Abstract:
Hundreds and thousands of people are affected by cancer each year; it is one of the most life-threatening diseases and a leading cause of death and disability for humans. Breast cancer is amongst the leading cancers in developed countries along with non-melanoma skin cancer. (1) At present, breast cancer is still a major public health concern across the world, affecting and killing thousands of women every year. This degenerative condition is caused by an uncontrollable cellular growth that spreads in your body. One of the major problems associated with breast cancer is the failure to detect cancer at an early stage, thus causing the tumor to grow and/or spread in the breast. Some early signs and symptoms of breast cancer include: lumps in the breast, breast pain, nipple discharge (bloody or watery), change in shape or size of the breast and thickening of the skin of the breast. (2) Breast cancer can be diagnosed after an abnormal screening mammogram, screening breast ultrasound or screening breast MRI and sometimes can be detected by breast –self-examination (BSE) and breast examination carried out by a physician. This early detection of breast cancer can literally save lives. A vast number of patients suffer from late diagnosis or reappearance of their disease despite all the advances in diagnosis and treatment of breast cancer.
Introduction:
Cancer:
A tumor, otherwise known as a neoplasm, occurs when there is irregular cellular growth which forms a lesion or in numerous cases, a lump. There are two main types of tumors that can grow in any part of the body. The first type is cancerous and is known as a malignant tumor. The other is non-cancerous and is referred to as a benign tumor. There are several prolonged methods used to treat cancer. However, this depends on the stage of the cancer and whether it has spread to other areas of the body. TNM and TNMF are systems used by clinicians to inform on prognosis and to plan the treatment. The ‘T’ refers to the size of the tumor and how far it has spread into surrounding tissue; it ranges from 1-4, 1 being small and 4 being large. The ‘N’ is referring to the lymph nodes and whether or not the cancer has spread to them; it ranges from 0, signifying that there is no cancer in the lymph nodes, to 3, signifying that there is cancer present in the lymph nodes. The ‘M’ refers to the cancer spreading to other areas of the body; it ranges from 0-1, 0 meaning the cancer has not spread and 1 meaning the cancer has spread. Finally, the ‘F’ (in TNMF) refers to risk factors that the clinician might need to be made aware in the instance that a more aggressive treatment is needed. Surgery, radiation therapy and chemotherapy have been used for many years to treat cancer (3).
Breast Cancer:
Breast cancer is still a major health problem that women are facing today and the need for a painless, inexpensive method for its early detection is vital. Breast cancer control relies on the early detection and diagnosis of the cancer. (4) A woman’s age, which is the strongest prognosticator, body mass index, breast density, age at first birth, family history, breast cancer in another breast, BRCA1 and BRCA2 gene mutations are several factors that contribute to the risk of developing breast cancer (5). There are increased chances of a woman developing breast cancer between the ages of 30-65. (6) A woman can be diagnosed with breast cancer after an abnormal screening mammogram, screening breast ultrasound, screening breast MRI or physical examination. Unfortunately, some breast cancers are not screen-detected and clinicians will not become aware of the cancer until they are blatant masses. (7) This literature review will discuss several methods of detecting breast cancer. The advantages, disadvantages, and comparisons of each method of detection will be discussed. The developments of new methods for early detection of breast cancer will also be examined in this literature review.
Mammography
A mammogram is a breast cancer screening procedure used by physicians to detect breast cancer at an early stage. This early detection of breast cancer can prevent the cancer from growing and spreading. (8) The procedure, called screening mammography, involves taking two or more x-ray pictures of each breast and it is used when there are no signs or symptoms of breast cancer. During the procedure, the breast is compressed between two clear plates which can be a painful experience but is more often described as uncomfortable. The reasoning behind the compression of the breast between two plates is that it flattens and reduces the thickness of the breast, thus, giving a better x-ray image.
Mammograms are more accurate than a physical examination of the breast as it is possible to detect tumors that cannot be felt by the physician. The detection of microcalcification, which are tiny deposits of calcium, is another advantage of using a screening mammogram. Microcalcification can sometimes indicate the presence of breast cancer and can be a very important finding in asymptomatic patients in the early stages of breast cancer, studies show that between 30% and 50% of nonpalpable breast cancer tumors exist as microcalcifications. (9) However, the sensitivity and specificity of a screening mammogram are significantly reduced as the density of the breast tissue is increased. This can be improved using digital mammography; however, the accuracy is never 100% and this is one of the major problems associated with mammograms. Using mammography alone is inappropriate for these women with extremely dense breast tissue and heterogeneously dense breast tissue. (6)
Screen Film Mammography
Mammograms have changed and developed throughout the years. There are currently three main types of mammograms used for the early detection of breast cancer. Firstly, the traditional screen film mammography is a 2-dimensional image taken on a film. This type of mammogram is taken by a technologist and later analysed by a radiologist. This procedure has several disadvantages, one being that it can be very time consuming and exhausting for the physician which can then lead to false negative or false positive readings. (8) A false positive result has occurred when a mammogram of the breast looks abnormal even though there is no cancer present in the breast. In stark contrast, a false negative result occurs when the breast mammogram looks normal and healthy even though there is cancer present in the breast. This results in radiologists failing to detect 10% to 30% of breast cancers. (https://www.sciencedirect.com/science/article/pii/S0899707112002938) Out of all the three methods being discussed, a false positive and false negative result is more likely to occur in screen film mammography causing the patient extra stress and anxiety. This is a major limitation for mammography and ideally, the early detection of breast cancer should produce low false positive and low false negative results. (8)
Full Field Digital Mammography
Another type of mammogram is the full field digital mammography. This method also uses x-ray images but unlike screen film mammography, it takes several images of the breast from different angles which provide a clearer, more enhanced image of the breast, thus, making it easier to diagnose breast cancer at earlier stages. This method has several advantages over the screen film mammography. Firstly, it saves time for the radiologist and scans can be stored on a computer file and transferred electronically. This method has better accuracy when it comes to diagnosing asymptomatic patients and has better identification of microcalcifications. Furthermore, the image quality is improved due to the numerous amount of x-ray images obtained from the breast and the overall sensitivity and reliability of this method far exceed that of the screen film mammography.
Digital Breast Tomosynthesis Mammography
Finally, digital breast tomosynthesis mammography is a 3-dimensional image of the breast. A technologist creates this 3-dimensional image of the breast by taking a series of x-ray images of the breast at multiple angles. This method is recommended for older women, for example, women that are over the age of 40 and for women that have extremely dense breast tissue. Out of all the mammography techniques, digital breast tomosynthesis has the best accuracy and has shown to reduce recall rates for all ages and significantly increase cancer detection rates in women by around 15%. (10; 6) Digital breast tomosynthesis exposes patients to less radiation than the conventional mammography. The only disadvantage of this method is that it is more expensive than the other two methods. However, the advantages outweigh the disadvantages, it is much less likely of obtaining a false positive result because of the accuracy of the 3-dimensional images. Like the full field digital mammography, this method can also transfer the images digitally through the computer and these images can be further evaluated and enhanced which gives a better diagnosis and result.
In summary, mammography is the “gold standard” screening examination for the detection of breast cancer, it is the most effective and reliable tool for the early detection of breast cancer and has been seen to decrease mortality from breast cancer. (11) Mammography can detect extremely small cancers and microcalcifications which is essential for the early detection of breast cancer. With all the techniques of mammography, there are advantages and disadvantages. The early detection of tiny cancers and microcalifications are the two main benefits of mammography. The chief disadvantage is that mammography does not perform well on breasts with dense tissue and the images can be affected by mammogram artifacts which reduces the quality of the image. With mammography, biopsies are necessary. To achieve higher accuracy rate and better detection, ultrasounds and MRIs are used in conjunction with mammograms.
Computer Aided Detection/Diagnosis (CAD)
CAD systems can be used in all imaging modalities (mammography, ultrasound, CT, and MRI) to assist in the reading of images and to help the radiologist make informed decisions to increase diagnostic accuracy. (12) Computer-aided detection and computer-aided diagnosis are the two main categories in CAD. They are used to improve the accuracy and capability of the radiologist. There are four main stages of CAD and they are, preprocessing, segmentation, feature extraction and selection, and classification. (4)
Preprocessing
Image preprocessing is the first stage in the CAD system and this involves enhancing the image and reducing speckle without demolishing significant features of the breast ultrasound image under examination. Low contrast and interference with speckle are both significant limitations of breast ultrasound imaging. (4) Basically, this stage involves preparing the image for further analysis and inspection.
Segmentation
The second stage of CAD is called image segmentation. This involves separating the image into sections of non-overlapping regions, and objects from the background will also be divided. Finally, the regions of interest (ROI) will be assigned for feature extraction. This step is necessary to simplify the image for easier analysis. (4)
Feature extraction and selection
Stage three of CAD is feature extraction and selection. This stage is crucial in the extraction and selection of the most essential features from the cleaned image. This step requires correctly distinguishing between normal and cancerous in a set of breast cancer lesions. (12)
Classification
The final stage of CAD is the classification stage. After the features have been extracted and selected, the classification of the suspicious regions will be carried out. Those regions will be assigned classes or labels and the identification of a lesion/non-lesion or benign/malignant will be determined. (12)
Overall, CAD’s were developed to reduce expense and improve the accuracy of image readings, therefore, reducing false positives, false negatives and call back rates.
Ultrasound
Introduction
Ultrasound imaging is one of the most frequently used diagnostic tools for the detection of breast cancer. An ultrasound uses high-frequency sound waves, over 20,000Hz (Hertz), to image an object. An ultrasound of the breast produces detailed images of inside the breast and any tumors or breast abnormalities that may be present. After the doctor carries out a physical breast examination, a coupling gel is applied to the breast, this is used to improve the transmission between the tissue and the ultrasound. The ultrasound transducer probe will then be moved around the breast in search for the location of the tumor or abnormality. The transducer transmits and receives ultrasonic waves and this is what produces the image. An ultrasound of the breast is a real-time image and it is usually carried out after an abnormal clinical examination, an abnormal mammography or on breasts that are extremely dense. (11) Breast ultrasound imaging is a painless, non-invasive procedure that does not expose the patient to any harmful ionising radiation. In comparison to other imaging modalities, such as MRI, ultrasounds are a much less expensive procedure and they are widely available. A breast ultrasound image is recommended for younger women, women with extremely dense breasts, pregnant women, women that are breastfeeding, and woman that have breast implants. Ultrasounds are successful in recognising lumps, fibroadenomas, cysts, and abnormal masses. The main limitation of ultrasound imaging is that an ultrasound image cannot establish whether the lump is cancerous or non-cancerous. This method of breast cancer detection is often used in conjunction with mammography to reduces the need for a biopsy. More sensitive than mammography, therefore better for younger women. CAD is needed. Well trained radiologists to read the sonography. Mention the 4 stages of the CAD. Identify cysts. No need for biopsy. Non-invasive. Implants. Cannot detect calcifications. Cannot replace mammography. The two main types of ultrasound will be discussed and compared in this section:
Handheld breast ultrasound:
Handheld ultrasounds are usually used in addition with mammography to the accuracy. There are many problems facing handheld ultrasounds, one being that it is limited by the operator dependency which can be a problem when a physician is carrying out several ultrasounds a day causing fatigue which can then lead to vital pieces of information being missed. (13) Along with operator dependency, other limitations include, lack of standardisation and reproducibility. (14)
Automated whole breast ultrasound
The use of an automated whole breast ultrasound can overcome most of the limitations of a handheld ultrasound. (14) These machines are automatic and therefore do not rely on an operator and does not require a highly trained specialist. During the procedure, a large transducer paddle is placed over the breast, after a coupling gel has been applied, and small compression is applied. (13) On an average size breast, this type of ultrasound examination takes approximately 15 minutes with minimal discomfort. The physician can adjust the angle and pressure of the transducer to get optimal results. Compared to a handheld ultrasound, the scan coverage of an automated whole breast ultrasound is expanded considerably while maintaining the image quality. This real-time imaging technique can provide new diagnostic information by the generated coronal plane (e.g. retraction sign in the coronal plane for breast cancer)
Conclusion
Breast ultrasound imaging is more sensitive, less expensive and, safer in comparison to mammography. They are recommended for women with extremely dense breast, implants, pregnant or, breastfeeding. As regards safety, women are not exposed to any radiation during an ultrasound examination. Automated whole breast ultrasounds overcome many of the limitations that a handheld ultrasound faces. They provide better reproducibility and standardisation while maintaining good quality imaging. Similar to mammography, ultrasounds can be improved by using a CAD system. The CAD system will diagnostic accuracy by assisting the physician in reading the images.
Magnetic resonance imaging
A magnetic resonance imaging machine use a combination of magnetic fields, radio waves and computers to create a series of images of structures in the body. An MRI cannot be performed on patients with pacemakers, or any type of metal implants as they will be affected by the magnet and will cause harm or in severe cases death to the patient. During an MRI, the patient is surrounded by a magnetic tube which patients sometimes find daunting or claustrophobic. MRI is a very expensive imaging modality that can be quiet time consuming and for that reason it should be reserved for populations that have high risks of breast cancer. (15)
It has been seen that MRI has higher sensitivity compared to ultrasound and mammography in the early detection of breast cancer. This consists of a 3D maximum intensity
projection (MIP) image They demonstrate
that in a cohort of asymptomatic women with intermediate
to slightly high rate of breast cancer risk with negative
mammographic imaging, MIP analysis alone has a sensi-
tivity and negative predictive value of 98.9%, NO radiation
In most cases, MRI is used in conjunction with mammography or as a “second look” option. A “second look” lesion is a lesion that can be seen on an MRI but was not initially detected in a mammography or a breast ultrasound examination. (16) Palpable masses that cannot be detected by a breast ultrasound or mammography are often detectable on MRI images. Furthermore, an MRI of the breast can distinguish between normal breast tissue and breast tissue containing cancer. Similar to ultrasound, MRI cannot detect, calcifications and this is a very important factor to consider when examining a breast for the early detection of breast cancer. MRI is frequently used on women that have dense breast tissue, breast implants, and younger women. The use of an MRI can find the precise location of a breast cancer tumor without using any ionising radiation.
Biopsy
A biopsy is a medical procedure which removes a section of abnormal tissue or sometimes fluid from the breast, this is then examined under a microscope by a highly trained pathologist. It is the only way to know for sure if cancer is present in the breast. There are several types of biopsies that can be performed. In the United States, approximatelty 1.6 million women have breast biopsies each year. (17)
