Quantification of intratumoral heterogeneity of HER2 status in breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1036-1036
Author(s):  
Rie Horii ◽  
Masaaki Matsuura ◽  
Hiro Nitta ◽  
Yoshinori Ito ◽  
Shinji Ohno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Intratumoral Heterogeneity ◽  
Gene Copy ◽  
Her2 Status ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Protein Status ◽  
Positive Breast Cancer

1036 Background: Intratumoral heterogeneity (ITH) occurs as a consequence of epigenetic aberrations in tumor cells with genetic diversity. HER2 ITH can be classified into genetic (a mixture of tumor cells with and without HER2 gene amplification) and epigenetic ITH (a mixture of HER2 gene-amplified tumor cells with and without HER2 protein overexpression). However, the both effects of genetic and epigenetic ITH on HER2-targeted therapy have not been clearly demonstrated. In order to implement ITH as a referenced factor for treatment selection, the ITH quantification is necessary. Gene-protein assay (GPA), in which immunohistochemistry and dual in situ hybridization are simultaneously performed on a single slide, allows bright-field analyses of both gene and protein status. We aimed to quantify HER2 ITH by the combination of gene and protein status and clarify its clinical significance. Methods: Fifty three patients with HER2-positive breast cancer, who underwent neoadjuvant trastuzumab with chemotherapy, were examined. Five representative microscopic images were captured from a GPA slide of a pre-therapeutic biopsy material. All evaluable tumor cells in the images were scored according to the HER2 status determined by the combination of gene copy number and protein expression (Table). We investigated the relationship between the HER2 scores and pathological complete response (pCR) to the neoadjuvant treatment by the logistic analysis. Results: The average of HER2 scores, indicating the degree of the HER2 status, varied from 2.21 to 5.98. It was significantly related to pCR (Estimate: 1.21, Std. error: 0.46, RR: 3.34, P=0.009, 95%CI: 1.35-8.25). The standard deviation of HER2 scores, indicating the degree of the HER2 ITH, varied from 0.13 to 1.37. It was significantly related to pCR (Estimate: -2.09, Std. error: 0.83, RR: 0.12, P=0.012, 95%CI: 0.02-0.63). Conclusions: HER2 ITH, quantified by GPA, is a predictive factor for the therapeutic effect to trastuzumab-based treatment in HER2-positive breast cancer. [Table: see text]

scholarly journals Somatic Mutations in HER2 and Implications for Current Treatment Paradigms in HER2-Positive Breast Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Maria Gaibar ◽  
Laura Beltrán ◽  
Alicia Romero-Lorca ◽  
Ana Fernández-Santander ◽  
Apolonia Novillo
Keyword(s):  
Breast Cancer ◽  
Somatic Mutations ◽  
Tyrosine Kinase Domain ◽  
Her2 Overexpression ◽  
Breast Cancer Patients ◽  
Trastuzumab Resistance ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

In one of every four or five cases of breast cancer, the human epidermal growth factor receptor-2 (HER2) gene is overexpressed. These carcinomas are known as HER2-positive. HER2 overexpression is linked to an aggressive phenotype and a lower rate of disease-free and overall survival. Drugs such as trastuzumab, pertuzumab, lapatinib, neratinib, and the more recent afatinib target the deregulation of HER2 expression. Some authors have attributed somatic mutations in HER2, a role in resistance to anti-HER2 therapy as differential regulation of HER2 has been observed among patients. Recently, studies in metastatic ER + tumors suggest that some HER2 mutations emerge as a mechanism of acquired resistance to endocrine therapy. In an effort to identify possible biomarkers of the efficacy of anti-HER2 therapy, we here review the known single-nucleotide polymorphisms (SNPs) of the HER2 gene found in HER2-positive breast cancer patients and their relationship with clinical outcomes. Information was recompiled on 11 somatic HER2 SNPs. Seven polymorphisms are located in the tyrosine kinase domain region of the gene contrasting with the low number of mutations found in extracellular and transmembrane areas. HER2-positive patients carrying S310F, S310Y, R678Q, D769H, or I767M mutations seem good candidates for anti-HER2 therapy as they show favorable outcomes and a good response to current pharmacological treatments. Carrying the L755S or D769Y mutation could also confer benefits when receiving neratinib or afatinib. By contrast, patients with mutations L755S, V842I, K753I, or D769Y do not seem to benefit from trastuzumab. Resistance to lapatinib has been reported in patients with L755S, V842I, and K753I. These data suggest that exploring HER2 SNPs in each patient could help individualize anti-HER2 therapies. Advances in our understanding of the genetics of the HER2 gene and its relations with the efficacy of anti-HER2 treatments are needed to improve the outcomes of patients with this aggressive breast cancer.

scholarly journals Circulating tumor cells and brain metastasis outcome in patients with HER2-positive breast cancer: the LANDSCAPE trial

2013 ◽  
Vol 24 (12) ◽  
pp. 2999-3004 ◽  
Author(s):  
J.-Y. Pierga ◽  
F.-C. Bidard ◽  
C. Cropet ◽  
P. Tresca ◽  
F. Dalenc ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

scholarly journals The first results of the national programme for the diagnosis and treatment of HER2-positive breast cancer in Turkmenistan

2018 ◽  
Vol 20 (2) ◽  
pp. 42-44
Author(s):  
M B Berdimyradova ◽  
S M Khadjiev ◽  
D N Khommadova ◽  
G O Polatova ◽  
A O Kakajanova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Rates ◽  
Diagnosis And Treatment ◽  
Her2 Status ◽  
Advanced Stage ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
First Results ◽  
Advanced Stage Cancer ◽  
Positive Breast Cancer

Abstract The article deals with the changes in diagnosis and treatment of early and advanced HER2-positive breast cancer (BC) in Turkmenistan during 2010-2018. Early BC detection programme started in Turkmenistan in the year 2010 and the percentage of stage I-II BC detection in the country increased by 8.8% and reached 69.6% in 2017. Automated HER2-testing method in diagnostic breast tumors was carried out in December 2016; the number of immunohistochemical studies was increased in 2 times from December 2016 to December 2017 and the percentage of HER2 status assessment in patients with newly diagnosed disease reached 99%. The central programme of targeted therapy for HER2-positive BC with trastuzumab and pertuzumab, first in patients with advanced-stage cancer, and then in patients with early HER2-positive BC started within the country in 2016. The first results of the application of anti-HER2 therapy in Turkmenistan of advanced-stage cancer showed promising results: the higher clinical efficacy and favourable safety profile in the treatment. The first results of anti-HER2 blockade in the neoadjuvant chemotherapy confirmed the high percentage of the complete morphological regression in HER2-positive BC, and gave us hope for the future associated with higher survival rates.

Expression of hormone receptors ERα, ERβ and PgR in HER2-positive breast cancers

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10525-10525
Author(s):  
M. Litwiniuk ◽  
V. Filas ◽  
J. Moczko ◽  
R. Kaleta ◽  
J. Breborowicz
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Detection System ◽  
Statistical Significance ◽  
Her2 Status ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

10525 Background: HER-2/neu gene is amplified and overexpressed in 15–20% of invasive breast cancers. HER2-positive breast cancers have a worse prognosis than HER2-negative tumors and distinctive clinical features. They express hormone receptors for estrogen (ERα) and for progesterone (PgR) less frequently than HER2-negative tumors. The identification of the other human estrogen receptor, receptor beta (ERβ), raises a question of ERβ occurrence in HER2-positive breast cancer. Patients and methods: Formalin-fixed, paraffin embedded tissues from 90 patients with invasive HER2-positive breast cancer and from 99 patients with HER2-negative breast cancer were used in this study. The HER2 status was analyzed using HercepTest TM (IHC), and IHC 2+ results were confirmed with FISH test. Immunostaining for ERα, ERβ and PgR was performed using monoclonal antibodies against ERα, PgR (DakoCytomation) and against ERβ (CHEMICON). The EnVision detection system was applied. The data were analyzed using nonparametric Fisher-Freeman-Halton test; the statistical significance was considered when p < 0.5. Results: Only 33% of the HER2-positive breast cancers were ERα-positive compared with 63% in the HER2-negative group (p < 0.001). The expression of ERβ protein was observed in almost equal frequency in both groups (57% of HER2-positive breast cancers and 57.7% of HER2-negative tumors, p = 0.889). The expression of PgR was observed in 30% of HER2-positive breast cancers and in 68.7% of HER2-negative tumors (p < 0.001). Conclusion: The expression of ERβ (unlike that of ERα and PgR) was similar in HER2-positive and in HER2-negative breast cancers. Thus, ERβ may be a potential target in future endocrine therapy for women with HER2-positive breast cancers. No significant financial relationships to disclose.

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