The common methods used to detect breast cancer are :

• Clinical examination of the breast
• Mammography
• Biopsy

Other screening methods which are in trial are :

• Magnetic Resonance Imaging (MRI)
• Positron Emission Tomography (PET)
• X-ray diffraction study of hair
• Immunoassay to detect tumour markers and other antibodies
• Ductal lavage
• Flow cytometry to detect cancer cell division rate

Clinical examination of the breast:

Clinical examination aids in early diagnosis of breast cancer. A lump felt during the examination can roughly give clues as to the size of the tumour, its texture, and details such as whether it is mobile etc. If the initial suspicions are well-warranted, the patient will be counselled to seek more detailed investigations.

Mammography:

The mammogram is an X-ray of the breast which detects cancer at an early and curable stage. Mammography can even identify breast cancers that are too small to be palpated by physical examination. It can also detect the presence of lumps if it is localised (Ductal Carcinoma in situ). Observational studies have found that the positive predictive value of mammography increases with age and is highest among older women and among women with a family history of breast cancer. Digital mammography is an emerging technique which uses computers and specially designed detectors to produce a digital image of the breast that can be displayed on high-resolution monitors. However, these tests cannot say whether the cancer is benign or malignant. Biopsy is needed to confirm the diagnosis. A detailed account of mammography is given in this external link.

Biopsy:

In a biopsy, a small amount of tissue or fluid is removed from the breast tissue and examined for its pathology. There are three types of biopsy:

1. Fine Needle Aspiration Cytology (FNAC)

2. Needle biopsy

3. Surgical Biopsy

1.FNAC:
In this technique, a thin needle is used to withdraw fluid or cells from the breast tissue and examined for the presence of cysts or tumour. The presence of cyst is further confirmed by ultrasound .

2.Needle biopsy:
In this technique, a tissue sample is removed with the help of a needle from the suspected region, which perhaps may not have been detected even in a mammogram.

3.Surgical Biopsy:
There are two types of biopsy.

• Incisional biopsy
• Excisional Biopsy

In Incisional biopsy, a sample of the lump is excised for studying its pathology whereas in Excisional biopsy the entire lump along with an area of normal tissue is removed to study its spread.

More recently, a technique has been developed known as sentinel lymphnode biopsy. The sentinel node is the first lymph node where the lymphatic vessels drain and most likely to contain cancer cells. In this method, a small amount of dye is injected into the area around the tumour. Lymphatic vessels carry these substances into the sentinel node. The dye can then be detected using geiger counter.

From the biopsy, a pathologist can determine whether the tumor is

• benign or malignant
• ductal or lobular
• invasive or non-invasive

Magnetic Resonance Imaging (MRI) :

This is an non-invasive imaging technique which uses a strong magnet and radiofrequency waves to produce images of internal organs. The clinical role of MRI in breast cancer imaging include
- determining the true edges of the tumour prior to surgery
- to differentiate a palpable mass from breast scar or a dense tissue
- assessing palpable masses following surgery or radiation therapy
- detecting mammographically and sonographically occult breast cancer in patients with axillary nodal metastasis
- assessing recurrence in silicon breast implants

Though MRI has potential applications, it is not routinely used in breast cancer.

Positron Emission Tomography (PET) :

PET technique involves the use of radioactive material in the diagnosis of breast cancer. In this technique, the patient is injected with the radioactive substance (glucose-8-fluorodeoxyglucose-FDG), a compound taken up by metabolically active tissues. As cancer cells are more metabolically active than normal tissues, the tumor tissue will take up relatively more radiolabelled substance. The patient is  placed in a scanner to detect the radiation. This test may be particularly useful to determine the spread of cancer to other sites in the body. The main advantage of PET is that it can diagnose diseases even before the structural changes are visible. Since, it utilizes isotopes of basic biological elements like carbon, oxygen, and nitrogen, it reveals the disease status at a more cellular level than other types of imaging techniques.

X-ray diffraction study using hair :

X-ray diffraction is a technique which uses x-rays to diffract a given molecule. When the molecule is diffracted, the structure of the given molecule can be studied. Using this technique with synchroton radiation , researchers have found that hair of breast cancer patients have a different intermolecular structure than the normal population. Briki et al., studied the hair of breast cancer patients and normal persons using X-ray diffraction. The difference was reported as the presence of an extra ring with a spacing of 4.44 nm in breast-cancer patients. Hence, hair analyses may be used as a simple, non-invasive screening method for breast cancer. However, the sensitivity and specificity of this method are yet to be determined. [37]

Immunoassay to detect Tumour Markers:

Tumour markers are the substances that are produced by the tumour or by the body itself in response to the presence of cancer. They are found in body fluids such as blood, urine or tissues. These substances are both diagnostic and prognostic. A common breast cancer tumour marker is the CA 15-3 antigen, which is elevated in advanced stages of breast cancer. Another marker, CA 27-29 antigen is found in the blood of most breast cancer patients.[38] , [39] , [40] , [41] .

Immunoassay to detect antibodies:

Genetic tests have always been expensive and time consuming. In order to overcome that, researchers have detected a new and cheap method to identify carriers of BRCA1 mutation. They have developed an antibody test for detecting the normal BRCA1 protein. The antibody hunts for the BRCA1 protein and binds to it. If it does not bind to the protein, then the test proves negative giving clues of abnormal BRCA1 gene product which could be the reason for cancer development. Further, these patients can go for other confirmatory tests to identify the mutation.
(Source: BBC news )

Ductal lavage:

This test is carried out by inserting a tiny catheter into the nipple where a small amount of fluid is removed from the ductal cells after a saline flush. This process is known as ductal lavage. The cells are then viewed under the microscope for their appearance and analysed for genetic changes such as methylation which are the markers to identify the disease. Most of the breast cancer patients were found positive for these markers.
(Source - BBC news )

Flow cytometry to detect cancer cell division rate:

Cell cycle is essential for every cell to carry out its various functions and it takes place in a controlled manner. When this cell cycle is out of control, it results in cancer. The rate at which cancer cells divide can be determined by:

• Ki-67 test
  
• S-phase fraction test

The S-phase fraction (SPF) prepared from biopsy specimen of the cancerous cells is usually subjected to flow cytometry to determine the rate at which cancer cells divide to replicate their genetic material (DNA).
Ki-67 test is a immunostaining technique where the antibody identifies the cells which are in the process of dividing and not the cells at the resting stage (Go). The source material for this test is also a biopsy specimen.
A low value of SPF/Ki-67 indicates slower cell division whereas higher values denote cell division at a higher rate.

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