**Non-Invasive Devices for Early Detection of Breast Tissue Oncological Abnormalities Using Microwave Radio Thermometry**

Tahir H. Shah, Elias Siores and Chronis Daskalakis *Institute of Materials Research and Innovation (IMRI), University of Bolton United Kingdom*

#### **1. Introduction**

Breast cancer is the most common cancer in women worldwide, comprising 16% of all female cancers and is the leading cause of cancer-related deaths in women ages 40-55. Each year in the U.S.A. over 180,000 women are diagnosed with breast cancer and 46,000 women die of this disease. One in twelve women in the United Kingdom develops breast cancer and the annual death toll stands at around 14,000. Over 33,000 new cases are being monitored year on year basis in the UK. In all, 10%-11% of all women can expect to be affected by breast cancer at some time during their lives. The causes of most breast cancers are not yet fully understood. Sixty years ago, MacDonald proposed that the biological behaviour of a neoplasm is established during its preclinical growth phase (MacDonald, 1951). This view is supported by some data on the behaviour of metastatic lesions such as poor cytological differentiation, lymphatic permeation, blood vessel invasion and the invasion of the surrounding soft tissue by the tumour (Nealon et al, 1979). Screening and early diagnosis are currently the most effective ways to reduce mortality from this disease. Early diagnosis and treatment are the keys to surviving breast cancer. Breast cancer survival rates vary greatly worldwide, ranging from over 80% in North America, Sweden and Japan to around 60% in middle-income countries and below 40% in low-income countries. It is believed that the low survival rates in less developed countries are mainly due to the lack of early detection programmes, resulting in a high proportion of women presenting with late-stage disease, as well as by the lack of adequate diagnosis and treatment facilities. Studies from the American National Cancer Institute show that 96 percent of women whose breast cancer is detected early live five or more years after treatment. Early diagnosis remains an important detection strategy, particularly in low- and middle-income countries where the disease is diagnosed in late stages and resources are very limited. There is some evidence that this strategy can produce "down staging" of the disease to stages that are more amenable to less aggressive treatment. Therefore, thousands of lives and considerable healthcare costs could be saved each year with treatment if early symptoms of breast cancer are detected. Taking full advantage of early diagnosis and treatment means that screening technology should have the characteristics that have high detection success rate, speed of procedure, comfort to the subject and very low health risk.

Non-Invasive Devices for Early Detection of

combine the following characteristics:

positive and false-negative results).

 The test should be simple to perform. The test should be non-invasive.

are not likely to progress.

 The test should be widely available. The test should be acceptable to women.

**1.1 Anatomy and physiology of female breast** 

treatments.

year saved).

The test should present a low risk of harm from screening

 The test results should have uniform high quality and repeatability. Interpretation of test results should be straightforward (objective).

detection and diagnosis of the breast tissue oncological abnormalities.

the collarbone, behind the breastbone and in various other parts of the body.

Breast Tissue Oncological Abnormalities Using Microwave Radio Thermometry 449

Microwave radiometry principles can be employed to obtain sensor information from subcutaneous tissues up to a few centimetres in depth. The device based on these principles can provide an early breast cancer detection/warning technique that is simple, quick and may also be used for diagnosis of other types of cancers such as prostate cancer in men. The evidence indicates that screening mammography, when correctly performed at recommended intervals and combined with appropriate interventions, can reduce, but not eliminate, breast cancer mortality. This conclusion is based on evidence of efficacy in clinical trials and evidence of effectiveness in the general population. The "ideal" breast cancer screening tool has not yet been developed. All of the tests available for the screening and diagnosis of breast cancer have different strengths and limitations. The ideal test would

The test should have high degrees of specificity and sensitivity (low rates of false-

The test should be able to detect breast cancer at a stage that is curable with available

The test should have the ability to distinguish life-threatening lesions from those that

The test should be cost-effective (usually considered <\$50,000 per quality-adjusted life

Each modality has different strengths and limitations therefore it seems to be feasible to adopt a multi modality approach in order to achieve the optimum methodology for the

It is important to consider the physiology of the breast, as the changes seen in the breast during a woman's life will have an effect on the properties of the tissues. The female breast is a complex and sensitive organ, which is composed of a mass of glandular, fatty, and fibrous tissues positioned over the pectoral muscles of the chest wall and attached to the chest wall by fibrous strands called Cooper's ligaments (Figure 1). A layer of fatty tissue surrounds the breast glands and extends throughout the breast. The fatty tissue gives the breast a soft consistency. The glandular tissues of the breast house the lobules and the ducts. The female breast has a network of arteries and capillaries that carry oxygen- and nutrientrich blood to the breasts. The axillary artery extends from the armpit and supplies blood to the outer half of the breast. The internal mammary artery, which extends down from the neck, supplies blood to the inner part of the breast. The breast also contains lymph vessels. The lymphatic system is part of the immune system and is composed of blood vessels, lymph ducts and lymph nodes. Clusters of lymph nodes are located under the arm, above

The principal aim of early breast cancer detection is to identify the disease at a more curable stage and thus improve the prognosis and other vital clinical outcomes. Currently breast cancer detection is a three part procedure. The first part is identification of the abnormality in the breast tissue either by physical examination or by an imaging technique. Secondly, the abnormality is diagnosed as a benign or a malignant condition by using additional diagnostic methods or by biopsy and microscopic examination of the tissue morphology. The third part is concerned with biochemical characterisation of the malignant tissue in order to stage the cancer according to the size of the tumour and extent of invasion and metastasis. Of particular importance is the ability to clearly distinguish between malignant and benign tumours and early detection. This then determines the prognosis and appropriate course of treatment. A review of the published literature shows that all current breast cancer detection techniques have limited capability and surgery is often required to establish the true nature of the tumour.

Currently, the frontline strategies for breast cancer detection still depend essentially on clinical and self-examination and mammograms. The limitations of mammography, with its reported sensitivity rate often below 70% are recognized (Sickles, 1984) and the proposed value of self-breast examination is being queried (Thomas et al, 1997). Mammography is accepted as the most reliable and cost-effective imaging technique, however, its contribution continues to be challenged with persistent false-negative results - ranging up to 30% (Moskowitz, 1983 & Elmore et al, 1884). However, most of the research and development activity related to cancer detection and diagnosis is focussed on the analysis of the existing condition and is costly, time-consuming and requires trained personnel to use the equipment. Furthermore, the incidence of the earliest form of breast cancer, Ductal Carcinoma in Situ (DCIS), has increased significantly over the last few years in the United States and this seems to be directly related to successful screening programmes. This clearly shows that there is a need and scope for developing early breast cancer detection techniques that are simple, quick and can be used by women by themselves.

In this chapter a review of some of the most promising techniques that are being developed for breast cancer detection is presented. A comparison of the various breast cancer detection techniques that are in the developmental stages with the established procedures has been carried out and a state-of-the-art in all the areas is briefly described and the concept of a wearable breast cancer detection device - the 'smart bra'- is also discussed. Particular emphasis has been placed on the non-invasive thermometry based methodologies for early detection of the oncological condition. When infrared thermography was first introduced in medicine, the instrumentation was not sensitive enough to detect the subtle changes in temperature that are involved in diseases such as breast cancer. However, more recently the sensitivity of infrared instrumentation has greatly improved and the IR thermography imaging is being developed and used to monitor the health of the breast and detection of cancerous tumours. Recent literature shows that the technique has the ability to detect tumours that are 3cm in size and are located deeper than 7 cm from the skin surface and tumours smaller than 0.5 cm can be detected if they are close to the surface of the skin. Noninvasive techniques based on profiling of the breast tissue using microwave radiometry are also being developed and investigated as early warning systems for breast cancer. These techniques involve the measurement of the passive electromagnetic thermal radiation emitted from human body using suitable combination of microwave antenna internal temperature sensor and infrared surface temperature sensor, with an appropriate configuration to determine the temperature profile of the concerned area of the body. Microwave radiometry principles can be employed to obtain sensor information from subcutaneous tissues up to a few centimetres in depth. The device based on these principles can provide an early breast cancer detection/warning technique that is simple, quick and may also be used for diagnosis of other types of cancers such as prostate cancer in men.

The evidence indicates that screening mammography, when correctly performed at recommended intervals and combined with appropriate interventions, can reduce, but not eliminate, breast cancer mortality. This conclusion is based on evidence of efficacy in clinical trials and evidence of effectiveness in the general population. The "ideal" breast cancer screening tool has not yet been developed. All of the tests available for the screening and diagnosis of breast cancer have different strengths and limitations. The ideal test would combine the following characteristics:


448 Advances in Cancer Therapy

The principal aim of early breast cancer detection is to identify the disease at a more curable stage and thus improve the prognosis and other vital clinical outcomes. Currently breast cancer detection is a three part procedure. The first part is identification of the abnormality in the breast tissue either by physical examination or by an imaging technique. Secondly, the abnormality is diagnosed as a benign or a malignant condition by using additional diagnostic methods or by biopsy and microscopic examination of the tissue morphology. The third part is concerned with biochemical characterisation of the malignant tissue in order to stage the cancer according to the size of the tumour and extent of invasion and metastasis. Of particular importance is the ability to clearly distinguish between malignant and benign tumours and early detection. This then determines the prognosis and appropriate course of treatment. A review of the published literature shows that all current breast cancer detection techniques have limited capability and surgery is often required to

Currently, the frontline strategies for breast cancer detection still depend essentially on clinical and self-examination and mammograms. The limitations of mammography, with its reported sensitivity rate often below 70% are recognized (Sickles, 1984) and the proposed value of self-breast examination is being queried (Thomas et al, 1997). Mammography is accepted as the most reliable and cost-effective imaging technique, however, its contribution continues to be challenged with persistent false-negative results - ranging up to 30% (Moskowitz, 1983 & Elmore et al, 1884). However, most of the research and development activity related to cancer detection and diagnosis is focussed on the analysis of the existing condition and is costly, time-consuming and requires trained personnel to use the equipment. Furthermore, the incidence of the earliest form of breast cancer, Ductal Carcinoma in Situ (DCIS), has increased significantly over the last few years in the United States and this seems to be directly related to successful screening programmes. This clearly shows that there is a need and scope for developing early breast cancer detection techniques

In this chapter a review of some of the most promising techniques that are being developed for breast cancer detection is presented. A comparison of the various breast cancer detection techniques that are in the developmental stages with the established procedures has been carried out and a state-of-the-art in all the areas is briefly described and the concept of a wearable breast cancer detection device - the 'smart bra'- is also discussed. Particular emphasis has been placed on the non-invasive thermometry based methodologies for early detection of the oncological condition. When infrared thermography was first introduced in medicine, the instrumentation was not sensitive enough to detect the subtle changes in temperature that are involved in diseases such as breast cancer. However, more recently the sensitivity of infrared instrumentation has greatly improved and the IR thermography imaging is being developed and used to monitor the health of the breast and detection of cancerous tumours. Recent literature shows that the technique has the ability to detect tumours that are 3cm in size and are located deeper than 7 cm from the skin surface and tumours smaller than 0.5 cm can be detected if they are close to the surface of the skin. Noninvasive techniques based on profiling of the breast tissue using microwave radiometry are also being developed and investigated as early warning systems for breast cancer. These techniques involve the measurement of the passive electromagnetic thermal radiation emitted from human body using suitable combination of microwave antenna internal temperature sensor and infrared surface temperature sensor, with an appropriate configuration to determine the temperature profile of the concerned area of the body.

establish the true nature of the tumour.

that are simple, quick and can be used by women by themselves.


Each modality has different strengths and limitations therefore it seems to be feasible to adopt a multi modality approach in order to achieve the optimum methodology for the detection and diagnosis of the breast tissue oncological abnormalities.

#### **1.1 Anatomy and physiology of female breast**

It is important to consider the physiology of the breast, as the changes seen in the breast during a woman's life will have an effect on the properties of the tissues. The female breast is a complex and sensitive organ, which is composed of a mass of glandular, fatty, and fibrous tissues positioned over the pectoral muscles of the chest wall and attached to the chest wall by fibrous strands called Cooper's ligaments (Figure 1). A layer of fatty tissue surrounds the breast glands and extends throughout the breast. The fatty tissue gives the breast a soft consistency. The glandular tissues of the breast house the lobules and the ducts. The female breast has a network of arteries and capillaries that carry oxygen- and nutrientrich blood to the breasts. The axillary artery extends from the armpit and supplies blood to the outer half of the breast. The internal mammary artery, which extends down from the neck, supplies blood to the inner part of the breast. The breast also contains lymph vessels. The lymphatic system is part of the immune system and is composed of blood vessels, lymph ducts and lymph nodes. Clusters of lymph nodes are located under the arm, above the collarbone, behind the breastbone and in various other parts of the body.

Non-Invasive Devices for Early Detection of

accounts for about 80% of invasive breast cancers.

Fig. 2. Growth of ductal carcinoma

Fig. 3. Growth of lobular carcinoma

connective tissue.

type.

stage can be cured.

Breast Tissue Oncological Abnormalities Using Microwave Radio Thermometry 451

*Ductal carcinoma in situ (DCIS):* This is the most common type of non-invasive breast cancer. DCIS means that the cancer is confined to the ducts. It has not spread through the walls of the ducts into the fatty tissue of the breast. Over 70% of breast cancers are ductal carcinomas, which are associated with the milk ducts. Nearly all women with cancer at this

*Infiltrating (invasive) ductal carcinoma (IDC):* This type of cancer starts in a duct and breaks through the wall of the duct, and invades the fatty tissue of the breast (Figure 2), then spreading to other parts of the body. IDC is the most common type of breast cancer. It

Lobular carcinoma in situ (LCIS): This condition begins in the milk-making glands but does not go through the wall of the lobules. Although not a true cancer, having LCIS increases a woman's risk of getting cancer later. For this reason, it is important that women with LCIS follow the screening guidelines for breast cancer. 10% - 15% are lobular carcinomas associated with the lobes, and the rest are relatively rare forms of cancer such as of the

*Infiltrating (invasive) lobular carcinoma (ILC):* This type of cancer starts in the lobules and can spread to other parts of the body (Figure 3). About 10% of invasive breast cancers are of this

Fig. 1. The anatomical structure of the female breast

The shape and appearance of female breast undergo a number of changes as a woman ages. In young women, the breast skin stretches and expands as the breasts grow, creating a rounded appearance. Young women tend to have denser breasts, due to the presence of more glandular tissue, than older women. The denser breasts lead to poorer contrast between healthy and diseased tissue in x-ray mammography. However the occurrence of breast cancer in younger women is low, with 80 % of breast cancers occurring in women over the age of 50. The growth of breast tissue is mainly influenced by the relative concentrations of progesterone and oestrogen in the body. During each menstrual cycle, breast tissue tends to swell due to variation in the oestrogen and progesterone levels. The milk glands and ducts enlarge resulting in retention of water by the breast. During menstruation, breasts may temporarily appear swollen and this can give rise to breast pain, tenderness, or they may feel lumpy. At menopause, a woman's body stops producing oestrogen and progesterone, which causes a variety of symptoms in many women including hot flushes, night sweats, mood changes and vaginal dryness. During this period breasts also undergo many changes, such as mentioned earlier for the menstrual cycle, and sometimes appearance of cysts may be observed. The glandular tissue tends to shrink after menopause and is replaced with fatty tissue. The breasts also tend to increase in size and droop because the fibrous tissue loses its strength. The breasts become less dense after menopause, which makes the detection of breast cancer often easier in older women. A woman's risk of breast cancer increases with age thus all women are recommended for breast cancer screening at regular interval beyond the age of 40.

#### **1.2 Main types of breast cancer**

Treatment of cancer depends on the type and stage of the cancer along with other issues such as the individual circumstances of the patient. Mostly breast cancer develops in the glandular tissue and is classified as adenocarcinoma, which is a cancer of the epithelium that originates in the glandular tissue. The common types of breast cancers are:

*Carcinoma in situ:* This term is used for early stage cancer, when it is confined to the place where it started. In breast cancer, it means that the cancer is confined to the ducts or the lobules, depending on where it started. It has not gone into the fatty tissues in the breast nor spread to other organs in the body.

*Ductal carcinoma in situ (DCIS):* This is the most common type of non-invasive breast cancer. DCIS means that the cancer is confined to the ducts. It has not spread through the walls of the ducts into the fatty tissue of the breast. Over 70% of breast cancers are ductal carcinomas, which are associated with the milk ducts. Nearly all women with cancer at this stage can be cured.

*Infiltrating (invasive) ductal carcinoma (IDC):* This type of cancer starts in a duct and breaks through the wall of the duct, and invades the fatty tissue of the breast (Figure 2), then spreading to other parts of the body. IDC is the most common type of breast cancer. It accounts for about 80% of invasive breast cancers.

Fig. 2. Growth of ductal carcinoma

450 Advances in Cancer Therapy

The shape and appearance of female breast undergo a number of changes as a woman ages. In young women, the breast skin stretches and expands as the breasts grow, creating a rounded appearance. Young women tend to have denser breasts, due to the presence of more glandular tissue, than older women. The denser breasts lead to poorer contrast between healthy and diseased tissue in x-ray mammography. However the occurrence of breast cancer in younger women is low, with 80 % of breast cancers occurring in women over the age of 50. The growth of breast tissue is mainly influenced by the relative concentrations of progesterone and oestrogen in the body. During each menstrual cycle, breast tissue tends to swell due to variation in the oestrogen and progesterone levels. The milk glands and ducts enlarge resulting in retention of water by the breast. During menstruation, breasts may temporarily appear swollen and this can give rise to breast pain, tenderness, or they may feel lumpy. At menopause, a woman's body stops producing oestrogen and progesterone, which causes a variety of symptoms in many women including hot flushes, night sweats, mood changes and vaginal dryness. During this period breasts also undergo many changes, such as mentioned earlier for the menstrual cycle, and sometimes appearance of cysts may be observed. The glandular tissue tends to shrink after menopause and is replaced with fatty tissue. The breasts also tend to increase in size and droop because the fibrous tissue loses its strength. The breasts become less dense after menopause, which makes the detection of breast cancer often easier in older women. A woman's risk of breast cancer increases with age thus all women are recommended for

Treatment of cancer depends on the type and stage of the cancer along with other issues such as the individual circumstances of the patient. Mostly breast cancer develops in the glandular tissue and is classified as adenocarcinoma, which is a cancer of the epithelium

*Carcinoma in situ:* This term is used for early stage cancer, when it is confined to the place where it started. In breast cancer, it means that the cancer is confined to the ducts or the lobules, depending on where it started. It has not gone into the fatty tissues in the breast nor

that originates in the glandular tissue. The common types of breast cancers are:

Fig. 1. The anatomical structure of the female breast

breast cancer screening at regular interval beyond the age of 40.

**1.2 Main types of breast cancer** 

spread to other organs in the body.

Lobular carcinoma in situ (LCIS): This condition begins in the milk-making glands but does not go through the wall of the lobules. Although not a true cancer, having LCIS increases a woman's risk of getting cancer later. For this reason, it is important that women with LCIS follow the screening guidelines for breast cancer. 10% - 15% are lobular carcinomas associated with the lobes, and the rest are relatively rare forms of cancer such as of the connective tissue.

*Infiltrating (invasive) lobular carcinoma (ILC):* This type of cancer starts in the lobules and can spread to other parts of the body (Figure 3). About 10% of invasive breast cancers are of this type.

Fig. 3. Growth of lobular carcinoma

Non-Invasive Devices for Early Detection of

Limited availability of the technology

Modality Description

 Limited accessibility, Need of intravenous access,

 Patient discomfort, Restricted imaging area, Difficult interpretation

Full-field digital mammography

imaging

(MRI)

Positron emission tomography (PET)

Ultrasound : Compound imaging and Threedimensional ultrasound

Magnetic resonance imaging

Breast Tissue Oncological Abnormalities Using Microwave Radio Thermometry 453

These modalities are in fact more suited as the second-line options to pursue the already abnormal screening evaluations. This stepwise approach currently results in the nonrecognition, and thus delayed utilization of any second-line technology in approximately 10% of established breast cancers (Moskowitz, 1995). This view is supported by another study of infrared screening of breast cancer [Keyserlignk & Ahlgren, 1998). A list of the

> Detector responds to X-ray exposure, sends electronic signal to computer to be digitized and processed.

mammograms and classification as benign or malignant.

Uses high-frequency sound waves to generate an image.

Makes use of the property of nuclear magnetic resonance (NMR) to image nuclei of atoms inside the body. Image generated by signals from excitation of nuclear particles in a magnetic field. Breast tumours show increased uptake of

Uses tracers such as labelled glucose to identify regions in

skin surface temperature, which is detected by infrared cameras. Dynamic area telethermometry detects changes

current through breast. Changes in cancerous tissue

more in cancer tissues than in normal tissues.

the body with altered metabolic activity.

Separates detector and image display.

Computer-assisted detection Computer programs to aid in identification of suspicious

contrast agent.

in blood flow.

Table 1. FDA approved modalities for breast cancer detection

Scintimammography Image created with radioactive tracers, which concentrate

Infrared Thermography Measures heat emitted by the body. Tumours can raise

Electrical impedance imaging Measures voltage at skin surface while passing small

decrease impedance of tissue.

established breast cancer detection modalities approved by FDA is given in Table 1.

*Benign conditions:* There are many lesions and conditions that are non-cancerous but still affect the health of the breast and could be mistaken for cancer. These include fibroadenomas, cysts, mastalgia, breast calcifications, duct ectasia and periductal mastitis, fat necrosis, hyperplasia, intraductal papilloma, phyllodes tumour and sclerosing adenosis.
