Correlation of Expression of Breast Biomarkers in Primary and Metastatic Breast Carcinomas: A Single-Institution Experience

2016 ◽  
Vol 60 (5) ◽  
pp. 481-489 ◽  
Author(s):  
Yanjun Hou ◽  
Rulong Shen ◽  
Shweta Chaudhary ◽  
Faye Gao ◽  
Zaibo Li
Keyword(s):  
Small Sample Size ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Small Sample ◽  
Her2 Status ◽  
Study Cohort ◽  
Breast Carcinomas ◽  
Status Change ◽  
Primary Tumors ◽  
The Status

Objective: Changes in the status of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in metastatic breast carcinomas are frequently reported. We examined the change in the status of biomarkers in metastatic breast carcinomas. Study Design: This study cohort was composed of 137 metastatic breast carcinomas (58 surgical and 79 cytological specimens) with existing primary tumors during a study period from 2013 to 2015. Results: The overall change rates in metastases were 9, 21 and 6% for ER, PR and HER2, respectively. All changes were from positive in the primary tumor to negative in the metastases. The ER change rate was significantly higher in the cytological than in the surgical metastases. Six of 14 cytological metastases with positive HER2 in primary tumors showed a change in HER2 status, including 5 fluid specimens and 1 fine-needle aspiration (FNA); the other 8 had no change in HER2 status, and included 7 FNAs and 1 fluid specimen. Conclusion: The significant percentage of cases with a change in biomarker status supports the recommendation by the College of American Pathologists to test breast biomarkers in metastases. HER2 status change was mostly identified in fluid specimens; however, the small sample size in our cohort and the fact that HER2 fluorescence in situ hybridization was not performed may warrant further studies.

scholarly journals Prospective Study Evaluating the Impact of Tissue Confirmation of Metastatic Disease in Patients With Breast Cancer

2012 ◽  
Vol 30 (6) ◽  
pp. 587-592 ◽  
Author(s):  
Eitan Amir ◽  
Naomi Miller ◽  
William Geddie ◽  
Orit Freedman ◽  
Farrah Kassam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prospective Study ◽  
Treatment Plan ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Primary Tumors ◽  
Receptor Status ◽  
Metastatic Recurrence ◽  
The Impact

Purpose Decisions about treatment for women with metastatic breast cancer are usually based on the estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor 2 (HER2) status of the primary tumor. Retrospective data suggest that discordance between primary and metastatic lesions leads to detrimental outcome. This prospective study investigated receptor status of primary tumors and metastases in the same patient and assessed the impact of discordance on patient management and survival. Patients and Methods Biopsies of suspected metastases were analyzed for ER, PgR, and HER2. Primary tumors and metastases were analyzed using similar methodology. The treating oncologist indicated a treatment plan before and after biopsy to determine whether the result influenced management. Patients were followed up for progression or death. Results Of 121 women undergoing biopsy, 80% could be analyzed for receptor status. Discordance in ER, PgR, and HER2 between the primary and the metastasis was 16%, 40%, and 10%, respectively. Biopsy led to a reported change of management in 14% of women (95% CI, 8.4% to 21.5%). Fine-needle aspiration and biopsy of bone led to reduced ability to analyze receptors. After a median follow-up of 12 months, there were no trends for an association between receptor discordance and either time to treatment failure or overall survival. Conclusion Biopsy of metastases is technically feasible. Clinicians alter immediate management in one of seven patients on the basis of results of the biopsy, and discordance is not then associated with detrimental effects on outcome. Tissue confirmation should be considered in women with breast cancer and suspected metastatic recurrence.

scholarly journals New Insights to Reshape the Management of Patients with Metastatic Breast Cancer - Focus on Overcoming Challenges in HER2 Status Interpretation

2020 ◽  
Vol 10 (1) ◽  
pp. 38-46
Author(s):  
Katarzyna Rygiel
Keyword(s):  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Predictive Biomarker ◽  
Her2 Status ◽  
Breast Cancers ◽  
Metastatic Progression ◽  
The Status ◽  
Patient Prognosis ◽  
Therapeutic Decision Making ◽  
The Impact

Approximately 20% of invasive Breast Cancers (BCs) are characterized by Human Epidermal growth factor Receptor 2 (HER2) protein overexpression or HER2 gene amplification. HER2 represents a standard diagnostic test and a predictive biomarker for the use of HER2-directed treatments in patients with BC. At present, the HER2 Immunohistochemistry (IHC) assay is applied for screening purposes, and the In Situ Hybridization (ISH) test serves as a confirmation, when HER2 IHC results are equivocal. However, an accurate assessment and interpretation of the HER2 status can be complicated in many women with BC. These difficulties can be attributed to various factors such as HER2 Intratumoral Heterogeneity (ITH) and changes of HER2 in the process of BC metastatic progression or post neoadjuvant Chemotherapy (CHT). In particular, the status of biomarkers (e.g., HER2 and co-expressed Hormone Receptor (HR)) can be altered in patients with metastatic BC and such receptor changes influence the therapeutic responses and clinical outcomes. The goal of this article is to present challenges in the assessment of HER2 expression and to underscore a need for the biomarker status reevaluation in patients with metastatic BC. This mini-review also provides some insights into the interpretation of equivocal HER2 status in women with metastatic BC and discusses the impact of HER2 and HR biomarker conversions on therapeutic decision-making and the patient prognosis in metastatic BC. It is crucial to correctly interpret the HER2 biomarker status and to assess conversions of HER2 and HR in the BC metastatic lesions since timely detection of such alterations is critical to management modifications of individual patients with metastatic BC.

scholarly journals DVL3 is over-expressed in the tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
The United States ◽  
Breast Cancer Patients ◽  
Gene Encoding ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
Unbiased Manner

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published and public microarray and gene expression data (3, 4) to discover in an unbiased manner the most striking transcriptional features of trastuzumab treatment. We identified significant differential expression of the gene encoding the Wnt pathway molecule dishevelled-3, DVL3 (5-7), in the primary tumors of breast cancer patients treated with trastuzumab. DVL3 expression in primary tumors of the breast in patients treated with trastuzumab was significantly higher than in patients not treated with trastuzumab.

scholarly journals DCC is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Messenger Rna ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
The United States ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Deleted In Colorectal Cancer

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased manner the most striking transcriptional features of trastuzumab treatment. We identified the deleted in colorectal cancer locus DCC (5, 6) as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed higher levels of DCC messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of DCC in primary tumors of the breast, demonstrating that a gene encoding for a netrin receptor, cellular machinery utilized for axon guidance in the central nervous system (5-9), is transcriptionally induced in primary tumors of the breast following treatment with trastuzumab.

Utility of Immunohistochemistry in Distinguishing Primary Adenocarcinomas From Metastatic Breast Carcinomas in the Gastrointestinal Tract

2005 ◽  
Vol 129 (3) ◽  
pp. 338-347 ◽  
Author(s):  
Fionnuala P. O'Connell ◽  
Helen H. Wang ◽  
Robert D. Odze
Keyword(s):  
Estrogen Receptor ◽  
Epidermal Growth Factor Receptor ◽  
Gastrointestinal Tract ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Receptor Protein ◽  
Breast Carcinomas ◽  
Estrogen Receptor Protein ◽  
Gastric Carcinomas ◽  
Epidermal Growth

Abstract Context.—Breast carcinoma often metastasizes to the gastrointestinal tract, especially the stomach, where it is frequently difficult to distinguish from a primary gastric carcinoma. Objective.—To evaluate the utility of immunohistochemical stains in differentiating primary gastric carcinomas from metastatic breast carcinomas. Design.—Mucosal biopsy specimens from 47 adenocarcinomas involving the gastrointestinal tract (28 primary gastric carcinomas and 19 metastatic breast carcinomas) and 16 control cases of primary breast carcinomas without metastasis were immunohistochemically stained for estrogen receptor protein (ER), progesterone receptor protein (PR), gross cystic disease fluid protein (GCDFP), human epidermal growth factor receptor 2 protein, cytokeratin (CK) 5/6, CK/7, CK/20, a panel of mucin glycoprotein antigens (MUC2, MUC3, MUC5AC, and MUC6), monoclonal antibody DAS-1, and caudal-type homeobox transcription factor CDX2 and compared between primary and metastatic adenocarcinomas. Results.—Highly significant proportions of metastatic breast carcinomas were positive for ER (72%), PR (33%), GCDFP (78%), and CK5/6 (61%) compared with primary gastric carcinomas (ER, 0%; PR, 0%; GCDFP, 0%; and CK5/6, 14%) (P < .001, P = .002, P < .001, and P = .004, respectively). Of these immunostains, ER, PR, and GCDFP were 100% specific. Primary breast tumors and their metastases showed a similar phenotypic profile. In contrast, primary gastric carcinomas showed significantly higher proportions of cases that stained with CK20 (50%), MUC2 (54%), MUC5AC (71%), MUC6 (39%), DAS-1 (43%), and CDX2 (67%) compared with metastatic breast carcinomas (CK20, 0%; MUC2, 24%; MUC5AC, 6%; MUC6, 0%; DAS-1, 0%; and CDX2, 0%) (P = .001, P = .01, P < .001, P = .02, P = .009, and P < .001, respectively). No significant differences were observed with regard to any of the other immunostains (human epidermal growth factor receptor 2 protein, CK7, and MUC3) between the patient groups. Conclusions.—Estrogen receptor protein, PR, GCDFP, CK5/6, CK20, MUC5AC, MUC6, DAS-1, and CDX2 are helpful in distinguishing primary gastric carcinomas from metastatic breast carcinomas. Of these, ER, PR, and GCDFP are highly specific for metastatic breast carcinomas, whereas CK20, DAS-1, MUC2, MUC5AC, MUC6, and CDX2 are highly specific for primary gastric carcinomas.

Mutations of HER2 gene in HER2-positive metastatic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13118-13118 ◽  
Author(s):  
T. Prempree ◽  
C. Wongpaksa
Keyword(s):  
Breast Cancer ◽  
Gene Mutations ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Trastuzumab Resistance ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Primary Tumors ◽  
Trastuzumab Therapy ◽  
One Year

13118 Background: HER2 status of Breast Cancer has been assessed by IHC and FISH and used for therapeutic decision with a high degree of success. However, there were numbers of HER2-positive MBC who finally failed the Trastuzumab treatment after initial good response. Mechanisms of intrinsic and acquired Trastuzumab resistance are not yet known. Our Objective is to identify factor or factors responsible for Trastuzumab resistance. Methods: DNA extraction and Sequencing of HER2 gene were performed on primary tumors of HER2-positive 14 MBC patients undergoing Trastuzumab therapy. Re-biopsy were done on new metstatic sites of those cases discovered to have Trastuzumab resistance. Results: Of 14 MBC cases whose tumors showing positive IHC and FISH, there were no mutation found in their HER2 gene, exons 18,19, 20 and 21. However, 3 of 14 cases of MBC undergoing continuous Trastuzumab therapy with excellent response for more than one year, developed the resistance. All three cases had new metstatic sites biopsied, and showed D880N and E837Y mutations in the exon 21 of their HER2 genes. All three cases showed no response to trastuzumab therapy. Conclusions: 1) HER2-positive MBC tumors did not have any HER2 gene mutations in them. 2) Mutations arised in their HER2 gene, exon 21 may be responsible for the intrinsic and acquired Trastuzumab resistance. Additional work in this area is needed to further substantiate our findings. No significant financial relationships to disclose.

Bevacizumab (BEV) plus second-line taxane (TAX) or other chemotherapy (CT) for triple-negative breast cancer (TNBC): Subgroup analysis of RIBBON-2.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 290-290
Author(s):  
A. Brufsky ◽  
V. Valero ◽  
B. Tiangco ◽  
S. R. Dakhil ◽  
A. Brize ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Endpoint ◽  
Small Sample Size ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Small Sample ◽  
Second Line ◽  
First Line ◽  
Free Survival

290 Background: In three randomized trials in the first-line metastatic breast cancer (MBC) setting, combining BEV with CT significantly improved progression-free survival (PFS; primary endpoint) and objective response rate (ORR) vs. CT alone. BEV also showed a significant PFS benefit in the second-line MBC setting (RIBBON-2) when combined with TAX or other CT. We analyzed data from the subgroup of patients (pts) with TNBC in RIBBON-2. Methods: Eligible pts had MBC that had progressed on first-line CT without BEV. Second-line CT (TAX, gemcitabine, capecitabine, or vinorelbine) was chosen before 2:1 randomization to CT with either BEV (10 mg/kg q2w or 15 mg/kg q3w) or placebo (PLA). All pts could receive BEV at progression. The primary endpoint was PFS. Results: RIBBON-2 included 684 pts; 159 (23%) had TNBC and of these, 67 (42%) received TAX with BEV/PLA. Baseline characteristics were broadly similar in the two treatment arms. In an exploratory analysis of pts with TNBC, BEV + CT led to significantly improved PFS and ORR vs. CT alone, and a trend toward improved overall survival (OS). The magnitude of the effect was particularly pronounced in pts receiving TAX CT. Conclusions: Pts with TNBC derive significant ORR and PFS benefit from BEV combined with second-line CT. Despite the small sample size, there was a trend (HR 0.624; p = 0.0534) toward OS benefit in pts treated with BEV, especially with TAX CT. [Table: see text]

Survival of patients with HER2-positive gastric cancer with introduction of trastuzumab.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 128-128
Author(s):  
Kohei Shitara ◽  
Yasushi Yatabe ◽  
Masato Sugano ◽  
Keitaro Matsuo ◽  
Chihiro Kondo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Small Sample Size ◽  
Small Sample ◽  
Her2 Status ◽  
First Line ◽  
Her2 Positive ◽  
Line Therapy ◽  
The Impact ◽  
Time Varying Covariates ◽  
Line Chemotherapy

128 Background: ToGA study showed that trastuzumab given in combination with first-line chemotherapy (fluoropyrimidine plus cisplatin) improved the overall survival of HER2-positive patients with advanced gastric cancer (AGC). Meanwhile, the prognostic value of HER2 or the efficacy of trastuzumab in second- or further-line chemotherapy remains controversial. Methods: We retrospectively analyzed 567 patients with AGC who initiated systemic chemotherapy before March 2011. Among them, 287 were evaluated for their HER2 status. HER2 positivity was defined as IHC 3+ or IHC 2+ with amplification by FISH. Treatment outcomes were compared between patients with HER2-positive and HER2-negative AGC. To evaluate the impact of exposure to trastuzumab in any line of chemotherapy, we applied time-varying covariates (TVC) analysis to avoid possible lead-time bias. Results: The median survival time (MST) of HER2-evaluated patients (n=287) tended to be better than that of HER2-non-evaluated patients (n=280, 14.5 vs. 13.2 months; P=0.03). Among the HER2-evaluated patients, 47 (16.3%) were HER2-positive and had longer survival than HER2-negative patients (24.1 vs. 13.4 months; P=0.05). Among the HER2-positive patients, 35 received trastuzumab; 15 patients received it as first-line therapy and 20 received it as second- or further-line therapy. The MST of HER2-positive patients with trastuzumab treatment was significantly longer than that of HER2-positive patients without trastuzumab (26.6 vs. 13.5 months; P=0.015). HER2-negative patients and HER2-positive patients without trastuzumab had similar survival durations. According to multivariate analysis with TVCs, exposure to trastuzumab was independently associated with better prognosis (HR 0.54, P=0.04). Conclusions: Although the retrospective nature and small sample size are major limitations of this study, recent HER2-positive AGC patients showed a better prognosis than HER2-negative patients, especially with the introduction of trastuzumab.

Serum CEA and CA 15-3 levels according to breast cancer subtypes.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11511-e11511 ◽  
Author(s):  
Isa Dede ◽  
Gungor Utkan ◽  
Hakan Akbulut ◽  
Yuksel Urun ◽  
Dilsa Mizrak ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Markers ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Serum Levels ◽  
Carbohydrate Antigen ◽  
Breast Cancer Subtypes ◽  
Her2 Status ◽  
Cancer Subtypes ◽  
Serum Cea

e11511 Background: Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 15-3 are frequently elevated in patients with metastatic breast cancer (MBC). In this study we aimed to correlate levels according to breast cancersubtypes with MBC. Methods: From January 2008 to December 2012, ninety-eight patients with MBC who were treated at Ankara University School Of Medicine, Department of Medical Onkology were included in this study.Serum levels of CEA and CA 15-3were measured and compared according to tumor estrogen receptor (ER), progesteron receptor (PR), and human epidermal growth factor receptor 2 (HER2) status. Results: In this cohort, overall ER,PR and HER2 positivity rates were 65 %,68%,and 58%, retrospectively. Positivite ER status was associated with elevated levels of CA 15-3 and cea. Of these, CA 15-3 levels elevated in 40.5% of ER positivite and 24.1 % of ER negativite patients (p=0.027). Similarly, 46.8 % of ER positivite and 18.2% of ER negativite patients had elevated levels of CEA (P=0.022). no association between PR and HER2 status and tumor markers was observed. Conclusions: The breast cancer subtypes are correlated with serum levels of tumor markers in patients with MBC. Tumor markers elevation may be associated with biological background of breast cancer subtypes. Further validation is needed to determine the role of these markers in diffrent tumor types for monitoring patients with MBC.

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