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]

Circulating Tumor Cells in HER-2 Positive Metastatic Breast Cancer Patients Treated with Trastuzumab and Chemotherapy

2009 ◽  
Vol 24 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Raquel A. Nunes ◽  
Xiaochun Li ◽  
Soonmo Peter Kang ◽  
Harold Burstein ◽  
Lisa Roberts ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Response ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Her 2

The detection of circulating tumor cells (CTCs) in peripheral blood may have important prognostic and predictive implications in breast cancer treatment. A limitation in this field has been the lack of a validated method of accurately measuring CTCs. While sensitivity has improved using RT-PCR, specificity remains a major challenge. The goal of this paper is to present a sensitive and specific methodology of detecting CTCs in women with HER-2-positive metastatic breast cancer, and to examine its role as a marker that tracks disease response during treatment with trastuzumab-containing regimens. The study included patients with HER-2-positive metastatic breast cancer enrolled on two different clinical protocols using a trastuzumab-containing regimen. Serial CTCs were measured at planned time points and clinical correlations were made. Immunomagnetic selection of circulating epithelial cells was used to address the specificity of tumor cell detection using cytokeratin 19 (CK19). In addition, the extracellular domain of the HER-2 protein (HER-2/ECD) was measured to determine if CTCs detected by CK19 accurately reflect tumor burden. The presence of CTCs at first restaging was associated with disease progression. We observed an association between CK19 and HER-2/ECD. The association of HER-2/ECD with clinical response followed a similar pattern to that seen with CK19. Finally, the absence of HER-2/ECD at best overall response and a change of HER-2/ECD from positive at baseline to negative at best overall response was associated with favorable treatment response. Our study supports the prognostic and predictive role of the detection of CTCs in treatment of HER-2-positive metastatic breast cancer patients. The association between CK19 and markers of disease burden is in line with the concept that CTCs may be a reliable measure of tumor cells in the peripheral blood of patients with metastatic breast cancer. The association of CTCs at first restaging with treatment failure indicates that CTCs may have a role as surrogate markers to monitor treatment response.

HER2/neu status in primary breast cancer and in metastatic site as detected using FNA.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11502-e11502
Author(s):  
Francesco Giotta ◽  
Maria Consilia Asselti ◽  
Stella Petroni ◽  
Onsina Popescu ◽  
Vincenza Rubini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Proliferative Activity ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Significant Loss ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Metastatic Site ◽  
Her 2 ◽  
Metastatic Sites

e11502 Background: As for hormonal receptor (ER, PgR), also human epidermal growth factor receptor-2 (HER-2) expression in breast cancer primitive tumor (PT) could be different from that of metastatic site (MS). These differences arise some questions about clinically useful information given and accuracy of methods to detect biological features. Fine Needle Aspiration (FNA) of metastatic sites could be an available tool to characterize biologic pattern of lesions, using immunocytochemical and/or molecular assay. The aim of the study is to compare prognostic and predictive factors obtained from PT and corresponding MS. Methods: Thirty-eight consecutive metastatic breast cancer patients underwent FNA on metastatic sites in order to re-evaluate receptor status, proliferative activity and HER-2/Neu amplification. In MS the material was achieved using FNA with a 21-23 G needle and obtaining monolayer and the corresponding cito-inclusion. MS were localized in liver (21), lung (8) and distant lymph-nodes (9). ERs, PgRs and Ki-67 were detected in both PT and MS, in 38 cases by immunochemistry, whereas HER-2/Neu amplification was detected on citoinclusion in 35 evaluable cases by FISH. Results: ERs, PgRs and Ki-67 were detected in both PT and in MS, in 36, 34, 25 out of 38 cases respectively, showing a significant loss of hormonal receptors and a decreased proliferative activity in MS versus PT (t-test p: 0.0195, <0.0001 and 0.0120 respectively). Regarding to HER-2/Neu amplification, 28 out of 35 evaluable cases were not amplified while 6 were amplified both in PT and in MS (Pearson Test: r=0.9 p: <0.0001). Another case, HER/Neu amplified in TP, after therapy with trastuzumab resulted not amplified in MS. Conclusions: According to other authors, our data demonstrated that the lost of HER/Neu amplification in MS is a possible event and that FNA samples of MS are available for HER/Neu detection.

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).

scholarly journals Serum epidermal growth factor receptor/HER-2 predicts poor survival in patients with metastatic breast cancer

Cancer ◽  
2006 ◽  
Vol 107 (10) ◽  
pp. 2337-2345 ◽  
Author(s):  
Christopher Souder ◽  
Kim Leitzel ◽  
Suhail M. Ali ◽  
Laurence Demers ◽  
Dean B. Evans ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Poor Survival ◽  
Her 2 ◽  
Epidermal Growth

scholarly journals SP140L is differentially expressed in metastasis to lymph nodes in human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Human Breast Cancer ◽  
Metastatic Breast ◽  
Human Breast ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the brain and the breast resides the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in human breast cancer. We found that the SP140 nuclear body protein like, encoded by SP140L, was among the genes whose expression was most different in the lymph nodes metastases of patients with metastatic breast cancer as compared to primary tumors of the breast (4). SP140L was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). SP140L mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Importantly, expression of SP140L in primary tumors was significantly correlated with patient overall survival, in lymph node positive patients but not in lymph node negative patients. Modulation of SP140L expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph node and to the brain in humans with metastatic breast cancer.

scholarly journals IL-6 is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.

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

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 cytokine interleukin-6 (IL-6) (5) 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 IL-6 messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of IL-6 in primary tumors of the breast, suggesting that increased primary tumor expression of IL-6 in the primary tumors of patients with breast cancer, a cytokine whose serum levels are correlated with worse patient survival outcomes in metastatic breast cancer (6), is a direct transcriptional result of treatment with trastuzumab.

scholarly journals CCDC155 is differentially expressed in metastasis to lymph nodes in human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Human Breast Cancer ◽  
Metastatic Breast ◽  
Human Breast ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the brain and the breast resides the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in human breast cancer. We found that the coiled-coil domain containing 155, encoded by CCDC155, was among the genes whose expression was most different in the lymph nodes metastases of patients with metastatic breast cancer as compared to primary tumors of the breast (4). CCDC155 was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). CCDC155 mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Importantly, expression of CCDC155 in primary tumors was significantly correlated with patient recurrence-free survival, in lymph node positive patients but in lymph node negative patients. Modulation of CCDC155 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph node and to the brain in humans with metastatic breast cancer.

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