bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steroid hormone status and HER2/neu expression in pregnancy-associated breast cancer
Authors: Litwiniuk M. , Breborowicz E. , Breborowicz D. , Filas V. , Breborowicz J. 
Published: March 2020

21115 Background: Breast cancer occurring during pregnancy or within the first year after delivery is considered to be a pregnancy-associated breast cancer. Some studies have shown a decreased estrogen receptor-positive and progesterone receptor-positive status in pregnant patients with breast cancer, others, however, have not. Moreover, little information is available about the expression of HER2/neu and about the other human estrogen receptor, estrogen receptor beta (ERbeta) in pregnancy-associated breast cancers. The aim of this work was to determine the extent of the expression of ER alpha and beta, progesterone receptor (PgR) and HER2/neu in pregnancy- associated breast cancer. Material and Methods: Formalin-fixed, paraffin embedded tissues from 16 patients with pregnancy- associated breast cancer were used in this study. Immunostaining for ERalpha, ERbeta and PgR was performed using monoclonal antibodies against ERalpha, PgR (DakoCytomation) and against ERbeta (CHEMICON). The EnVision detection system was applied. Tumors were considered to be expressing receptors if a positive reaction (regardless of intensity) could be identified in at least 10% of cells. The HER-2 status was analyzed using HercepTest TM (IHC), and IHC 2+ results were confirmed with FISH test. Results: 44% of the tumors (7/16) were ERalpha and PgR positive. The expression of ERbeta protein was observed in 94% of pregnancy-associated breast cancers. As many as 50% of ERbeta positive tumors showed no expression of ERalpha. Further, 31% (5 of 16) of breast cancers were HER2/neu positive. Conclusions: This frequent expression of ERbeta in pregnancy-associated breast cancer may result from their prodifferentiative functions which increase during pregnancy and lactation. No significant financial relationships to disclose.
Noninvasive diagnostic test in breast cancer; utopia or option with serum proteomics?
Authors: de Noo M. , van der Werff M. , Gelderblom H. , Deelder A. , Tollenaar R. 
Published: March 2020

21118 Background: With a lifetime risk currently estimated 1 in 9, breast cancer is among the most common diagnosed malignancies. Proteomic expression profiling generated by mass spectrometry has been suggested as a potential tool for the early diagnosis of cancer. The objective of our study was to assess and validate the feasibility of this approach for the detection of breast cancer. Methods: In a randomized block design pre-operative serum samples obtained from 63 breast cancer patients and 73 controls were used to generate high-resolution MALDI-TOF protein profiles as a calibration set. The median age of the patient and control group was respectively, 52 (20–81) and 57 years (39–87). The MALDI-TOF spectra generated using WCX magnetic beads assisted mass spectrometry (Ultraflex) were smoothed, binned and normalized after baseline correction. After pre-processing of the spectra, linear discriminant analysis with double cross-validation, based on principal component analysis, was used to classify the protein profiles. Consequently, the classifier constructed on the first 2 plates was applied on the spectra of an independent validation set. This validation set consisted of serum samples from 29 breast cancer patients and 38 controls. The median age was 59 years (26–87) and 57 years (24–71) for the patient and control group respectively. Results: Double cross-validatory analysis carried out on the protein spectra of the calibration set yielded a total recognition rate of 86%, a sensitivity of 88% and a specificity of 84% for the detection of breast cancer within the calibration set. The AUC of this classifier was 90.3%. When this classifier was applied on the spectra of the independent validation set a total recognition rate of 80.9%, a sensitivity of 72% and a specificity of 89% were found. Conclusions: The use of a randomized block design, but mainly an independent validation set proves that discriminating protein profiles can be detected between breast cancer patients and healthy controls. Although further validation in larger series and identification of the discriminating proteins must be achieved, the high sensitivity and specificity indicate that serum protein profiles could be an option for the detection of breast cancer. No significant financial relationships to disclose.
Oncogenotoxicology: A new approach to individual therapy and to the follow-up of patients
Authors: Gamulin M. , Grgic M. , Bonassi S. , Lucas J. N. , Fucic A. 
Published: March 2020

21131 Background: The growing awareness of differences in inter-individual response to radiochemical exposure calls for a new approach in the therapy and follow-up of cancer patients. Results obtained by genotoxicological methods (Bonassi, 2006) showed that surrogate tissue could be used to predict cancer risk. Chromosome aberration (CA) and micronucleus (MN) assay enables:determination of radio- and chemosensitivity level in a patient, adjustment of therapy and detection of chromosomal rearrangements possibly related to the development of secondary cancer using fluorescent in situ hybridization (FISH) Methods: Ten women with breast cancer (BP) and 10 men with oropharinx cancer (OP) were analyzed before, during and after radiotherapy by CA and MN assay. Confounding parameters (age, diagnostics, smoking, drinking) were monitored and matched. Results were compared with 20 matched control subjects. The BP group received an irradiation dose of 60 Gy and the OP group of 62 Gy Results: Before therapy, the OP patients had a significantly higher MN frequency than BP and controls (23.2±4.9‰ versus 6.3±1.6 ‰ and 6.7±3.7‰). On measurements taken 6 and 12 months after the therapy, OP patients continued to have a significantly higher MN frequency than BP patients (60.2±11.4‰ vs. 8.4±2.4‰ and 30.7±4.7‰ vs.5.11±2.5‰, respectively). CA frequency was similar in both groups before therapy (2.5±1.1% in BC and 3.4±1.3% in OP; controls 1.2%). Twelve months after the therapy, the elimination of CA in OP patients was significantly slower than in BC patients (17.7±10.9% vs. 8±5.4%, respectively). As OP patients consumed more than 120 g/day of pure alcohol, it is possible that alcohol could have caused additional genome damage (Maffei, 2002). The highest inter-individual difference in genome damage was observed in BP patients Conclusions: The results show that the CA and MN assay are sensitive methods which can be used to introduce a new concept, oncogenotoxicology, whose goal is to improve the therapy results by evaluating inter-individual differences in response to radiochemical treatment and to improve the evaluation of risk of secondary cancer development. FISH in suspension (Wu, 2005) will allow automation of CA detection, and facilitate a more accurate prospective study of the same population. No significant financial relationships to disclose.
Intraoperative radiotherapy (IORT) impairs surgical wound-stimulated breast cancer cell invasion
Authors: Baldassarre G. , Belletti B. , Vaidya J. S. , D'Andrea S. , Roncadin M. , Perin T. , Trova M. G. , Candiani E. , Veronesi A. , Colombatti A. , Massarut S. 
Published: March 2020

21139 Background: Risk of local recurrence after complete excision of breast cancer is higher in the area around the original tumor, suggesting that wound healing may be implicated. Methods: We collected blood samples (BS) before surgery and wound fluid (WF) in the 24 hours after breast conserving surgery from 50 patients. Twenty five of these patients were also treated with TARGeted Intraoperative radioTherapy (TARGIT, 20Gy to tumor bed surface in one session), immediately after the surgical excision. The ability of the BS and WF to stimulate growth and motility of a panel of normal and mammary carcinoma cells was studied. A proteomic approach was used to analyze the expression pattern of WF and BS. Results: We assayed five cell lines in a transwell based assay using individual patient BS and wound fluids WF as potential chemo-attractants. WF strongly attracted cells from all 5 types of breast cancer cell lines that we tested including MDA- MB 231, MCF-7, MDA-MB 453, T47D and SKBR-3. The WF attracted the cells better than both the respective BS. Importantly, in all tested cell lines TARGIT significantly impaired the ability of WF to attract cancer cells (p=0.03 MDA-MB 231 and MCF-7. p=0.01 for MDA-MB 453, and SKBR-3). Moreover, while BS did not stimulate 3D motility over the control WF strongly stimulated 3D movement of MDA-MB 231 and MDA-MB- 453 cells. This stimulatory effect was abrogated in the WF taken from patients who had received TARGIT (p=0.01 for MDA-MB 231 and p<0.0001 for MDA-MB 453). Similar results were obtained when cell proliferation was evaluated using the same cell lines and BS or WF samples. Finally, proteomics analyses demonstrated that TARGIT modifies the expression levels of several key proteins involved in tumor cell growth and dissemination. Conclusion: TARGIT delivered to the tumor bed alters the cytokines and growth factors expression patterns in the surgical wound and abrogates its stimulatory effect on cancer cell growth and motility. This novel mechanism of action of radiotherapy could partly explain the very low recurrence rates found in large pilot studies of this technique and open new avenues for peri-operative therapies. No significant financial relationships to disclose.
Pathologic complete remission of cytologically proven axillary node metastases may be a strong prognostic factor in HER2-positive breast cancer
Authors: Sakakibara M. , Nagashima T. , Nakamura R. , Fujimoto H. , Arai M. , Kadowaki M. , Miyazaki M. 
Published: March 2020

21149 Background: Preoperative chemotherapy has become one of the standard modes of treatment in patients with breast cancer, and pathologic complete remission (pCR) thus obtained has become an important prognostic factor. However, the number of cells in the main lesion is enormous and changes over time in a heterogeneous manner. Thus, time and individual differences in sensitivity influence the acquisition of pCR, and questions about the coincidence with the effects of metastatic lesions also remain. On the other hand, although pCR of axillary lymph node metastasis lesions with relatively lower numbers of the cells is considered one of the best surrogate prognostic markers, evaluation criteria have not yet been established because definitive preoperative diagnosis is difficult. In our department, preoperative axillary cytodiagnosis has been conducted in all surgical breast cancer cases. In this study, we investigated pCR of the axillary lymph nodes (ALN- pCR) in cytologically proven axillary node metastasis cases. Subjects and Methods: ALN-pCR, DFS, and OS were investigated in 52 surgical breast cancer cases (observation period: 15–52 months; medial level: 28 months) positive for cytological axillary metastasis and received preoperative chemotherapy (AC-Paclitaxel) during the period from 2002 to 2005. Results: ALN-pCR was found in 21 of 52 cases (40.4%). Rates of disease-free survival (DFS) at 36 months in ALN-pCR and non-ALN-pCR cases were 85.0% and 42.3% (P=0.031) and those of overall survival (OS; 48 months) were 100% and 87.9% (P=0.353), respectively. DFS (36 months) was very favorable 100% in ALN-pCR cases that obtained the effect of 1b or higher on evaluation of the main lesion effect and ALN-pCR cases with Her2-positive results on sub-type analysis. Conclusions: ALN-pCR of cytologically proven axillary node metastasis was indicated to be a prognostic factor in cases of breast cancer. Especially, its importance was demonstrated in HER2-positive breast cancer. From these findings, HER2-positive and cytologically axillary lymph node-positive cases were considered the best indications for preoperative chemotherapy. No significant financial relationships to disclose.
Effects of low molecular weight heparin on angiogenic factors in advanced cancer patients
Authors: Coskun H. , Karakus N. , Vural H. , Akturk O. , Alanoglu G. 
Published: March 2020

21158 Background: The relationship between cancer and thrombosis is known for many years. Thrombosis can be associated with the biology and therapy of the disease in cancer patients. Low molecular weight heparin (LMWH) is shown to increase the duration of life in several types of cancer in clinical trials. Low molecular weight heparin is thought to be inhibiting with tumor growth and metastasis in several ways. In our study, we evaluate effects of LMWH therapy on angiogenic factors. Methods: Thirty-two advanced cancer patients who used prophylactic LMWH before chemotherapy. Median age was 64.5 years with range from 18 to 80. Sixteen healthy volunteers that are of same age and gender with study patients comprised the control group. VEGF, HGF, FGF, EGF, PDGF, ICAM, p-selectin, e-selectin levels were evaluated before and 7 days after LMWH therapy. Results: In baseline measurements HGF and ICAM levels were higher in treatment group compared the control group. But, levels of EGF and VEGF were not statistically significant higher in the treatment group compared to control group. After LMWH therapy, VEGF, FGF, PDGF, ICAM, e-selectin levels appeared to decrease and HGF, EGF, p-selectin levels appeared to increase but none of these changes were statistically significant. In a subset of seventeen patients with adenocarcinoma, levels of ICAM declined significantly after LMWH therapy this group. Before LMWH therapy; HGF was correlated with PDGF, VEGF, p-selectin, e-selectin; EGF was correlated with p-selectin; e-selectin was correlated with p- selectin. After therapy HGF was correlated with PDGF and EGF; PDGF was correlated with FGF and p-selectin; EGF was correlated with ICAM levels. Conclusions: In summary, with a short course of LMWH therapy a change in anjiogenic biomarkers was observed only in adenocarcinoma patients and this change was limited only to ICAM levels. The study focused on long term course was warranted. No significant financial relationships to disclose.
Examining ethnic differences for bevacizumab-induced hypertension and proteinuria
Authors: Choi Y. M. , Shord S. , Cuellar S. , Villano J. 
Published: March 2020

21168 Background: Bevacizumab is an increasingly used anti-cancer treatment with common side effects including hypertension (htn) and proteinuria which occur in approximately 10% and 20% of the patients, respectively. Little is known regarding ethnic variations of bevacizumab induced htn and proteinuria, particularly in African-Americans (AA) who have a high prevalence of htn and susceptibility to kidney disease. Methods: We conducted a retrospective chart review of patients who completed bevacizumab alone or as a chemotherapy regimen at the University of Illinois at Chicago for an 18-month study period. We collected blood pressure (BP) measurements and urinanalyses before starting bevacizumab, during bevacizumab and after stopping bevacizumab, in addition to concurrent medications, past medical history and demographics. Htn and proteinuria were graded by CTC v3.0. Patients with less than two successive doses of bevacizumab or unreliable ethnicity were excluded. Results: 27 subjects were eligible. Eighteen AA (67%) and 9 (33%) non-AA were included. Twenty-two (81%) had colorectal cancer. AA received a median of 10 cycles and non-AA received a median of 6 cycles. Six subjects (22%) developed any grade htn toxicity; maximum grade: grade 2=4 (15%), grade 3=2 (7%). Htn toxicity occurred in 28% AA and 11% non-AA (p=NS). Previous history of hypertension was found in 15 subjects (55%): AA=14 vs. non-AA=1 (p=0.002) and was not correlated with hypertensive toxicity. Twelve subjects (44%) developed any grade proteinuria; maximum grade: grade 1=9 (33%), grade 2=3 (11%). Proteinuria toxicity occurred in 50% AA and 33% non-AA (p=NS). Presence of hypertensive toxicity was associated with increased risk of proteinuria. Clinical benefit (PR, SD) was seen in 15 subjects (55%). Rate of clinical benefit was 67% in AA and 33% in non-AA (p=NS). Clinical benefit did not correlate with hypertensive or proteinuria toxicities. Conclusions: AA were more prone than non-AA to bevacizumab induced hypertension and proteinuria toxicity in this retrospective study. Higher clinical benefit was seen in AA. No significant financial relationships to disclose.
Inmunophenotypic profiles of male breast cancer
Authors: Martin Gomez T. , Torio B. , Ruiz I. , Arranz F. , Arizcun A. 
Published: March 2020

21180 Background: Recently, inmunophenotypic characterization methods have allowed identification of female breast carcinomas into separate groups showing different behaviour and response to therapy: luminal A phenotype (RE +, HER2-neu - ), luminal B (RE +, HER2- neu + ), basal like (RE -, HER2-neu - ). In this study, we used immunohistochemistry to investigate the inmunophenotypic profile distribution of male breast cancer. Methods: all the male breast cancers were obtained from the files of the Departments of Pathology of Hospital Río Carrión in Palencia, Spain, since 1996. A total of 9 cases were reviewed to confirm the diagnosis and to characterize each tumour. The following CK immunohistochemistry was performed: 8/18 and 5 (Dako, Carpinteria, CA, USA) in a Dako autostainer. ER was interpreted as positive if > 10% of the cells were staining. Normal skin and tonsils were used as positive controls for the CK and a known breast cancer for the ER immunohistochemistry. Results: five cases expressed RE and were HER2-neu negative, so they have a luminal-A phenotype. The four cases that expressed the luminal-B pehnotype expressed RE and HER2-neu; we demonstrated gene amplification of the HER-neu gene using fluorescent in situ hybridisation (FISH) in those cases. Respect the CKs profile, all cases were positive for CK 8/18 and negative with CK 5, vimentin and p63, characteristic of luminal-like CK expression profile, according wiht the literature. Conclusions: this is the first case series of male breast cancer patients that provides inmunophenotypic profile data on this rare disease in only one center in Spain. We comunicate that the vast majority of these tumours express the phenotype of luminal-like CKs. None of our patients were basal-like tumours. The percentage expression of Her-2 parallels the finding in female breast cancers and this should be analysed for its predictive significance, according to new specific biological treatments. No significant financial relationships to disclose.
A genotype-directed phase I study of irinotecan in advanced cancer patients
Authors: Innocenti F. , Janisch L. , Das S. , Ramirez J. , House L. , Maitland M. L. , Salgia R. , Ratain M. J. 
Published: March 2020

2502 Background: The risk of severe toxicity of irinotecan is in part related to the presence of common polymorphisms in UGT1A1, which codes for the enzyme responsible for the inactivation of SN-38, the active metabolite of irinotecan. The most common polymorphism in non-Asian populations is an extra TA repeat in the promoter (7 vs. 6), which reduces the enzyme expression. The three most common genotypes are: 6/6 (40–50%), 6/7 (40–50%), and 7/7 (10–15%). The 7/7 genotype confers the highest risk of toxicity, and it has been suggested that dose reduction is appropriate for patients with this genotype. As one published study has suggested that doses up to 500 mg/m2 q3w can be tolerated by some patients, we hypothesized that higher doses can be safely administered based on genotype by excluding patients with the 7/7 genotype. This study seeks to find the maximum tolerated dose (MTD) in patients with 6/6 and 6/7 genotypes. Methods: Advanced cancer patients (5 SCLC, 4 esophageal, 5 other tumors) have been genotyped for the UGT1A1 polymorphism. 6/6 and 6/7 patients have been treated with 700–850 mg (flat dose, corresponding to about 400–500 mg/m2) of q3w irinotecan. Dose-limiting toxicity (DLT) at cycle 1 is defined as grade =3 nonhematological toxicity, grade 4 neutropenia lasting more than 4 days, and febrile neutropenia. Results: Three 6/6 patients tolerated 700 mg (no grade >2 toxicity). Three additional 6/6 patients have been treated at 850 mg, and one DLT (grade 4 neutropenia lasting more than 4 days) was observed; 3 additional 6/6 patients will be enrolled at 850. Six 6/7 patients have been treated at 700 mg, with only one DLT (febrile neutropenia). Two additional 6/7 patients have been treated at 850, and one DLT (febrile neutropenia) has been observed. Conclusions: Higher doses of irinotecan can be safely administered in patients with selected UGT1A1 genotypes. On the basis of these interim results, a phase II trial in metastatic colorectal cancer patients with 6/6 and 6/7 genotypes has been designed to evaluate the efficacy of higher doses of irinotecan. [Table: see text]
Phase I study of LY573636-sodium, an acylsulfonamide anti-cancer compound with a novel mechanism of action, administered as 2-hour IV infusion in patients with advanced solid tumors
Authors: Ilaria R. L. , Simon G. R. , Sovak M. , Burton M. K. , Cleverly A. L. , Sykes A. K. , De Alwis D. P. , Wagner M. M. , Spriggs D. R. 
Published: March 2020

2515 Background: LY573636 -sodium (hereafter referred to as LY573636 ) is a novel anti-cancer compound that induces apoptosis by a mitochondrial-mediated mechanism. Methods: A phase I study was conducted to determine the maximum tolerated dose (MTD) and pharmacokinetic (PK) profile of LY573636 administered as an intravenous infusion over 2 hours every 21 days. Results: 53 patients (pts) were enrolled on study, 16 males, 37 females, with a median age of 58 (range: 18–83). LY573636 was dose-escalated using a flat dosing paradigm in the first 34 patients (range 100 mg to 2400 mg). PK analysis of this cohort revealed that LY573636 had a low total plasma clearance (CL = 0.02L/hr) and terminal elimination half-life of approximately 340 hours due to high-albumin binding (∼99%). The dose limiting toxicity (DLT) for the flat dose escalation was bone marrow (BM) suppression, which included CTC (ver2) grade 3/4 thrombocytopenia/neutropenia. In some patients, significant BM suppression occurred in cycle 2 and later, attributed to the accumulation of albumin-bound drug with repeated flat dosing. Based on these findings, the dose-finding strategy was modified to an idealized dosing paradigm which calculated LY573636 doses based on pt lean body weight, and used a loading/maintenance dose regimen to achieve a specific Cmax target value. All 3 pts in the first 400 μg/mL Cmax cohort completed at least 2 cycles and no DLTs were reported. Of the 16 pts enrolled to the 420 μg/mL targeted dose group: 1 pt reported a DLT, a transient grade 3 elevation of ALT/AST which did not recur in subsequent cycles; 8/16 pts received 4 or more cycles prior to disease progression and 2 remain on treatment. Overall, 23/53 pts had stable disease (SD) after 2 or more cycles. Seven pts received >8 cycles (SD > 6 mos), including heavily pre-treated pts with ovarian cancer, non-small cell lung cancer, soft tissue sarcoma, and thymoma. Conclusions: LY573636 is a novel anti-cancer compound with a unique mechanism of action. The most common DLT was BM suppression. The individualized, target Cmax dose of 420 μg/mL has been taken forward into phase II clinical trials. No significant financial relationships to disclose.