancer (EBC), at 33 months median follow up the risk of recurrence in the hormone receptor positive (HR+) population was reduced by 22%.The BIG 1–98 Trial, evaluating letrozole (L) in PM women with EBC, showed a significant benefit in favor of L over T at a median follow up of 26 months, with a 19% reduction in the risk of recurrence; in subgroup analyses, L significantly decreased the risk of recurrence in LN+ patients and in patients who received adjuvant chemotherapy. This study is a head to head comparison of L and A in HR+, LN+ PM patients with EBC and aims to compare L vs A in the adjuvant treatment of these patients. Design and Methods: This is a Phase IIIb open-label, randomized, multicentre study including 4000 PM patients from up to 250 international sites. PM patients with HR+, LN+ BC who have recently undergone surgery for primary BC will be randomized to either receive L 2.5 mg or A 1 mg daily. Treatment will commence following completion of standard chemotherapy (if given) and concurrently with radiotherapy (if given)Patients will receive treatment until disease recurrence/relapse for up to 5 years. Patients will be stratified by number of LN and HER2 status. The primary objective is disease free survival at 5 years for L and A. Secondary objectives include safety, overall survival, time to distant metastases and time to contralateral breast cancer. Data analysis will be conducted by an independent group of investigators. Summary: Updated patient accrual figures, including any available early safety data, will be presented at the meeting. No significant financial relationships to disclose.
Effect of microscopic residual tumor (MRT) at surgical margin of resection (SMR) in ductal carcinoma in-situ (DCIS) on survival of non-Hispanic white women in central Pennsylvania (PA)
Authors: Kumar P. , Ingle A. M. , Baney B. , Day K. , Dagen T. , Galley A. S. , Dixon R. H. 
Published: March 2020

10706 Background: Few studies that have investigated the long-term effect of MRT in DCIS, have demonstrated conflicting results. Mount Nittany Medical Center (MNMC) is located in an agricultural, ethnically-homogenous (Non-Hispanic White) county in PA. To the best of our knowledge, there have been no similar studies conducted on such populations. Our study has investigated the effect of MRT at SMR on overall survival (OS) and event-free survival (EFS) of patients with DCIS. Methods: All women diagnosed with DCIS from 04/1992 to 06/2005 at MNMC were deemed eligible. Log-rank statistics and Cox proportional hazard models (CPHM) were used for obtaining survival rates. Results: Of the 266 eligible women analysis were performed on 167 women (age range 33–89 years; median 56 years) with complete data on diagnosis, surgical margins and treatment modalities. With median follow-up time of 4.6 years (range 0.03–11.6years), 148 (88.6%) patients had no residual tumor at SMR. 78 (46.7%) patients received radiation therapy (RT) ± hormonal therapy (HT), 42 (25.2%) received HT ± RT. The CPHM demonstrated no statistical significance of MRT on OS (hazard ratio 2.9, p = 0.19), and EFS (hazard ratio = 1.9, p = 0.43) after adjusting for treatment and age. Univariate 5-year OS rate in patients with no MRT was 93.9% (95% confidence interval (CI) 87.6% to 97.1%), versus 89.2% (95% CI 63.1% to 97.2%) in patients with MRT (p-value = 0.38). Five-year EFS was observed to be 92.6% (95% CI 85.6% to 96.3%) in patients with no MRT, versus 89.2% (95% CI 63.1% to 97.2%) in patients with MRT (p-value = 0.49). Conclusions: In our study, patients with DCIS who have MRT at surgical margin of resection have a 2.9 times the risk of death and 1.9 times the risk of recurrence as compared to patients with no MRT. However, this difference is statistically not significant over time. No significant financial relationships to disclose.
Neoadjuvant dose-dense (DD) concurrent doxorubicin (A) and docetaxel (T) for stage III breast cancer (BC)
Authors: Abu-Khalaf M. , Kim R. , Cohenuram M. , Chung G. , Digiovanna M. , Haffty B. , Carter D. , Horvath L. , Tavassoli F. , Burtness B. 
Published: March 2020

10721 Background: The addition of taxanes to anthracycline therapy results in improved disease-free survival (DFS) in the adjuvant setting, and increased pathologic complete response rates (pCR) in the neoadjuvant setting. DD chemotherapy improves DFS and overall survival (OS). We evaluated neoadjuvant DD concurrent AT. Methods: Eligible patients (pts) with stage III BC were treated with AT q 14 days at 1 of 3 dose levels; L1 = 60 mg/m2 for both drugs (4 pts), L2 = A 75 mg/m2 and T 60 mg/m2 (6 pts) or L3 = 75 mg/m2 for both drugs (7 pts) × 6 cycles with G-CSF. Dexrazoxane was given after a cumulative dose of 300 mg/m2 of A. Pts were stratified to post-operative moderate risk (ModR) (≥ partial response, ≤ 3 lymph nodes (LN)) and received adjuvant IV cyclophosphamide (C) 600 mg/m2, methotrexate 40 mg/m2, 5FU 600 mg/m2 IV q 21 d × 6 (CMF), or high risk (HiR) (≤ minor response +/or ≥ 4 LN) and received C 3 gm/m2 q 14 d x 3. Primary endpoints were clinical and pathologic response rates of neoadjuvant AT. Sample size was 42 pts to estimate pCR and provide 90% confidence the true incidence of severe toxicity is <10%. Results: 17 pts with stage III BC were enrolled between 2/1999 and 7/2001; accrual was halted after data on pre-operative trastuzumab were presented. Median age was 50 yrs [range: 34–69]. 3/17 pts (17.6%) had a pCR, and 3 pts had near pCR (residual foci ≤ 1mm), 4/17 (23.5%) had path (-) LN, 7/17 (41%) had a lumpectomy, 7/17 (41%) required dose reductions of AT due to grade 4 neutropenia (5 pts) and grade 3 neuropathy (2 pts). 3 pts required treatment cessation; 1 pt (L2) for prolonged neutropenic fever and 2 pts (L3) for decreased ejection fraction and for acute renal failure. 15 pts were ModR and received adjuvant CMF, 1/2 pts stratified to high dose C declined it and received CMF. Median follow-up is 63 months [range: 28–80] with 13/17 (76.5%) pts surviving, and 12/17 (70.5%) pts surviving and free of disease. Conclusion: Neoadjuvant DD AT every 2 weeks is well-tolerated, with promising activity and survival in locally advanced BC. [Table: see text]
Study on the effects of c-erbB-2-specific antisense oligonucleotides on c-erbB-2 overexpressing breast cancer cells
Authors: Liu X. , Fan P. , Wu Z. 
Published: March 2020

10724 Background: Overexpression of c-erbB2 oncoprotein was always correlated with bad prognostic. In this study, we will research on the effects of c-erbB-2-specific antisense oligonucleotides (ODNs) on c-erbB-2 expression, cell proliferation and apoptosis of c-erbB-2 over-expressing breast cancer TM40D cells, and to further study the effects of c-erbB-2-specific oligonucleotides on breast cancer xenografts in Balb/c mice. Methods: Balb/c mouse derived breast cancer cell line TM40D was incubated with liposome-mediated ODNs for 4 h and cultured for another 72 h, then the effects of ODNs on c-erbB-2 expression, cell proliferation and activation of apoptosis were examined by western blot, MTT assay and flow cytometry. Twenty-six mice with breast cancer xenografts were randomized into three groups—9 in control group, 9 in lipsome group and 8 in therapy group, which were injected hypodermically with 0.1 ml serum-free RPMI-1640 culture-medium, lipsome (10 ug/ml) solution, and the mixture of lipsome solution (10 ug/ml) and anti-sense ODN (1 uM) weekly for consecutive 6 weeks, respectively. After the therapy, the incidence of skin ulcer was recorded, the lumps were removed and weighted, and part of them were used for Flow Cytometry. Results: Western Blotting showed treatment of TM40D cells with c-erbB-2-specific antisense ODNs resulted in inhibition of c-erbB-2 expression. The effects of antisense ODNs on c-erbB-2 protein levels correlated with their effects on cell proliferation. MTT Assay showed antisense ODNs inhibited cell growth by about 50%. Flow cytometry analysis revealed that antisense ODNs increased cell apoptosis by38.5%, compared with cultured cells group 9.13% and liposome group 9.29%. The weight of lumps in the therapy group was significantly lower than that of in the other two groups. Flow Cytometry showed that in the therapy group the ratio of G0/G1 cells in cell cycles was 87.18%, which is higher compared with the other two and proliferation index was lower. Conclusions: Antisense ODNs reduced c-erbB-2 expression, inhibited cell proliferation and induced cell apoptosis. Anti-sense ODNs can inhibit the growth of c-erbB2-overexpressing breast cancer xenogarfts in Balb/c mice. No significant financial relationships to disclose.
First line treatment of HER-2/neu positive advanced breast cancer patients with liposomal doxorubicin (Myocet), docetaxel and trastuzumab. A phase I-II study
Authors: Amadori D. , Gasparini G. , Vannozzi M. O. , Milandri C. , Serra P. , Di Costanzo F. , Di Blasio B. , Lunardi G. 
Published: March 2020

10744 Background: Our preclinical data showed synergic effect of Adriamicyn followed by Taxotere in BC cell lines. The combination of anthracyclines, taxanes and trastuzumab could potentially obtain a high number of objective responses and a consistent impact on the time to progression and on the overall survival. The aim of this phase I-II study was to assess the maximum tolerated dose (MTD) of liposomal doxorubicin (Myocet-M) and Taxotere (T) in combination with Herceptin (H). A reduction of cardiotoxicity risk without reducing chemotherapy activity was supposed. Methods: Locally advanced or metastatic her-2/neu positive BC patients (pts) with LVEF ≥ 60% were enrolled in an open, single arm, non-randomized phase I-II escalation trial in 3 to 6 pts/cohorts. The treatment schedule was: M 50 mg/m2 (or 60, depending on dose level assignment) on day 1, T 30 mg/m2 on day 2 and 9, H 4 mg/kg on day 2 followed by weekly dose of 2 mg/kg, every three weeks. MTD dose was identified on the basis of DLT defined according to WHO grade classification of toxicity or specific conditions of LVEF decrease. A pharmacokinetic (PK) analysis of doxorubicin until 72 hours after M administration was planned. Results: Seven pts, median age 63 yrs, were enrolled. Four pts were allocated to dose level 50/30 (M/T) and other 3 pts to dose level 60/30. At the dose level 60/30 febrile neutropenia (DLT) occurred in 2 pts. Other 2 pts experienced febrile neutropenia (no DLT). One event of tachicardia (WHO grade 1) at maximum tolerated dose level was completely recovered without treatment. LVEF values were unmodified. Six patients were enrolled in the PK analysis. T pharmacokinetic data obtained on day 2 and on day 9 were not statistically different. Conclusions: The MTD was defined at M 50 mg/m2 in combination with T 30 mg/m2. The cardiac tolerability was good, with no significant change in LVEF values from baseline to the end of therapy. PK data indicated that the residual concentration of M found on day 2 was did not influence T pharmacokinetics, according to literature data. A phase II study is ongoing to assess activity and PK interactions between drugs. Till now 25 patients have been enrolled, the planned sample size is 45. No significant financial relationships to disclose.
Safety of long-term administration of capecitabine in metastatic breast cancer patients
Authors: Lomas M. , Salvador J. , Ruiz M. , Bayo J. L. 
Published: March 2020

10755 Background: To evaluate the effectiveness and tolerability of long -term treatment with capecitabine in metastatic breast cancer patients. Capecitabine (C) has been administered offering clinical benefit to women with metastatic breast cancer (MBC) (ORR: 42%). The aim of this trial was to evaluate the efficacy and tolerance of capecitbine in long-term treatment, administered as first, second and third line treatment in MBC. Methods: Patients ≥ 18 years old with MBC, ECOG performance status (PS) ≤2, HER-2 neu negative, non-chemotherapy naive were included in this prospective, multicentre, non-randomized. To date, twenty-two ambulatory patients were evaluable for toxicity and response. Median age 59.2 years (37–81). All of patients had previously received adjuvant treatment. Hormonal therapy were allowed as clinically required. They received three weekly cycles of oral capecitabine 1000–1250 mg/m2 twice daily, days 1–14, followed one week rest until progression or relapse. Results: The overall response rate (ORR) is including PR, CR, and EE 78%. The median treatment duration was 14 months, median range (3–32). Median progression-free and overall survival have not yet been reached. The most common grade ½ (NCIC CTC) treatment related adverse events were /23, hand foot syndrome 4/23, diarrea 1/23. Conclusions: These preliminary data confirm that the treatment with capecitabine (C) is an effective and well tolerated regiment in metastatic breast cancer patients. No significant financial relationships to disclose.
Observations of differences in laterality imbalance of breast biopsies and breast disease between Caucasian and African American women
Authors: Jordan R. , Brzeski H. , London W. P. , Mural R. , Liebman M. N. , Hooke J. , Shriver C. D. , Hu H. 
Published: March 2020

10781 Background: A number of published reports have indicated that the left breast is at greater risk of cancer than the right breast (laterality imbalance) in women of all ages. In addition, a woman’s left breast is usually larger than her right breast. In the Clinical Breast Care Project, more than 2400 subjects have been enrolled following HIPAA compliant, IRB approved protocols. Of these, 1200 have undergone a biopsy and completed demographic and pathological questionnaires. We investigated whether there is a laterality imbalance among the patients with respect to ethnicity, menopausal status or pathological diagnoses. Methods: Female patients with biopsies on only one breast whose pathological questionnaire was completed within 90 days of the demographical questionnaire were included in this analysis but patients who were surgically post-menopausal were excluded. Multiple biopsies on one breast for each woman were counted as one event. For statistical analysis, Pearson’s chi-square test in SPSS was used. Results: Of the 1200 patients, 708 (546 caucasian; CA and 172 African American; AA) satisfied the above criteria. Although the total number of biopsy events are essentially evenly distributed on either breast for either ethnicity, statistical analysis showed that post menopausal CA women have fewer biopsy events on the left breast (41%, n=264) than their pre-menopausal counterparts (52%, n = 282; p < 0.05); On the contrary, post-menopausal AA women have significantly more biopsy events on the left breast (62%, n=50) than their pre-menopausal counterparts (42%, n = 122; p = 0.02). Further analysis based on pathological diagnoses indicated that benign, pre-menopausal, AA patients have fewer events on the left breast (42%, n = 98) compared to CA (54%, n = 211; p < 0.05). Discussions: Despite the small sample size, the data nonetheless suggest that there are significant, menopausal status dependent, laterality imbalances of breast disease biopsy among CA and AA women. These differences await evaluation. No significant financial relationships to disclose.
A novel low molecular weight inhibitor of focal adhesion kinase and insulin-like growth factor-1 receptor, TAE226, inhibits glioma growth
Authors: Rich J. N. , Shi Q. , Hjelmeland A. B. , Keir S. T. , Wickman S. , Wu G. , Jackson D. , Ohmori O. , Bigner D. D. , Friedman H. S. 
Published: March 2020

11505 Background: Glioblastomas are highly lethal cancers that resist current therapies. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase overexpressed in glioblastoma patient specimens that may promote glioma growth and invasion by increasing cellular adhesion, migration, invasion, proliferation. TAE226 is a novel low molecular weight inhibitor of several kinases that demonstrates in vitro activity primarily against FAK with activity against insulin-like growth factor-1 receptor (IGF1R) at higher concentrations. Methods: As FAK and IGF1R are potential molecular targets in glioblastomas, we examined the efficacy of TAE226 against human glioma cell lines and xenografts. Results: TAE226 inhibited the activating phosphorylation of FAK at submicromolar concentrations with residue specific preference. Downstream effectors (Akt and ERK) were inhibited at slightly higher concentrations. TAE226 demonstrated a concentration-dependent decrease in cellular proliferation with an associated G2 cell cycle arrest in multiple glioma cell lines, whereas TAE226 potently induced apoptosis in a concentration-dependent manner in only one of four cell lines tested. TAE226 also induced a concentration-dependent decrease in cellular adhesion, migration, and invasion. In preliminary animal studies, a limited course of orally administered TAE226 (100 mg/kg qd 5 days on/2 days off/5 days) was well tolerated with minimal weight loss. TAE226 induced a modest growth delay of human glioma xenografts grown in a subcutaneous location in athymic mice (3 to 4 days delay, p < 0.001). In addition, mice bearing orthotopic intracranial human glioma xenografts demonstrated a modest increase in median survival (3.5 days, p = 0.078). Despite the modest degree of the tumor responses, these results are superior to other low molecular weight inhibitors, such as epidermal growth factor receptor (EGFR) inhibitors. As glioma xenografts often grow without invasion, these results may underestimate the efficacy of targeting FAK as FAK plays a major role in tumor invasion. Conclusion: TAE226 demonstrates modest activity as monotherapy against malignant gliomas and warrants further investigation, potentially in combination with other therapies. [Table: see text]
Post-operative concomitant radiochemotherapy in the treatment of primitive CNS high grade gliomas. A retrospective analysis
Authors: Costa P. , Braga F. , Sottomayor C. , Honavar M. , Resende M. , Romaõ H. , Teixeira J. 
Published: March 2020

11528 Background: The authors analyse retrospectively the impact on tumour control and toxicity of concomitant radiotherapy (RT) and Temozolomide (TMZ) in high grade gliomas (HGG) of the CNS, in patients treated in the Clínica de Radioterapia do Porto - Portugal. Methods: This cohort represents all patients with HGG treated between January 2002 and January 2006, with concomitant RT a median total dose of 60 Gy, 2 Gy per treatment given once daily 5-days/week and TMZ 75mg/m2 for 42 days, followed by adjuvant treatment with TMZ 5-days schedule every 28 days (150 mg/m2 for the first cycle increased to 200mg/m2). The cohort was retrospectively analyzed for gender distribution, age, extent of surgical resection, initial KPS, median overall survival (OS) and haematological toxicity. Results: 23 with HGG (6 females, 17 males) were treated with concomitant RT (44–72 Gy) and TMZ followed by adjuvant TMZ; median age was 58 (ranging from 17–72); median KPS was 80 (ranging from 40–90); 3 patients had complete resection, 17 partial resection and 3 biopsy. All patients except one, who had treatment interruption for thrombocytopenia, completed the concomitant phase of treatment; 19 patients continued to received adjuvant treatment with TMZ (median number of cycles was 5 (ranging from 1–20). Median OS (measured from the date of diagnosis to the date of death) was 20.4 month and 1 yr OS was 54%. During concomitant phase, one patient had grade 3–4 thrombocytopenia. During the adjuvant TMZ therapy 4 patients had grade 3–4 haematological toxicity (anaemia: 1; thrombocytopenia: 1; leucopoenia and thrombocytopenia: 2). Conclusions: The results of concomitant RT+TMZ followed by TMZ in these patients with HGG showed values in accordance with the latest data published on literature for this association. Differences observed might be due to the small sample size.RT+TMZ followed by adjuvant TMZ is a well tolerated treatment with better results in median OS comparatively with previous results of RT only treatment in HGG. Treatment related toxicity was within acceptable levels, and this approach became routine practice in this set of patients. No significant financial relationships to disclose.