The gene encoding the estrogen receptor, ESR1, is differentially expressed in the primary tumors and metastases of patients with breast cancer based on survival outcomes and its expression correlates with survival.

Patient Survival ◽

Metastatic Breast ◽

Receptor Expression ◽

Survival Outcomes ◽

Primary Tumors ◽

Esr1 Expression

Breast cancer is a leading cause of cancer death for women in the United States (1). Metastatic breast cancer is a major public health problem with a 5-year survival rate of 27% (1). We mined published microarray datasets to identify genes whose expression was most significantly different when comparing primary and metastatic tumors based on survival outcomes at 24 months (2, 3). In the primary tumors of patients with breast cancer, we identified the estrogen receptor alpha, ESR1 (also known as ER) as one of the most significantly differentially expressed genes when comparing tumor transcriptomes based on disease-free survival at 24 months. When comparing the transcriptomes of metastases from patients with stage IV metastatic breast cancer, we again found that ESR1 was among the genes whose expression was most significantly different based on overall survival at 24 months. In metastatic tissues, expression of ESR1 positively correlated with overall patient survival. Stratifying patients based on ESR1 expression revealed that higher ESR1 expression in both primary and metastatic tissues was generally associated with enhanced patient survival. Though established immunohistochemical classification of breast cancers groups tumors in a binary fashion based on ER expression at the protein level as ER+ and ER-, these data suggest that graded interpretation of estrogen receptor expression at the mRNA level, in primary tumors and in metastatic tissues, may be useful for prognostic purposes.

Expression of LINC00968 correlates with overall survival in normal-like breast cancer.

10.31219/osf.io/hbgr6 ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Survival Data ◽

Patient Survival ◽

Molecular Subtype ◽

Metastatic Breast ◽

Survival Outcomes ◽

Significant Differential Expression ◽

Primary Tumors

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer, and integrated these findings with unbiased examination of patient survival outcomes based on molecular subtype. We have previously found significant differential expression of the gene encoding long intergenic non-protein coding RNA 968, LINC00968, when comparing primary tumors of the breast to the tissue of origin, the normal breast and in the brain metastases of patients with metastatic breast cancer4. Here we demonstrate through analysis of human survival data that expression of LINC00968 in primary tumors of the breast is correlated with overall survival in patients with normal-like subtype cancer, demonstrating a relationship between primary tumor expression of a differentially expressed non-coding RNA and patient survival outcomes influenced by PAM50 molecular subtype. LINC00968 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

TSHZ3 is differentially expressed in lymph node metastasis in human breast cancer.

10.31219/osf.io/kxjqn ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Primary Tumors ◽

Node Metastases ◽

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside 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 humans with metastatic breast cancer. We found that teashirt zinc finger homeobox 3, TSHZ3, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that TSHZ3 was also differentially expressed in brain metastatic tissues. TSHZ3 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of TSHZ3 in primary tumors of the breast was correlated with patient post-progression survival, in lymph node positive patients but not in lymph node negative patients. Modulation of TSHZ3 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

TMEM98 is differentially expressed in lymph node metastasis in human breast cancer.

10.31219/osf.io/hpjc8 ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Primary Tumors ◽

Node Metastases ◽

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside 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 humans with metastatic breast cancer. We found that transmembrane protein 98, TMEM98, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that TMEM98 was also differentially expressed in brain metastatic tissues. TMEM98 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of TMEM98 in primary tumors of the breast was correlated with patient overall survival, in lymph node positive patients but not in lymph node negative patients. Modulation of TMEM98 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

CD69 is differentially expressed in the lymph nodes of patients with metastatic breast cancer.

10.31219/osf.io/utpcq ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Primary Tumors ◽

Node Metastases ◽

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside 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 humans with metastatic breast cancer. We found that cluster of differentiation 69, CD69, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that CD69 was also differentially expressed in brain metastatic tissues. CD69 mRNA was present at increased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of CD69 in primary tumors of the breast was correlated with patient overall survival, more significantly in lymph node negative patients than in lymph node positive patients. Modulation of CD69 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

GRIK3 is differentially expressed in the lymph nodes of patients with metastatic breast cancer.

10.31219/osf.io/zec8n ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Primary Tumors ◽

Node Metastases ◽

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside 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 humans with metastatic breast cancer. We found that the glutamate receptor, ionotropic kainate subunit 3, GRIK3, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that GRIK3 was also differentially expressed in brain metastatic tissues. GRIK3 mRNA was present at increased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of GRIK3 in primary tumors of the breast was correlated with patient recurrence-free survival, in lymph node negative patients but not in lymph node positive patients. Modulation of GRIK3 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

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

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.26_suppl.155 ◽

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 ◽

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).

SFRP2 is differentially expressed in lymph node metastasis in human breast cancer.

10.31219/osf.io/y8nzv ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Primary Tumors ◽

Node Metastases ◽

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside 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 humans with metastatic breast cancer. We found that secreted frizzled related protein 2, SFRP2, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that SFRP2 was also differentially expressed in brain metastatic tissues. SFRP2 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of SFRP2 in primary tumors of the breast was correlated with patient overall survival, in lymph node positive patients but not in lymph node negative patients. Modulation of SFRP2 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

TSPY is differentially expressed in lymph node metastases in human breast cancer.

10.31219/osf.io/rwunm ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Primary Tumors ◽

Node Metastases ◽

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside 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 humans with metastatic breast cancer. We found that the testis-specific protein on Y chromosome, TSPY, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that TSPY was also differentially expressed in brain metastatic tissues. TSPY mRNA was present at increased quantities in lymph node metastases as compared to primary tumors of the breast. Modulation of TSPY expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

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

10.31219/osf.io/pcmnt ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Messenger Rna ◽

Growth Factor Receptor ◽

Metastatic Breast ◽

The United States ◽

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.

TSPAN9 is differentially expressed in lymph node metastasis in human breast cancer.

10.31219/osf.io/8f5zj ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Primary Tumors ◽

Node Metastases ◽

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside 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 humans with metastatic breast cancer. We found that tetraspanin 9, TSPAN9, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that TSPAN9 was also differentially expressed in brain metastatic tissues. TSPAN9 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of TSPAN9 in primary tumors of the breast was correlated with patient distant metastasis-free survival, in lymph node positive patients but not in lymph node negative patients. Modulation of TSPAN9 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.