scholarly journals GATA3 as an Adjunct Prognostic Factor in Breast Cancer Patients with Less Aggressive Disease: A Study with a Review of the Literature

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 604
Author(s):  
Patrizia Querzoli ◽  
Massimo Pedriali ◽  
Rosa Rinaldi ◽  
Paola Secchiero ◽  
Paolo Giorgi Rossi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Value ◽  
Tissue Microarrays ◽  
Routine Practice ◽  
Lower Grade ◽  
Breast Cancer Patients ◽  
Wild Type ◽  
Ki 67 ◽  
Luminal B

Background: GATA binding protein 3 (GATA3) expression is positively correlated with estrogen receptor (ER) expression, but its prognostic value as an independent factor remains unclear. Thus, we undertook the current study to evaluate the expression of GATA3 and its prognostic value in a large series of breast carcinomas (BCs) with long-term follow-up. Methods: A total of 702 consecutive primary invasive BCs resected between 1989 and 1993 in our institution were arranged in tissue microarrays, immunostained for ER, progesterone receptor (PR), ki-67, HER2, p53, and GATA3, and scored. Clinico-pathological data were retrospectively collected. Results: GATA3 was evaluable in 608 (87%) of the 702 cases; it was positive in 413 (68%) cases and negative in 195 (32%) cases. GATA3 positivity was significantly associated with lower grade (p < 0.0001), size (p = 0.0463), stage (p = 0.0049), ER+ (p < 0.0001), PR+ (p < 0.0001), HER2− (p = 0.0175), and p53 wild-type pattern (p < 0.0001). The median follow-up was 183 months, GATA3 positivity was associated with better overall survival (HR 0.70, p = 0.001), and its prognostic value was retained in a multivariate analysis. The association with better overall survival was stronger in patients with grade 1–2, pT1–2, pN0, stage I–II, ER+, PR+, ki-67 < 20%, HER2−, a wild-type p53 immunohistochemical pattern, and in luminal B BC. Conclusions: Our findings indicate that GATA3 is a positive prognostic marker in BC patients, especially in patients with biologically less aggressive BC. Incorporating GATA3 immunohistochemistry into routine practice could help further stratify BC patients for their risk.

scholarly journals P14.95 Is the pathological-grade relevant in “IDH-wild type, TERT-mutant” diffuse-gliomas? An analysis in 147 patients

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii90-iii90
Author(s):  
A E Danyeli ◽  
C B Akyerli ◽  
A Dinçer ◽  
E Coşgun ◽  
U Abacıoğlu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
Lower Grade ◽  
Wild Type ◽  
Ki 67 ◽  
Who Grade ◽  
Free Survival ◽  
Tert Promoter ◽  
Diffuse Gliomas

Abstract BACKGROUND Although the word “glioblastoma” still denotes a grade-IV pathology, basic molecular studies have clearly indicated that a significant proportion of lower-grade gliomas harbor genetic alterations typical of glioblastomas. Based on these findings cIMPACT-NOW update 3 has defined an entity called the “diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”. A TERT-promoter mutation is one of these typical molecular markers of glioblastomas. In this study we analyzed IDH-wild type, TERT-mutant diffuse gliomas of different pathological grades to look for differences in demographic, clinical and survival characteristics. MATERIAL AND METHODS 147 adult hemispheric diffuse-gliomas with wild-type IDH1/2 and mutant TERT-promoter (C228T or C250T) were retrospectively analyzed. Primary thalamic, cerebellar brainstem or spinal cases were excluded. 126 (86%), 16(11%) and 5(3%) patients were WHO grade IV, III and II respectively. After surgical treatment or stereotactic biopsy all patients underwent chemoradiation. Median follow-up was 16mo (1–110). Tumors of different grades were compared for age, gender, multifocality, gliomatosis pattern, Ki-67 index, progression-free survival and overall-survival. RESULTS Mean age at presentation for grade II, III and IV were comparable (58.1, 58 and 58.1; ANOVA, p=0.72). There was a slight male predominance in both lower-grades and WHO-grade IV (M:F ratios 1.625 and 1.74). Mean Ki-67 index was significantly higher in higher grades (0.06, 0.14 and 0.25 for grades II, III and IV; ANOVA, p=0.001). Multifocality was comparable (chi-sq, p=1) in lower-grades (3/21; 14.3%) vs. WHO-grade IV (18/126; 14.3%). Gliomatosis pattern was comparable (chi-sq, p=0.095) in lower-grades (2/21; 9.5%) vs. (3/126; 2.3%). Median recurrence free survival (RFS) was 16 months (0–63) in lower-grades and 8months (1–50) in WHO-grade IV. PFS was significantly different between 3 WHO-grades (Log rank, p=0.007) and also between lower-grades and WHO-grade IV (Log rank, p=0.002). Median overall survival was 26 months(2–110) in lower-grades and 15mo(1–91) in WHO-grade IV. OS was significantly different between 3 WHO-grades (Log rank, p=0.014) and also between lower-grades and WHO-grade IV (Log rank, p=0.007). CONCLUSION Increasing pathological grades of hemispheric “IDH-wild type, TERT-mutant diffuse gliomas” have similar demographic and clinical characteristics but incrasing proliferation indices, decrasing progression free survival and shorter overall survival. The findings may be suggesitve of different grades of one common tumor entity.

Prognostic value of Ki67LI in HER2-negative luminal (HNL) early breast cancer (EBC): A 14-year single institution experience with long follow-up.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11569-e11569
Author(s):  
Antonella Ferro ◽  
Lucianna Russo ◽  
Claudio Eccher ◽  
Alessia Caldara ◽  
Renza Triolo ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Prognostic Significance ◽  
Routine Practice ◽  
Prognostic Information ◽  
Ki 67 ◽  
Younger Age ◽  
Independent Prognostic Significance ◽  
Her 2 ◽  
Biological Entities

e11569 Background: Several studies have emphasized the biologic and prognostic value of Ki67LI and its role in routine practice, particularly to define prognostic subgroups of luminal tumors. Methods: Ki67LI was identified by immunohistochemical staining in 3760 consecutive EBC pts followed from 1995 to 2008. Median age was 61 y. The relationship with clinic-pathological parameters and the prognostic significance of KI67LI were investigated in all EBCs and in 2380 HER2 negative luminal (HNL) cases, stratified on homogeneous grading (594 G1, 1282 G2, 504 G3). Results: Median Ki67LI values were 22% in all cases, 20% in HNL and 10%, 20% and 35% in HNL- G1,G2,G3 respectively. Ki67LI > 22% (1873 pts) was significantly (p<0.001) associated with younger age, ductal type, greater size, positive N, poor G, absent or low ER /PR, positive HER-2, triple negative subtypes. Local and Distant Relapses were 138 (7.3%) and 355 (18.9%) in < or > 22% Ki67LI respectively. Median time to first event was 31.7 ms in > 22% vs 50.1 ms in < 22% Ki67. At a median f-up of 77 months EFS and OS were 91.9 and 92.1% in < 22% vs 78.9% and 81% in > 22% Ki67 respectively (p <0.001). The prognosis was consistently worse for > 22% Ki 67 in all clinical-pathological subsets, except in negative ER group. In multivariate analysis, KI67 maintained an independent prognostic significance for DFS and OS. In HNL, EFS and OS were 93.7 and 92% in < 20% vs 81.7 and 83.3% in >20% Ki67(p <0.001). Using median ki67LI value for different homogenous HNL-GG as cutoffs, we stratified these populations in low and high risk. Results are summarized in the Table. Conclusions: Our study confirms the prognostic value of Ki67LI in EBC,as well as other clinical pathological characteristics such as age, tumor size, histological type, nodal and hormonal receptors status. Cutoffs are different into HNL.They could identify different biological entities in each grading group providing additional prognostic information in outcome prediction. [Table: see text]

Neoadjuvant Chemotherapy Induces the Appearance of New Copy Number Aberrations in Breast Tumor and is Associated with Metastasis

2020 ◽  
Vol 20 (9) ◽  
pp. 681-688
Author(s):  
Nikolai V. Litviakov ◽  
Marina K. Ibragimova ◽  
Matvey M. Tsyganov ◽  
Artem V. Doroshenko ◽  
Eugeniy Y. Garbukov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Copy Number ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Luminal B ◽  
Cell Clones ◽  
Genetic Landscape ◽  
Intelligent Approach

Background: In this study, we examined the CNA-genetic landscape (CNA – copy number aberration) of breast cancer prior to and following neoadjuvant chemotherapy (NAC) and correlated changes in the tumor landscape with chemotherapy efficiency as well as metastasis-free survival. Objective: Breast cancer patients (n = 30) with luminal B molecular subtypes were treated with anthracycline- based therapy. Methods: To study CNAs in breast tumors, microarray analysis was performed. Results: Three effects of NAC on tumor CNA landscape were identified: 1 – the number of CNA-bearing tumor clones decreased following NAC; 2 – there were no alterations in the number of CNA-containing clones after NAC; 3 – the treatment with NAC increased the number of CNA-bearing clones (new clones appeared). All NAC-treated patients who had new tumor clones with amplification (20%) had a 100% likelihood of metastasis formation. In these cases, NAC contributed to the emergence of potential metastatic clones. Our study identified the following loci – 5p, 6p, 7q, 8q, 9p, 10p, 10q22.1, 13q, 16p, 18Chr and 19p – that were amplified during the treatment with NAC and may be the markers of potential metastatic clones. In other patients who showed total or partial elimination of CNA-bearing cell clones, no new amplification clones were observed after NAC, and no evidence of metastases was found with follow-up for 5 years (р = 0.00000). Conclusion: Our data suggest that the main therapeutic result from NAC is the elimination of potential metastatic clones present in the tumor before treatment. The results showed the necessity of an intelligent approach to NAC to avoid metastasis stimulation.

Prognostic subset of metastatic and non-metastatic luminal B breast cancer (LBBC) subtype based on Ki67 index.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12570-e12570
Author(s):  
Lalnun Puii ◽  
Lalram Sangi ◽  
Hrishi Varayathu ◽  
Samuel Luke Koramati ◽  
Beulah Elsa Thomas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Disease ◽  
Ki67 Index ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Her2 Positive ◽  
Ki 67 ◽  
Luminal B ◽  
Therapeutic Implications ◽  
Significant Difference

e12570 Background: Gene expression profiling for breast cancer has classified ER positive subtype into luminal A and luminal B. Luminal B breast cancer (LBBC) have a higher proliferation and poorer prognosis than luminal A tumors. Ki-67 index is the commonly used proliferation marker in breast cancer; however Ki67 expression can also be used to identify a subset of patients among LB with a favorable prognosis. This study attempts to verify this subset of LBBC patients based on DFS and PFS in non-metastatic and metastatic patients respectively. Methods: We retrospectively analyzed 80 IDC breast cancer patients diagnosed in 2013-2016 with complete follow-up till January-2021. We defined LBBC as ER+, PR+ or PR- , HER2+ or HER2- with a Ki67 index >20%. PFS was considered as the endpoint in patients presenting with metastatic disease whereas DFS was used in non-metastatic disease. The cut-off for ki67 was calculated using an X-tile plot (version 3.6.1, Yale University) by dividing Ki67 data into two populations: low and high, with randomized 1:1 “training” and “validation” cohorts. Results: Median age was 51.5 years. 18.7% (n=15) presented with metastasis at the time of diagnosis and their overall median PFS was found to be 25.8 months. The incidence of HER2 positive LBBC was found to be 15% (n=12) and none of them were found to be presented with metastasis. Survival and frequency of various sub groups in our study are enlisted in the given table. We estimated a Ki67 cut-off of 30% in patients with upfront metastatic disease and PFS was found to be higher in <30% compared to a Ki67 index >30% (38.9 months vs 19.7 months, p-0.002). Overall median DFS was not achieved in non-metastatic group (Mean DFS: 64.7 months) where as a statistically significant difference was observed in the survival of HER2 positive (median DFS: 53.5 months, mean DFS: 50.9) than HER2 negative patients (median DFS not achieved, mean: 66.97 months) ( p-0.021). We obtained a Ki67 cut-off of 32% in non- metastatic group and mean DFS was found to be higher in Ki67<32% (69 months) compared to Ki67>32% (61.4 months), however it failed to exhibit a statistically significant relationship ( p-0.373). Conclusions: Our study indicates that a subset of patients exists within metastatic and non-metastatic LBBC with differing prognosis based on Ki67. Larger studies are further required to confirm the findings and therapeutic implications.[Table: see text]

scholarly journals The Prognostic Value of NANO Scale Assessment in IDH-Wild-Type Glioblastoma Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Johannes Kasper ◽  
Tim Wende ◽  
Michael Karl Fehrenbach ◽  
Florian Wilhelmy ◽  
Katja Jähne ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Univariate Analysis ◽  
Extent Of Resection ◽  
Survival Prediction ◽  
Wild Type ◽  
Prognostic Information ◽  
Nano Scale ◽  
Scale Assessment ◽  
General Physical

BackgroundIDH-wild-type glioblastoma (GBM) is the most frequent brain-derived malignancy. Despite intense research efforts, it is still associated with a very poor prognosis. Several parameters were identified as prognostic, including general physical performance. In neuro-oncology (NO), special emphasis is put on focal deficits and cognitive (dys-)function. The Neurologic Assessment in Neuro-Oncology (NANO) scale was proposed in order to standardize the assessment of neurological performance in NO. This study evaluated whether NANO scale assessment provides prognostic information in a standardized collective of GBM patients.MethodsThe records of all GBM patients treated between 2014 and 2019 at our facility were retrospectively screened. Inclusion criteria were age over 18 years, at least 3 months postoperative follow-up, and preoperative and postoperative cranial magnetic resonance imaging. The NANO scale was assessed pre- and postoperatively as well as at 3 months follow-up. Univariate and multivariate survival analyses were carried to investigate the prognostic value.ResultsOne hundred and thirty-one patients were included. In univariate analysis, poor postoperative neurological performance (HR 1.13, p = 0.004), poor neurological performance at 3 months postsurgery (HR 1.37, p &lt; 0.001), and neurological deterioration during follow-up (HR 1.38, p &lt; 0.001), all assessed via the NANO scale, were associated with shorter survival. In multivariate analysis including other prognostic factors such as the extent of resection, adjuvant treatment regimen, or age, NANO scale assessment at 3 months postoperative follow-up was independently associated with survival prediction (HR 1.36, p &lt; 0.001). The optimal NANO scale cutoff for patient stratification was 3.5 points.ConclusionNeurological performance assessment employing the NANO scale might provide prognostic information in patients suffering from GBM.

scholarly journals Right Ventricular Dysfunction in Patients Experiencing Cardiotoxicity during Breast Cancer Therapy

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Anna Calleja ◽  
Frédéric Poulin ◽  
Ciril Khorolsky ◽  
Masoud Shariat ◽  
Philippe L. Bedard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Right Ventricular ◽  
Prognostic Value ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Breast Cancer Patients ◽  
Lv Dysfunction ◽  
Her2 Breast Cancer

Background. Right ventricular (RV) dysfunction during cancer therapy related cardiotoxicity and its prognostic implications have not been examined.Aim. We sought to determine the incidence and prognostic value of RV dysfunction at time of LV defined cardiotoxicity.Methods. We retrospectively identified 30 HER2+ female patients with breast cancer treated with trastuzumab (± anthracycline) who developed cardiotoxicity and had a diagnostic quality transthoracic echocardiography. LV ejection fraction (LVEF), RV fractional area change (RV FAC), and peak systolic longitudinal strain (for both LV and RV) were measured on echocardiograms at the time of cardiotoxicity and during follow-up. Thirty age balanced precancer therapy and HER2+ breast cancer patients were used as controls.Results. In the 30 patients with cardiotoxicity (mean ± SD age 54 ± 12 years) RV FAC was significantly lower (42 ± 7 versus 47 ± 6%,P=0.01) compared to controls. RV dysfunction defined by global longitudinal strain (GLS < −20.3%) was seen in 40% (n=12). During follow-up in 16 out of 30 patients (23 ± 15 months), there was persistent LV dysfunction (EF < 55%) in 69% (n=11). Concomitant RV dysfunction at the time of LV cardiotoxicity was associated with reduced recovery of LVEF during follow-up although this was not statistically significant.Conclusion. RV dysfunction at the time of LV cardiotoxicity is frequent in patients with breast cancer receiving trastuzumab therapy. Despite appropriate management, LV dysfunction persisted in the majority at follow-up. The prognostic value of RV dysfunction at the time of cardiotoxicity warrants further investigation.

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