bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic role of c-met tyrosine kinase receptor expression in breast carcinoma
Authors: Gisterek I. , Matkowski R. , Suder E. , Lacko A. , Ramsey D. , Szelachowska J. , Kornafel J. 
Published: March 2020

10552 Background: Hepatocyte growth factor is a pleotropic growth factor that regulates cell proliferation, survival, tumor angiogenesis and metastasis. Its biological effects are mediated through interaction with its receptor: c-met protein.In this study, we evaluated c-met expression in the homogenous group of 99 patients diagnosed with stage II ductal breast carcinomas (G2, G3). We analyzed 5 and 10-years overall (OS) and disease free survival (DFS). Methods: Microscopic studies were performed on formalin-fixed, paraffin-embedded tumor tissue, obtained during surgery and stained routinely with haematoxylin and eosin. Expression of c-met was evaluated using a standard immunoperoxidase technique and percentage of cells with protein expression was counted. Survival was estimated using Kaplan-Meier method. Results: The expression of c-met was found in 37 (37.37%) tumors, with the strong expression of c-met observed only in 7 (7.07%) specimens. The 5-year DFS in patients with overexpression of c-met was statistically significantly worse (p =0.00493) compared with the group with low or no expression (recurrent rates: 57.14% vs 20.65%). Also with a time horizon of 10 years, high values of c-met expression were associated with the higher rate of recurrences (71.43% vs 30.77%, p = 0.01351). The 5-years OS rate in patients with c-met overexpression was 71.43% compared with 84.78% in the group with low or no expression, but this result did not reach statistical significance (p = 0.30345). Comparable tendency was seen in 10-years OS, which was 42.86% in patients with overexpression and 73.63% with low or no expression (p = 0.06154). Conclusions: The results of the study suggest that c-met overexpression is associated with shorter disease-free survival and it may be a useful prognostic indicator of more aggressive disease in patients with breast carcinoma. No significant financial relationships to disclose.
Screening mammography in old women saves lives: A simulation model
Authors: Barrajon E. , Lopez A. , Adrover E. 
Published: March 2020

10561 Background: Screening mammography has shown to decrease breast cancer specific death rate by 20–25% and has been recommended in women aged 40 and above, nevertheless, some country service screen programs stop screening in women older than 69, even though the sensitivity and specificity of screening mammography is highest in older women, especially those older than 80 years. The size of the older population is growing exponentially and old women have the highest incidence of breast cancer; one third of breast cancer diagnosis and half the deaths of breast cancer in USA occurred in women aged 70 and above in the year 2000. The aim of this study is to estimate the impact of mammographic screening in women aged 70 and above on breast cancer mortality. Methods: US Census, SEER, CISNET, CDC, HMD, ULTD databases were searched to obtain population data and rates of incidence and mortality of breast cancer by age. In addition, mammography screening bibliography from randomized clinical trials, meta-analysis, and service health programs publications were reviewed to estimate the impact of screening mammography on results for different strata. Analytical and simulation methods were applied for modeling the data with the aid of Mathematica to calculate breast cancer reduction rate. Results: A reduction in breast cancer mortality was observed with a magnitude proportional to age, even after taking into account competing risks of death by other causes in the aging population. Simulation of different scenarios revealed a decrease in breast cancer mortality in the range of 5 to15% for women younger than 50 years, 15 to 25% in the group of women aged 50 to 69, and 25 to 35% in women older than 69. Factors such as population life expectancy, breast cancer incidence, attrition rate in screening or cross-over, overall specificity of mammographic detection, interval of screening, impact the estimations, explaining in part some of the negative results of prevention trials. Conclusions: Reduction of breast cancer mortality by mammographic screening is proportional to age. Women aged 70 and above benefit more from mammographic screening than younger women. No significant financial relationships to disclose.
Phase I study to determine the safety of oral administration of TAS-102 on a twice daily (BID) schedule for five days a week (wk) followed by two days rest for two wks, every (Q) four wks in patients (pts) with metastatic breast cancer (MBC)
Authors: Green M. C. , Pusztai L. , Theriault R. L. , Adinin R. B. , Hofweber M. , Fukushima M. , Mita A. , Bindra N. , Hortobagyi G. N. 
Published: March 2020

10576 Background: TAS-102 is an oral combination of 5-trifluorothymidine (FTD) and a thymidine phosphorylase (TP) inhibitor. FTD is an antineoplastic antimetabolite that causes DNA-fragmentation after passive incorporation into DNA. The TP inhibitor prevents degradation of FTD when orally administered. This agent is active against many tumor cell lines including breast cancer. In animal studies, the use of divided daily dosing of TAS-102 has resulted in increased FTD incorporation into tumor DNA. This study was conducted to determine the phase II dose and the dose limiting toxicity (DLT) of TAS-102 in pts with solid tumors/MBC. Methods: Pts with MBC refractory to standard therapy (tx) or for whom no standard tx existed were eligible to participate on study. Pts with either measurable or evaluable MBC were enrolled at an initial dose level of 80 mg/m2/day given in divided doses BID days 1–5 of 7 days for 2 wks q 4 wks with standard 3+3 design. DLT was defined as any of the following in cycle 1 a. ≥ grade (gr) 3 non-hematologic toxicity (excluding nausea/vomiting); b. inability to take ≥ 75% of planned study dose per cycle; c. gr 4 granulocytopenia (GCP) lasting ≥ 3 days or febrile ≥ gr 3 GCP of any duration or gr 4 thrombocytopenia (TCP); d. > 1 week delay in administration of the next scheduled dose. Evaluation of response was conducted every 8 wks. The recommended phase II dose was defined as the highest dose level that did not cause a DLT in 1/3 or more pts in that cohort. Results: 19 pts with MBC (median age: 56; median prior tx: 4) received tx with TAS-102. A median of 2 cycles were received (range 1–24) with one pt still on study. The initial starting dose resulted in DLT in 2/3 pts. Two additional dose levels were studied. The main cycle 1 toxicities were gr 3–4 GCP in 11/19 pts; gr 4 TCP in 1/19 pt. Other grade 3–4 toxicities were rare with minimal alopecia. The recommended phase II dose was determined to be 50 mg/m2/day given in divided doses BID days 1–5 of 7 days for 2 wks q 4 wks. Clinical activity was seen including prolonged disease control (> 12 weeks) in 7 pts. Conclusions: TAS-102 given BID as described is an active agent against heavily pretreated MBC with primarily hematologic toxicity. [Table: see text]
Hepatic intra-arterial infusion (HAI) for liver metastases in pretreated metastatic breast cancer patients
Authors: Zanon C. , Airoldi M. , Pedani F. 
Published: March 2020

10579 Background: Breast cancer patients (pts) with liver metastases have a poor prognosis. HAI has been frequently used for liver metastases from colorectal cancer, with better response and possibly survival than with intravenous administration. We evaluated the activity of HAI in pretreated breast cancer patients with liver metastases only. Methods: From December 2001 to October 2005 thirty patients previously treated with anthracyclines, taxanes and vinorelbine were enrolled. Median age 58 years (44–68) and median PS 1 (0–2). Eight patients (27%) had 5 or more liver nodes, seventeen (57%) had 5 to 10 metastases and five (16%) more than 10 nodes. Eighteen patients received 2 previous lines of chemotherapy (67 %), eleven 3 lines (30%) and one (3%) three lines and one cicle of high dose chemotherapy followed by ABMT. Seventeen pts received prior hormonotherapy. Two patients had been submitted to liver metastasectomy. Patients underwent percutaneous implantation of an arterial hepatic port-a-cath. HAI regimen administered on days 1–3 every 4 weeks, consisted of cisplatin 10 mg/sqm bid, mitomycin-C 1 mg/sqm bid, 5-fluorouracil 1000 mg/sqm 72 hours continuous infusion. Results: On an intent-to-treat analysis, four pts had CR (13%) with a duration of responses of 12, 18, 24 and 36 months. Fourteen pts (47%) had PR with a median duration of 7 months. Six patients had stable disease (20%) with a median duration of 3 months. Six patients (20%) had PD. Responses were more frequent in patients with PS 0 (10/13, 77%) and in patients treated with 2 previous lines of chemotherapy (13/18, 72%) than 3 or more (5/12, 42%). Median survival for the whole population was 11.8 months (5–44; 95% CI, 10.0 to 13.9). For pts with CR or PR and those who had SD, median survival was 16 months (10–44) and 10 months (8–18), respectively. No treatment-related death occurred. Grade 3–4 neutropenia in 7 % of pts. Grade 4 thrombocytopenia and grade 3 anemia 3 % of patients. Most frequent G3 non-haematologic toxicities were nausea and vomiting (3%) and alopecia (3%). We observed 2 dislodgements of catheter (7%), 3 cases (10%) of gastroduodenal ulcers, neither cases of thrombosis, nor sclerosing cholangitis. Conclusions: This intra-arterial regimen seems active in this patient population, with a very good safety profile. No significant financial relationships to disclose.
Paclitaxel, carboplatin and trastuzumab (TCH) achieves high pathological complete remission rate after in vivo response directed 2–4 cycles of doxorubicin and cyclophosphamide (AC) in breast cancer patients
Authors: Mehta R. S. , Schubbert T. , Kong K. 
Published: March 2020

10583 Background: A pathological complete remission (pCR) predicts improved survival in breast cancer (BC). Treatment with AC followed by concurrent TCH improved pCR rates to 87.5% in Her2 positive 8-patient pilot study (SABCS 2004, abs #1110), confirmed by a subsequent phase II study. We hypothesized that response adjusted AC (2–4 cycles), TCH (3–4 cycles) sequence targets topoisomerase II alpha amplified and deleted clone, respectively (SABCS 2005, abs # 5056). We report here the combined analysis of the Her2 positive (fluorescence in situ hybridization + or immunohistochemistry 3+) subset of these studies. Material and Methods: Thirty-one patients with stage IIB-IV BC were accrued. Twenty-eight of 31 patients received AC in a dose dense manner with GM-CSF support. Patients received carboplatin calculated at AUC of 2 and paclitaxel at 80 mg/m2 for 3 weeks followed by 1 week of rest (1 cycle) for a maximum of 4 cycles. Concurrent trastuzumab 4 mg/kg loading dose, then 2 mg/kg/wk was administered for 12–16 weeks. Results: Twenty-nine of 31(94%, CI, 0.79–1) patients showed a clinical complete or partial response (cCR, or cPR). Nineteen of 27 patients (70%, CI, 0.50–0.86) achieved a pCR at surgery; two additional patients had ≤3 mm residual invasive cancer; and lymph node negativity rate was 73%. Of the 3 additional patients with cCR, 1died (underlying cirrhosis), 1 refused surgery, and 1 awaits surgery. A fourth patient with cPR awaits surgery. Ninety percent of the patients (28/31, CI, 0.74–0.98) are alive, and 77% (24/31, CI, 0.59–0. 90) are progression free at median follow up of 19 months (range 6–35 months). Median ejection fraction by echocardiogram was 60% (range 50–74); no patient had clinical cardiac dysfunction. One patient each on GM-CSF and peg-GCSF developed neutropenic fever. Conclusion: Short course of TCH following response adjusted 2–4 cycles of AC will have an improved therapeutic ratio with minimum cardiac toxicity and maximal response. [Table: see text] [Table: see text]
Quality assurance in surgical trials of new techniques
Authors: Mansel R. E. , McNeill F. 
Published: March 2020

10584 Most surgical trials include quality assurance for data and documentation, but the variable of surgical performance is often ignored, even when new techniques form one arm of the trial. Recent trials of sentinel node biopsy (NSABP-B32, ALMANAC, and AMAROS) have have attempted to control this variable by pre randomisation audit of surgical performance, but logistics and cost have limited this approach. The B-32 and ALMANAC trials did show that defined and validated pre trial audits produced high rates for localisation of the sentinel node (>95%) and false negative rates of <10%. However these results from motivated trial surgeons/teams may not be reproduced when the techniques are rolled out for general use. In the UK participation in the NEW START national training programme has been endorsed by the Health Department as evidence of satisfactory training in sentinel node biopsy. Surgeons and their teams attend a standardised theory session backed up with detailed training material on DVD. Then a training team visits with the surgical team and supervises the first 5 procedures performed by the surgeon in his own OR, after which a further 25 procedures with completion ALND are performed. All these data are evaluated prospectively centrally. A performance standard of >90% localisation rate and <10% false negative was set prospectively to determine if the surgeon is eligible for certification. The programme is currently achieving 98% localisation and <5% false negative rates in surgeons who have never performed the procedure previously, and 50% of breast surgeons in England have attended the theoretical module of the training. These data suggest that surgical trials involving new techniques should be preceeded by training and individual surgeon audit prior to randomising patients. Abbreviations OR = Operating Room ALND = Axillary Lymph Node Dissection. No significant financial relationships to disclose.
Optimal tolerance of an all-oral combination chemotherapy (CT) of oral vinorelbine (NVBo), capecitabine (C) with/without trastuzumab (T) in metastatic breast cancer (MBC) patients (pts): Safety Results of two international multicenter studies
Authors: Chan A. , Tubiana N. , Ganju V. , Conte P. , Bougnoux P. , Aubert D. , Bourlard T. , Becquart D. 
Published: March 2020

10607 Background: Combination therapy of T and Vinorelbine has recently been reported to be an active and safe regimen for HER2 positive MBC pts. The current safety analysis investigated NBVo and C, which offers the convenience of an all-oral regimen given alone or in combination with T, if pts were HER2 positive, as first-line therapy for MBC patients, KPS ≥ 70%. Methods: In the HER2 negative study ([A]) (IHC 0- 2+/FISH−) 38 pts received: NVBo 60 mg/m2 (Cycle 1) or 80 mg/m2 (from Cycle 2) D1 & D8 and C 2000 (1500 if ≥ 65 y) mg/m2/d D1-D14 every 3 weeks. In the HER2 positive study ([B]) (IHC 2+ or 3+ confirmed by FISH+) 25 pts received : NVBo, and C at the same doses as [A] + T, 4 mg/kg on D 1 as loading dose and then 2 mg/kg i.v. weekly starting on D8. Treatment was continued in both studies till progression. Results: Median age: [A] 61.5y (17 pts ≥ 65 y), [B] 53.0 y (5 pts ≥ 65 y); Prior (neo)adjuvant CT: [A] 21 pts (55.3%), [B] 16 pts (64%); Visceral involvement: [A] 28 pts (73.7%), [B] 22 pts (88%); > 2 metastases: [A] 15 pts (39.5%), [B] 10 pts (40%); Median dose intensity (%): NVBo [A] 45.1 mg/m2/w (90.5%), [B] 39.5 mg/m2/w (75.7%); C [A] 7733 mg/m2/w (87%), [B] 7140 mg/m2/w (83.7%); T [B] 2.1 mg/kg/w (98.1%). NVBo dose escalation to 80 mg/ m2: [A] 33 pts (94.3%), [B] 23 pts (92%). Tolerance: ([A] n = 38 pts, [B] n = 25 pts) (% of pts with G3/4 NCI CTC v2): Neutropenia [A] 29/16, [B] 52/16; Infection with G3/4 neutropenia [A] 3/3, [B] 8/0; Stomatitis [A] 5/3, [B] 0/4; Bilirubin [A] 3/0, [B] 0/0; HF Syndrome [A] 3/0, [B] 8/0; Nausea [A] 3/0, [B] 0/4; Vomiting [A] 10/0, [B] 4/4; Diarrhoea [A] 5/0, [B] 12/4; Ileus [A] 0/0, [B] 4/0; Febrile Neutropenia: [A] 5%, [B] 8%. Efficacy: the preliminary results on the evaluable pts confirm an optimal disease control (CR + PR + SD): [A] 25/27 pts (92.6%), [B] 22/24 pts (91.7%). Conclusion: The combination of NVBo and C can be safely administered in the palliative setting of MBC and calls for further comparative studies vs i.v. combinations. The addition of T in HER2 positive patients does not alter the favourable safety profile. [Table: see text]
Usage trends of minimally absorbed vaginal estrogens in breast cancer patients versus patients with non-breast malignancies
Authors: Castiel M. , Masakhalia S. , Krychman M. , Stier B. , Amsterdam A. , Gemignani M. , Kauff N. 
Published: March 2020

10620 Background: To determine if differences exist in the use of minimally absorbed vaginal estrogens in a breast cancer population versus one with non-breast malignancies. Methods: A retrospective review of all patients with documented malignancy who were prescribed vaginal 17-β-estradiol tablets (Vagifem, Novo-Disc, Princeton, New Jersey) through the General Gynecology Service from July 1, 2003 to June 30, 2004. Data were accessed from the pharmacy health information computerized system. All patients complained of dyspareunia, and examination was consistent with vaginal atrophy. Comparison between groups was performed using the Fisher Exact Test and t-test. Results: 152 patients were identified_81 patients with breast cancer diagnoses and 71 with non-breast malignancies. There was no difference in the mean age of patients in either group, 56.9 vs. 55.1 years. (p = 0.30). Overall, 60 of the 152 patients refilled their prescriptions through the time of last follow-up. There was no difference in the proportion of breast versus non-breast cancer patients who continued vaginal estradiol, 39.5% (32/81) versus 39.4% (28/71) respectively. When the cohorts were stratified by age ≤ 50 or >50 at the time of initial consultation, 79% (11/14) of breast cancer patients age ≤ 50 years refilled their prescriptions at follow-up compared to 31.3% (21/67) of patients >50 (p = 0.002). In women with non-breast malignancies there was no age-related difference in the proportion who obtained refills: 35% (7/20) ≤ 50 years versus 41.2 % (21/51) >50 years (p = 0.79). Conclusions: Minimally absorbed vaginal estrogens appear to be viewed favorably amongst the younger breast cancer patient population. The older breast cancer population does not appear to continue vaginal estradiol use long-term. This may be due to differences in relationship status, interval from menopause to diagnosis, prior exposure to estrogen, or relief of symptoms with alternative therapies. These findings are different than those observed for similar patients with non-breast malignancies. Further studies looking at the use of minimally absorbed vaginal estrogens are needed to further evaluate the usage trends in differing patient populations. No significant financial relationships to disclose.
Expression of critical genes used as prognostic biomarkers and DNA damage in lymphocytes from breast cancer patients
Authors: Franke F. , Agnoletto M. , Saffi J. , Guecheva T. 
Published: March 2020

10641 Breast cancer is the most common malignancy among women and its rate of mortality is still high. The increase knowledge of breast cancer biology is heaving great impact on determining the clinical prognosis and response to treatment. Impaired DNA repair may elevate the risk of malignant transformation of breast cells due to the accumulation of spontaneous mutations in target genes and increasing susceptibility to exogenous carcinogens. The present study was designed to evaluate the relationship between DNA damage and expression of some critical genes including TP53, c-ERBB2, ER (Estrogen Receptor) and PR (Progesterone Receptor) in breast cancer. Blood samples were obtained from female patients with diagnosed breast cancer before chemotherapy as well as from healthy individuals, and were processed in 24 hours. To evaluate the role of DNA repair in breast cancer we determined the level of DNA damage and the capacity to remove DNA damage induced by hydrogen peroxide in the peripheral blood lymphocytes. For this purpose the alkaline version of the comet assay, which provides a sensitive tool to investigate DNA damage and repair, was applied. The level of basal DNA damage was higher in breast cancer patients compared to the control group. Considerable inter-individual variations of DNA damage and repair in breast cancer patients were observed both before and after the treatment. The correlation between DNA damage in peripheral blood and expression of p53, c-erbB-2, PR and ER was analyzed. This preliminary study indicates that the DNA damage accumulation, observed in peripheral blood lymphocytes of breast cancer patients in early stages, could be attributed to impaired DNA repair. Our results suggest that DNA damage, as evaluated by the comet assay, seems to be useful molecular biomarker for monitoring ongoing exposures to DNA damaging agents. Such a research on the mutagen sensitivity and efficacy of DNA repair could impact on the development of new diagnostic and screening strategies. Work Supported by FAPERGS and GENOTOX (UFRGS). No significant financial relationships to disclose.
Benefits of zoledronic acid compared with placebo in breast cancer patients with bone metastases based on analysis of pain, analgesic use, and performance status
Authors: Aogi K. , Kohno N. , Minami H. , Takashima S. 
Published: March 2020

10653 Background: We previously reported that zoledronic acid significantly reduced skeletal complications by 39% compared with placebo in breast cancer (BC) patients with bone metastases in a multicenter randomized trial conducted in Japan. To assess the effect of zoledronic acid in the maintenance of patient’s mobility or autonomy, we conducted a retrospective analysis of pain, analgesic use, and performance status (PS) among patients of this trial. Methods: 228 women with bone metastases were randomized to 4 mg zoledronic acid (n = 114) or placebo (n = 114) every 4 weeks for 1 year. At baseline and every 4 weeks during treatment, pain scores were assessed using the Brief Pain Inventory (BPI) on a scale of 0 to 10, and analgesic use was scored on a 4-point scale from none (0) to strong narcotics such as morphine (4). Eastern Cooperative Oncology Group (ECOG) PS was assessed at baseline and at study end. Results: Unlike patients receiving placebo who’s pain scores increased, patients treated with zoledronic acid had a significant decrease from baseline BPI composite pain score from week 4 to week 52: mean decrease of 0.86 in the zoledronic acid group at week 52 versus a mean increase of 0.62 in the placebo group; P < .05. Patients treated with zoledronic acid had very little change in analgesic scores, whereas patients in the placebo group had a mean increase in analgesic score (approximately 0.5) by study end. Shift table analysis of ECOG PS showed that 61% of patients in the zoledronic acid group had no change in PS, and 28% had worsening of ECOG PS of at least 1 grade from baseline to study end. In comparison, 54% of patients in the placebo group had no change in PS, and 36% had worsening of PS. Approximately 10% of patients in both treatment groups had an improvement in PS. Conclusions: This analysis shows that treatment with zoledronic acid reduced pain and prevented a worsening of ECOG PS in a larger percentage of patients compared with placebo, consistent with the demonstrated reduction in the rate of skeletal complications. This suggests that zoledronic acid may improve quality of life and maintain autonomy and mobility in breast cancer patients with bone metastases. No significant financial relationships to disclose.