Impact of biomarkers in predictivity of the efficacy and toxicity of a combination of panitumumab plus FEC 100 followed by docetaxel in a phase II neoadjuvant trial for triple-negative breast cancer (TNBC) patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1051-1051
Author(s):  
Jean-Marc A. Nabholtz ◽  
Marie-Melanie Dauplat ◽  
Catherine Abrial ◽  
Beatrice E. Weber ◽  
Marie-Ange Mouret-Reynier ◽  
...  
Keyword(s):  
Ductal Carcinoma ◽  
Skin Toxicity ◽  
Ki 67 ◽  
Cutaneous Toxicity ◽  
Before And After ◽  
Hand Foot Syndrome ◽  
Grade Ii ◽  
Cutaneous Toxicities ◽  
Grade Iii

1051 Background: We evaluated the combination of a standard chemotherapy with panitumumab as neoadjuvant therapy of operable TNBC. Complete pathologic response (pCR) was the primary endpoint, with toxicity and biologic ancillary studies as secondary endpoints. Methods: Sixty patients with stage II-IIIA disease were prospectively included in this multicentre pilot study. Systemic therapy (ST) consisted of 4 cycles of FEC 100 (500/100/500 mg/m2) q.3 weeks followed by 4 cycles of T (100 mg/m2) q.3 weeks, in combination with panitumumab (9 mg/kg) for 8 cycles q.3 weeks. All patients underwent surgery at completion of ST. Paraffin-embedded samples and frozen samples have been systematically realised before and after neaodjuvant treatment in order to evalutate the biological profile of the tumor. Patients characteristics are : median age 50 ; median tumor size : 40 mm ; invasive ductal carcinoma : 96% ; Scarff-Bloom-Richardson Grade III : 70%, grade II : 30%, ki-67-positive : 100%, EGFR-positive : 78%, cytokeratine5-6-positive : 48% and p53-positive : 59%. Pathological response showed a pCR according to Sataloff’s classification of 52.38% and according to Chevallier’s classification of 46.52%. Skin toxicity was the main side-effect : Cutaneous toxicity grade IV : 5%, grade III : 30%, grade II : 20%. Neutropenia grade IV : 27% ; febrile neutropenia : 5%. Infection : 0%. Hand-foot syndrome grade III : 3.3%. Ungueal toxicity grade III : 1.6%, grade II : 20%. Results: We have tested the predictive value of ki-67, EGFR, cytokeratine 5-6 and p53. Only ki-67 is predictive of a pCR according to Chevallier’s classification (p=0.026), with a cut-off of 40% of positive cells (ROC curve): 62% of pCR if ki-67> 40% versus 23% if not (relative risk : 2.7). Low EGFR, high p53, and high cytokeratine 5-6 tended to be associated with poor reponse. No correlations were found between cutaneous toxicities and these biomarkers. The cutaneous toxicities were not predictive. Conclusions: HighKi-67 is predictive of more pCR. High EGFR, low p53 and low cytokeratine 5-6 tended to be associated with better response, but the data are not significant.

Cetuximab in combination with docetaxel (T) in patients with operable, triple-negative breast cancer (TNBC): Preliminary results of a multicentre neoadjuvant pilot phase II study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1057-1057
Author(s):  
Jean Marc Nabholtz ◽  
Marie-Ange Mouret-Reynier ◽  
Isabelle Van-Praagh ◽  
Véronique Servent ◽  
Jean-Philippe Jacquin ◽  
...  
Keyword(s):  
Ductal Carcinoma ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Complete Response ◽  
Conservative Surgery ◽  
Median Number ◽  
Clinical Response Rate ◽  
Preliminary Results ◽  
Grade Ii ◽  
Grade Iii

1057 Background: Cetuximab is an antiboby targeting the epidermal growth factor receptor (EGFR) to which a role has been suggested in TNBC. Therefore, we evaluated the combination of docetaxel with cetuximab as neoadjuvant therapy of operable TNBC. Methods: 35 patients with stage II-IIIA disease were prospectively included in this multicentre pilot study. Systemic therapy (ST) consisted of 6 cycles of T (100 mg/m2) q.3 weeks, in combination with weekly cetuximab (first dose : 400mg/m², then : 250 mg/m²/week) for 6 cycles. All patients underwent surgery at completion of ST. Complete pathologic response (pCR) was the primary endpoint (Sataloff : J Am Coll Surg 1995 ; Chevallier : Am J Clin Oncol 1993), with toxicity and biologic ancillary studies as secondary endpoints. Results: Patients characterisctics are as follows : mean age 48 [28-67] ; T1 : 3%, T2 : 73%, T3 : 24% (mean tumor size : 40 mm [15-100]) ; N0 : 61% and N1-N2 : 39%; invasive ductal carcinoma : 100%; Scarff-Bloom-Richardson Grade III : 73%, grade II : 27%. The median number of cycles was : T : 6 [1-6], cetuximab : 15 [1-18]. Pathological complete response was 24% according to Chevallier and Sataloff’s classifications and 28% if we consider response in breast. Preliminary results on 23 patients show an overall clinical response rate of 57% (22% CR). Conservative surgery was performed in 75% of cases. Skin toxicity was the main side-effect : grade II : 39%, grade III : 36%, grade IV : 3%. Neutropenia grade IV : 12.7%, febrile neutropenia : 1.3%, infection : 0%. Hand-foot syndrome grade III : 3%, grade II : 3%. Ungueal toxicity grade III : 3%, grade II : 33%. Conclusions: These preliminary results suggest that cetuximab in combination with Tappears to have a modest efficacy in operable TNBC. Clinical trial information: NCT00600249.

scholarly journals Modulation of Molecular Biomarker Expression in Response to Chemotherapy in Invasive Ductal Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Mana Oloomi ◽  
Neda Moazzezy ◽  
Saeid Bouzari
Keyword(s):  
Ductal Carcinoma ◽  
Growth Factor Receptor ◽  
Molecular Classification ◽  
Her2 Status ◽  
Ki 67 ◽  
Pathological Characteristics ◽  
Response To Chemotherapy ◽  
Before And After ◽  
Epidermal Growth

Breast cancer (BC) has varied morphological and biological features and is classified based on molecular and morphological examinations. Molecular classification of BC is based on biological gene-expression profiling. In this study, biomarker modulation was assessed during BC treatment in 30 previously untreated patients. Heterogeneity among patients was pathologically diagnosed and classified into luminal and basal-like immunohistochemical profiles based on estrogen, progesterone, and human epidermal growth factor receptor (ER/PR/HER2) status. Marker heterogeneity was compared with mRNA biomarker expression in patients with BC before and after therapy. Reverse transcription-polymerase chain reaction was performed for molecular characterization. Expression and modulation of biological markers, CK19, hMAM, CEA, MUC, Myc, Ki-67, HER2/neu, ErbB2, and ER, were assessed after treatment, where the expression of the biomarkers CK19, Ki-67, Myc, and CEA was noted to be significantly decreased. Marker expression modulation was determined according to different stages and pathological characteristics of patients; coexpression of three markers (CK19, Ki-67, and Myc) was specifically modulated after therapy. In the histopathologically classified basal-like group, two markers (CK19 and Ki-67) were downregulated and could be considered as diagnostic biomarkers. In conclusion, pathological characteristics and marker variation levels can be evaluated to decide a personalized treatment for patients.

scholarly journals NIMG-53. GLUTAMATE/GABA RATIO ON MRS IS ELEVATED IN PATIENTS WITH LOWER GRADE GLIOMAS AND SEIZURES

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii159-ii160
Author(s):  
Roberta Rudà ◽  
Riccardo Pascuzzo ◽  
Francesca Mo ◽  
Alessia Pellerino ◽  
Peter B Barker ◽  
...  
Keyword(s):  
Tumor Location ◽  
Resonance Spectroscopy ◽  
Lower Grade ◽  
Lack Of Information ◽  
Baseline Evaluation ◽  
Grade Ii ◽  
Grade Iii

Abstract BACKGROUND There is lack of information on the role of excitatory and inhibitory neurotransmitters in the development of seizures in patients with lower grade gliomas. Increase of glutamate and downregulation of GABA have been suggested in preclinical models and human surgical samples to be associated with brain tumor-related epilepsy. MATERIAL AND METHODS We prospectively investigated with the use of magnetic resonance spectroscopy (MRS) the differences in the ratio of metabolites (glutamate/GABA, glutamate/creatine and GABA/creatine) in the peritumoral areas between patients with or without seizures in a series of lower grade gliomas. Tumors were classified according to WHO Classification of 2016 as follows:11 grade II IDH mutated and 1p/19q codeleted; 3 grade III IDH mutated and 1p/19q codeleted; 6 grade II IDH mutated and 1p/19q intact; 1 grade III IDH mutated and 1p/19q intact; 1 grade II IDH wild-type. Patients received surgery alone or followed by temozolomide chemotherapy according to the presence of risk factors. RESULTS At baseline evaluation, maximum glutamate/GABA values were significantly higher (p=0.023) in the peritumoral area of patients with seizures (1.008 ± 0.368) with respect to those without seizures (0.691 ± 0.170). No other metabolites ratio showed significant differences between the two groups. Similar results were obtained when analyzing the metabolites ratio in the examinations during the follow-up. In the cohort of patients with seizures (n.14) variations of metabolite ratios were not associated with tumor location, 1p/19q codeletion, use of AEDs, concomitant chemotherapy or seizure characteristics (type, duration, frequency). CONCLUSIONS The study is ongoing with the aim of analyzing further the correlations between ratio of metabolites and status of the tumor (stable vs progressive).

USE OF Ki-67 (MIB-1) IMMUNOREACTIVITY IN DIFFERENTIATING GRADE II AND GRADE III GLIOMAS

1996 ◽  
Vol 55 (5) ◽  
pp. 605 ◽  
Author(s):  
D. W. Hsu ◽  
D. N. Louis ◽  
J. T. Efird ◽  
E. T. Hedlev-Whyte
Keyword(s):  
Ki 67 ◽  
Grade Ii ◽  
Grade Iii ◽  
Mib 1

scholarly journals The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors

Neurosurgery ◽  
2015 ◽  
Vol 78 (3) ◽  
pp. 401-411 ◽  
Author(s):  
Mohammed Jaber ◽  
Johannes Wölfer ◽  
Christian Ewelt ◽  
Markus Holling ◽  
Martin Hasselblatt ◽  
...  
Keyword(s):  
Aminolevulinic Acid ◽  
Methylation Status ◽  
Imaging Features ◽  
High Grade ◽  
Ki 67 ◽  
Who Grade ◽  
Fet Pet ◽  
Grade Ii ◽  
Grade Iii ◽  
Mib 1

Abstract BACKGROUND: Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. OBJECTIVE: The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [18F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. METHODS: Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and 18F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. RESULTS: Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and 18F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. CONCLUSION: Age, tumor volume, and 18F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether fluorescence in grade II gliomas identifies a subtype with worse prognosis remains to be determined.

scholarly journals Clinicohistopathological study of astrocytomas along with Ki-67 proliferative index

2018 ◽  
Vol 6 (2) ◽  
pp. 665 ◽  
Author(s):  
Basumitra Das ◽  
Kurimella Vamsya Raj ◽  
Bhagyalakshmi Atla
Keyword(s):  
Histological Grade ◽  
Research Work ◽  
Low Grade ◽  
Proliferative Index ◽  
Ki 67 ◽  
Biologic Marker ◽  
Grade Ii ◽  
The Mean ◽  
The Difference ◽  
Grade Iii

Background: Astrocytomas form the largest group of gliomas (>75%) and diffusely infiltrating    accounting for more than 60% of all the primary brain tumors. The ki67 proliferative index is a potent biologic marker that estimates the growth of neoplasms quantitatively and thus will aid in identifying the prognosis for patients with neoplasms.  The aim of the research work was to study various histopathological and clinical features of Astrocytomas in detail, to evaluate Ki-67 proliferative index in patients of Astrocytomas and to compare the results of Immunohistochemistry with histological grade of Astrocytomas.Methods: A   total   number   of    40 cases of   Astrocytomas were included in the study.  Ki-67 immunostaining was done on all cases and compared with WHO histological grading of astrocytomas.Results: The mean Ki‑67 LI in Grade I astrocytomas was 4.66, range 4-5 ,  in Grade II astrocytomas mean was 8.07, range 5-12 ,in Grade III astrocytomas mean was 13.5 , range 8-20,  in Grade IV astrocytomas mean was 22.93, range 15-50. There was a highly significant correlation between the histopathological grade of astrocytomas and Ki-67 LI (p<0.05).Conclusions: The monoclonal antibody Ki-67 has proven its prognostic and diagnostic power in astrocytic tumors. Ki-67 LI is the simplest and the most reliable method for evaluating cell proliferation. Ki-67 LI increased with histological grade and the difference between low grade (I and II astrocytomas) and high grade (grade III and IV) is significant. In the present study Ki-67 LI is not dependent on factors like age and sex and is solely dependent on histological grade.

Classification of subtype using IHC patterns for treatment decision of DCIS.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12035-e12035
Author(s):  
Yuko Date ◽  
Masafumi Takimoto ◽  
Toshio Morohoshi ◽  
Seigo Nakamura
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Prognostic Index ◽  
Receptor Expression ◽  
Luminal A ◽  
Ki 67 ◽  
Risk Of Recurrence

e12035 Background: Ductal carcinoma in situ (DCIS) is a heterogenous group of breast lesion and demands a broad range of surgical management techniques. Previous studies reported the importance of receptor expression and referred to the risk of recurrence.We classified ductal carcinoma in situ (DCIS) into 4 subtypes using IHC staining (ER, PgR, HER2 and Ki-67) and investigated the frequency and their characteristics. Also we investigated whether this classification is related to the risk of recurrence. Methods: 117 women who underwent operation between 2010 and 2012 were included our study. We defined 4 subtypes as follows; luminal A (LA), ER and/or PgR (HR)(+) HER2(-) Ki-67(low), luminal B (LB), HR(+) HER2(-) Ki-67(high) or HR(+) HER2(+),HER2(H), HR(-) HER2(+), and basal-like(BL), HR(-) HER2(-).We also evaluated the risk of recurrence using Van Nuys Prognostic Index (VNPI), an algorithm based on DCIS size, nuclear grade (NG), necrosis, margin width and patient age. Results: The frequency of subtype was as follows; LA 77 cases (65.8%), LB 18 (15.3%), H 14 (12.0%) and BL 8 (6.8%). LA tended to smaller size (average: 3.2cm, range: 0.2-12), low NG (NG1 was 97.4%). In a contrary, H and BL were larger size (average: 3.7cm (H), 4.5cm (BL)) and high NG (these percentages of NG3 were 64.3% (H) and 50.0% (BL)). All of the BL had necrosis. About half of the LA was VNPI 6 and 7, but many of the other subtypes were more than VNPI 7 (p=0.02). Conclusions: Classification of subtypes using IHC patterns is simple, useful and, moreover, that are related to the risk of recurrence. Though it is important whether the woman is BRCA1/2 mutation carrier, we might be determined a treatment of DCIS by the subtype.

Discrimination between low-grade oligodendrogliomas and diffuse astrocytoma with the aid of 11C-methionine positron emission tomography

2011 ◽  
Vol 114 (6) ◽  
pp. 1640-1647 ◽  
Author(s):  
Natsuki Shinozaki ◽  
Yoshio Uchino ◽  
Kyosan Yoshikawa ◽  
Tomoo Matsutani ◽  
Azusa Hasegawa ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Histological Type ◽  
Labeling Index ◽  
Low Grade ◽  
Astrocytic Tumors ◽  
Ki 67 ◽  
Oligodendroglial Tumors ◽  
Grade Ii ◽  
The Mean ◽  
Grade Iii

Object The diagnostic usefulness of 11C-methionine PET scans in gliomas is still controversial. The authors investigated the clinical significance of 11C-methionine PET findings in preoperative diagnosis of histological type and grade. Methods The tissue uptake of 11C-methionine was assessed using PET in 70 patients with histologically confirmed intracerebral gliomas. The ratio of maximum standard uptake values in tumor areas to the mean standard uptake values in the contralateral normal brain tissue (tumor/normal tissue [T/N] ratio) was calculated and correlated with tumor type, histological grade, contrast enhancement on MR imaging, Ki 67 labeling index, and 1p/19q status. Results The T/N ratio was significantly increased as tumor grade advanced in astrocytic tumors (WHO Grade II vs Grade III, p = 0.0011; Grade III vs Grade IV, p = 0.0007). Among Grade II gliomas, the mean T/N ratio was significantly higher in oligodendroglial tumors than in diffuse astrocytomas (DAs) (p < 0.0001). All T/N ratios for oligodendroglial tumors were ≥ 1.46, and those for DA were consistently < 1.46, with the exception of 2 cases of gemistocytic astrocytoma. The Ki 67 labeling index significantly correlated with T/N ratio in astrocytic tumors, but not in oligodendrogliomas. Oligodendroglial tumors without 1p/19q deletion had a significantly higher T/N ratio than those with the codeletion. In combination with Gd-enhanced MR imaging, 67% of nonenhanced tumors with a T/N ratio of ≥ 1.46 were proved to be Grade II oligodendrogliomas. Conclusions These results clearly show that 11C-methionine PET T/N ratios in Grade II oligodendrogliomas were higher than those in DAs independently of their proliferative activity. This information contributes to preoperative differential diagnoses of histological type, especially in suspected low-grade gliomas.

Novel histopathological classification of meningiomas based on dural invasion

2020 ◽  
pp. jclinpath-2020-206592
Author(s):  
Makoto Murase ◽  
Ryota Tamura ◽  
Yuki Kuranari ◽  
Mizuto Sato ◽  
Kentaro Ohara ◽  
...  
Keyword(s):  
Brain Parenchyma ◽  
Ki 67 ◽  
Who Grade ◽  
Histopathological Classification ◽  
Simpson Grade ◽  
Grade Ii ◽  
Meningioma Recurrence

AimsHistological invasion into the adjacent brain parenchyma is frequently investigated in meningioma because it is an important morphological criterion for grade II meningioma according to the 2016 WHO classification. However, few studies have focused on dural invasion of meningiomas. Herein, we propose a novel histopathological classification based on dural invasion of meningiomas.MethodsForty-nine cases with WHO grade I meningiomas who underwent Simpson grade I removal were collected. After the meningeal layer (ML) and periosteal layer (PL) of dura mater were visualised by Masson’s trichrome stain, we evaluated the depth (to the ML and PL) and the patterns (1, expanding; 2, infiltrating) of dural invasion of meningiomas using serial paraffin sections. Invasion-associated markers, including Ki-67, matrix metalloproteinase (MMP)-1, MMP-9 and MMP-13, aquaporin 1 and Na-K-2Cl cotransporter, were quantitatively analysed by immunohistochemistry.ResultsThirty-five cases (71.4%) showed the dural invasion. In 27 of these 35 cases (77.1%), dural invasion was localised in ML. Type 1 (expanding type) and type 2 (infiltrating type) invasions were observed in 23 and 12 cases, respectively. The recurrence rate in cases with type 2 invasion was significantly higher than that in cases with type 1 invasion. The percentage of MMP-1-positive tumour cells was also significantly higher in cases with dural invasion than those without, suggesting involvement of MMP-1 in dural invasion.ConclusionsWe quantitatively evaluated the depth and patterns of dural invasion in meningiomas. The patterns of dural invasion were associated with meningioma recurrence.

scholarly journals Expression of PDL-1 and Its Correlation with TIL in Triple Negative Cases of Breast Carcinoma

2021 ◽  
Vol 8 (6) ◽  
pp. A136-141
Author(s):  
Neha Sharma ◽  
Akashdeep Singh ◽  
Arshdeep Kaur ◽  
Mridu Manjari
Keyword(s):  
Breast Carcinoma ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Histological Grade ◽  
Breast Carcinomas ◽  
Not Otherwise Specified ◽  
Infiltrating Ductal Carcinoma ◽  
Grade Ii ◽  
Patient Prognosis ◽  
Grade Iii

Background:  In the present study, we aimed to determine the expression of PDL1 and its correlation with TIL in Triple Negative (ER, PR and Her 2neu negative) cases of breast carcinoma (immune-histochemical study)  Methods: Expression of PD-L1 was seen on 40 proven triple negative cases of breast carcinomas (TNBC) and to correlate it with other parameters affecting prognosis of the disease. All the cases were infiltrating ductal carcinoma NOS (not otherwise specified) Result: Maximum cases were Grade III (67.5%) followed by Grade II (32.5%). PD-L1 positivity was seen in 32.5% cases whereas TIL was positive for PD-L1 in 27.5 %. 5 cases were positive for both epithelial cell and TIL. Out of 13 PD-L1 positive tumors, 38.5% cases showed TIL positivity whereas out of 27 PD-L1 negative tumors, only 22.2% were TIL positive. PD-L1 expression in TIL was seen in 38.5% of cases however there was no statistically significant correlation between PD-L1 positivity and TIL positivity. PDL-1 positivity was more in Grade III (33.3%) as compared to Grade II (23%) lesions. Thus, it was observed that PD-L1 positivity increased from grade II to grade III lesions. Conclusion: Intra-tumoral expression of PD-L1 is directly proportional to histological grade, aggressive subtypes in TNBC cases however there was no statistically significant correlation between PD-L1 positivity in tumor cells and TIL positivity. We thus postulate that measurement of PD-L1 expression in TNBC cases could enhance the accuracy of predicting patient prognosis and allow for optimal treatment selection.

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