bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zoledronic acid (ZOL) treatment (Rx) of ≥2 years in patients (pts) with metastatic bone disease (MBD) or multiple myeloma (MM): Six-month results from the LOTUZ study
Authors: Duck L. , Delforge M. , Doyan C. , Wildiers H. , MacDonald K. , Lechat I. , Abraham I. 
Published: August 2020

9630 Background: The bisphosphonate (BP) ZOL is frequently used to prevent skeletal-related events (SRE) in cancer pts. However, data are limited on its use beyond 2 years. LOTUZ is among the first studies to examine Rx and outcomes in pts with ZOL Rx for >2y. We report 6-month results. Methods: Prospective (18m), multicenter (50), pharmacoepidemiologic study. Baseline (0m) and 6m data available on 205 pts (of 298 enrolled), all free from osteonecrosis of the jaw (ONJ) at 0m. Prior to ZOL Rx, 27.8% had non-ZOL BP Rx. Mean pre-enrollment BP duration was 42 mo (23–145) with 38 mo (23–80) for ZOL. Results: Mean age: 64 y (38–88); M/F: 29/71%; 67.8% with MBD vs 32.2% MM. 89.3% continued ZOL RX 0–6m; 90% with dose 4mg. From 0–6m, 10 pts (4.8%) developed ONJ (4 with MM, 6 with MBD): 5 mild, 3 moderate, 2 severe (median BP duration: 38.4, 46.5, and 34.8 months, respectively). Five pts with ONJ continued on ZOL RX 0–6m (3 mild, 2 moderate). 4/10 pts with ONJ had baseline dental conditions or procedures, 8/10 at 6m (only 1/10 at neither). SREs and pain levels remained constant 0–6m compared to 6m prior to baseline (see Table ). Conclusions: Beyond 2y, 90% of pts were continued on ZOL. SREs did not increase, but ONJ was diagnosed in 10/205 pts 0–6m, of which 5 were on ZOL RX beyond 24m. Long-term data are needed to better understand the risk/benefit of long-term ZOL Rx. [Table: see text] [Table: see text]
Placebo and nocebo effects in randomized double-blind clinical trials for fatigue in advanced cancer patients
Authors: de la Cruz M. , Hui D. , Parsons H. A. , Lynn P. , Parker C. , Urbauer D. , Bruera E. 
Published: August 2020

9640 Background: We have previously reported significant placebo response in randomized controlled treatment trials for cancer related fatigue (CRF). We conducted a retrospective study to determine the frequency and predictors of response to placebo and nocebo effect in patients with CRF. Methods: We reviewed patients that received placebo in two previous randomized clinical trials conducted by our group and determined the proportion of patients who demonstrated clinical response to fatigue using an increase (ΔFACIT-F score) > 7 from baseline to day 8, and those with nocebo response as those who reported side effects. Baseline patient characteristics and symptoms recorded from the Edmonton Symptom Assessment Scale (ESAS) were analyzed to determine their association with placebo and nocebo effects. Results: A total of 105 advanced cancer patients received placebo. 59 (56%) patients responded to placebo (median Δ FACIT-F score of 22). Worse baseline anxiety and well-being subscale score (univariate) and well-being (multivariate, MR) were significantly associated with placebo response. Common side effects reported were insomnia (79%), anorexia (53%), nausea (38%) and restlessness (34%). MR analysis showed that worse baseline (ESAS) sleep, appetite, nausea, and restless are associated with increased reporting of these side effects ( Table ). Conclusions: Nearly half of advanced cancer patients enrolled in the fatigue trials responded to placebo. Worse physical well-being score was associated with placebo response. Patients experiencing specific symptoms at baseline were more likely to report these as side effects of the medication. These findings should be considered in fatigue clinical trial design. [Table: see text] No significant financial relationships to disclose.
TAC (docetaxel, doxorubicin, and cyclophosphamide) adjuvant chemotherapy supported by G-CSF without dose-reduction in node-positive breast cancer
Authors: Suh Y. , Oh S. , Song B. , Jung S. 
Published: August 2020

e11606 Background: For node-positive breast cancer, TAC (Docetaxel-Doxorubicin-Cyclophosphamide) chemotherapy is preferred as an adjuvant treatment. However, due to its high toxicity profiles such as severe neutropenia, TAC is a lot beyond enthusiasm. G-CSF support or even prophylaxis has been recommended to help patients recover from nadir, along with some dose-reduction schedule. We tried to evaluate whether TAC with G-CSF support from day 5 can be sustained without dose reduction in women under 69-years old. Methods: After getting IRB approval, between Mar. 2005 and Oct. 2008, 61 node-positive breast cancer patients (33 - 69 years old) had underwent TAC chemotherapy as an adjuvant treatment after curative resection after getting informed consent. Total of 366 cycles (6 cycles per patient, 75–50–500 mg/m2)were completed, G-CSF support was initiated from day 5 to full neutrophil recovery. In case of neutropenia, prophylactic antibiotics (cefoperazone 2 g and tobramycin 200 mg iv) were given. Results: Among 366 cycles, not a single cycle should be delayed to recover from any hematologic shortcomings such as neutropenia, anemia or thrombocytopenia. Interval of three weeks between each cycle could be maintained. No other problem happened for any patient to stop or postpone scheduled chemotherapy. None of antibiotics except prophylaxis with cefoperazone and tobramycin was needed. Conclusions: Maximum tolerable dose of chemotherapeutic agents should be given to patients to get the best oncologic outcome to fight against cancer. It is evident that huge scale prospective clinical trials can answer this question, but we presume that node-positive breast cancer patients between in her fourth and seventh decade can stand TAC chemotherapy with G-CSF support without dose reduction as routine. No significant financial relationships to disclose.
Treatment of early breast cancer (EBC): A long-term follow-up study—GOCS experience
Authors: Iturbe J. , Zwenger A. , Lacava J. A. , Perez Verdera P. , Vallejo C. , Romero A. , Leone J. P. , Perez J. , Maccihavelli M. , Leone B. 
Published: August 2020

e11610 Background: Most cases of breast cancer are diagnosed at early stage of disease, therefore treatment is oriented to increase the relapse-free survival (RFS) and overall survival (OS). The prognosis, in comparison to other malignancies, has improved in the last decades as a result of mammographic screening. The objective of this study was to evaluate the incidence of local and distant recurrence, RFS and OS in women with EBC. Methods: From 01/1978 to 12/2004, 929 women with EBC were identified, 350 were stage I and 579 stage II (AJCC 2002). RFS was analyzed from the date of initial diagnosis to the date of local or distant recurrence. OS was estimated from the date of initial diagnosis to the last follow-up or date of death. Multivariate regression analyses were carried out using proportional hazard model proposed by Cox. RFS and OS were evaluated by the product-limit method of Kaplan and Meier, and differences between curves were assessed by means of log-rank test. Results: Median age was 51 years (28–92). Conservative surgery was performed in 69.7% of patients (pts). The median number of nodes examined was 17. Hormone receptors were ER+ in 65% and PR+ in 62% of pts. Adjuvant radiation therapy was administered to 73% of pts, whereas adjuvant chemotherapy to 29% and adjuvant hormone therapy to 18.5% of cases. Combined chemotherapy and hormone therapy was given to 34% of women. The median follow-up was 8.4 years (0.3–30). Local recurrence was documented in 37 pts (3.8%) whereas 269 developed metastatic disease (29%). Bilateral breast cancer was seen in 102 cases (10.9%) and 91 pts (9.7%) developed 2nd malignancies. RFS rate at 5, 10, 15, 20 and 25 years was 71%, 67%, 65%, 65% and 64% respectively. OS at 5, 10, 15, 20 and 25 years was 82%, 62%, 49%, 39% and 28% respectively. Factors that had an effect in OS demonstrated by the multivariate regression analysis were: histologic grade, tumor size, ER status, vascular and nodal involvement (p < 0.001). Conclusions: Clinical outcomes in EBC in our experience are similar to that reported in international literature. This group of pts continues to have a good prognosis as shown by the OS rate at 5, 10, 15, 20 and 25 years, although high percentage of pts continue to have recurrence and die from breast cancer after 5, 10, 15, 20 and 25 years of follow-up. No significant financial relationships to disclose.
Outcome of operable breast cancer with triple negative phenotype
Authors: Izarzugaza Y. , Khosravi-Shahi P. , Soria Lovelle A. , Pérez Manga G. 
Published: August 2020

e11621 Background: Breast cancer(BC)is the most frequent neoplasm in women. Triple negative phenotype(TNP)is characterized by lack of expression of estrogen receptor(ER),progesterone receptor(PgR) and Her-2, and it is associated with a worse prognosis. Patients and Method: We conducted a retrospective study of consecutive cases of BC with TNP by immunohistochemistry(IHC),treated in our center within the last 5 years,with primary endpoint of analyzing the disease-free-survival (DFS).Second endpoints of the study were overall survival (OS),place of the first recurrence and cause of death. Results: After reviewing 295clinical histories of localized BC(with available ER,PgR and Her-2 by IHC),we found a total of 24 patients(p)with TNP(Prevalence=8.14%[95CI%: 5.3–11.9%].Ps characteristics:median age=50 years(26–74);premenopausal=55%;tumor grade:G3=40%;G2=60%;85.7% had high Ki-67(>40%);63.2% had stageIIB-III;median tumoral size=2.1cm;node positive=80%(25% with 4 or more positive nodes);96% was ductal carcinoma;56.5% was treated with mastectomy;78% with radiotherapy.Eighty-three percent of ps were treated with neoadjuvant and/or adjuvant chemotherapy with anthracyclines and taxanes:34.8% with adjuvant chemotherapy (AC60/600x4–>Paclitaxel-175x4);21.7% with neoadjuvant ATX(doxorubicin, docetaxel and capecitabine);and 26.1% with neoadjuvant AT(doxorubicin and docetaxel), and only 4 ps with adjuvant CMFx6.With a median follow-up of 36 months(m),median DSF was 42 m(95%CI: 33–51),and the probability of DSF at 3y was 67%.Median OS was 82m(95%CI: 41–123),with a probability at 5y of 52%.Thirty-eight percent(9/24)of ps had an event(3 recurrences and 6 deaths),and 100%of the deaths were caused by tumoural progression. Deaths according to the chemotherapy:75%(3/4 patients)in CMF group vs 15%(3/20)in anthracycline and taxane group(P=0.040; Fisher test).Mainly localization of the first recurrence was multiple in the 44.4%of the cases, followed by the liver(22.2%),lung(11.11%),bone(11.11%)and brain (11.11%). Conclusions: Our study confirmed the worse prognosis associated with triple negative BC.This subtype of BC must be treated with the most active cytostatic drugs in the adjuvant setting. No significant financial relationships to disclose.
Short-term biological effects of zoledronic acid combined with letrozole in postmenopausal women with estrogen receptor-positive invasive breast cancer
Authors: Bundred N. J. , Landberg G. , Coleman R. E. , Morris J. , Winter M. C. , Holen I. , Cramer A. , Renshaw L. , Grassby S. , Dixon J. M. 
Published: August 2020

e11625 Background: Aromatase inhibitors (AIs) reduce tumor cell proliferation and improve breast cancer survival. Recent evidence from in vivo models and the ABCSG-12 Trial suggests that bisphosphonates such as zoledronic acid add to the inhibitory effect of AIs but the mechanism is unclear. We assessed the effect of letrozole alone and in combination with zoledronic acid in a 14 day pre-surgical study in women with primary breast cancer. Methods: Postmenopausal women (n=109) aged 50–75 years with untreated estrogen receptor positive invasive breast cancer (no prior hormonal therapy) gave written informed consent to the study and were randomized to letrozole (2.5mg) or placebo tablets (2:1). Letrozole treated patients were randomized further to zoledronic acid 4mg intravenously or no treatment 2–4 days prior to surgery. Epithelial proliferation and apoptosis was measured pre and post treatment by immunohistochemistry for Ki67 and activated caspase 3 respectively counting at least 1,000 cells. Smooth Muscle Actin immunohistochemistry was also assessed pre and post treatment to determine fibroblast activation. Results: The study is powered to detect a 10% difference in epithelial proliferation with the combination arm (80% chance) compared to the letrozole alone arm. Conclusions: This preoperative biological study should provide important insight into the cellular mechanism or action of zoledronic acid in addition to AIs on primary breast cancer. [Table: see text]
Benefits of dexrazoxane in female patients with stage II breast cancer treated with anthracycline-based adjuvant chemotherapy
Authors: Schnirer I. I. 
Published: August 2020

e11626 Background: In Israel, the majority of patients receiving doxorubicin (A) are treated with dexrazoxan (D). A retro-active study was carried out on cardiac effects of A and D on female patients receiving adjuvant chemotherapy for Stage 2 breast cancer. Methods: 34 newly-diagnosed chemotherapy-naïve female patients with Stage 2 breast cancer, received anthracycline-based chemotherapy treatment A with D ± Herceptin (HER). Cardiotoxicity was assessed by echo-cardiograph pre- and post- treatment, and thereafter every 3 months for a period of 2 years, and was defined by presence of CHF or a reduction in resting LVEF to <45% or to ≥15% below baseline echo-cardiograph. Results: 34 patients were eligible for assessment. The mean age was 52, ranging from 24 to 78. Chemotherapy regimen consisted of 4 cycles of A + cyclophosphamide + D ± HER (HER treatment over a period of one year) + paclitaxel (PAC) (12 courses). Of the 34 patients, 7 (20.5%) were Her2 new positive. 17 patients (50%) were estrogen (ER)/progesterone (PR) positive. 9 patients (26.4%) were triple negative. 2 of the Her2 new positive patients were also ER/PR positive. Average m2 per study population was 1.63 (mean range being 1.39 - 1.87). Average A dosage was 60mg/m2 and mean D dose was 391.2mg (between 333.6mg and 448.8mg). Ratio of A to D was 1:10. Echo-cardiograph pre- treatment ranged from 80% - 60%, a normal range according to the New York Health Association (NYHA). Post-treatment echo-cardiograph ranged from 70% - 45%. One patient from HER positive group (generally experiencing increased cardiotoxicity by 4%) showed decrease in LVEF by 14.3% (14.2% of Her2 new patients). Remaining patients showed no change. One patient from ER/PR positive group experienced a 12.3% reduction in LVEF, representing 5.88% of the ER/PR patients. Remaining ER/PR positive patients remained unchanged, with one patient showing increased LVEF from 60% to 70%. The triple negative patient showed no change in their echo- cardiograph results. Conclusions: This study confirms that no scientific or clinical-based evidence was found of anthracycline- based cardiotoxicity following administration of A plus D, in accordance with published medical evidence. D should be a standard of care for anthracycline-based chemotherapy. No significant financial relationships to disclose.
Profile of axillary nodal disease from the Irish National Breast Cancer Screening Program in the era of sentinel node biopsy
Authors: Barry M. , Kell M. R. 
Published: August 2020

e11629 Introduction: Ireland offers a socialized national breast cancer screening program (Breastcheck) to women between 50 and 65 years of age with the aim of reducing breast cancer mortality. Historical axillary staging for screen detected breast cancer has shown nodal positivity in 25% of cases. This study examines axillary nodal disease from the Irish national breast cancer screening program in the era of sentinel lymph node biopsy (SLNB). Methods: Patients with clinically and radiologically early stage screen detected breast cancer and negative axillae are offered therapeutic surgery with SLNB. We examined prospective Breastcheck data collected from 2006 and 2007. Results: 136,527 women attended for routine screening and from these 574 invasive breast cancers were detected. 55 (9.6%) were clinically/radiologically axillary node positive at diagnosis. 519 clinically node negative patients proceeded to therapeutic surgery with SLNB, 113 (22%) were found to have a positive SLNB. Overall nodal positivity was 29.3% in this asymptomatic population. We examined tumour characteristics, hormone profile and HER-2 status from the SLNB group and tumor size was the only factor significantly associated with a positive SLNB (20.1mm vs. 14.3mm, p, 0.01). Conclusions: SLNB accurately detects axillary nodal disease from a purely screen detected population. Based on historic data, SLNB is superior to axillary sampling in this population. No significant financial relationships to disclose.
Acute interstitial pneumonitis following adjuvant tamoxifen therapy
Authors: Ahmed S. , Shahid R. K. 
Published: August 2020

e11637 Background: Tamoxifen is a serum estrogen receptor modulator that is widely used in the treatment of women with breast cancer and has a low incidence of serious side-effects. Although hypersensitivity reactions to tamoxifen have rarely been described, to our knowledge acute lung toxicity has not previously been reported. Objective: To report an unusual case of acute interstitial pneumonitis in a patient with early stage breast cancer treated with tamoxifen. Results: A 66 year old post-menopausal woman with past medical history of type 2 diabetes mellitus, and hypertension noted a lump in the right breast. An excision biopsy revealed 9 mm moderately differentiated invasive ductal carcinoma. Lymph nodes were not involvd by the tumor. The tumor cells were positive for estrogen and progesterone receptors and were negative for ErbB-2 over expression. The post operative course was complicated by wound infection treated with combination of clindamycin and ciprofloxacin. The patient was recommended adjuvant tamoxifen. Her other medication were metformin, valsartan, calcium and vitamin D. One week after the commencement of tamoxifen she noted increasing dyspnea, cough, and intermittent fever. X-ray chest showed bilateral lung infiltrates. She was hospitalized and treated with broad spectrum antibiotic. The patient condition deteriorated. She developed acute respiratory failure requiring intubation and mechanical ventilation. Tamoxifen was discontinued. A CT scan of chest showed bilateral interstitial infiltrates. Bronchoalveolar lavage was performed which was negative for infection. An open lung biopsy was done which showed focal diffuse alveolar damage consistent with interstitial pneumonia. No evidence of an infective agent, malignancy, or granuloma was noted. The patient was treated with high dose steroid. She gradually recovered and was discharge to home with normal lung function. Conclusions: Drug-induced lung injuries are usually idiosyncratic reactions and occur in an unpredictable manner. The presence of a temporal relationship between the lung injury and tamoxifen administration, a rapid clinical improvement after discontinuation of the drug, and absence of other causes strongly implicated tamoxifen as a potential cause of acute lung injury. No significant financial relationships to disclose.
Docetaxel plus capecitabine in the treatment of previous anthracycline-treated patients with metastatic breast cancer
Authors: Bensalem A. , Bouzid K. 
Published: August 2020

e12014 Background: Anthracyclines have been considered the challenge of the treatment of metastatic breast cancer. Docetaxel has changed this belief. We conducted a study in previously anthracyclines treated metastatic breast cancer by the regimen docetaxel 75 mg/m2 Day 1 - capecitabine 2500 mg/m2 day split-up over 2 daily doses from Day 1 to Day 14; every 21 Days. Methods: Patients were eligible if they had metastatic breast cancer after an adjuvant setting by anthracyclines. All patients had measurable disease, PS ≤ 2, adequate organ function. Results: From April 2004 to June 2006, 18 patients were enrolled in the study and were evaluated for the toxicity and preliminary responses to the treatment. 100 % of patients had metastatic breast cancer. The sites of metastases were liver in 14 ( 77.7%), lung in 5 (27.7%) and bone in 9 (50%). 11 patients (61.1%) had 1 or 2 metastatic sites, 7 (38.9%) had 3 metastatic sites. All of 18 patients were assessed for toxicity. The main toxicities were as follows: neutropenia grade 3 in 3 patients (16.6 %), anemia grade 2–3 in 2 patients (11.1%), fatigue in 2 patients (11.1%), hand-foot syndrome in 7 patients (38.9%), vomiting-nausea in 4 patients (22.2%), diarrhea in 2 patients (11.1%), liver toxicity in 3 patients (16.6%). The objective response was obtained in 8 patients (44.4%) (Complete response in 3 patients (16.6%), partial response in 5 patients (27.7%). Median response duration was 9 months (range 4 - 17). 7 Patients (38.9%) had stable disease, progression was observed in 3 (16.6%) of patients. Conclusions: In this preliminary analysis, the combination of docetaxel - capecitabine in the treatment of previously anthracyclines treated metastatic breast cancer appears to be an active schedule. It is safe and active, with a manageable toxicity profile and a good clinical activity. No significant financial relationships to disclose.
MGMT methylation status may predict survival in elderly patients with newly diagnosed glioblastoma (GBM)
Authors: Gerstner E. R. , Yip S. , Wang D. L. , Louis D. N. , Iafrate A. J. , Batchelor T. T. 
Published: August 2020

e13023 Background: Methylation of the MGMT gene promoter is associated with prolonged survival and response to temozolomide in GBM < 70. However, it is unclear if MGMT is a useful prognostic biomarker in the elderly GBM population who traditionally are viewed as less responsive to treatment. Methods: We retrospectively reviewed MGMT promoter methylation status and clinical characteristics in patients 70 years or older with newly diagnosed GBM undergoing resection at our institution from 1998–2008. MGMT analysis was performed by extracting tumor genomic DNA for bisulfite conversion. MGMT methylation specific PCR (MSP) was then performed using PCR primer sets specific for methylated and unmethylated MGMT promoter sequence. The logrank test was used to compare mPFS and mOS in patients who had methylated (ME) MGMT vs. unmethylated (UN) MGMT. Results: Thirty-four patients were included in the analysis. Twenty patients (59%) were ME while 14 (41%) were UN. Patients were treated with multimodality treatment (radiation + chemotherapy), radiation alone, or chemotherapy alone. ME was associated with a significantly prolonged mPFS and mOS as noted in the table below which also summarizes the characteristics of the study population. Conclusions: MGMT methylation status is associated with prolonged PFS and OS in elderly patients with newly diagnosed GBM. Knowledge of MGMT status may help improve prognostication in this patient population. [Table: see text] [Table: see text]