bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of genetic variations in orobanche crenata using inter simple sequence repeat (ISSR) markers
Authors: Abdalla M. M. F. , Saleh Heba A. M. A. , Khater M. A. 
Published: August 2020

Abstract
Background
This recent investigation aimed to detect and characterize the genetic variabilities and genetic similarity in Orobanche crenata collected from naturally Orobanche-infested field at Gemmeiza Research Station, Agriculture Research Center (ARC), Egypt. Five different ISSR primers were used in this study.

Results
Obtained results showed that a huge genetic variation has been detected by these ISSR primers; moreover, there were clear relationship/genetic similarity between and within all collected O. crenata parasite plants. However, the results revealed that there were high relationships where similarity matrix ranged from 0.837 (the highest) between R4 and R17 followed by 0.831 for R4/R25 and in the end, the lowest one was R1/R29 similarity matrix 0.655.

Conclusions
It was noticed that the relationship and similarity did not reach 100% but the maximum was 83.7% (there were no identical plants); therefore, each Orobanche plant in this study was different genotype than neighboring plant within location.
Impact of omission of completion axillary lymph node dissection (cALND) or axillary radiotherapy (ax RT) in breast cancer patients with micrometastases (pN1mi) or isolated tumor cells (pN0[i+]) in the sentinel lymph node (SN): Results from the MIRROR study
Authors: Tjan-Heijnen V. C. , Pepels M. J. , de Boer M. , Borm G. F. , van Dijck J. A. , van Deurzen C. H. , Adang E. M. , Menke-Pluymers M. B. , van Diest P. J. , Bult P. 
Published: August 2020

CRA506 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. No significant financial relationships to disclose.
Chemotherapy induces microssatelite instability (MIS) in plasma free DNA (pfDNA), peripheral blood mononuclear fraction (PBMNF) cells, and urine free DNA (ufDNA) of breast cancer (BC) patients as well as in normal PBMNF cells in vitro in the absence of amifostine (A)
Authors: Del Giglio A. , Pinto J. F. , Fonseca F. A. , Marsicano S. R. , Delgado P. O. , Coelho P. G. , Sant’Anna A. L. , Maeda P. 
Published: August 2020

e11505 Background: We have previously shown that alkylating agent based chemotherapy regimens (AQT) could induce MIS in the PBMNF of BC patients in parallel to a decrease in the expression of the protein hMSH2 in these cells (Fonseca et al., 2005, Breast Cancer Res, 7, R28–32). Since plasma DNA derives mainly from tumor cells, we wanted to know if chemotherapy would also produce MIS in tumor DNA and if this phenomenon could be reproduced in vitro. Methods: 33 previously untreated female BC patients with a mean age of 51 years received AQT(16 ACT;3FAC;2 TAC;1FEC;10AC). Samples from 3 additional patients who received Fulvestrant only as neoadjuvant therapy were also included. Blood (pfDNA and PBMNNF) and urine (ufDNA) were evaluated at time 0,3 and 6 months with 6 MIS markers (BAT40,BAT26, MR2,TP53 PCR15.1, APC and ALU). Levels of fpDNA and fuDNA were measured by spectrophotometry. We incubated in vitro cultures of MCF- 7 cells and PBMNF cells with M at a dose of 0.7μg/ml for 30 minutes with and without A at 20% of the M dose and evaluated serially for 48 hours for MIS and hMH2 expression by immunohistochemistry. Results: We observed at least one MIS event in the PBMNF, fpDNA or fuDNA in 87%, 80% and 80% of the patients, respectively, mainly in BAT40 and BAT 26 markers. There was only 14.74% of concordance of MIS alterations between PBMNF and fpDNA and 8. 42% between fpDNA and fuDNA. Patients receiving Hormones also exhibited MIS. Interestingly, fpDNA levels increased significantly in patients with measurable disease who responded to therapy (47.4 ± 13.34 vs 14.37± 5.32; p = 0.021). In vitro, incubating MCF-7 cells and normal PBMNF cells with M ±A, we observed that we could induce MIS in both MCF-7 cells and normal PBMNF cells but A prevented MIS only in normal PBMNF cells. In normal PBMNF cells without A that sustained MIS there was a significantly decreased percentage of cells expressing hMSH2 ( 96% vs 57% p < 0.001). Conclusions: We conclude that Chemotherapy as well as Fulvestran can induce MIS in normal and malignant cells and that in vitro these effects could be reproduced by treatment with M and prevented in normal cells by A. No significant financial relationships to disclose.
A phase I study assessing the feasibility and safety of intraductal pegylated liposomal doxorubicin (PLD) in women with breast cancer
Authors: Jacobs L. K. , Khouri N. , Jeter S. , Powers P. , Rudek M. , Gabrielson E. , Zhang Z. , Sukumar S. , Tsangaris T. , Stearns V. 
Published: August 2020

e11506 Background: Most breast cancers originate in epithelial cells lining the breast ducts. Preclinical data suggest that intraductal administration of chemotherapy including PLD decrease tumor volume, prevent the development of new lesions, and eradicate pre-malignant disease. We initiated a clinical trial to determine the feasibility, safety, and maximum tolerated dose of PLD administered into one duct of women awaiting mastectomy. Methods: Women 18 or older awaiting mastectomy for breast cancer were eligible. Preoperative chemotherapy was allowed. T4 tumors, prior breast irradiation, or surgeries that may have altered the ductal system were excluded. Nipple aspiration and ductal cannulation were completed and the first 3 women received 5 mL of intraductal dextrose. PLD was administered to subsequent participants on a dose escalation schema based on preclinical pharmacokinetic and safety data. Serial doxorubicin (Dox) and doxorubicinol (Doxol) concentrations were determined in plasma by LC/MS/MS. At mastectomy (completed at least 2 weeks after intraductal administration of PLD), blue dye was injected into the treated duct and tissue was obtained for pharmacokinetic and biomarker analysis. Results: From 2/06 to 6/08, 14 women enrolled, and 12 underwent all study procedures. All dose levels up to 10 mg PLD per one duct were completed without serious adverse events. Median pain score was 0.9 (0–2.3). Intraductal PLD resulted in a dose-dependent increase in both systemic and local exposure to dox and doxol. Neither dox nor the metabolite was detected in the contralateral breast. Systemic exposure was lower than with conventionally administered PLD. Inflammatory changes were not observed on histopathological review of mastectomy specimens. Conclusions: We have established the logistics of intraductal administration of agents in an outpatient setting and it is feasible in women with and without prior chemotherapy. Biomarker data will be completed prior to the meeting. Future studies will evaluate other agents administered to one or more ducts. [Table: see text]
Potential economic impact of the 21-gene expression panel according to tumor (T) size in lymph-node-negative (LNN), estrogen-receptor (ER)-positive early breast cancer (BC)
Authors: Prisco F. E. , Saad E. D. , Carvalho F. M. , Ojopi E. B. , Bacchi C. E. 
Published: August 2020

e11518 Background: Use of the 21-gene panel may save costs in patients with LNN, ER-positive BC. Our previous analysis suggests that such would be the case in Brazil (SABCS 2008). However, the impact of the test may vary according to T size. Methods: Using a web-based survey with 30 (of a total of nearly 700) medical oncologists and literature data, we developed a model of direct medical expenses in two hypothetic cohorts (one without and one with access to the 21-gene panel) of Brazilian women with LNN, ER-positive BC, from the perspective of third-party payers. The questionnaire assessed patterns of care relating to chemotherapy (CT) regimens in each T size, type of premedication, use of G-CSF, and use of intravenous antibiotics for febrile neutropenia. Medication and 21-gene panel costs were the manufacturers’ recommended prices at the time of the survey. T size and recurrence score distributions followed those reported by Paik et al (NEJM 2004). CT use in the cohort with no access to the 21-gene panel was modeled according to the survey. In the cohort with access to the test, we assumed that patients with intermediate or high scores would receive CT, whereas patients with low score would not. Results: The table displays the number of patients receiving CT and the costs (CT, premedication, G-CSF, antibiotics, and the 21-gene panel) for two hypothetic cohorts of 100 patients. Conclusions: Our economic analysis suggests that the 21-gene panel overall would be cost-saving in Brazil, from the perspective of third-party payers. However, testing could actually increase direct medical costs in LNN, ER-positive T1 tumors, and decrease costs in T >2 cm. [Table: see text] [Table: see text]
Induction of primary systemic therapy by weekly paclitaxel: Predictive value of hormone receptors, HER-2, topoisomerase II- alpha, and other biological markers in relation to pathological complete response
Authors: Takao S. , Miyashita M. , Kohno N. , Wakita K. , Konishi M. , Kokufu I. , Yoshimura H. , Kasahara Y. , Kohno S. , Ienaga T. 
Published: August 2020

e11525 Background: Randomized phase II study of epirubicin(E) plus cyclophosphamide (C) vs. weekly paclitaxel (P) as primary systemic therapy (PST) in stage II and III breast cancer(BC) have shown that there was no significant difference in the pathological complete response (pCR) rate between the EC and P groups (#568 ASCO 2008). The aim of this study is to evaluate the predictive value of hormone receptors, HER2, topoisomerase IIα(TOP II) and other biological markers in the EC and P groups as PST. Methods: Tissue samples were obtained before PST from pts who were randomized to either Arm A (EC: E 75 mg/m2 and C 600 mg/m2 every 3 W for 4 cycles) or Arm B (weekly P: P 80 mg/m2 weekly for 12 w). Pts received PST for 12 w, then underwent surgery. All pts received a crossover regimen as adjuvant chemotherapy.The pretreatment expression of estrogen receptor (ER), progesterone receptor(PgR), HER2, P53, Ki67, P21 and CD31 were analized by immunohistochemical staining. The status of TOP II gene was evaluated by FISH. Results: One-hundred- sixty pts (Arm A: n=82, Arm B: n=78 ) were estimable. The pCR rates were 13.4% in Arm A and 17.9% in Arm B(p=0.43). In both arms, pCR rate was significantly higher for pts whose tumors did not express ER nor PgR(ER/PgR-) compared with the receptor positive(ER/PgR+) pts. Pts with HER2 positive tumors tend to have higher pCR rate in Arm B compared with Arm A (32.2% vs. 12.5%;p=0.11). The pCR rate for pts with HER2 negative BC were not different in both Arms(A:14.0% vs. B:8.5%). Pts with triple negative (TN) (ER/PgR, HER2-) BC achieved almost same pCR in both Arms (A:25.0% vs. B:23.1%). However, the pCR rate for pts with nonTN BC was significantly higher in ArmB compared to Arm A (16.9% vs. 8.6%, p<0.001). The deletion and amplification of TOP II gene were not predictive of higher pCR rate to ArmA than to Arm B. The pretreatment expression of P53, Ki67, P21 and CD31 was unlikely to predict the higher response of any Arm. Conclusions: Althogh valuable predictive factor of pCR were not detected between EC and weekly P group, the efficacy of weekly P therapy as PST were equal to EC therapy regardless of HR,HER2 and TOP II gene status. Therefore, induction of PST by weekly P therapy seems to be promising. No significant financial relationships to disclose.
Adjuvant paclitaxel, capecitabine, and trastuzumab for HER-positive breast cancer
Authors: Jouhadi H. , Benider A. 
Published: August 2020

e11526 Background: Anthracyclines are integral components of most adjuvant chemotherapy regimens for surgically removed early breast cancer and are central to the accepted treatment standards. Recently the standard anthracycline regimen of doxorubicin plus cyclophosphamide was found to be inferior in preventing recurrence of breast cancer when compared to cyclophosphamide and docetaxel, questioning the necessity to expose patients to the potential cardiotoxicity of anthracycline in the adjuvant setting. Trastuzumab, cornerstone of treatment of breast cancers that overexpress HER2 produces Unfortunately, in combination with anthracyclines a high incidence of cardiotoxicity as seen in early trials of metastatic breast cancer. The trastuzumab adjuvant trial 006 from the Breast Cancer International Research Group shows for the first time that a nonanthracycline-containing regimen with trastuzumab has equivalent efficacy in decreasing the recurrence of breast cancer, with less incidence of cardiotoxicity when compared to anthracycline-containing trastuzumab adjuvant regimens. Methods: Our trial compared two adjuvant schemas of adjuvant chemotherapy arm1: paclitaxel(day 1-day 21: 6 courses), capecitabine(day1 to day 14: 6 courses) and trastuzumab (day 1 to day 21 for one year). Arm2: 4AC plus 4 TH plus trastuzumab for one year. Inclusion criteria: HER positive invasive ductal carcinoma, no lymphe node invaded at axillary dissection and no metatstasis, Negative ER and PR receptors Goal of study: evaluate efficacy and cardiac toxicity Results: From 2004 to 2005: 30 patient were included in each arm. After 3 years: DFS was respectively 93% in first arm and 90% in Second arm Four women developed severe cardiac toxicity in arm 2 versus no one in arm1 Conclusions: There is no difference in efficacy between the two arms but a significant increase in cardiac toxicity in the second arm. No significant financial relationships to disclose.
Predictors of tumor shrinkage after anthracycline-based preoperative chemotherapy
Authors: Ermacora P. , Driol P. , Russo S. , Andreetta C. , Pisa F. E. , Alessi B. , Minisini A. M. , Mansutti M. , Fasola G. , Puglisi F. 
Published: August 2020

e11531 Background: Anthracyclines are currently included in several chemotherapy (CT) regimens for the treatment of breast cancer (BC). However, increasing evidence suggests that benefit from these agents is limited to some subgroups of patients (pts). Aim of this study was to identify potential predictors of tumor shrinkage (TS) in a retrospective series of pts receiving preoperative anthracycline-based CT for operable BC. Methods: The study population consisted of 94 pts with large (>2 cm), any N, operable BC treated with preoperative anthracycline-based CT. Association between clinico-biological factors and clinico-radiological TS (by caliper and MRI) was assessed. TS was calculated as the difference between the maximum tumor diameter at baseline and the maximum tumor diameter after preoperative CT/ the maximum tumor diameter at baseline x 100. Immunohistochemical analyses for biological variables (ER, PgR, HER2, MIB1, topoisomerase II alpha) were performed on pretreatment biopsies. Results: In univariate analysis, the following variables were associated with clinical TS: high MIB-1 [Odd ratio (OR) 2.6, p = 0.03], type of taxane (docetaxel vs paclitaxel: OR 0.3, p = 0.01) and number of cycles of CT (> 4 vs ≤ 4: OR 9.2, p < 0.0001). In multivariate analysis, number of cycles of CT was the only independent predictor of clinical TS (OR = 9.2, p = 0.05). In univariate analysis, the following variables were associated with MRI TS: high MIB-1 (OR 2.4, p = 0.06), tumor size (≥ 40 mm vs < 40 mm: OR 5.6, p 0 0.01), taxane CT (yes vs no: OR 4.3, p = 0.02) and number of cycles of CT (> 4 vs ≤ 4: OR 4.4, p = 0.002). In multivariate analysis, high MIB-1 was the only independent predictor of MRI TS (OR = 3.7, p = 0.03). Conclusions: High MIB-1 expression and number of cycles of chemotherapy significantly predicted tumor shrinkage in patients treated with preoperative anthracycline-based chemotherapy. Further studies are warranted to better identify patients who derive benefit from anthracyclines. No significant financial relationships to disclose.
The impact of residual cancer removed during subsequent surgeries on the outcome of patients with localized breast cancer
Authors: Kouzminova N. B. , Aggarwal A. , Aggarwal S. , Lin A. Y. 
Published: August 2020

e11533 Background: A close or positive margin after breast cancer surgery is an important risk factor for local recurrence. A significant percentage of breast cancer patients need additional surgeries to obtain clear margins. This study evaluated the impact of residual cancer (RC) found upon subsequent operations on the outcome of the patients with localized breast cancer. Methods: Under IRB approved protocol, we retrospectively analyzed data on 573 patients with stage I-IIIA breast cancer treated at our institution during 1994–2004. 202 patients had complete tumor removal at single procedure with clear margins, 319 patients had subsequent surgery due to initially compromised margins and 52 patients with compromised margins did not have second surgery. Cox Proportional Hazard regression test was performed to evaluate the effect of RC found on subsequent surgery on distant recurrence (DR) and disease specific survival (DSS). Results: Median follow-up was 5.4 years. Among 319 patients who underwent second surgery, 57.7% did not have any RC; 13.1% had in situ RC and 29.2% had invasive RC. 12.9% (74/573) patients had DR. The risk of DR was higher in patients with RC found upon second surgery compared to those who had single procedure breast cancer removal (22.6% vs. 9.9%; HR 2.4, 95% CI 1.3–4.4, p=0.006). Similarly, finding of RC was a significant predictor of DSS (80.6% vs.92.6%; HR 2.9, 95% CI 1.4–5.7, p=0.003). Multivariate analysis revealed that tumor size above 5 cm, lymph nodes involvement and grade III were significant predictors of DR and DSS along with invasive RC found during subsequent surgeries. Delay in adjuvant chemotherapy due to need for subsequent surgeries strongly correlated with earlier DR in patients with invasive RC found on subsequent operations (rS = - 0.55, p = 0.019, two-tailed). Conclusions: Invasive residual carcinoma found during subsequent surgery after initial compromised margin is an important prognostic factor for DR and DSS, even after clear margins are eventually achieved. No significant financial relationships to disclose.
Cost-effectiveness analysis of oncotype DX-guided treatment in early breast cancer
Authors: Tsoi D. T. , Inoue M. , Kelly C. M. , Verma S. , Pritchard K. 
Published: August 2020

e11536 Background: Some early breast cancer patients with hormone receptor positive (HR+) disease may benefit from adjuvant chemotherapy in addition to hormonal therapy. Most guidelines recommend the addition of adjuvant chemotherapy for majority of women, leading to overtreatment causing considerable morbidity and cost. There has been recent incorporation of gene expression analysis to help aid in adjuvant chemotherapy decision making. We evaluated the cost-effectiveness of Oncotype DX-guided treatment as compared to treatment guided by Adjuvant! Online program. Methods: A Markov model was developed to compare the cost- effectiveness of treatment guided by either Oncotype DX or Adjuvant! Online in a cohort of 50-year-old women with HR+, lymph node negative breast cancer over a lifetime horizon. We assumed women assessed to be high risk all received chemotherapy followed by tamoxifen, and that those assessed to be low risk received tamoxifen only. The model took a health care payer's perspective with results reported in 2008 Canadian dollars ($). Event rates, costs and utilities were derived from the literature. Both costs and benefits were discounted at 5%. Sensitivity analysis for key parameters in the model was conducted. Outcome measures were life year gained, quality- adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Results: For a 50-year-old woman, Oncotype DX-guided treatment was associated with an incremental lifetime cost of $4,200 and a gain in 0.067 QALY, with an ICER of $61,800/QALY compared with treatment guided by Adjuvant! ICER was positively correlated to the cost of Oncotype DX and the age of patients. Results were most sensitive to probabilities relating to risk categorization and recurrence rate. Conclusions: Relative to Adjuvant!-guided treatment, Oncotype DX-guided treatment appears cost-effective with an ICER of $61,800/QALY from a Canadian health care perspective. [Table: see text]
Predictors of pathologic response to preoperative chemotherapy and concurrent radiotherapy for locally advanced breast cancer
Authors: Venkitaraman R. , Ramanan S. G. , Rajalekshmy K. R. , Sagar T. G. , Shanta V. 
Published: August 2020

e11545 Background: Combined modality treatment is essential for acheiving optimal results in the management of locally advanced breast cancer (LABC). Neoadjuvant chemoradiotherapy is considered a promising approach for LABC. Pathologic complete response to neoadjuvant treatment for LABC predicts prolonged survival. Aim: To determine the rate of pathologic complete response (pCR) after neoadjuvant chemotherapy and radiotherapy for locally advanced breast cancer and to identify the predictors of pCR. Methods: Female patients with noninflammatory LABC received neo-adjuvant chemotherapy with concurrent radiotherapy, and then underwent mastectomy and axillary clearance. The pathologic response was analysed with respect to the baseline clinical factors and the receptor status on immunohistochemical studies of the initial biopsy specimen. Results: Of the 296 patients included in the study, 286 underwent mastectomy. Ninety-two (31 %) patients achieved a pCR. The significant predictor of a pCR was Oestrogen receptor negative status (p = 0.025), while progesterone receptor negative status (p=0.069 ), HER2 status (p= 0.62), age (p= 0.074), stage (p=0.6), grade (p=0.86), type of chemotherapy (p=0.37) and number of cycles of chemotherapy (p = 0.23) did not predict for pathologic response. Clinical complete response predicted for a pathologic complete response (p=0.0001). Conclusions: Neoadjuvant concurrent chemoradiotherapy results in good pathologic complete response rates in LABC. High pathologic compete response rates are achieved in patients with endocrine receptor negative disease, with neoadjuvant chemoradiotherapy, which might result in improved outcome in this high risk subset of patients. No significant financial relationships to disclose.