bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-15-03: Comparison of efficacy of primary prophylaxis with pegfilgrastim, filgrastrim and a biosimilar filgrastim in TAC regimen (docetaxel, doxorubicin and cyclophosphamide)
Authors: Brito M , Esteves S , Andre R , Isidoro M , Moreira A 
Published: August 2014

Abstract
Background: Febrile neutropenia (FN) is a major toxicity of myelosupressive chemotherapy. Primary prophylactic use of granulocyte colony stimulating factors (G-CSF) is recommended in high risk FN regimens.
The comparison of pegfilgrastim (Peg) and filgrastim (Fil) FN prophylactic effectiveness is still an issue of debate. Very recently Nivestim (Niv), a new biosimilar filgrastim, has also become commercially available.
We aimed to compare the efficacy of the 3 mentioned types of G-CSF in the primary prophylaxis of FN.
Methods: Single-center, retrospective study to evaluate the incidence of FN in women with breast cancer treated with adjuvant or neo-adjuvant TAC (FN risk ≥20%). Patients (Pt) were divided in 3 consecutive cohorts according to G-CSF primary prophylaxis (Fil, Peg and Niv) FN was defined as axillary temperature ≥38,3 °C and absolute neutrophil count &lt; 500/ul.
Results: We included a total of 421 women (median age 51 y, 25–76) with Stage II (56%) and Stage III (44%) breast cancer. Age and stage distribution were similar in the 3 cohorts.
A single dose of Peg was administered in all 767 cycles (cy). The standard dose of Fil and Niv was 7 daily injections, only in in 13% Fil pt and 10% Niv pt &lt; 7 administrations were done.
The incidence of FN per patient and per cycle is presented in Table 1. In all cohorts, approximately half of NF episodes occurred in the 1st cycle (48% Fil, 59% Peg, 42% Niv).

Conclusions: No differences in terms of efficacy existed between Biosimilar Niv and original biological reference Fil.
Seven daily injections of Fil and Niv seem equivalent to single dose Peg.
Besides efficacy, questions like cost-effectiveness and convenience of administration should be taken into account when approaching this topic.
Our data showed a predominance of events in the 1st cycle (regardless of the type of G-CSF). This has been consistently described in the literature and may support the necessity to recommend other NF preventive measures in this cycle.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-15-03.
Abstract P1-15-04: The relationship of relative dose intensity and supportive care to febrile neutropenia rates in patients with early stage breast cancer receiving chemotherapy: a prospective cohort study of chemotherapy-associated toxicity
Authors: Culakova E , Poniewierski MS , Wogu AF , Kuderer NM , Crawford J , Dale DC , Lyman GH 
Published: August 2014

Abstract
Background: Febrile neutropenia (FN) represents a major dose-limiting toxicity of cancer chemotherapy resulting in considerable morbidity, mortality, and cost. Patients have the highest risk of the initial neutropenic event in cycle 1 when most patients receive full dose chemotherapy. This study evaluates time course of neutropenic events in patients receiving chemotherapy for early-stage breast cancer (ESBC) and supportive care interventions that modify FN risk in ESBC patients treated in actual oncology practice.
Methods: A prospective cohort study of adult cancer patients with solid tumors or lymphoma starting a chemotherapy regimen was conducted at 115 U.S. sites. Toxicities associated with chemotherapy were recorded in up to 4 cycles including severe neutropenia (SN), FN, and infection. Documented clinical interventions included reductions in chemotherapy relative dose intensity (RDI), the use of colony-stimulating factors (CSFs), and antibiotics.
Results: A total of 1202 ESBC patients starting chemotherapy were analyzed, of which 1154, 1099, and 896 reached the midcycle of cycles 2, 3, and 4, respectively. While the majority of neutropenic and infection events occurred in cycle 1, decreasing rates of FN and infection in later cycles correlated with increasing reductions in dose intensity and increased use of CSFs and antibiotics.

The overall risk of FN in all patients combined was 16.3 %. It reached 21.1% for patients who started with planned RDI≥85% and without primary CSF prophylaxis. There was no significant difference in FN rates by menopausal status or hormone receptors.

Conclusions: While the risk of neutropenic complications is highest during the first cycle of chemotherapy, reductions in neutropenic events during subsequent cycles are associated with reduced chemotherapy dose intensity or increased use of supportive care measures. Nevertheless, the cumulative risk of neutropenic events remains high in ESBC patients receiving full dose chemotherapy without prophylactic measures overall and across menopausal and hormone receptor subgroups.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-15-04.
Abstract P2-01-12: Circulating tumor cells and Epithelial Mesenchymal Transition in primary breast cancer patients.
Authors: Mego M , Karaba M , Minarik G , Benca J , Sedlackova T , Manasova D , Sieberova G , Gronesova P , Pechan J , Mardiak J , Reuben JM 
Published: August 2014

Abstract
Background: Circulating tumor cells (CTCs) are prognostic in breast cancer (BC) patients. CTCs represent a heterogeneous population of cells with different phenotypes and biological value. Epithelial-mesenchymal transition (EMT) gives rise to cells with stem cell-like properties with increased chemotherapy resistance and may be responsible for undetection of CTC by conventional methods in a fraction of patients with early or advanced breast cancer. The aim of this study was to characterize CTCs based on the expression of epithelial and mesenchymal markers in non-metastatic breast cancer patients before surgery.
Methods: This prospective ongoing translational study consists of 36 patients with non-metastatic breast cancer. CTCs were detected before surgery, before 1st cycle and before 2nd cycle of adjuvant therapy. Herein, we present preliminary data related to CTCs detection before surgery. Isolated peripheral blood mononuclear cells (PBMC) were depleted of cells of hematopoietic origin (CD45+) using RossetteSep kit (StemCell Technologies) negative selection with anti-CD45 antibody. RNA extracted from CD45-depleted (CD45−) PBMC was interrogated for expression of EMT-inducing transcription factors (TWIST1, SNAIL1, SLUG, FOXC2) and epithelial (CK19, EpCAM) gene transcripts by quantitative reverse transcription-PCR. Expressions of gene transcripts in CD45- PBMC from patients were compared to those of CD45- PBMC of 30 healthy donors (HD).
Results: Median age was 62 year (range: 40–80 years). TWIST1, SNAIL1, SLUG, FOXC2, CK19 and EpCAM were overexpressed in CD45- PBMC in 2.8%, 2.8%, 11.1%, 13.9%, 19.4% and 2.8% respectively. Totally, CTCs were detected in 36.2% of patients. CTCs with only epithelial markers were present in peripheral blood of 5.6% patients; CTC with EMT phenotype were present in 13.9% of patients, while in 16.7% of patients CTCs exhibited both epithelial and mesenchymal markers. Overexpression of different EMT-related transcription factors in peripheral blood samples were mutually exclusive. There was no association between the presence of CTCs and analyzed clinico-pathological variables.
Conclusions: CTCs with EMT phenotypes are more prevalent compared to CTCs with epithelial phenotype in early breast cancer patients before surgery, and EMT genes may be involved in the dissemination of CTCs. These data support the concept of CTCs heterogeneity in breast cancer patients.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-01-12.
Abstract P2-04-04: Prolactin cooperates with loss of p53 to promote mammary tumorigenesis.
Authors: O'Leary KA , Sullivan R , Rugowski DE , Schuler LA 
Published: August 2014

Abstract
Prolactin (PRL) is critical for mammary development and lactation. Epidemiological studies also support a role for PRL in breast cancer. In order to study the contributions of PRL to tumor development and progression, we developed a transgenic mouse model that expresses PRL in the mammary epithelial cells (NRL-PRL), mimicking the mammary PRL production in women. Loss of function of the tumor suppressor p53 is a common occurrence in many human cancers including breast tumors. Interactions between PRL and p53 were examined by crossing the NRL-PRL mouse to p53 knockout mice which were made congenic on the FVB/N background. To circumvent the problem that p53−/− mice are prone to multiple nonmammary tumors, mammary cells from 10–12 week old wild-type, NRL-PRL, p53−/−, and NRL-PRL/ p53−/− were transplanted to wild type mammary glands. Histological analysis of the donor glands showed that NRL-PRL glands displayed marked epithelial proliferation and focally dilated ducts, whereas p53−/− glands exhibited irregular ductal epithelium with increased stromal density compared to wild type mice. In contrast, glands of donor PRL/ p53−/− females showed widespread epithelial hyperplasias and highly irregular ductal epithelium often surrounded by dense stroma. By one year of age, no tumors had developed from either wild-type or NRL-PRL transplanted epithelium. However, recipients of either p53−/− or NRL-PRL/ p53−/− mammary epithelium developed histologically similar anaplastic carcinomas. The presence of transgenic PRL decreased tumor latency (205 vs 244 days) and significantly increased tumor cell proliferation. In addition, these carcinomas appeared to be more aggressive: 5/16 (32%) of the NRL-PRL/ p53−/− tumors invaded into the peritoneal cavity, compared to 0/10 p53−/− tumors. Expression of matrix metalloproteinase 9 (MMP-9), but not MMP-2, was found to be significantly higher in the NRL-PRL/ p53−/−, compared to p53−/− tumors. MMP-9 is regulated by the transcription factor, AP-1, and PRL can signal through AP-1. NRL-PRL/ p53−/− tumors displayed significantly increased expression of the AP-1 family members, c-Jun and FosL, but not JunD or c-Fos compared to tumors from p53−/− mice. In addition, levels of c-Jun and FosL proteins increased in a similar pattern. In summary, interactions between PRL and loss of p53 promote breast cancer by increasing proliferation and invasiveness, potentially via AP-1 target genes. Supported by CDMRP BC053412.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-04-04.
Abstract P2-05-03: Mouse double minute 2 nuclear expression as a prognostic marker in patients with breast cancer
Authors: Park HS , Park S , Koo JS , Cho JH , Park JM , Kim S-I , Park B-W 
Published: August 2014

Abstract
BACKGROUND: Mouse double minute 2 (Mdm2) is a negative regulator of tumor suppressor, p53, thus Mdm2 expression may play a role in cancer development and prognosis, however, the definite role of Mdm2 in breast cancer is unclear. The aim of the study is to evaluate the correlation between Mdm2 expression and prognosis of breast cancer.
METHODS: Mdm2 expression was determined from immunohistochemistry of tissue microarrays of 865 patients with breast cancer who underwent surgery. Clinicopathologic characteristics and survival data were analyzed using a univariate and multivariate analysis. Mdm2 expression was categorized into 3 groups: negative; no Mdm2 expression in nucleus and cytoplasm, cytoplasm-positive; cytoplasmic expression of Mdm2, nucleus-positive; nuclear with or without cytoplastimc expression of Mdm2.
RESULTS: Negative, cytoplasm-positive, and nucleus-positive groups were observed in 59.2%, 10.9%, and 29.9% of patients, respectively. Nucleus-positive group was associated with young age, high grade, negativity of estrogen and progesterone receptor, HER2 positivity, and high Ki-67 index. With median 86.0 follow-up months, nucleus-positive group showed poorer disease-free survival and overall survival than negative and cytoplasm-positive groups. In multivariate analysis, cytoplsmic expression of Mdm2 was not significantly associated with survival, whereas nuclear expression of Mdm2 was related to poor prognosis. (HR, 1.44; 95% CI, 1.041–1.993 for DFS; HR, 1.546; 95% CI, 1.060–2.255 for OS)
CONCLUSIONS: Nuclear expression of Mdm2 was an independent prognostic factor in patients with breast cancer. Patterns of Mdm2 expression in tumor cell should be rendered in the evaluation of Mdm2 in breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-03.
Abstract P2-05-08: Determination of HER2 amplification by dual-color in situ hybridization before and after neoadjuvant chemotherapy
Authors: Niikura N , Kumaki N , Iwamoto T , Tsuda B , Okamura T , Yuki S , Suzuki Y , Tokuda Y 
Published: August 2014

Abstract
Background: HER2-targeted therapies such as trastuzumab neoadjuvant chemotherapy for patients with HER2-positive breast cancer can increase pathological complete response (pCR) better than non-HER2-targeted therapies. Previous studies have suggested that trastuzumab may convert HER2-positive (HER+) primary breast tumors to HER2 negative (HER−) after neoadjuvant chemotherapy. We compared the HER2 status in breast cancer patients before and after neoadjuvant treatment by using dual-color in situ hybridization (DISH).
Methods: We retrospectively identified 46 patients from the Breast Cancer database at Tokai University Hospital, in whom HER2-positive primary breast cancer was diagnosed between 2000 and 2010, and who were treated with neoadjuvant chemotherapy or endocrine therapy with or without trastuzumab. Surgical specimens from patients achieving less than pCR were assessed to determine if there was enough residual tissue to evaluate the post-treatment HER2 status by DISH. HER2 status was defined as positive if DISH demonstrated a gene copy ratio of HER2:CEP17 &gt;2.0. Paraffin tissue sections (4-μm thick) were mounted on glass slides (New Sliane III, Catalog No. 5126–25; MUTO PURE CHEMICALS, CO. LTD., Tokyo, Japan) and stained using the newly developed, fully automated HER2 Dual ISH assay on a BenchMark® XT slide stainer according to the recommended procedure (Ventana Medical Systems Inc., Tucson, AZ). Thereafter, the stained slides were rinsed with tap water containing neutral detergent and then rinsed again with distilled water. The slides were dried at room temperature for at least 60 min and cover-slipped with cover grass for SGC (MUTO PURE CHEMICALS). HER2 Dual ISH and H&E images were obtained using an Olympus BX51 microscope.
Results: A pCR was achieved in 9 of the 46 patients (19.6%). Specimens from core needle biopsy were not sufficient to assess the pretreatment HER2 status in 3 patients. In 9 patients, the post-treatment HER2 status could not be assessed because residual tumors were DCIS only in 4 patients and there were less than 20 invasive cells in 5 patients. Residual tumor was sufficient to assess the post-treatment HER2 status in 25 patients. In pretreatment specimens, of the 25 patients identified as HER2 + by immunohistochemical analysis, 3 patients were identified as HER2− by DISH. No post-treatment specimens were found to be HER2− by DISH among the tumors identified as HER2+ by DISH at pretreatment. Among the 3 pretreatment tumors identified as HER2− by DISH, 1 tumor was found to be HER2+ by DISH at post-treatment, and 2 showed a stable HER2 status.
Conclusion: DISH revealed a stable HER2 status in pretreatment breast tumors and in residual tumors. However, we found a discrepancy in the HER2 status between the immunohistochemical analysis and DISH.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-08.
Abstract P2-06-03: Specific Transcriptional Response of Four Blockers of Estrogen Receptors on Estrogen-Modulated Genes in ZR-75-1 Breast Cancer Xenografts
Authors: Calvo E , Luu-The V , Martel C , Labrie F 
Published: August 2014

Abstract
Introduction: Acolbifene (ACOL) is a novel compound completely free of estrogen-like activity in both the human and rat mammary gland and uterus. In previous studies, it was observed that ACOL could have a cytotoxic or tumoricidal rather only tumorostatic activity, with a lack of development of tumor resistance. The objective of the present study was to obtain information on the molecular basis of the tumoricidal properties of acolbifene, as well as on the identity of the genes potentially implicated in the resistance to tamoxifen (TAM). The specificity of action of ACOL was compared to the pure antiestrogen fulvestrant (FUL) as well as to tamoxifen (TAM) and raloxifene (RAL).
Methods: The gene expression profile of the ZR-75-1 breast cancer xenografts was studied following treatment with ACOL, RAL, TAM and FUL. Ovariectomized female nude mice (10/group) bearing human ZR-75-1 breast cancer xenografts were supplemented with estrone (E1) (subcutaneous silastic implants) and were injected daily with the vehicle alone or 50 μg of ACOL, RAL, TAM or FUL for 6 months. Mice were killed 24h after the last injection and ZR-75-1 tumors were collected and processed for RNA extraction and microarray analyses (Affymetrix GeneChip U133 Plus 2.0).
Results: Long-term exposure of ZR-75-1 xenografts to E1 causes a massive modulation of E1-responsive genes. When the antiestrogens were administered simultaneously with E1, some compound-specific prevention of the effect of E1 was observed. Globally, the efficacy of the compounds was ACOL&gt;FUL or RAL&gt;TAM. ACOL significantly prevented the effect of E1 on 195 responsive genes. Among these, the most enriched gene ontological group in Molecular Function was Receptor Activity, including ER, insulin, retinoid and thrombospondin receptor activity. One of the transcriptional repressors of the estrogen signaling pathway, the NKX31, was down-regulated by E1 and completely blocked by ACOL (fold-change −1.64 and 2.54, respectively). The most enriched biological processes were associated with mammary gland development, positive regulation of glucose metabolic processes and blood vessel morphogenesis. Between the genes implicated in cell death/apoptosis of breast cancer cells, the changes of expression of 57, 51, 48 and 31 genes were significantly neutralized by ACOL, RAL, FUL and TAM, respectively. Sixteen genes implicated in tumor resistance to TAM were significantly blocked by ACOL, including DEGS1, a gene implicated in the inhibition of EGF receptor biosynthesis. The other 15 genes in the group were up-regulated by E1, changes which were significantly blocked by ACOL.
Conclusion: The present data offer a possible explanation for the potent tumoricidal action of acolbifene in human breast cancer xenografts, thus offering a new paradigm in the hormonal therapy of breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-06-03.
Abstract P2-10-25: Prognostic value of relative change in tumor marker CA 27.29 in early stage breast cancer – The SUCCESS trial
Authors: Hepp P , Tesch H , Forstbauer H , Rezai M , Beck T , Schrader I , Kleine-Tebbe A , Hucke J , Finas D , Soeling U , Zahm D-M , Weiss E , Beckmann MW , Janni W , Rack B 
Published: August 2014

Abstract
Background: MUC1 based tumor markers like CA27.29 (TM) in breast cancer are routinely used in metastatic disease as early marker for treatment efficacy. However, in early stage disease data is sparse. In this analysis, we looked at the impact of individual change in CA27.29 on prognosis instead of using a threshold.
Methods: The SUCCESS Trial compares FEC-docetaxel (Doc) vs. FEC-Doc-Gemcitabine (Doc-G) regime and two vs. five year treatment with Zoledronat in 3754 patients (pts) with primary breast cancer (N+ or high risk N0). We measured CA27.29 after surgery but before chemotherapy (CHT) as baseline and compared it to CA27.29 levels 2 years thereafter with the ST AIA-PACK Ca27.29 reagent using MUC-1 for AIA-600II (Tosoh Bioscience, Tessenderlo, Belgium).
Results: CA27.29 data is available of 2,015 pts. 119 pts (5.9%) had TM over the threshold of 32U/ml before CHT and 56 (2.8%) 2years thereafter. To examine the relative change of tumor marker, pts were divided into 3 groups:
increase: change &gt;=5 U/ml; stable: change &lt;±5U/ml; decrease: change &gt; = −5 U/ml.
123 (6.1%) pts had increasing (&gt;=5 U/ml), 1419 (70.4%) had stable, 473 (23.5%) had decreasing TM levels from before CHT to 2 years thereafter. The majority of pts with increasing TM (86 pts; 69.9%) had levels below the usual threshold of 32U/ml at all times. Patients with an increase &gt;=5 U/ml had an 81% increased risk for recurrence (HR = 1.810 [CI: 1.111–2.948]) and reduced overall survival (HR = 1.020 [CI: 1.004–1.037]). In the multivariate analysis taking into account tumor size, nodal status, grading, age, hormonal and HER2/neu receptor status increasing CA27.29 levels were an independent prognostic marker.
Conclusions: An increase of the tumor marker CA27.29 2 years after CHT compared to pre-chemotherapy baseline was associated with a worse prognosis. By using this approach, more patients at risk for recurrence were detected than with the standard threshold approach. Therefore, the use of relative change could help to identify more patients at risk for relapse who might benefit from an intensified follow up.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-25.
Abstract P2-10-35: The grade of accompanying DCIS in IDC as important prognostic factor
Authors: Kim JY , Moon H-G , Han WS , Noh DY 
Published: August 2014

Abstract
Backgrounds: The issue of whether concomitant ductal carcinoma in situ (DCIS) affects the prognosis of with invasive breast cancer is important but studies of this have reported inconsistent results. So we aimed to assess the character and prognostic difference in infiltrating ductal carcinoma (IDC) according to accompanying DCIS status.
Methods: We reviewed the medical records of the patients who underwent surgery for IDC. Male patients, patients who had received neoadjuvant chemotherapy, patients with synchronous bilateral breast cancer, follow-up periods &lt;6months or those with other malignancies were excluded from the study. In cases in which a DCIS component was present in IDC, the degree of differentiation and the presence of necrosis were assessed to subdivide DCIS into two groups; low and high grade.
Results: A total of 1751 patients were included, and 1384 patients (79.0%) had concomitant DCIS; 337 had low-grade DCIS, and 1047 patients had high-grade DCIS. The low-grade DCIS group had a significantly lower TNM stage than the high-grade DCIS group. The majority of cases with low-grade DCIS, were ER-positive (85.2%), PR-positive (81.3%) and had low Her-2 (98.7%).

When we analyzed the survival rates according to the presence of DCIS, no statistical significance was founded. However, a subgroup analysis showed that the patients with low-grade DCIS survived significantly longer than other patients, whereas those with high-grade DCIS had poorer survival (5 year event-free survival rate; low-grade DCIS vs. without DCIS vs. high-grade DCIS, 97% vs. 93% vs. 86%, p = 0.001). Specially, in patients with lymph node involvement, accompanying high-grade DCIS was independent predictor distant metastasis (HR 5.0, p = 0.026, 95% CI 1.21–20.92).

Conclusion: The important factor that affect prognosis of IDC with DCIS is not the presence itself of DCIS component but the grade of DCIS. The patients with low-grade DCIS had a good prognosis and those with high-grade DCIS had a poor prognosis.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-35.