bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER2 overexpression is associated with shorter disease-free survival (DFS) following neoadjuvant systemic therapy (NST) of primary breast cancer (PBC) patients with gemcitabine (G), epirubicin (E) and docetaxel (Doc)
Authors: Marmé F. , Rom J. , Schütz F. , Eichbaum M. , Sinn P. , Sohn C. , Schneeweiss A. 
Published: March 2020

11087 Background: To evaluate prognostic factors for disease-free survival (DFS) following NST with G, E and Doc of patients with PBC. Methods: From 1/02 to 12/04 113 patients with T2–4 N0–2 M0 PBC received either six cycles of GEDoc (G 800 mg/m2 day (d) 1+8, E 60–90 mg/m2 d 1, Doc 60–75 mg/m2 d 1 every three weeks; 63 patients) or five cycles of GE (1,250 mg/m2 d 1, E 90–100 mg/m2 d 1 every two weeks) sequentially followed by four cycles of Doc (80–100 mg/m2 d 1every two weeks) with prophylactic filgrastim. 71% of tumours were hormone receptor positive, 24% HER2 positive (3+ by immunohistochemistry), 46% grade 3. 28 patients (25%) achieved a pathologic complete response (pCR) defined as no invasive tumour residue in the removed breast tissue at surgery. 9 of these patients had non-invasive cancer residues in the breast, one patient showed persisting axillary lymph node involvement. Results: With a median follow up of 3.2 years there is no statistically significant difference in DFS, distant DFS (DDFS) and overall survival (OS) rates between patients with and without pCR (DFS 79 versus (vs) 81 %, p=0,61; DDFS 82 vs 84 %, p=0.69; OS 86 vs 91%, p=0.33). In a Cox proportional hazards model HER2 3+ before NST (hazard ratio (HR)= 4.7; 95% confidence interval (CI) 1.9 - 11.3; p=0.0006), positive hormone receptors before NST (HR=0.27; 95% CI 0.11 - 0.65; p=0.003) and clinically nodal involvement before NST (HR=3.3; 95% CI 1.2–9.1; p=0.02) were statistically significant prognostic factors for recurrence whereas tumour size and grade before NST, the achievement of pCR, nodal status at surgery and response after 6 weeks of NST did not reach statistical significance. Thus far, in multivariate analysis only Her2 3+ before NST retained its prognostic significance (HR= 2.8; 95% CI 1.03 - 7.5, p=0.04). Conclusions: With a median follow-up of 3.2 years in multivariate analysis only HER2 3+ is associated with shorter DFS following NST containing G, E and Doc for PBC. Thus far, there is no statistically significant prognostic value for pCR. No significant financial relationships to disclose.
Primary invasive breast cancer in 104 women: A single-center experience in the years 1995–2005
Authors: Beda M. , Ghiotto C. , Basso U. , Stefani M. , Lonardi S. , Bonavina M. , Monfardini S. 
Published: March 2020

11093 Background: To assess clinical, genetic and biological characteristics of breast cancer (BC) in women £ 35 years followed in a single Institution, along with patterns of disease recurrence and survival. Materials and Methods: All consecutive women £ 35 years with invasive BC registered at our Medical Oncology Department between 1995 and 2005 were enrolled in this retrospective analysis. Genetic testing for BRCA1/2 and P53 started in the year 2000. Results: Out of 4.120 cases, a total of 104 pts were identified, median age 32 years (range 22–35). Median age at menarche was 13 years, 48% were nulliparous. Approximately on third reported oral contraceptive use, while 23% reported a family history of BC. Almost 90% had a self -diagnosis of disease. Modified radical mastectomy was performed in 48%, conservative surgery in 46%, 6 metastatic pts were not operated. Axillary lymph node involvement was present in one half of cases. The prevalent histology was ductal carcinoma, 78% G2-G3, 26% hormone-receptor negative, 43% HER-2 positive. TNM stage was 29% I, 39% II, 22% III, 10% IV. Neo-adjuvant or adjuvant anthracycline based chemotherapy was administered to 86.7% of patients, combined with taxanes in 23% of cases. Twenty-four patients developed amenorrhea after stopping chemotherapy, the other ER/PgR positive patients received LH-RH analogues for 2 years. Tamoxifen was given to all ER/PgR positive patients. Genetic mutational analysis was available in 43 patients, and 9 mutations of BRCA 1 and 4 of BRCA 2 were found; two patients had a p53 mutation and one of them had an overt Li-Fraumeni syndrome. After a median follow-up of 5.5 years, 29 patients (28%) have recurred and 13 (12.5%) have died, with an estimated 5 year-DFS and OS of 82.4% and 87.5%, respectively. Conclusions: Our data confirm the aggressive biological features of BC in very young women. Intensive chemotherapy produces amenorrhea in 31% of cases. The 35% rate of BRCA1/2 or p53 mutation justifies a broader use of genetic testing in such patients in order to evaluate prophylactic measures for the female relatives. No significant financial relationships to disclose.
HER2 status of patients with invasive breast cancer in a population at a single UK centre: Correlation with tumor characteristics
Authors: Saleh B. , Jader S. , Singer J. , Jenkins S. , Bradpiece H. , Patel A. 
Published: March 2020

11094 Background: The human epidermal growth factor receptor 2 (HER2) overexpression, has been correlated with higher histological grade, increased tumour size, positive lymph node status, and negative or lower oestrogen receptor (ER) expression. Our aim was to look at the association between HER2 status, patient age and tumour histopathologic characteristics. Methods: We analysed retrospectively 735 cases of invasive breast cancer treated between the years 2000 and 2004. HER2 was measured by immunohistochemistry (IHC) and all IHC 2+ tumours were also tested by fluorescent in situ hybridisation (FISH). All information was collected from pathology reports in patient case records. Results: A total of 143 (19.5%) tumours were HER2 positive (120 IHC 3+ and 23 IHC 2+/FISH+). Of the 66 tumours that were IHC 2+, 23 (34.8%) were FISH-positive. The age of most patients (75.8%) was over 50 years but there was a higher incidence (28%) of HER2 overexpresion in the 40–49 age group compared to all other age groups, the incidence of HER2 overexpression was still at least 17–18% in all age groups, including patients aged =70 years. Although, a high proportion of patients (62.2%) had tumours less than 2 cm in size, comparison of tumours less than 2 cm with those greater than 2 cm showed no predictive effect of size on HER2 expression. Over half of the patients had lymph node-negative disease (55.2%) and despite some association of HER2 expression with lymph node involvement (odds ratio of 1.23 for comparison of lymph node-positive versus negative), 19% of lymph node-negative tumours overexpressed HER2. Most tumours were high grade (32.8% grade 3, 44.1% grade 2 ) and although the proportion of HER2 overexpression increased with increasing tumour grade, some grade 1 tumours still overexpressed HER2. A higher proportion (28%) of ER-negative tumours was HER2 positive compared to ER-positive tumours (18%); however, co-expression of HER2 and ER occurred in 14% (105/735) of all primary cancers. Conclusions: In conclusion, it is not possible to predict which patients will be HER2 positive. Therefore, it is essential that HER2 status should be determined in all patients with invasive breast cancer to allow a decision on the use of trastuzumab and guide the choice of chemotherapy. No significant financial relationships to disclose.
Updated results from a phase II study of sequential treatment epirubicin, cyclophosphamide (EC), surgery and docetaxel (DTX) in stage II and III breast cancer
Authors: Grecea D. , Neamtiu L. , Tanasescu R. , Rancea A. , Resiga L. , Galatar M. , Postescu D. , Daicoviciu D. , Popita V. , Ghilezan N. 
Published: March 2020

11096 Background: The study was designed to evaluate the efficacy and safety of sequential administration of epirubicin plus cyclophosphamide (EC) followed by surgery and docetaxel (DTX). Methods: All patients (74) with untreated breast cancer stage II and III received epirubicin (E) 100mg/m2 given in 30 min followed by cyclophosphamide (C) 600mg/m2(q3w).After four cycles of neoadjuvant chemotherapy, the pts were evaluated for response: 46 ( 62.1%) presented PR, 2 (2.7%) CR and 26 ( 35.2%) SD and then they underwent surgery: conservative (17.57%) or radical mastectomy (82.43%).After surgery, the patients received four cycles of docetaxel (DOC) 100mg/m2 (1 hour , q3w). The median age was 46 ( 24–66) years, with 51 ( 69%) premenopausal and 23 (31%) postmenopausal patients. Results: The pathological response was pT1 lower to 2 cm, 41 patients ( 55.41%), pT 2–5 cm, 33 pts ( 44. 59%); pN+ 1–3: 13 pts ( 17.56%); pN+ = 4 and more than four: 61 pts ( 82.44%). Overall survival at 60 months was 59. 57% and DFS was 41.25%. For patients with pN+1–3 , at 5 years DFS was 46.35% and for those with pN+ = 4 and more 4, DFS was 38.25% (p=0.045).Overall survival at 5 years follow-up was 65.74% for pts with pN+ 1–3 and 57.36% for those with pN+=4 and more than 4. Conclusions: Previous interim analysis results of sequential chemotherapy with DTX demonstrate the efficacy and safety of these treatment in breast cancer stage II and III. At 5 years follow-up, we conclude that the use of four cycles of EC followed by sugery and then four cycles of DTX is a reasonable treatment choice for at least some patients with breast cancer st II and III. No significant financial relationships to disclose.
Clinical outcome of node-negative (NN) breast cancer (BC) patients
Authors: Atalay Basaran G. , Cabuk D. , Dane F. , Teomete M. , Iyikesici S. , Meltem E. , Gulluoglu B. , Kaya H. , Abacıoglu U. , Yumuk F. , Turhal S. 
Published: March 2020

11102 Background: Breast cancer patients (pts) with NN disease have diverse clinical outcomes. An optimal treatment decision- making tool has not been defined for this heterogeneous group. Methods: We identified pts with NN disease who have been treated between 1998–2006 in our department. We recorded the clinical/pathological, treatment characteristics and analyzed their survival outcome. High risk (HR) was defined as having at least one of the following features: age<35 yr-old, pts with grade 3 tumors (tms), ER and PR negative tms, tm size >2 cm. Results: Out of 597 early BC pts, 275 pts with NN disease were identified, 190 pts with HR, 85 with low risk (LR) features.The median age was 51 (26–83). The median follow up was 40 months (4–120 months). 47% pts were premenopausal. 31% pts had breast conserving surgery (BCS).58/29% pts had grade 2/3 tms. 34% pts with BCS or T3 tms received adjuvant radiotherapy. All receptor positive pts received adjuvant endocrine therapy (ET). In the HRNN group, 5% pts had tms>5cm, 51/40% pts had grade 2/3 tms, 43% pts had ER/PR negative tms. In the LRNN group 25/74% pts had grade 1/2 tms, no pt had receptor negative tm. 86%/51% pts received adjuvant chemotherapy (CT) in the HR and LRNN groups. 12%/48% pts received adjuvant ET alone in the HR and LRNN groups. 5pt in the HR and 1 pt in the LR group received no adjuvant systemic therapy due to their comorbidities and/or negative receptor status. So far, 14 pts had relapsed (8 from the HR, 6 from the LR group) and 3 pts died due to BC (1 from the HR, 2 from LR group). The 5-yr DFS was %94 in the HR and was %90 in the LR groups. HRNN pts had %98 and LRNN pts had %95 5-yr OS. Conclusion: It seems that prognostic information based merely on clinical/pathological characteristics might not accurately quantify the risk of recurrence and death, so that the decisions about adjuvant chemotherapy in NN breast cancer patients. Prospective evaluation of the performance of the new genomic prognostic tools compared to traditional prognostic factors is needed in order to more clearly define the HR vs LR subsets of NNBC pts. No significant financial relationships to disclose.
Heterogeneity in disease-free survival in breast cancer patients
Authors: Yahyazadeh Jabbari S. , Khodabakhshi R. , Gohari M. R. , Mortzavi S. , Alidoosti A. , Shahidi J. , Moradi A. , Bahoor F. 
Published: March 2020

11106 Background: Breast cancer is the most common cancer and women’s health problems in Iran. There are some known prognostic factors for occurrence of metastasis after surgery. However, there are some other unknown factors affect the risk of metastasis. The purpose of this study was to determine the value of known prognostic factors by accounting for patient-specific effect, the rate metastasis in breast cancer patients who received surgical treatment followed by adjuvant treatment in Iran. Methods: Among 174 women whom have been undergone surgery followed by adjuvant therapy at three hospitals in Tehran, Iran during 3 years 117 have met the including criteria. Women with defined breast cancer with no distant metastases in time of diagnosis whom have been undergone MRM or BCS were enrolled. Tumors were classified according to the TNM system of the American Joint Committee on cancer (AJCC). Grading was performed according to Scarff-Bloom-Richardson method. ER and C-erb2 was measured by immunohistochemistry (IHC) method. The patients have been followed regularly by routine clinical, lab profile, serologic markers (CEA,CA15–3) and Para clinical examinations. Results: The median relapse- free survival for patients in study was 49.6 month. The median time to experience second metastasis was 22.5 month. 44 (38% ) patients developed metastasis. 20 (45%) of those experienced second metastasis. the Frailty model showed that age, size of tumor, number of positive lymph nodes and histologic grade had a significant effect on the risk of metastasis (p<.05) and there was a heterogeneity between patients after adjusting for covariates. Conclusion: Many patients who referred to cancer centers were not detected at early stage and they will meet more risk for relapse. The known risk factors describe the risk of metastasis partly and other unknown or unmeasured factors, such as environmental or genetics, are important to describe the risk of metastasis in breast cancer. Family history has no significant effect on event- free survival. No significant financial relationships to disclose.
Phase II evaluation of liposomal doxorubicin combined with docetaxel in patients with metastatic breast cancer
Authors: Fasano J. , Hershman D. , Novik Y. , Blozie K. , Tiersten A. 
Published: March 2020

1112 Background: The combination of anthracyclines and taxanes are effective in the treatment of metastatic breast cancer. Liposomal doxorubicin has been shown to be as effective as doxorubicin with less toxicity and it can be combined safely with docetaxel. Methods: Monthly liposomal doxorubicin (30 mg/m2) in combination with weekly docetaxel (30 mg/m2) was evaluated in women with metastatic breast cancer. Cycles were continued until disease progression or unacceptable toxicity. Radiologic assessment was performed every two months. The primary outcome was time to progression. Secondary endpoints included overall response rate, median survival and toxicity. Results: Between 12/2002 and 9/2005, 12 women were enrolled and received this combination as front- line chemotherapy for metastatic breast cancer. The mean age was 46.5 (31–60) years. Nine (75%) patients had tumors that were ER+ or PR+. Five (41.7%) women had tumors that over-expressed her-2/neu. Ten women had an EGOG performance status of 1. Two women had an ECOG performance status of 2. The median number of cycles received was 4 (1–12). Four (25%) women were taken off study due to intolerable toxicity and 7 (58.3%) due to progressive disease. One (8.3%) woman remains progression free. Ten (83.3%) women had a partial response, one (8.3%) woman had a mixed response and one (8.3%) was not evaluable for response to chemotherapy. The median time to progression was 21 (6–52) weeks. Three women remain alive with disease. One woman remains alive and progression-free. Ten (83%) patients experienced Grade 3/4 toxicities, including: stomatits 6 (50%), nausea/vomiting 1 (8.3%), neutropenia 3 (25%), infection 3 (25%), dyspnea 2 (16.7%), and PPE 1 (8.3). Conclusions: Monthly liposomal doxorubicin plus weekly docetaxel in women with metastatic breast cancer resulted in an encouraging response, but was difficult to tolerate. Further evaluation of this combination with improved supportive care may be warranted. [Table: see text]
Bisphosphonate-induced osteonecrosis of the jaw: Incidence and risk factors in patients with breast cancer and gynecological malignancies
Authors: Beck V. , Solomayer E. , Krimmel M. , Reinert C. , Fehm T. 
Published: March 2020

1113 Background: Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption. They are successfully used in conditions of increased bone turnover such as osteoporosis or bone metastases. Since 2003 multiple cases of bisphosphonate-induced osteonecrosis of the jaw (ONJ) were reported. Our purpose was to describe the incidence and risk factors of ONJ in patients with breast cancer or gynecological malignancies. Patients and Methods: ONJ was assessed retrospectively for all patients with breast cancer or gynecological malignancies treated with bisphosphonates at the Department of Gynecology and Obstetrics, University Hospital Tuebingen during April 1999 until May 2006. Results: 10 of 310 (3%) patients with breast cancer or gynecological malignancies developed ONJ while receiving bisphosphonate therapy. All patients with ONJ were treated for bone metastases. Except one all patients with ONJ had a history of recent dental procedures. All patients had received zoledronic acid as part of their bisphosphonate regimen. In 4 of 10 patients this was the only bisphosphonate given. The remaining 6 patients had received at least one of the other bisphosphonates (alendronate, ibandronate, clodronate or pamidronate) before or after zoledronic acid therapy during their course of disease. Time of exposure to bisphosphonates and the number of treatment cycles were significant risk factors for the development of ONJ (p<0.001). In patients diagnosed with ONJ the mean number of treatment cycles was 27 ±18 cycles (median: 21 cycles, range 6–62 cycles) and the mean duration of bisphosphonate therapy was 29 ±20 months (median: 22 months, range 1–67 months). In contrast, the mean number of treatment cycles in patients without manifestation of ONJ was 11 ±12 cycles (median: 6 cycles, range 1–90 cycles). The mean duration of therapy was 12 months (median: 7 months, range 1–81 months). Conclusion: Osteonecrosis of the jaw is regarded a major side effect of bisphosphonate therapy. Length of exposure to bisphosphonates and the number of treatment cycles seem to be the most important risk factors for the development of ONJ. In addition, recent dental procedures favours the development of an ONJ. No significant financial relationships to disclose.
Improved renal function in patients switched from zoledronic acid to ibandronate: A retrospective review of medical records
Authors: Diel I. J. , Weide R. , Köppler H. , Antràs L. , Smith M. , Green J. , Wintfeld N. , Neary M. , Duh M. 
Published: March 2020

11500 Background: The renal safety profile of ibandronate (IA) was assessed retrospectively across a spectrum of oncology patients including multiple myeloma, breast, prostate, and non-small cell lung cancer. Patient groups were classified as IA switchers (with prior zoledronic acid (ZA) therapy) (n=34) or early IA (without prior ZA therapy) (n=72). Renal impairment rates and trends in renal function were compared during ZA and IA treatment periods in patients switching from ZA to IA (n=32 observable in both treatment periods). Methods: Medical records from two German oncology clinics, spanning May 2001 to March 2006, were reviewed. Serum creatinine (SCr) was analyzed from baseline to last evaluation. Renal impairment was defined as a SCr increase of =0.5mg/dL or =1.0mg/dL from baseline values of <1.4mg/dL or =1.4mg/dL, respectively; or =25% decrease in glomerular filtration rate (GFR) from baseline. Results: Both groups had similar baseline renal function. Physicians reported that renal-related problems led to 22 patients (69%) switching from ZA to IA. Patients switched from ZA therapy to IA showed a significant trend towards renal function deterioration during the ZA treatment period (p=0.016) but experienced a trend towards improved renal function after switching to IA (p=0.082). Patients receiving IA with prior ZA therapy exhibited significantly higher renal impairment rates versus those without prior ZA therapy (50.0% versus 11.1%, relative risk (RR)=4.5, p<0.0001 [SCr] and 70.6% versus 38.9%, RR=1.8, p=0.0024 [GFR] for patients with and without prior ZA therapy, respectively). Cox proportional hazards models, adjusted for significant covariates, found significantly higher hazards ratios (HRs) in the IA switchers group versus the early IA group (HR=7.7, p<0.01 [SCr] and HR=4.3, p<0.01 [GFR]). Conclusions: ZA naïve patients had a significantly lower renal impairment risk compared to those who received ZA followed by IA. Patients switching from ZA to IA showed recovery of renal function, suggesting that patients may benefit from IA early in the treatment cycle or by switching to IA treatment. A prospective randomized study is warranted. No significant financial relationships to disclose.
Diabody vinorelbine conjugate (DVC) composed of vinorelbine-tartrate conjugated to anti-DNMT1/SHH di-diabody induce ADCC, CDC, AMP and inhibit DNA methylation
Authors: John G. N. , Giannios J. , Seraj E. , Kanelopulos G. , Ginopulos P. , Alexandropulos N. 
Published: March 2020

11503 Background: Hormone refractory breast cancer (HRBC) is incurable due to malignant stem cells,which represent a potential nidus for the recurrent cancer that arises after treatment failure. Methods: From 126 metastatic HRBC patients,we obtained CSCs from recurrent tumor reservoirs missed from current chemotherapy,which had eradicated bulky tumor foliage.HRBC-CSCs were treated with DVC composed of vinorelbine linked onto anti-DNMT1/anti-SHH di-diabody. Results: Post treatment ,we observed antibody dependent cellular toxicity (ADCC),complement dependent cellular toxicity (CDC) ,and antibody mediated phagocytosis (AMP) mediated by the di-diabody.Next,we observed inhibition of SHH, which is overexpressed in CSCs,blocking HH binding to PTCH,and signaling from SMO and GLI. DNMT1 was downregulated blocking DNA methylation.This inhibited hTERT transcription blocking the telomerase activity of CSCs. DNA demethylation reactivated DEAF-1 upregulating PTEN,which antagonised PKB/mTOR,PI3K/AKT,src/VEGF , HIF-1a/survivin angiogenic and antiapoptotic pathways leading to synergistic inhibition of telomerase activity. RKIP was re-expressed inhibiting Raf-1/MEK1–2/ERK1–2,NFkB and STAT3 leading to downregulation of CD46 mediating CDC. PTEN by inhibiting AKT,it upregulated Drg-1.Also,PTEN re-expression inhibited synergistically with vinorelbine,the oncogenes bcl-2,bcl-xL and mcl-1 leading to upregulation of bid,bax and bak. DNA demethylation reactivated CDH1,RASSF1A,EDNRB,Kip1/p27,RhoE,NKX31,DLC-1,GSTP1, TIG1,TAP,Necl-1,RARb,NTRK2,MFPC7–8,p16/Rb,p53/p21,DOC- 2/DAB2,BTG2,maspin and DEFB1. Ki67,BrdU and MTT exhibited inhibition of CSC proliferation. DFF,PARP,TUNEL,SEM and TEM exhibited PCD type I,II and III in CSCs.We observed aponecrosis based on lysosomal damage independent of caspases.PCR exhibited inhibition of CSC markers CD44/a2b1/CD133,b-catenin,Sca1,Notch-1 and methylation marker SCNN1B. Conclusions: DVC eradicated efficiently HRBC-CSCs. No significant financial relationships to disclose.