Correlation of serum HER-2/neu extracellular domain levels in metastatic breast cancer with the expression of HER-2/neu in corresponding primary tumors

2004 ◽  
Vol 2 (3) ◽  
pp. 178
Author(s):  
I Witzel ◽  
V Müller ◽  
W Wiczak ◽  
W Bubenheim ◽  
F Jänicke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Extracellular Domain ◽  
Primary Tumors ◽  
Her 2

The effect of trastuzumab therapy on clinical benefit from fulvestrant treatment for metastatic estrogen receptor-positive breast cancer patients.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 155-155
Author(s):  
Mahmoud Charif ◽  
Elyse E. Lower ◽  
Diane Kennedy ◽  
Harriet Kumar ◽  
Shugufta Khan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Clinical Benefit ◽  
Primary Tumor ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Primary Tumors ◽  
Duration Of Therapy ◽  
Her 2

155 Background: Overexpression of HER2/neu is associated with tamoxifen resistance in breast cancer (Osborne CK et al. J Natl Canc Inst 2003; 95:353-361). However pts may present with both estrogen receptor (ER) and HER2/neu + tumors. The benefit of adding fulvestrant to trastuzumab is unclear. The objective of the study was to determine the effect of trastuzumab on fulvestrant therapy. Methods: This was an IRB approved record review of patients (pts) from three medical oncologists with biopsy-proven ER+ metastatic breast cancer treated with fulvestrant who also had their primary tumor tested for HER2/neu. Demographic data collected included age at diagnosis, type and stage of cancer, original and metastatic ER, progesterone receptor (PR), and HER-2/neu biomarkers, and site(s) of metastasis, and primary local and systemic treatment. All pts with HER-2/neu + primary tumors received trastuzumab. The duration of fulvestrant therapy was calculated. Time to clinical disease progression on fulvestrant was measured as a surrogate for duration of clinical benefit. Results: Eighty-five metastatic ER+ fulvestrant treated breast cancer pts with known primary tumor HER2/neu status were identified and the duration of therapy calculated. All eleven (13%) pts with documented HER2/neu + primary tumors received trastuzumab. The duration of therapy for HER2/neu + pts (772 (51-1911) days (median (range)) was longer than HER2/neu negative pts (360 (60-2,739) days, p=0.059). The median duration of fulvestrant therapy was 425 days. Pts with HER2/neu + tumors were more likely to be treated beyond the median fulvestrant therapy with an odds ratio of 6.2 (1.26 to 30.92 95% confidence interval, p=0.0249). Conclusions: Trastuzumab plus fulvestrant therapy was associated with a more prolonged clinical response than fulvestrant alone in pts with metastatic breast cancer. This synergism may be due to the effect of trastuzumab inhibiting the activation of transcriptional coactivator MED1, a recently discovered key crosstalk point between HER2/neu and ER signaling pathways in mediating endocrine resistance (Cancer Res 2012;72(21):5625;PLoS One 2013; 8:e70641).

Prognostic and Predictive Impact of the HER-2/neu Extracellular Domain (ECD) in the Serum of Patients Treated with Chemotherapy for Metastatic Breast Cancer

2004 ◽  
Vol 86 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Volkmar Müller ◽  
Isabell Witzel ◽  
Hans Joachim Lück ◽  
Günter Köhler ◽  
Gunther von Minckwitz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Extracellular Domain ◽  
Her 2

Genomic of circulating tumor cells in metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1002-1002 ◽  
Author(s):  
J. M. Reuben ◽  
B. N. Lee ◽  
C. Li ◽  
K. R. Broglio ◽  
V. Valero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Notch 1 ◽  
Primary Tumors ◽  
Metastatic Site ◽  
Her 2 ◽  
Pre Treatment

1002 Background: Metastatic breast cancer (MBC) is an incurable condition and palliative treatments are selected by considering pre-treatment prognostic and predictive factors. Recently, we reported the detection of CTCs to be predictive of prognosis and treatment efficacy and reasoned they might also be used to assess biological characteristics of the patient’s tumor to improve on treatment selection. Methods: Twenty patients with newly diagnosed MBC were enrolled in a prospective clinical trial designed to assess the baseline value of CTCs, evaluate the expression of selected genes in CTCs, and compare the expression of same biomarkers in the primary tumor (PT) and/or metastatic site (MS), as determined by standard IHC and FISH. CTCs were assessed by CellSearch, and subjected to real-time PCR (qPCR) for the expression of transcripts for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER-2), notch-1, and mammaglobin (MGB) using commercial primers. Results: Sixteen of patients had =1CTCs. With respect to biomarkers of PT, 17 were ER+, 11 PR+, and 3 HER-2 amplified. Among the 15 patients with MS, the biomarkers were as follows: 9 ER+, 7 PR+, and 2 HER-2 amplified. There were significant associations between the primary and metastatic tumors with respect to the presence of ER (χ2 = 6.516, P = 0.0107), PR (χ2 = 5.529, P = 0.0187), and HER-2 (χ2 = 3.938, P = 0.0472). The qPCR of CTCs detected transcripts: ER in 3 patients (15%); PR in none (0%); MGB and HER-2 in 2 (10%) and 11 patients (55%), respectively. Notch-1 transcripts were detected in 13 patients (65%). CTCs with detectable transcripts of HER-2 were more likely to co-express notch-1 transcripts (χ2 = 4.295, P = 0.038). Of the 4 samples without detectable CTCs, one was HER-2 positive, and three had notch- 1 transcripts. Conclusions: This study demonstrated a significant concordance in biomarkers expression between the tumor cells of the primary tumors and the metastatic site. Furthermore, it suggests that CTCs differ significantly from those tumor cells with regards to the expression of hormone-receptor and HER-2 status. Thus, CTCs may represent a unique and heterogeneous cell population which phenotype and “homing” properties should be further investigated. [Table: see text]

Prediction of response to antiestrogen therapy in advanced breast cancer patients by pretreatment circulating levels of extracellular domain of the HER-2/c-neu protein.

1997 ◽  
Vol 15 (7) ◽  
pp. 2518-2525 ◽  
Author(s):  
H Yamauchi ◽  
A O'Neill ◽  
R Gelman ◽  
W Carney ◽  
D Y Tenney ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Extracellular Domain ◽  
Primary Treatment ◽  
Survival Duration ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Her 2 ◽  
Circulating Levels

PURPOSE Overexpression of the HER-2/c-neu/c-erbB2 proto-oncogene is associated with a worse prognosis in patients with breast cancer, perhaps due to an association of the HER-2 proto-oncogene protein with resistance to hormone and/or chemotherapy. Circulating levels of the extracellular domain (ECD) of the HER-2/c-neu-related protein (NRP) are elevated in 20% to 40% of patients with metastatic breast cancer. We investigated whether pretreatment levels of NRP predict response to hormone therapy (HT). MATERIALS AND METHODS Circulating NRP levels were determined in 94 patients who participated in a randomized trial of three different doses of the antiestrogen, droloxifene (DRO), as first-line HT for metastatic breast cancer. RESULTS NRP levels were elevated (> or = 5,000 U/mL) in 32 of 94 patients (34%). Only three of 32 patients (9%) with elevated NRP levels responded to DRO, compared with 35 of 62 (56%) with nonelevated NRP levels (P = .00001). Low pretreatment NRP level was the most powerful predictor of response to DRO (odds ratio of response, 22.4; P = .0001). Elevated pretreatment NRP levels were also associated with a shorter time to progression (TTP) and survival duration. CONCLUSION Pretreatment circulating NRP levels predict a low likelihood of benefit from HT, specifically DRO, in patients with estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive or receptor-unknown metastatic breast cancer, even when adjusted for other known predictive factors, such as ER and/or PgR levels, site of disease, disease-free interval from primary treatment to recurrence, and prior adjuvant chemotherapy. These data suggest that pretreatment NRP levels may be useful in deciding whether to treat a patient who otherwise appears to be likely to respond to HT.

Rab11 family-interacting protein 4, RAB11FIP4, is a differentially expressed gene in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Interacting Protein ◽  
Primary Tumors ◽  
Free Survival ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that Rab11 family-interacting protein 4, encoded by RAB11FIP4, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. RAB11FIP4 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of RAB11FIP4 in primary tumors was significantly correlated with patient recurrence-free survival and distant metastasis-free survival. Modulation of RAB11FIP4 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

scholarly journals Regulatory T lymphocyte infiltration in metastatic breast cancer—an independent prognostic factor that changes with tumor progression

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Jenny Stenström ◽  
Ingrid Hedenfalk ◽  
Catharina Hagerling
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Prognostic Factor ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Metastatic Breast ◽  
Distant Metastases ◽  
Independent Prognostic Factor ◽  
Primary Tumors

Abstract Background Patients diagnosed with metastatic breast cancer have poor outcome with a median survival of approximately 2 years. While novel therapeutic options are urgently needed, the great majority of breast cancer research has focused on the primary tumor and less is known about metastatic breast cancer and the prognostic impact of the metastatic tumor microenvironment. Here we investigate the immune landscape in unique clinical material. We explore how the immune landscape changes with metastatic progression and elucidate the prognostic role of immune cells infiltrating primary tumors and corresponding lymph node and more importantly distant metastases. Methods Immunohistochemical staining was performed on human breast cancer tissue microarrays from primary tumors (n = 231), lymph node metastases (n = 129), and distant metastases (n = 43). Infiltration levels of T lymphocytes (CD3+), regulatory T lymphocytes (Tregs, FOXP3+), macrophages (CD68+), and neutrophils (NE+) were assessed in primary tumors. T lymphocytes and Tregs were further investigated in lymph node and distant metastases. Results T lymphocyte and Treg infiltration were the most clinically important immune cell populations in primary tumors. Infiltration of T lymphocytes and Tregs in primary tumors correlated with proliferation (P = 0.007, P = 0.000) and estrogen receptor negativity (P = 0.046, P = 0.026). While both T lymphocyte and Treg infiltration had a negative correlation to luminal A subtype (P = 0.031, P = 0.000), only Treg infiltration correlated to luminal B (P = 0.034) and triple-negative subtype (P = 0.019). In primary tumors, infiltration of T lymphocytes was an independent prognostic factor for recurrence-free survival (HR = 1.77, CI = 1.01–3.13, P = 0.048), while Treg infiltration was an independent prognostic factor for breast cancer-specific survival (HR = 1.72, CI = 1.14–2.59, P = 0.01). Moreover, breast cancer patients with Treg infiltration in their distant metastases had poor post-recurrence survival (P = 0.039). Treg infiltration levels changed with metastatic tumor progression in 50% of the patients, but there was no significant trend toward neither lower nor higher infiltration. Conclusion Treg infiltration could have clinical applicability as a prognostic biomarker, deciphering metastatic breast cancer patients with worse prognosis, and accordingly, could be a suitable immunotherapeutic target for patients with metastatic breast cancer. Importantly, half of the patients had changes in Treg infiltration during the course of metastatic progression emphasizing the need to characterize the metastatic immune landscape.

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