bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of aromatase inhibitors on bone mineral density measured by serial DXA scans
Authors: Whannel K. J. , Doughty J. C. , Wilson C. R. , McLellan A. 
Published: March 2020

11065 Background: We are now using aromatase inhibitors (AI) in increasing numbers of women as treatment in the breast cancer care pathway. Studies have reported a loss of bone mineral density (BMD) with use of all AIs. It has been shown in our unit that 5 years of tamoxifen (T) in post-menopausal women prior to commencing an AI does not offer sufficient protection to prevent significant BMD loss when an AI is introduced, with 25% requiring concurrent bisphosphonate (BP) therapy. The aim of this study was to determine changes in serial DXA scan results over a 12month period in women taking AIs. Method: 62 women being considered for or in early stages of use of an AI attended for a DXA scan and re-scan at 12 months. Vertebral morphometry and fracture rate were assessed and risk factors for osteoporosis noted. Scan results were compared ( Table 1 ). Results: Mean age was 67yrs [standard deviation (SD) 9yrs]. The patients were grouped according to initial endocrine therapy. 13 (21%) switched from tamoxifen to arimidex after 2years, 3 (4.8%) switched from tamoxifen to exemestane after 3 years and 30 (48.4%) switched from tamoxifen to letrozole after 5 years. 11 (17.7%) had been on arimidex as first line endocrine therapy for <=2 years and 5 (8.1%) had been on letrozole as first line endocrine therapy for <=1 year. Mean t-score and SD was calculated at each site and results categorised by lowest t-score at any site. The overall decrease in BMD measured at 1.66% over the 12 months. Conclusion: We have demonstrated a decrease in BMD with AI treatment of 1.66% per year as well as an increase in fracture incidence and increased need for bisphosphonate therapy whilst on an AI. We would recommend that all patients on any AI receive annual DXA scans. [Table: see text] No significant financial relationships to disclose.
Utilization of oncotype DX in node-negative, ER-positive breast cancer patients
Authors: Patel H. , Hook K. , Kaplan C. , Davidson R. , DeMichele A. , Fox K. R. , Domchek S. M. 
Published: March 2020

11067 Background: The 21 gene RT-PCR assay Oncotype DX (Genomic Health, CA) stratifies patients into low, intermediate and high risk for systemic recurrence. The objective of this study was to examine the patterns of use of Oncotype DX in a single institution. Methods: All patients who had ODX testing requested by the University of Pennsylvania were identified and recurrence scores (RS) obtained. Patient and tumor characteristics, as well as treatment administered, were obtained by chart review for analysis. Results: 100 ODX tests were ordered between 1/1/05–11/30/06. RS results classified 51% of breast cancers as low risk, 38% intermediate risk, and 11% high risk. Characteristics of the tumors of the overall population and by RS group are shown in Table . 99% of patients received hormonal therapy. Of the low risk patients, only one patient was treated with chemotherapy (2%) while 34% of the intermediate risk group and 80% of the high risk group received chemotherapy. Notably, only 4/100 patients with ODX were under age 35 and 17/100 had tumors over 2cm. Conclusions: In this series, ODX use is accelerating. The results of the ODX tests appear to be used clinically as demonstrated by the very low use of chemotherapy in the low risk group. Comparison to the overall population of ER positive, node negative patients seen at this institution is underway. [Table: see text] No significant financial relationships to disclose.
A phase II study of dose-dense chemotherapy (doxorubicin (A), cyclophosphamide (C), paclitaxel (T), gemcitabine (G)) supported by pegfilgrastim (P) and darbepoetin-alfa (D) for patients with high-risk early stage breast cancer (ICANDO)
Authors: Mainwaring P. N. , Shannon C. 
Published: March 2020

11068 Background: The primary objective of this study was to estimate the proportion of chemotherapy dose delays in a dose- dense regimen consisting of A (60mg/m2), C (600 mg/m2) x 4 cycles q2 weeks followed by T (175 mg/m2) G (1g/m2) x 4 cycles q2w with pegfilgrastim (6 mg/m2 sc d2) and darbepoetin-alfa (2.25 microg/kg if Hb < 110g/L) as treatment for patients with high-risk early stage breast cancer. Dose delay was defined by the proportion of subjects experiencing delay = 7 days in any cycle. Entry criteria path stage IIA-IIIA breast adenocarcinoma; node positive patients > 6 axillary lymph nodes removed or sentinel LN biopsy positive for metastasis. Treatment commenced within 8 weeks. Secondary endpoints included proportion of delays by cycle, causes of delay by cycle, causes of dose reduction by cycle, as well as time to haematological engraftment. Patients underwent weekly FBC, electrolytes, LFTs, with a normal baseline echo assessment. Herceptin therapy was approved in Australia 1st October 2006 and was added to TG therapy for FISH/CISH/IHC 3+ positive patients. All patients completed FACT-F QOL forms. The half-width confidence interval to predict for delay based on the AC-T data is 0.17 for n = 20 patients. Results: Twenty (20) women; median age 50 (41–66) met the criteria for treatment. No patients had treatment delays ≥ 2 days for any reason. One (5%) patient underwent a blood transfusion for a rapid decline in haemoglobin (Hb) prior to darbepoetin therapy. One (5%) patient was admitted for uncontrolled vomiting. Seven (35%) patients received darbepoetin therapy without secondary Hb rise above 130 g/L. One (5%) patient had a 20% dose reduction in A dose due to mucositis. For nausea >G1 aprepitant therapy was added. There have been no dose modifications due to hepatic toxicity. Final cycle, QOL and pharmacogenomic data will be presented at the meeting. [Table: see text] No significant financial relationships to disclose.
Predicting axillary lymph node involvement in breast cancer patients by ultrasonography
Authors: Rokutanda N. , Horiguchi J. , Koibuchi Y. , Nagaoka R. , Iino Y. , Takeyoshi I. 
Published: March 2020

11075 Background: About 20% of breast cancer patients eligible for sentinel node (SN) biopsy have axillary node metastases. The purpose of this study is to evaluate the sensitivity of preoperative ultrasonography (US) for SN involvement. Methods: Between October 2004 and May 2006, a total of 141 breast cancer patients without clinically node involvement were eligible for SN biopsy. The size (length and height) and cortical thickness of lymph nodes (LN) was measured by US before surgery. Results: Twenty-four (20%) of 141 patients had pathologically involved LN (Positive Group), and 118 (80%) were negative for LN metastases (Negative Group). No LN was detected in 25 patients (21%) of the negative group by US. The number of detected LN was more in the positive group than the negative group (1.59 vs 1.13, p<0.05). There was no significant difference in the size of LN between the two groups. The cortical layer of LN was thicker in the positive group than the negative group (3.11 vs 2.12, p<0.05). Eighteen patients had the LN with more than 4mm of cortical thickness, nine (50%) of which revealed pathologically LN involvement. Conclusions: The measuring of cortical thickness is useful for predicting axillary LN involvement by US. This approach may improve the selection of patients for SN biopsy. No significant financial relationships to disclose.
Locoregional control significantly reduces the risk of subsequent distant metastases in patients with locally advanced breast cancer managed with radiotherapy as the primary locoregional treatment
Authors: Rogowski W. , Badzio A. , Dziadziuszko R. , Madrzak J. , Welnicka-Jaskiewicz M. , Jassem J. , Barrett-Lee P. 
Published: March 2020

11076 Background: The treatment results of patients with locally advanced breast cancer still remain far from satisfactory. Both lack of locoregional control and distant metastases remain the most common pattern of failuire. The aim of this study was to evaluate whether achieving locoregional control decreases the subsequent risk of distant metastases a large series of consecutive locally advanced breast cancer patients managed with radiotherapy as the primary locoregional treatment. Methods: The records of 261 primarily inoperable locally advanced breast cancer patients treated between 1991 and 1997 at two institutions: Medical University of Gdansk, Poland and Velindre NHS Trust, Cardiff, UK were analysed. All patients received megavoltage radiotherapy to the breast with two tangential fields, and the adjacent lymph node areas were irradiated using customised fields. In 241 patients radiotherapy constituted the only local treatment and the remaining 20 patients were subsequently subjected to mastectomy. Most patients received chemotherapy and/or endocrine therapy prior or after radiation therapy. Results: Follow-up ranged from 6 to 133 months (median 37 months). Five- year overall survival was 36% (95%CI: 28–43%) and 5-year loco-regional relapse-free survival was 48% (95%CI: 40–57%). Recurrence occurred in 167 patients (67%), including local recurence in 30 patients (12%), distant metastases - in 72 patients (27%) and both distant and local recurrence - in 65 patients (26%). Median time to distant metastases was significantly shorter among a subgroup of patients who presented locoregional failuire - 33 months as compared to patients who were free of locoregional recurrence or progression before presenting distant metastases-43 months (p<0.05) Conclusions: This study demonstrated that treatment results in patients with locally advanced breast cancer are still far from satisfactory. However it confirmed the importance of putting much effort in achieving locoregional control in that group of patients as it significantly reduces the risk of subsequent distant metastases. No significant financial relationships to disclose.
Vitamin D (vD) deficiency (def) in breast cancer (BC) patients (pts)
Authors: Presant C. A. , Bosserman L. 
Published: March 2020

11082 Background: Vitamin D metabolism is important for maintaining bone health and perhaps cancer prevention. Prior studies have reported vD def in 88% of brca pts (Lonning et al ASCO 2006 abst 554), and 79% of women (Chlebowski et al ASCO 2006 abst 6) . Methods: In order to determine the frequency of vD def, we studied 41 consecutive brca pts. Levels of vD were correlated with clinical features. Pts were classified as vD def if 25OH D <20, 1.25 diOH D <14, or D3 <20. Insufficiency (ins) of vD was 25OH D 20–29. Results: 8 pts had vD def (19.5%). This was more common in young pts <60 (37.5%) compared to older pts (8%) (p4) in 5/6 pts <60 and 5/7 older pts. vD def did not correlate with bone disease: 25% def in pts without bone disease, 17% in pts with osteopenia, and 17% in pts with osteoporosis. In older pts, vD was normal in 12/14 pts on anastrazole, and in 7/11 pts not on anastrazole, indicating no relation of anastrazole to vD def. Bisphosphonate (bis) usage was slightly higher in older pts (60%) versus younger pts (38%) but not significantly (p<0.2). While only 19% of pts on bis had vD ins or def, 50% of pts not on bis had ins or def vD (p<0.05). Although only 5% of pts on bis had vD def, 30% of pts not taking bis had vD def (p<0.05). Conclusions: In brca pts, vD def is less than reported, but still frequent. All brca pts should be tested for vD periodically. VD def may be less frequent in pts on bis, and confirmatory trials should be performed. VD levels should also be monitored even if pts report taking vD. VD def or ins should be treated and monitored by oncologists. Since vD may be related to cancer incidence, and to bone disease, all brca trials collecting data on bone events, bone density, and second cancers should also report relationship to vD levels in individual study participants. No significant financial relationships to disclose.
Dose scheduling and pharmacokinetic (PK) study of trastuzumab in patients (pts) with HER2/neu overexpressing breast cancer?
Authors: Felici A. , Segni S. Di , Contestabile M. , Nuvoli B. , Fabi A. , Papaldo P. , Ferretti G. , Sperduti I. , Citro G. , Cognetti F. 
Published: March 2020

1109 Has been demonstrated that 10–20 μg/mL is the minimum serum trough concentration (Cmin) of trastuzumab that causes maximal tumor growth inhibition. This concentration was shown to be achievable using a weekly (4 mg/kg loading dose followed by 2 mg/kg weekly) and a three-weekly (8 mg/kg loading dose followed by 6 mg/kg) schedule, but only indirect comparisons of the two schedule have been performed. We prospectively analysed the PK distribution of trastuzumab in three different schedules, as follows: weekly (cohort I), bi-weekly (trastuzumab 6 mg/kg loading dose followed by 4 mg/kg, cohort II) and three-weekly schedule (cohort III). The PK analysis was performed in 18 pts (4 pts receiving the loading dose of cohort III, 8 pts receiving the maintenance dose of cohort III, 3 pts receiving the maintenance dose of cohort II, and 3 pts receiving loading dose of cohort I). Of the 18 pts analyzed, 9 were metastatic. The median age was 54 years (range 39–76), the median weight was 61,5 kg (range 53–80). At diagnoses, 10 pts had stage I disease, 5 and 3 pts had stage II and III respectively, ER was negative in 10 pts and PgR was negative in 12 pts; Ki67 was highly expressed in 14 pts; Her/neu was overexpressed and amplified in 16 and 2 pts respectively. To evaluate preliminary interpatient variability, 3 pts receiving 6mg/kg of trastuzumab repeated the PK analysis after four cycles: the comparison between two groups was not statistically significative. Comparison of Cmax and AUC mean between groups was statistically significative (P<0.05, Bonferroni test) except for 8 mg/kg vs 6 mg/kg AUC.All the doses and schedules analysed are able to reach the minimum serum concentration of trastuzumab that causes the maximal tumor growth inhibition. [Table: see text] No significant financial relationships to disclose.
Long-term toxicity of high-dose sequential chemotherapy with autologous hematopoietic stem cells support in very high-risk early breast cancer patients (pts)
Authors: Bernardi A. , Zamagni C. , Quercia S. , Massari F. , Cacciari N. , Martoni A. A. 
Published: March 2020

11101 Background: High-dose chemotherapy with autologous haematopoietic stem cells support (HDCT) in the adjuvant treatment of breast cancer has been abandoned by many, but it remains unclear the real role of this treatment and a meta-analysis of high-dose chemotherapy adjuvant trials is ongoing. Methods: Twenty-five consecutive high risk early breast cancer pts with at least 40 months of follow-up treated at our institution with HDCT are included in the present analysis. Median age was 44 (range 24–59 years) and 15 pts were premenopausal. The median number of axillary lymph-nodes metastases was 13 (range 3–49) and the pathological stage was IIB in one pt, IIIA in 3 pts, IIIB in one pt and IIIC in 20 pts. Estrogen and/or progesterone receptors were positive in 15 pts and both negative in 10 pts. The 10- year risk of relapse of pts with disease characteristics similar to those included in our study population is 80–85%. The HDCT regimen used was cyclophosphamide 7g/m2 plus G-CSF (followed by apheresis of peripheral haematopoietic stem cells), methotrexate 8 g/m2 followed by thiotepa 600 mg/m2 and melphalan 160 mg/m2 or by mitozantrone 60 mg/m2 and melphalan 180 mg/m2 and stem cells reinfusion. Results: At a median follow-up of 7 years (range 3,5 - 8 years) 13 pts (52%) relapsed and 10 pts (40%) died. The most common sites of recurrence were lung, liver and bones; 6 pts developed brain metastases and in 2 cases a bone marrow infiltration was documented. No toxic deaths and no long term toxicities, except irreversible amenorrhoea in all the premenopausal pts, were observed. No secondary malignancies occurred.The median relapse-free survival is 65,1 months, while the median overall survival has not been reached yet. Conclusions: In our experience high-dose sequential chemotherapy with autologous stem cells support is a safe treatment with no toxic deaths and no long-term toxicities. This regimen should therefore be further investigated if translational research will be able to identify subgroups of pts with the highest probability to benefit from intensive chemotherapy. No significant financial relationships to disclose.
Vorinostat (suberoylanilide hydroxamic acid) as salvage therapy in metastatic breast cancer (MBC): A California Cancer Consortium phase II study
Authors: Luu T. H. , Leong L. , Morgan R. , McNamara M. , Lim D. , Portnow J. , Frankel P. , Aparicio A. , Chew H. , Gandara D. R. , Somlo G. 
Published: March 2020

11502 Background: MBC patients (pts) have a median survival of 27 mo. Vorinostat is a small molecule inhibitor of histone deacetylase that exerts its targeted action during post-translational acetylation of core nucleosomal histones, affecting chromatin structure, thereby regulating genes implicated in cell survival, proliferation, differentiation, and apoptosis. The primary end point was to evaluate the response rate. Secondary endpoints included: time to progression, overall survival, toxicity, and assessment of biologic correlates. Method: From 6/05 to 3/06, we enrolled 14 pts with measurable MBC. Response and progression were evaluated using RECIST criteria. Two pts had no, 5 pts had one, and 7 pts had two prior regimens. Median age was 60.5 years (37- 89). Six were ER/PR positive, four were Her2neu overexpressers. Sites of metastatic disease included brain (1), liver, lungs, and bone (5), pelvic and chest wall (1), liver and bone (2), distant lymph nodes (3), pleura and bone (1). Pts received Vorinostat 200mg oral twice daily for 14 of 21 days per cycle. Tumor measurements were performed after every 2 cycles. Biopsies (pre and on-treatment) were collected from 6 of 14 pts. Results: The mean cycles delivered was 5 (range: 1–18). Four pts had SD for a median of >8.7 mo (4–13 mo); 1 pt with ER/PR/Her2neu negative tumor who received no prior treatment for MBC to mediastinal nodes and chest wall continues to receive treatment having completed cycle 18 with stable disease for >11.4 mo. The median duration on treatment for all pts is 3.2 mo (1–12 mo). Toxicities included gr 3 fatigue (1), gr 2–3 diarrhea (3), gr 2–3 nausea (2), gr 2 mucositis(1), gr 4 lymphopenia (1), gr 2–3 lymphopenia (6). Correlative studies of pre- and on-treatment tumor samples will be presented describing gene expression profiling using custom Agilent oligonucleotide microarrays optimized for analysis of RNA isolated from formalin fixed paraffin embedded tissues (FFPET). Conclusion: In this trial Vorinostat demonstrated disease stabilization rate in 4/14 (29%) pts by intention to treat analysis. With ease of administration, further investigation in combination with other agents is warranted. (NCI-NO1-CM- 62209) No significant financial relationships to disclose.
Serum glycan analysis in metastatic breast cancer
Authors: Chew H. K. , Miyamoto S. , An H. , Rocke D. , Lebrilla C. 
Published: March 2020

11504 Background: There is a need for a reliable breast cancer biomarker that can predict a patient’s response to therapy. Serum glycans, or oligosaccharides, are of particular interest as over half of all proteins are glycosylated and alterations in glycosylation influence growth, adhesion, metastasis and immune surveillance of tumor, among other important functions. Serum glycans can be analyzed by high resolution mass spectrometry. Methods: Sera from patients with known metastatic breast cancer and age-matched healthy controls without medical problems were prospectively analyzed by mass spectroscopy. Women over the age of 18, who were not pregnant or breastfeeding, and who were without other active cancers were eligible. Samples were de-identified for laboratory personnel who analyzed sera by matrix-assisted laser desoprtion/ionization (MALDI) and Fourier transform ion-cyclotron resonance mass sepctrometry (FT ICR MS). Glycans were also profiled by chromatographic separation using a microchip nanoLC (Agilent) with a time-of-flight (TOF) mass analyzers. Results: Sera from 25 patients with metastatic breast cancer and 25 controls were evaluated. The mass profiles were obtained corresponding to both N-linked oligosaccharides (N-glycans) and O-linked oligosaccharides (O-glycans). Distinct variations in glycosylation were observed among sera analyzed from patients with metastatic breast cancer compared to controls. Specific glycan masses were analyzed and found to correspond to N-glycans. The chromatographic glycan profile showed individual glycans that were distinct for the cancer patients. Conclusions: Analysis of serum gylcans by mass spectrometry represents a new paradigm of cancer biomarker studies, focusing on post-translational modifications of proteins, rather than protein expression. Further refinement of this technology may be clinically useful in monitoring response to therapy in metastatic breast cancer. No significant financial relationships to disclose.
Altered chemotherapeutic response of primary human breast cancer epithelial cells (HBCEC) and breast cancer cell lines
Authors: Hass R. , Lueck H. , von Wasielewski R. , Jin H. , Pich A. , Kuehnle H. , Grothuesmann D. , Hille U. , Bertram C. 
Published: March 2020

11506 Background: A novel technique to obtain individual primary cultures of human breast cancer biopsies was filed for patent (PCT/DE 2006/000608). The different individualized HBCEC (human breast cancer epithelial cell) cultures will be characterized and chemotherapeutic effects will be compared to established breast cancer cell lines. Methods: Primary HBCEC from 20 different breast cancer patients were characterized for epithelial cell and tumor markers by immunofluorescence and PCR. Following treatment with 1μM epirubicin for 1h up to 72h differences in protein expression patterns were compared to the similarly treated MCF-7 cell line by 2D gel electrophoresis. Differentially expressed protein spots were identified by mass spectrometry and confirmed by appropriate Western blot analysis. Results: Characterization of primary HBCEC revealed continuous mitosis and cell cycle progression for more than one year in culture with no significant contamination by fibroblasts or other cell types. Whereby HBCEC underwent cell death within 72h of epirubicin treatment analysis by 2D gel and subsequent protein identification by MALDI-TOF/TOF mass spectrometry exhibited a variety of differences compared to MCF-7 cells including HSP27 and prohibitin. Appropriate Western blots confirmed these differences and revealed altered expression levels for HSP27 and prohibitin in the course of epirubicin exposure in HBCEC and MCF-7 cells, respectively, suggesting altered signalling pathways in either primary breast cancer cells or the tumor cell line. Conclusions: Individualized primary HBCEC from various patients could provide a cellular platform beyond breast cancer cell lines, which eventually meet the requirements for an appropriate breast cancer testing system including the characterization of biomarkers and the identification of potential molecular targets. No significant financial relationships to disclose.