Overview of some laboratory tests used in the detection of breast cancer

1.0. Introduction to Cancer

Cancer is a genetic disease of the cell. A normal cell transforms to a cancer cell by acquiring an estimated four to seven chromosome mutations which cause the cell to become undifferentiated and undergo tumourigenesis if the alterations confer a selective advantage to the cell. These alterations or mutations can occur spontaneously in the cell due to errors during DNA replication and/or cellular repair mechanisms. They can also be induced by mutagenic agents such as UV light and in most cases these alterations only occur in tumour cells or cells on the verge of becoming cancerous and so are somatic mutations.(1)

Alterations in three types of genes are responsible for tumorigenesis: oncogenes, tumour-suppressor genes and stability genes. Oncogenes can become mutated in ways that render the gene constitutively active or active under conditions in which the wild-type gene is not. Tumour-suppressor genes are targeted in the opposite way by genetic alterations in that mutations reduce the activity of the gene product. The third class of cancer genes called stability or caretaker genes operate in a different way when mutated. Since stability genes keep genetic alterations to a minimum, mutations in other genes occur at higher rates when they are inactivated.(5)

1.1. General Characteristic of Cancer Cells

Cancer cells differ from normal cells in a number of ways. They can operate independently of growth factors thus the cell can proliferate uncontrollably, have unlimited cell division capabilities, can acquire their own blood supply (angiogenesis), can spread via diffusion and metastasis and can avoid apoptotic cell death.(2) The metastatic process is a complex cascade of events in which tumour cells in the primary site must erode the basement membrane, penetrate a blood vessel and spread to distant sites (13)

2.0. Brief introduction to Breast Cancer

Breast cancer is the most common malignancy in women and the second-most common cause of cancer related mortality. (2)It is nearly twice as common in the first-degree relatives of women with the disease, as in the general population.(3) The breast consists of fatty tissue and lobules that are connected to the nipples by ducts. Breast cancer usually begins in a cell lining a duct or a lobule (an epithelial cell).(6)

3.0. Current Diagnostic tests for breast cancer

The goals of breast cancer testing are to identify genetic risk in people with a familial risk, to detect and diagnose breast cancer in its earliest stages, to determine the degree of metastasis if any, to evaluate the cancer characteristics in order to guide treatment and to monitor the effectiveness of treatment or detect cancer recurrences.

Table 1: Some  Laboratory Tests Used in the Detection of Breast Cancer

Test Name Principal Use: Test Sample
BRCA-1 or BRCA-2 gene mutation (7) A mutation in either gene indicates that the patient has a significantly higher risk of breast cancer (up to 80%) Used in women who could be at high risk due to a strong personal or family history of ovarian or early onset breast cancer.(However only about 5-10% of familial breast cancer cases are caused by mutations in these genes.) Blood
Estrogen Receptor/Progesterone Receptor (7,8) Estrogen and/or receptor positivity indicates sensitivity to these hormones. Increased levels suggest that patient may be good candidate for anti-hormone therapy Tissue
CA 15.3 and CA 27.29 (7,11,12) CA 15-3 and CA 27.29 are well-characterized assays that allow the detection of circulatingMUC-1 antigen in peripheral blood.(12) Not used to screen for breast cancer but can be used to follow it in patients that have been diagnosed .However low sensitivity has limited its use.(11) (FDA approved).Recommended to use in conjunction with imaging techniques and physical exams i.e. not as a standalone test(12) Blood
MammaPrint (Agendia) (10,12) Evaluates gene activity patterns in 70 tumour genes Used to predict whether a breast cancer will recur or metastasize in women with early stage cancer, who are under 61 and who have cancer-negative lymph nodes.(1st breast cancer predicting tool to get FDA approval) Tissue
DNA Ploidy (7) Determines rate of tumour cell growth (S phase) To determine prognosis and treatment guidelines: Elevated rates of tumour cell growth suggest poorer prognosis. Often indicates need for chemotherapy. Tissue
Her 2/neu (7,8) Her2/neu is an oncogene.In about 20-30% of invasive breast cancers, this gene is amplified and its protein (a growth-factor receptor) is over-expressed. Patients that have this gene amplified respond well to Herceptin (Tastuzumab) that blocks the protein receptors, inhibiting continued replication and tumour growth. Blood
Tissue Biopsy(7) Malignant cells show changes in cell shape, size of cell nuclei and evidence of increased cell division. Tissue stained using immunohistochemical techniques. Screening tool. Also used to determine if cancer is early stage or invasive. Tissue
Cellsearch System (9) Detecting elevated numbers of CTC’s in peripheral blood of metastatic breast cancer patients is accompanied by a decreased disease free and overall survival. Enriches and enumerates circulating tumour cells (CTC’s) from peripheral blood. Blood
upA +PAI1 (12) uPA (Urokinase Plasminogen Activator)and PAI-1(Plasminogen Activator inhibitor) are part of the plasminogen activating system, which includes the receptor for uPA and other inhibitors (PAI-2 and PAI-3). This system has been shown experimentally to be associated with invasion, angiogenesis,and metastasis. Used for the determination of prognosis in patients with newly diagnosed, node-negative breast cancer.  Low levels of both markers are associated with a sufficiently low risk of recurrence (especially in hormone receptor–positive women who will receive adjuvant endocrine therapy). Tissue


1.Serre,J.L.,ed, (2006) ‘Diagnostic Techniques in Genetics’,Sussex: John Wiley and Sons Ltd,pgs 139-141

2.Zhong,L., et al, (2008) ‘Autoantibodies as potential biomarkers for breast cancer’ Breast Cancer Research,10(3), available: http://breast-cancer-research.com/content/10/3/R40 [accessed: 27 Feb 2009]

3. Easton, D.F., et al, (2007) ‘Genome-wide association study identifies novel breast cancer susceptibility loci’ Nature,447:1087 1095

4. Venkitaraman,A.R., (2009) ‘Linking the Cellular Functions of BRCA Genes to Cancer Pathogenesis and Treatment’ Annu. Rev. Pathol. Mech. Dis. 4:461–87

5. Vogelstein, B and K.W., Kinzler, (2004) ‘Cancer genes and the pathways they control’ Nature Medicine,10(4): 789-799

6. Breast Cancer Briefsheet,available: http://publications.cancerresearchuk.org/WebRoot/crukstoredb/CRUK_PDFs/CRBSBRC08.pdf [accessed:01 Feb 2009]

7. Lab Tests Online available: www.labtestonline.org/understanding/conditions/breast-3.html [accessed: 20 Feb 2009]

8. Ross,J.S. et al.(2007) ‘Standardizing Slide-Based Assays in Breast Cancer:Hormone Receptors, HER2, and Sentinel Lymph Nodes’ Clin.Cancer.Res., 13(10):2831-2835

9.Riethdorf,S. et al (2007) ‘Detection of Circulating Tumor Cells in Peripheral Blood of Patients with Metastatic Breast Cancer:A Validation Study of the CellSearch System’ Clin.Cancer.Res. 13(3):920-928

10.Ross,J.S. (2008) ‘Multigene predictors in early stage breast cancer: moving in or moving out?’ Expert.Rev.Mol.Diagn. 8(2):129-135

11. Thorat,M.A. and S.Badve (2007)’Prognostic factors in invasive breast carcinoma: Do new molecular techniques/profiling add significantly to traditional histological factors?’ Curr.Diag.Path.13:116-125

12.Harris,L. Et al (2007) ‘American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumour Markers in Breast Cancer’ J.Clin.Oncol. 25(33):1-26

13. Liotta, L. A., and W. G. ,Stetler-Stevenson,(1992) ‘Cancer: Principles and Practice of

Oncology’ pgs. 98–115. Philadelphia: J. B. Lippincott Co.

Further reading on recent discoverys in breast cancer research and general diagnostic methods e.g mammograms





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