bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of IKKe expression by androgen receptor and NF-kB transcriptional factor in prostate cancer
Authors: Péant B. , Diallo J. , Lessard L. , Mes-Masson A. , Saad F. 
Published: March 2020

10106 Background: In unstimulated cells, NF-kB transcription factor is sequestered in the cytoplasm as an inactive p65/p50 dimer through interaction with a member of the inhibitor of kB protein family (IkBa). Prominent constitutive activation of NF-kB was observed in prostate cancer (PCa) cell lines lacking androgen receptor (AR) expression (PC3 and DU145) whereas only very low levels of NF-kB activity were seen in androgen-dependent cell lines (LNCaP and CWR22Rv1). As IkB kinase-e (IKKe) has recently been shown to be controlled by NF-kB, we hypothesize that IKKe may be involved in PCa progression based on its interaction with the NF-kB protein, and that these interactions are influenced by AR signaling. Methods: LNCaP cells were used to study IKKe expression with or without stimulation by the analog of androgen R1881 and by the tumor necrosis factor (TNF)-a. IKKe protein and RNA expression were characterized by immunoblot assay and quantitative PCR, respectively. IKKe expression was then correlated with p65 nuclear localisation. NF-kB activity was inhibited using an IkBa dominant negative construction. Inhibition of AR synthesis was performed using a siRNA against AR. Results: IKKe gene expression was stimulated by TNF-a treatment in LNCaP cells and inhibited by transfection of a dominant negative form of IkBa which prevented the nuclear translocation of p65. We also observed constitutive IKKe expression in hormone-refractory cells. Furthermore, we showed that TNF-a-induced IKKe expression is inhibited by R1881 in hormone-responsive PCa cells and this inhibition was correlated with the modulation of IkBa expression by R1881. Finally, we observed that the expression of IKKe is constitutively induced after blocking AR expression in LNCaP cells. Conclusions:. Our results show that IKKe expression is regulated by NF-kB in PCa cell lines. Moreover, IKKe appears to be down-regulated by ligand-dependent AR signaling through the control of IkBa expression. Further studies will be needed in order to determine the implications of this phenomenon with regard to NF-kB regulation, androgen resistance and effect on PCa progression. No significant financial relationships to disclose.
Lymphatic mapping of ductal carcinoma in situ diagnosed by stereotactic core needle biopsy
Authors: Meijnen P. , Van Rijk M. C. , Oldenburg H. S. , Loo C. E. , Valdés Olmos R. A. , Nieweg O. E. , Peterse J. L. , Van de Vijver M. J. , Rutgers E. J. 
Published: March 2020

10507 Background: About 20% of ductal carcinoma in situ (DCIS) lesions diagnosed by stereotactic core needle biopsy (SCNB) are shown to be invasive on postoperative pathology examination. Sentinel lymph node biopsy (SLNB) is an accurate method of evaluating axillary lymph nodes in patients with invasive breast cancer. The aim of this study was to review our experience with lymphatic mapping in patients with a SCNB diagnosis of pure DCIS, to evaluate the DCIS underestimation rate and consequently the risk of lymph node metastases. Methods: Files from 160 patients diagnosed with pure DCIS by SCNB between July 1999 and March 2005 were retrieved from our database. Patients with DCIS were selected for SLNB if there was concern for presence of an invasive component on the basis of size, palpability or imaging. Results: The median age of the study group was 55 years (range 29–85 years) and median DCIS size on mammography was 25 mm (range 4–96 mm). Thirty-six (23%) out of the 160 women underwent a SLNB. Macrometastases in the sentinel node were detected in seven (19%) patients and one (3%) patient was found to have a micrometastasis. Twenty (56%) of these 36 patients had invasive lesions on final pathology. Of the 124 women who did not receive SLNB, 29 (24%) turned out to have invasive lesions on postoperative evaluation. In total, 49/160 (31%) patients with pure DCIS diagnosed by SCNB had invasive breast cancer (range pT1mic-pT2) on final pathology. Finally, 88 patients underwent lymphatic staging by SLNB, basal node sampling or complete axillary lymph node dissection. Nodal involvement was present in 14 (16%) out of these 88 patients with initially diagnosed DCIS: 36% in patients with invasive breast cancer and 2% with pure DCIS on final pathology. Conclusion: Postoperative pathology examination of the specimen demonstrates DCIS underestimation in nearly one third of SCNB diagnosed DCIS patients. SLNB is of benefit for these patients as in 19% of the patients who undergo a SLNB macrometastatic disease in the sentinel node can be found. No significant financial relationships to disclose.
hTert, MMP1, Her2 expressions by preneoplastic lesions and breast cancer risk
Authors: Hernandez J. , Mathieu M. , Taranchon E. , Spielmann M. , Delaloge S. , Soria J. , André F. 
Published: March 2020

10510 Background: Although it is well established that preneoplastic lesions are associated with an increased risk of breast cancer, there is no available tool to identify which patients will develop breast cancer. Telomerase, matrix metalloprotease 1 (MMP1) and Her2 have all been involved in the early steps of carcinogenesis. In the present study, we have looked at whether the expression of hTert, MMP1 and her2 in preneoplastic lesions were associated with higher risk of breast cancer. Methods: hTert, MMP1 and Her2 expressions by preneoplastic lesions were determined by immunohistochemistry in 34 patients who have subsequently developed a breast cancer (cases), and in 32 patients who did not present breast cancer in the follow-up (control). Patients were matched for age, length of follow-up and type of preneoplastic lesion. The expression of the three biomarkers was compared in the two groups. The initially planned sample size of the study was 90 matched patients, but only 66 samples could be proceed for technical reasons. Results: Median age was 47 and 49 years old in patients with and without further cancer respectively. In the group of patients who subsequently developed breast cancer (cases), preneoplastic lesions consisted in lobular hyperplasia or lobular in situ carcinoma in 17 cases, ductal atypical hyperplasia in 12 cases and mixed lesions in 5 cases. In the control group, preneoplastic lesions consisted in lobular hyperplasia or lobular in situ carcinoma in 18 cases, ductal atypical hyperplasia in 12 cases, mixed lesions in 2 cases. The median interval between the diagnosis of preneoplastic lesion and the occurrence of breast cancer was 72 months (17–291). hTert was expressed in 8 (27%) and 2 (7%) assessable lesions in cases and controls respectively (p = 0.04). MMP1 was expressed in 21 (65%) and 22 (73%) assessable lesions in cases and control respectively (p = 0.49). Her2 was expressed in 6 preneoplastic lesions both in cases and controls (20%). Conclusions: This study suggests that hTert expression by preneoplastic lesions could be associated with an increased risk breast cancer. No significant financial relationships to disclose.
Biological effects of pegfilgrastim after myelosuppressive chemotherapy in breast cancer
Authors: Danova M. , Bencardino K. , Grasso D. , Manzoni M. , Collovà E. , Ferrari S. , Travaglino E. , Rovati B. , Porta C. , Invernizzi R. 
Published: March 2020

10521 Background: The dose and schedule of chemotherapy (CT), that play a crucial role in the outcome of pts with chemosensitive tumors, were made feasible with the primary use of colony stimulating factors. Few data are available on the in vivo biological effects of the “long-lasting” cytokine pegfilgrastim. We have focused on the cytokinetic effects on the CD34+/38+ peripheral blood (PB) progenitor cell subset and on its influence on neutrophils functional parameters. Methods: We studied PB samples from 14 breast cancer pts (median age 47 yrs; 35–61 yrs), treated with Docetaxel (80 mg/sqm, d 1) + Epirubicin (75 mg/sqm, d 1) + pegfilgrastim (6 mg s.c. on d +1). The % of CD34+/38+ circulating progenitor cells (CPCs) (sorted with immunomagnetic procedure) undergoing G0/G1, S and G2/M phases of the cell cycle or showing apoptotic features were evaluated using flow cytometry. Annexin V was quantitated at a single cell level and correlated with cell cycle phases. On PB buffy coat smears, alkaline phosphatase activity by cytochemistry, actin polymerization using FITC-labelled phalloidin and apoptosis by TUNEL technique, were evaluated on neutrophils. Results: Seven days following CT + pegfilgrastim the CD34+/38+ absolute numbers were: 46 (27–74) and 41 (25–66) on day 14+ from CT.On day 7+ the % of CD34+/38+ CPCs in S-phase was 13.0 ± 9 while 3.7% ± 6 of this cell subset showed apoptotic features. One week later, these values were 8.4% ± 7 and 7.7% ± 5, respectively. We also observed: stability of the absolute neutrophil count for all the duration of treatment; a significant increase of the leucocyte alkaline phosphatase; abnormalities of actin assembly in neutrophils, indicative of changes in cytoskeleton organization, and a significant reduction of neutrophil apoptosis. Conclusions: 1) pegfilgrastim exerts stimulatory effects on cell cycle status of PB CD34+/38+ CPCs, protecting them from apoptosis; this is evident 7 days after its administration and tends to decrease one week later 2) pegfilgrastim improves the neutrophil function by inhibiting their accelerated apoptosis and prolonging survival. These data could be useful when dose-dense CT is planned with pegfilgrastim support. No significant financial relationships to disclose.
Phase I/II trial in patients with metastatic breast cancer (MBC) previously treated with a taxane and an anthracycline: Final safety data
Authors: Vahdat L. T. , Klimovsky J. , Bunnell C. A. 
Published: March 2020

10528 Background: Ixabepilone, a semi-synthetic analog of the natural product epothilone B, has shown anti-tumor activity in a broad range of tumor types including breast cancer. Preclinical studies suggest synergy between ixabepilone and capecitabine in breast cancer models and has fuelled interest in the clinical setting. Methods: This open-label Phase I/II study was conducted to determine the recommended Phase II (and III) doses of ixabepilone and capecitabine using a 3-hour infusion of ixabepilone given on Day 1 (Schedule A) or a 1-hour infusion of ixabepilone given for 3 days (Schedule B) in combination with capecitabine given orally on Days 1–14 every 21 days in patients (pts) with MBC previously treated with a taxane and an anthracycline. Eligible pts were aged ≥18 years with pathologic diagnosis of breast cancer and evidence of MBC, who had received prior treatment with a taxane and an anthracycline in the adjuvant or metastatic setting. Pts were excluded if they had received >3 prior chemotherapy regimens in the metastatic setting or had ≥Grade 2 neuropathy. Toxicity was continuously monitored using NCI CTC v2. Results from the 62 pts treated with 40 mg/m2 as a 3 hr-infusion ixabepilone and 2000 mg/m2 capecitabine are shown here. Results: 56 of the 62 pts (90%) were aged <65 years. 80% of pts had visceral disease; 44% were ER/PR/HER-2 negative. 44% of pts had received ≥ two prior chemotherapies in the metastatic setting. Grade 3 neuropathy (sensory and motor) was reported in 12 pts and 1 pt (19%, 2%), respectively. Hand-foot syndrome, reported in 39 pts (63%), was primarily Grade 2 (26%) or 3 (34%). Hematologic toxicities included Grade 4 leukopenia (7 pts, 12%) and Grade 4 neutropenia (16 pts, 26%). Dose reductions were used to manage sensory neuropathy and hematologic abnormalities. Conclusions: The recommended Phase II (and III) doses are 40 mg/m2 ixabepilone (3-hour infusion on Day 1 every 21 days) and 2000 mg/m2 capecitabine (divided BID on Days 1–14 every 21 days). This ixabepilone/capecitabine combination demonstrated a manageable safety profile and promising clinical anti-tumor activity in pts with MBC previously treated with a taxane and an anthracycline. [Table: see text]
Breast sentinel lymphadenectomy—Is immediate intra-operative assessment warranted?
Authors: Tafe L. J. , Tsongalis G. J. , Kaufman P. A. , Moore C. P. , Wells W. A. 
Published: March 2020

10533 Background: Sentinel lymphadenectomy is the standard of care in breast cancer evaluation. Since conventional axillary dissection is only considered for patients (pts) with sentinel lymph node positive (SLN+) disease, there is increasing interest in immediate intra-operative assessment of SLN by frozen section or RT- PCR. Methods: Institutional SLN cases (2003–2004) were retrospectively reviewed. Each SLN (submitted in toto for processing with 21 tissue levels/block, H&E staining, and cytokeratin (CK) immunostudies) was evaluated for tumor deposit size, distribution and extranodal extension. Results: 80% (n = 222) of pts had SLN biopsy: 50% at primary excision, 21% at mastectomy, 9% at re-excision and 20% as a separate procedure. 1–4 SLN were sampled in 41%, 25%, 19%, and 14% respectively with no node identified in 1 case. Of all, 31% (n = 68) had >/=1 (+) node and 72% of those (n = 50) had a completion axillary dissection. 50% of pts required separate surgical procedure. Only 21% (n = 14) of pts with SLN+ had subsequent (+) axillary nodes on completion dissection. Nodal deposits ranged in size from </= 0.02 cm (13%) to >2.0 cm (1%). The majority (26%) were in the micrometastasis range of >0.02<0.2 cm, where CK-immunostaining was useful to confirm detection. 19% were >/=0.2< 0.5 cm, 25% >/= 0.5<1.0 cm, and 15% >/= 1.0<2.0 cm. 3% SLN showed CK(+)-only cells without H&E confirmation. Tumor sites were parenchymal (1%), subcapsular (31%), or both (68%). Only 7% of nodes with subcapsular metastases were associated with subsequent positive axillary nodes. In 91% (n = 62) of SLN+ cases, metastases were identified in the first 3 tissue levels. Extranodal extension was seen in 22%. Conclusions: Overall, 31% were SLN+; 21% of those were node + in subsequent axillary sampling. These findings do not support the labor and expense of immediate intraoperative SLN assessment. 3-level tissue processing with simultaneous RT-PCR could be performed on all SLN. Subsequent tissue leveling and immunostaining could potentially only be performed on PCR+ cases to provide metastasis size and extranodal extension. PCR probes can also facilitate detection of novel prognostic markers. Additionally, identification of only subcapsular deposits may warrant foregoing subsequent axillary sampling in some clinical scenarios. No significant financial relationships to disclose.
Phase II study of docetaxel plus epirubicin versus docetaxel plus cisplatin as first-line chemotherapy for treatment of advanced breast cancer (CHN TAX-618)
Authors: Wang Y. J. , Fu Q. , Wu Q. , Su F. X. , Zhou L. Z. , Ye Z. B. , Yang J. Q. 
Published: March 2020

10535 Background: The combination of docetaxel plus epirubicin (TE) have demonstrated a significant activity in advance breast cancer (ABC) as first-line chemotherapy. In the meantime, some emerging literatures suggest that docetaxel-cisplatin (TP) combination has a powerful synergistic interaction with less cardiotoxicity. The main objectives of this multicenter study are to evaluate the efficacy and safety of TE versus TP. Methods: From August 2003 to February 2005, 80 patients with at least one measurable lesion were randomized with ratio of 2:1 to receive TE or TP as as first-line chemotherapy. Dosages were as follows: docetaxel 75 mg/m2 plus epirubicin 60 mg/m2 or docetaxel 75 mg/m2 plus cisplatin 75 mg/m2 intravenously once every 3 weeks for a maximum of 6 cycles. Baseline characteristics were well balanced. Results: A total of 55 patients were assigned to TE (median age 48 yearas) and 25 patients were treated with TP (median age 50 yearas). The same of median 4 cycles treatment were administered for two arms. A complete clinical response was observed in 3.6% and 4.0% of patients treated with TE and TP, respectively (P = 1.00). Overall (complete and partial) clinical response rates for TE and TP were 48% and 56%, respectively (P =0.469). Disease control rates (CR + PR + SD) for TE and TP were 83.6% and 80%, respectively (P = 0.755). The median TTP were TE: 10.8months,TP: 11.2 months days (P = 0.247). Grade 3/4 toxicities included: nausea/vomiting (16.3% TE; 12.0% TP); diarrhea (1.8% TE; 0% TP); alopecia (32.7% TE; 12.0% TP); anemia (1.8% TE; 4.0%TP); neutropenia (65.5% TE; 4.8% TP); febrile neutropenia (3.6% TE; 0% TP). Conclusions: Both TE and TP were active and tolerant regimens for ABC. While there may have been a trend toward lower toxicities in favor of the docetaxel/cisplatin combination, although no significant difference was observed during our study. No significant financial relationships to disclose.
High malignancy yield in core needle biopsy of BIRADS 3 breast lesions with calcification
Authors: Larke A. , O’Doherty A. , Quinn C. 
Published: March 2020

10568 Background: Breast cancer screening programmes reduce mortality but result in increased numbers of breast biopsies. Stereotactic and ultrasound-guided core needle biopsy yield similar results to each other and to open biopsy. Study: Analysis of prospectively-acquired data relating to 174,338 screening mammograms performed in BreastCheck between Jan 2001 to Oct 2004. Relative use of ultrasound and stereotactic guidance for core needle biopsy is ascertained, and malignancy yields analysed. Results: In this time period, 174,338 screening mammograms discovered a total of 2782 lesions requiring further assessment. Of 2760 complete records, 1066 were BiRads R3–5 (39%) and 1033 of these (97%) had CNB. Guidance was provided exclusively by ultrasound in 737 (71%), and by stereotaxis in 270 (26%) of cases. There were no differences in malignancy yield of ultrasound versus sterotactically-guided CNB of R4 and R5 lesions (approximately 50% and 90% respectively). The malignancy yield in R3 lesions was significantly higher when performed with stereotactic guidance (12%) than when performed with ultrasound-guidance (5%) and both were significantly higher than R3 biopsy malignancy yields reported in the literature. Conclusion: Almost all BIRADS 3, 4 and 5 lesions are biopsied. The relatively high malignancy yield in R3 biopsies, particularly those with calcification, supports current practice. No significant financial relationships to disclose.
Brachial plexopathy in breast cancer
Authors: Terstriep S. , Amrami K. , Spinner R. , Moynihan T. 
Published: March 2020

10601 Background: Brachial plexopathy is a well-recognized complication of breast cancer, most attributed to late effects of radiation. However, direct involvement of brachial plexus by recurrent breast cancer occurs. Misdiagnoses may lead to inappropriate attribution of the plexopathy to radiation, and therefore inappropriate therapy. Methods: We report fourteen cases of brachial plexopathy secondary to breast cancer diagnosed at the Mayo Clinic-Rochester from 2003 to 2005. Results: Thirteen of fourteen primary tumors and 12/14 recurrences were ER/PR positive. Only 1/14 patient had Her 2 neu overexpression. The median time from the original breast cancer diagnosis to first brachial plexus symptom was 14 years. The median time from the development of symptoms to diagnosis was 8 months with the range being 1 month to 8 years. MRI revealed a distinct mass in 3/13 patients, plexus thickening in 5/13, and was normal in 5/13. Only 5/13 original MRI interpretations suggested tumor. In four patients that the 1.5 T MRI was either interpreted as normal or unlikely cancer the 3 Tesla MRI revealed abnormal uptake suggestive of malignancy. PET scan suggested malignancy in 3/6 patients. Two of these cases had other metastatic disease. In the other three cases that PET scans were done the uptake was mild, suggesting inflammation rather than malignancy. Reinterpretations of the PET scan and MRI in combination by an experienced musculoskeletal radiologist was highly suggestive of malignancy in all cases. Definitive diagnosis was eventually obtained by biopsy of the brachial plexus (7/14) or another site of metastasis in (4/14). Conclusions: The often slowly progressive nature of hormonally driven breast cancer can mimic radiation induced brachial plexopathy. In the cases reviewed, PET was not reliable in differentiating inflammation from tumor. MRI findings are nonspecific and higher resolution 3T MRI may be needed to detect an abnormality. Interpretation of MRI and PET together is useful. Patients with a history of breast cancer, and brachial plexus symptoms should be carefully evaluated with consideration for recurrent disease as a cause. Biopsy of the brachial plexus can be done safely and has an important role in diagnosis. No significant financial relationships to disclose.
Micrometastasis in sentinel (SLN) and non-sentinel lymph nodes of breast cancer: An update including clinico-pathologic impact and survival
Authors: Masci G. , Di Tommaso L. , Del Prato I. , Orefice S. E. , Gullo G. , Rubino A. , Eboli M. W. , Morenghi E. , Roncalli M. , Santoro A. 
Published: March 2020

10602 Aims: To assess the rate of positive axillary clearance when the SLN biopsy contains micro-metastatic disease and to evaluate the survival impact of local lymph nodes with micro-metastases. Materials and Methods: From 1997 to 2005 2,750 consecutive patients (pts) underwent breast surgery with SLN biopsy or axillary dissection. Of these, 87 pts had lymph node micro-metastases assessed with haematoxylin and eosin or cytokeratine staining and defined according to the current TNM classification. Lymph node micro-metastases were found after axillary dissection in 27 pts and after SLN biopsy in 60 cases; 55 (63.2%) were micro-metastases 0.2–1 mm, 22 (25.3%) measured 1–2 mm, 7 were isolated tumor cells and in 3 cases size was not available; micro-metastases were located within lymph node sinuses in 43 and in nodal parenchyma in 37 cases. Age: median 53 years (range 34–78), surgery: 77 (88.5%) conservative and 10 radical mastectomy; histotype: 79 (90.8%) ductal, 4 lobular, 2 tubular and 2 other histotypes. T stage: pT1a/pT1b in 16 (18.4%), pT1c in 54 (62.1%) and pT2 in 17 (19.5%) pts; grading 3 in 24 pts (27.6%); 76 pts (87.3%) had positive Er/Pgr; vascular invasion: present in 30 pts (34.5%); HER-2/neu overexpression in 16 (18.4%) pts; 64 pts (73.6%) received adjuvant chemotherapy (49 AC, 11 CMF ev, and 4 FEC); 69 pts (79.3%) had radiotherapy and hormonal therapy. Results: Among 60 pts with SLN micro-metastases, 8 (13%) had further axillary involvement; in 5/8 cases size of micro-metastases was >1 mm, in 7/8 cases micro-metastases were located in the nodal parenchyma. These 8 pts were not considered for survival analysis. Of the remaining 79 patients with micro-metastases, survival data were as follow: at median follow-up time of 32 months (range 2–158) 69 pts were alive without any evidence of disease, 4 pts died of disease and 6 pts were alive with disease. Three years DFS was 87.75% and OS 95.57%. Conclusions: Further axillary involvement was found in 13% of pts with micrometastases in the SLN biopsy supporting complete nodal dissection in all pts.Our preliminary results show that even minimal nodal involvement could correlate to worse prognosis and may require adjuvant treatment. No significant financial relationships to disclose.