scholarly journals ERBB2 Overexpression

2020 ◽  
Author(s):  
Keyword(s):  
Erbb2 Overexpression

Neuregulin (NRG) expression modulates clinical response to trastuzumab in patients with metastatic breast cancer (MBC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10069-10069
Author(s):  
E. De Alava ◽  
M. Abad ◽  
C. A. Rodriguez ◽  
J. C. Montero ◽  
E. Serrano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast ◽  
Response To Treatment ◽  
Tissue Samples ◽  
Cytoplasmic Staining ◽  
Frozen Tissue ◽  
The Relationship ◽  
Erbb2 Amplification ◽  
Erbb2 Overexpression

10069 Background: ErbB2 overexpression is the major determinant of response to trastuzumab (Herceptin, H). Recently, some authors have reported the potential role of the expression of NRG on ErbB2 activation in breast cancer cells, and its consequences in response to treatment with H. In the present study we analyze the relationship between response to H and expression of ErbB2 and NRG in patients (pt) with MBC. Methods: Data and frozen tissue samples from 30 consecutive pt with MBC and positive ErbB2 at diagnosis [Immunohistochemistry (IHC)] were collected. All pt were treated with an Herceptin-based regimen. Central Pathologic review of ErbB2 expression was performed in all samples (Herceptest and FISH). NRG expression was studied by IHC on paraffin embedded material and by Western blotting on frozen tissue using an antibody raised against the intracellular domain of NRG. NRG expression by IHC was evaluated using a semiquantitative scoring system that assesses both extension and intensity of cytoplasmic staining. Correlation between ErbB2 and NRG expression and its influence in response to H was analyzed. Characteristics of pt: Median Age: 54; Median mts sites: 2; Treatment: H alone:1 pt; H+Taxol:15 pt; H+Taxol+Carbo: 4 pt; H+Taxol+Lip.Doxorub:2 pt, H+Vinorelbine:7 pt; H+CDDP:1 pt. Results: ORR: 76% (CR:23%, PR:53%). Median TTP: 7.8 m. After central Pathologic review, a total of 20 tumors showed ErbB2 amplification by FISH and 19 of them were Herceptest 3+. A positive correlation was observed between ErbB2 amplification and NRG expression. All complete responses (n=7) were seen in pt with ErbB2 amplification. Interestingly, in the group of tumors without ErbB2 amplification (n=10), 7 had high NRG expression levels, as assessed by IHC. Six out of these 7 tumors having high levels of NRG expression, exhibited partial responses. NRG expression, in turn, did not have impact on response among ErbB2 amplified tumors. Conclusions: These preliminary results suggest that responses to H regimens in pt with MBC can be seen in pt lacking ErbB2 amplification in presence of high levels of expression of transmembrane ligand NRG. This suggests that the group of pt that may benefit from treatment with H could be broader than currently established. A confirmatory study is ongoing in a larger series. No significant financial relationships to disclose.

scholarly journals Suppression of the Negative Regulator LRIG1 Contributes to ErbB2 Overexpression in Breast Cancer

2008 ◽  
Vol 68 (20) ◽  
pp. 8286-8294 ◽  
Author(s):  
Jamie K. Miller ◽  
David L. Shattuck ◽  
Ellen Q. Ingalla ◽  
Lily Yen ◽  
Alexander D. Borowsky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Negative Regulator ◽  
Erbb2 Overexpression

scholarly journals Stiffness of the microenvironment upregulates ERBB2 expression in 3D cultures of MCF10A within the range of mammographic density

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Qingsu Cheng ◽  
Cemal Cagatay Bilgin ◽  
Gerald Fontenay ◽  
Hang Chang ◽  
Matthew Henderson ◽  
...  
Keyword(s):  
Cell Line ◽  
Mammographic Density ◽  
Colony Formation ◽  
Maximum Level ◽  
Stable Cell Line ◽  
Mcf10a Cell ◽  
Molecular Response ◽  
Genome Wide ◽  
High Mammographic Density ◽  
Erbb2 Overexpression

Abstract The effects of the stiffness of the microenvironment on the molecular response of 3D colony organization, at the maximum level of mammographic density (MD), are investigated. Phenotypic profiling reveals that 3D colony formation is heterogeneous and increased stiffness of the microenvironment, within the range of the MD, correlates with the increased frequency of aberrant 3D colony formation. Further integrative analysis of the genome-wide transcriptome and phenotypic profiling hypothesizes overexpression of ERBB2 in the premalignant MCF10A cell lines at a stiffness value that corresponds to the collagen component at high mammographic density. Subsequently, ERBB2 overexpression has been validated in the same cell line. Similar experiments with a more genetically stable cell line of 184A1 also revealed an increased frequency of aberrant colony formation with the increased stiffness; however, 184A1 did not demonstrate overexpression of ERBB2 at the same stiffness value of the high MD. These results suggest that stiffness exacerbates premalignant cell line of MCF10A.

Amplification units and translocation at chromosome 17q and c-erbB2 overexpression in the pathogenesis of breast cancer

1998 ◽  
Vol 7 ◽  
pp. S72
Author(s):  
R Van den Broecke ◽  
E Coene ◽  
V Schelfhout ◽  
R Serreyn ◽  
C R De Potter
Keyword(s):  
Breast Cancer ◽  
Chromosome 17Q ◽  
Erbb2 Overexpression

Prognostic significance of bcl-2 expression in stage III breast cancer patients who received doxorubicin and cyclophosphamide followed by paclitaxel as adjuvant chemotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 670-670 ◽  
Author(s):  
K. Lee ◽  
B. Kim ◽  
S. Lee ◽  
W. Han ◽  
D. Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Stage Iii ◽  
Breast Cancer Patients ◽  
Stage Iii Breast Cancer ◽  
Erbb2 Overexpression ◽  
Er Expression

670 Background: Bcl-2 is an anti-apoptotic marker and regulated by hormonal receptor pathways in breast cancer. We performed this study to assess the prognostic significance of ER, PR, p53, c-erbB2, bcl-2, Ki-67, and EGFR as a marker for relapse in breast cancer patients who received same adjuvant therapy in a single institution. Methods: A cohort of 154 curatively resected breast cancer patients who had 4 lymph nodes or more and received doxorubicin and cyclophosphamide followed by paclitaxel (AC/T) as adjuvant chemotherapy was analyzed for clinicopathologic characteristics including disease-free survival (DFS). Patients with ER and/or PR expression received 5 years of tamoxifen following AC/T. The markers were analyzed by immunohistochemistry. Results: Median f/u duration was 25 months and 32 patients (20.8%) had recurrences. Stage (IIIa vs. IIIc) affected recurrences significantly, however, types of surgery, histology, histologic grade, presence of endolymphatic emboli, or close resection margin did not. Among the immunohistochemical markers, bcl-2 expression was the only one to be associated significantly with prolonged DFS (median 54 mo in bcl-2 (−) vs. not reached in bcl-2 (+); p=0.016). Furthermore, bcl-2 was an independent prognostic factor for DFS in multivariate analysis. Bcl-2 expression was significantly correlated with ER expression (p<0.001), and inversely correlated with c-erbB2 overexpression (p=0.027). Patients with both ER and bcl-2 expression had a longer DFS compared to the other patients (not reached vs. 54 mo, p=0.019). Patients with bcl-2 expression had a significantly longer DFS even in ER (+) subgroups (not reached vs 54 mo; p=0.011). Patients with c-erbB2 overexpression, ER (−) and bcl-2 (−) had a shorter DFS than the others (38 mo vs. not reached; p=0.029). Conclusions: In our homogenous patient cohort, bcl-2 expression was correlated with ER expression, and inversely correlated with c-erbB2 overexpression. Bcl-2 was an independent prognostic factor for DFS in curatively resected stage III breast cancer patients. No significant financial relationships to disclose.

Pertuzumab plus trastuzumab (P+T) in patients (Pts) with colorectal cancer (CRC) with ERBB2 amplification or overexpression: Results from the TAPUR Study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 132-132 ◽  
Author(s):  
Ranju Gupta ◽  
Elizabeth Garrett-Mayer ◽  
Susan Halabi ◽  
Pam K. Mangat ◽  
Stacy D. D'Andre ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Infusion Reaction ◽  
Left Ventricular ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity ◽  
Erbb2 Amplification ◽  
Erbb2 Overexpression

132 Background: TAPUR is a phase II basket trial evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of CRC pts with ERBB2 overexpression or amplification treated with P+T are reported. Methods: Eligible pts had advanced CRC, no standard treatment (tx) options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts had ERBB2 overexpression or amplification, or certain ERBB2 mutations. Recommended dosing after initial dosing was P, 420 mg IV over 30-60 mins every 3 weeks (wks) and T, 6 mg/kg over 30-60 mins every 3 wks. Simon two-stage design was used to test a null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16+ wks per RECIST (SD16+)), 18 more pts enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-eight pts enrolled from November 2016 to September 2018 were evaluable for efficacy and safety. Demographics and outcomes are summarized in Table. All pts had ERBB2 amplification; 1 also had an ERBB2 mutation. 79% of pts had at least 3 prior txs. Four PR and 10 SD16+ were observed for DC and OR rates of 50% (90% CI, 36% to 60%) and 14% (95% CI, 4% to 33%), respectively. Two pts had at least one grade 3 AE or SAE at least possibly related to P+T including anemia, infusion reaction, and left ventricular dysfunction. Conclusions: The combination of P+T showed anti-tumor activity in heavily pre-treated CRC pts with ERBB2 amplification . Additional analyses by RAS mutation status are pending. Further study is warranted to confirm efficacy of P+T in this population. Clinical trial information: NCT02693535. [Table: see text]

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