Loss of heterozygosity in normal breast epithelial tissue and benign breast lesions in BRCA1/2 carriers with breast cancer

2004 ◽  
Vol 149 (1) ◽  
pp. 38-43 ◽  
Author(s):  
Luciane R Cavalli ◽  
Baljit Singh ◽  
Claudine Isaacs ◽  
Robert B Dickson ◽  
Bassem R Haddad
Author(s):  
John R. Mackey ◽  
Justine Lai ◽  
Utkarsh Chauhan ◽  
Erwan Beauchamp ◽  
Wei-Feng Dong ◽  
...  

Abstract Purpose N-myristoyltransferases 1 and 2 (NMT1 and NMT2) catalyze the addition of 14-carbon fatty acids to the N-terminus of proteins. Myristoylation regulates numerous membrane-bound signal transduction pathways important in cancer biology and the pan-NMT inhibitor PCLX-001 is approaching clinical development as a cancer therapy. The tissue distribution, relative abundances, and prognostic value of the two human NMTs remain poorly understood. Methods We generated and validated mutually exclusive monoclonal antibodies (mAbs) specific to human NMT1 and NMT2. These mAbs were used to perform immunohistochemical analysis of the abundance and distribution of NMT1 and NMT2 in normal breast epithelial samples and a large cohort of primary breast adenocarcinomas from the BCIRG001 clinical trial (n = 706). Results NMT1 protein was readily quantified in normal and most transformed breast epithelial tissue and was associated with higher overall histologic grade, higher Ki67, and lower hormone receptor expression. While NMT2 protein was readily detected in normal breast epithelial tissue, it was undetectable in the majority of breast cancers. Detectable NMT2 protein correlated with significantly poorer overall survival (hazard ratio 1.36; P = 0.029) and worse biological features including younger age, higher histologic grade, lower hormone receptor expression, higher Ki67, and p53 positivity. Treatment of cultured breast cancer cells with PCLX-001 reduced cell viability in vitro. Daily oral administration of PCLX-001 to immunodeficient mice bearing human MDA-MB-231 breast cancer xenografts produced significant dose-dependent tumor growth inhibition in vivo. Conclusions These results support further evaluation of NMT immunohistochemistry for patient selection and clinical trials of NMT inhibition in breast cancer patients.


2019 ◽  
Vol 6 (1) ◽  
pp. 12
Author(s):  
Shuaeb Bhat ◽  
Tania R. P. ◽  
Saleem Hussain ◽  
Bushra Sahaf ◽  
Irfan Ansari

Background: Breast cancer is the most frequent cancer in India. During the last few years, several investigators have focused on tumor angiogenesis as a critical step in cancer development and progression. Among these, vascular endothelial growth factor (VEGF) is emerging as a prognostic marker in patients with several type of cancer including breast cancer. The aim of the study was to analyse the expression of VEGF in human breast cancer as compared to normal breast tissue and benign breast lesions by immunohistochemistry. Also, to assess the usefulness of VEGF as a predictor of aggressiveness of breast lesions.Methods: Formalin fixed paraffin embedded sections of 10 cases of normal breast tissue, 20 cases of benign breast lesions and 20 cases of malignant breast lesions were taken up for the study and subjected to immunohistochemistry using VEGF.Results: The intensity of VEGF immunostaining in normal breast, benign and malignant breast lesions was evaluated and scoring was graded as 0, 1+, 2+, 3+ and 4+. Statistical analysis was performed with Chi-Square test and significant differences were noted between these 3 groups (p value <0.05).Conclusions:VEGF expression correlated well with the grade and stage of tumor indicating that VEGF positive tumors are biologically aggressive and are associated with poor prognosis but little is known about the implication of genetic alterations of VEGF in benign breast lesions.


Oncogene ◽  
2003 ◽  
Vol 22 (48) ◽  
pp. 7600-7606 ◽  
Author(s):  
Chunyan Zhao ◽  
Eric W-F Lam ◽  
Andrew Sunters ◽  
Eva Enmark ◽  
Manuela Tamburo De Bella ◽  
...  

2019 ◽  
Author(s):  
George Plitas ◽  
Monica Morrow ◽  
Brandon R Bruns

A breast mass is the most common presenting symptom among patients in a breast clinic. The presence of a breast mass can cause a great deal of anxiety in women, as well as their physicians. The differential diagnosis of a palpable breast abnormality is broad, although the majority of breast masses are benign. The responsibility of the physician who is evaluating a breast mass is to exclude the presence of malignancy. Once cancer is ruled out, the physician should then attempt to provide an accurate diagnosis, appropriate treatment, and reassurance to the patient. This chapter discusses the assessment of normal breast physiology, identification of a breast mass, evaluation of the various classifications of breast mass (e.g., dominant mass with clinically benign features and dominant mass with suspicious features), differential diagnosis and management of common benign breast masses (e.g., cysts, fibroadenomas, phyllodes tumors, hamartomas, fat necrosis), and the risk of breast cancer associated with benign breast lesions. The chapter also discusses the diagnosis and management of a breast mass in male patients. Tables outline breast lesions that may present as a palpable abnormality, factors used for the assessment of breast cancer risk, physical characteristics of benign and malignant breast masses, the accuracy of fine-needle aspiration, and benign breast lesions by category. Figures illustrate diagnostic procedures, the anatomy of the human breast, visual inspection of the breasts, physical examination of the breasts, breast palpation technique, the evaluation and management of a new breast mass, and the identification of cysts. This review contains 10 figures, 14 tables, and 64 references. Keywords: breast mass, lobuloalveolar development, subareolar nodularity, parenchyma (glandular elements), stromal tissue, ovarian graafian follicles


2014 ◽  
Vol 21 (4) ◽  
pp. T183-T202 ◽  
Author(s):  
Gerard A Tarulli ◽  
Lisa M Butler ◽  
Wayne D Tilley ◽  
Theresa E Hickey

While it has been known for decades that androgen hormones influence normal breast development and breast carcinogenesis, the underlying mechanisms have only been recently elucidated. To date, most studies have focused on androgen action in breast cancer cell lines, yet these studies represent artificial systems that often do not faithfully replicate/recapitulate the cellular, molecular and hormonal environments of breast tumoursin vivo. It is critical to have a better understanding of how androgens act in the normal mammary gland as well as inin vivosystems that maintain a relevant tumour microenvironment to gain insights into the role of androgens in the modulation of breast cancer development. This in turn will facilitate application of androgen-modulation therapy in breast cancer. This is particularly relevant as current clinical trials focus on inhibiting androgen action as breast cancer therapy but, depending on the steroid receptor profile of the tumour, certain individuals may be better served by selectively stimulating androgen action. Androgen receptor (AR) protein is primarily expressed by the hormone-sensing compartment of normal breast epithelium, commonly referred to as oestrogen receptor alpha (ERa (ESR1))-positive breast epithelial cells, which also express progesterone receptors (PRs) and prolactin receptors and exert powerful developmental influences on adjacent breast epithelial cells. Recent lineage-tracing studies, particularly those focussed on NOTCH signalling, and genetic analysis of cancer risk in the normal breast highlight how signalling via the hormone-sensing compartment can influence normal breast development and breast cancer susceptibility. This provides an impetus to focus on the relationship between androgens, AR and NOTCH signalling and the crosstalk between ERa and PR signalling in the hormone-sensing component of breast epithelium in order to unravel the mechanisms behind the ability of androgens to modulate breast cancer initiation and growth.


2011 ◽  
Vol 33 (4) ◽  
pp. 855-863 ◽  
Author(s):  
Sunitha B. Thakur ◽  
Sandra B. Brennan ◽  
Nicole M. Ishill ◽  
Elizabeth A. Morris ◽  
Laura Liberman ◽  
...  

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