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INTRODUCTION

Every two minutes, a woman in the United States is diagnosed with breast cancer. In 2006, it is estimated that about 212, 000 new cases of invasive breast cancer will be diagnosed, along with 58,000 new cases of non-invasive breast cancer¹. According to the American Cancer Society, approximately 40,000 women are expected to die from the disease in 2006². This article provides an overview of breast cancer and its applications to mammographic imaging.

ACTIVITY OBJECTIVES:

Upon completion of the article, the reader will be able to:

• Describe the anatomical structures of the breast.
• Define what breast cancer is.
• Discuss the differences between in situ and invasive breast cancer.
• Discuss the major and minor risk factors for developing breast cancer.
• Distinguish between myths and facts concerning breast cancer.
• Discuss screening guidelines recommended by the American Cancer Society.
• Discuss the limitations of mammography.
• Discuss mammographic applications for breast imaging.
• Discuss clinical signs of breast disease.
• Differentiate mammographic findings of benign and malignant appearing breast pathology.
• Discuss the diagnostic options available when a breast abnormality is found on a mammogram.
• Identify the components of the pathology report.
• Discuss breast cancer staging.
• List available breast cancer treatment options.

The breasts or Mammary Glands are a pair of symmetrical hemispheric tissue mounds on the anterior wall of the chest. In the female, the breasts are accessory glands of the female reproductive system and represent secondary sex characteristics. Through physiological development they secrete milk for nourishment of the newborn.

The breasts extend from the 2^nd rib to the 6^th vertically and from the edge of the sternum to the midaxillary line (latissimus dorsi muscle) horizontally. Breast tissue can reach as far superior as the clavicle and extend laterally into the axilla to the edge of the Latissimus Dorsi muscle. Breast tissue can also form any where along the milk ridge, also called the mammary line. This line extends from the armpits in the axilla to the groin area of the body.

The breasts are enclosed in thin skin that contains hair follicles, sebaceous and sweat glands called the superficial fascia. The superficial fascia of the breast covers the pectoralis, serratus anterior and external oblique muscles of the chest. The pectoralis major muscle runs in an oblique line from the humerus to the midsternum.

Separating the breast from the pectoral muscle is a layer of adipose tissue and connective fascia referred to as the retromammary space. Other identifying structures of the breast include the base, axillary tail and the inframammary crease. The base of the breast is the posterior surface overlying the pectoralis muscle. Because the breast is loosely attached to the fascia covering the pectoralis major muscle, it is allowed to move over chest wall. The portion of breast extending from the base of the breast into the axillary fossa is called the axillary tail or Tail of Spence. The inframammary crease or fold is the junction of the inferior portion of the breast with the anterior chest wall.

Figure 1: Anatomy of the Breast. Courtesy of Mammography for Radiologic Technologists, 2nd Edition, Gini Wentz, McGraw-Hill, 19973

Centrally located on the surface of the breast is the areola – a circular pigmented area of skin 2-6 cm in size. Pigmentation of the areola is partially dependent upon estrogen levels. Elevations around the perimeter of areola are called the Morgani’s Tubercles. These tubercles are formed by the openings from the ducts of the Montgomery’s glands. The Montgomery’s glands secrete a fatty lubricant, which protects the nipple during lactation (nursing). In the center of the areola is the nipple protuberance, which contains 5-10 opening for the ducts that lead from the milk-producing lobes of the breast. A normal nipple can be flattened or inverted. However, sudden inversion or flattening of the nipple may indicate underlying malignancy.

The blood supply to the breast comes from the internal mammary and lateral thoracic arteries. An extensive capillary network allows exchange of hormones and secretions into and out of the lobules. This network is in close contact with the lymphatic system. Veins that drain the breast form a venous network under the nipple called the circulus venosus. This network then drains into the axillary and internal mammary veins.

There are both superficial and deep plexus of lymphatic vessels draining the breast. The main direction of drainage from the lateral half of the breast tends to be into the pectoral group of axillary lymph nodes and from the medial half into the internal mammary lymph nodes. 75% of lymph drainage is toward the axilla where the number of lymph nodes is 12-30. Most normal axillary lymph nodes are less than 2 cm in size. Enlarged lymph nodes or nodes with solid centers can indicate benign or malignant disease. Axillary nodes are usually the first to be involved with metastatic disease.

The breasts can either be divided into quadrants or in relationship to the face of a clock for purposes of location of abnormalities. The Four Quadrants are the:

• UIQ: Upper Inner Quadrant
• LIQ: Lower Inner Quadrant
• UOQ: Upper Outer Quadrant
• LOQ: Lower Outer Quadrant

The exact locations within the quadrants can be represented by viewing each breast separately as a clock face. The majority of breast cancers occur in the upper outer quadrant of the breast.

Figure 2: Quadrant and Clock Divisions of the Breast. Courtesy of Mammography & Breast Imaging: Just the Facts, Olive Peart, McGraw-Hill, 20054

The breast is made up of three types of tissues: fibrous, glandular and adipose. The fibrous and glandular tissues are generally described as one tissue– fibroglandular. Glandular tissue is primarily located in the central portion of breast and in the UOQ extending toward the axilla, surrounded by fibrous and adipose tissues. The glandular tissue is arranged in 15-20 lobes, with the fatty and fibrous tissue in between. The lobes are arranged like spokes of a wheel surrounding the nipple. Each lobe has a collecting duct called a lactiferous duct leading to the nipple.

Figure 3: Anatomy of the Internal Breast. Courtesy of Mammographic Imaging, 2nd Edition, Valerie Andolina, Lippincott, 20013

A network of fibrous / elastic bands called Cooper’s Ligaments envelope the glandular tissue and act as a supporting framework for the breast. They extend from the deep skin layer through the mammary tissue to the deep fascia covering the pectoralis muscle. The Cooper’s ligaments separate individual breast lobes from each other. The Cooper’s Ligaments are visible on a mammogram as thin, gently curving lines. They can be foreshortened or straightened by fibrosis associated with breast cancer, causing skin retraction or localized architectural distortion.

The lobes of the breast are composed of smaller lobules – the structural unit of the breast. Each lobule is composed of an intralobular terminal duct and multiple saclike ductules lined with a single layer of epithelial cells and a peripheral layer of myoepithelial cells (smooth muscle). Cellular layers are separated from other breast tissues by a boundary layer known as the basement or basal membrane. The lobule and duct form a histopathologic unit called the Terminal Ductal Lobular Unit or abbreviated as TDLU.

Figure 4: Diagram of the lining of a breast lobule. Courtesy of Mammographic Imaging, 2nd Edition, Valerie Andolina, Lippincott, 20016

Increased or decreased glandularity of the breast is a part of the normal physiological changes that take place within the breast and may also vary with age, body weight and heredity. It can be related to hormonal fluctuations (whether normal or synthetic) including:

• Menstruation
• Pregnancy
• Lactation
• Menopause

The female breasts are inactive during childhood because there are no lobules. The childhood breast will consist of small ducts within the fibrous tissue. Stimulation of breast growth is under the influence of the hormones produced in the ovaries. Estrogen causes elongation / branching of the ducts and increase in volume / elasticity of the connective tissue. Progesterone production in the ovaries occurs at ovulation forming the lobules.

The TDLUs (Terminal Ductal Lobule Unit) are referred to as acini in the lactating breast. Acini form only during pregnancy and reach full maturation during lactation. Lactation is influenced by progesterone and anterior pituitary hormones which stimulate production of milk. Prolactin is another significant hormone only present during initial breast growth, pregnancy and lactation. During lactation, the TDLUs increase in size and number. Epithelial cells secrete the milk, causing the myoepithelial cells to contract and express milk into the main lactiferous duct toward the nipple. After lactation, the TDLUs shrink.

During Menopause, breast tissue is replaced by fat in a process called involution. Involution begins at menopause and ceases 3-5 years later. Surgically induced menopause (hysterectomy and oophorectomy) and/or the ingestion of hormone replacement therapy (HRT) can retard the normal aging process.

Figure 5: Process of Breast Development from Puberty to Lactation. Courtesy of Mammographic Imaging, 2nd Edition, Valerie Andolina, Lippincott, 20017

Most benign and malignant lesions of the breast originate in the TDLU. It is believed that most breast cancers first develop as epithelial hyperplasia where the number of epithelial cells increase and change and are classified as carcinomas. There are generally considered two types of breast cancers: in-situ malignancies and invasive malignancies.

In-situ malignancies are the earliest form of breast cancer, with a 95% survival rate after 10 years. They comprise about 15-20% of all breast cancer diagnoses. In-situ malignancies can fill the ducts with necrotic debris and pleomorphic (many forms) calcifications, which appear radiographically on a mammogram. An in situ malignancy is confined to a lobule or duct and may be classified as isolated or non- invasive. Carcinoma in situ (CIS), ductal carcinoma in situ (DCIS), intraductal carcinoma or noninvasive carcinoma is a proliferation of cancerous epithelial cells lining the duct, where the malignant cells do not cross the basement membrane. Nearly all cancers at this stage can be cured. Many oncologists actually believe that lobular carcinoma in situ (also known as lobular neoplasia) is not a true cancer but rather is an indicator of increased risk of developing invasive breast cancer in the future.

Figure 6: In-situ Malignancy. Courtesy of Mammography for Radiologic Technologists, 2nd Edition, Gini Wentz, McGraw-Hill, 19978

Invasive Ductal Carcinoma is the most common form of breast cancer. It accounts for 80% of all breast cancer diagnoses. Invasive breast cancer occurs when the cancer cells break out of the ductal walls and infiltrate or invade the surrounding tissue. Malignant cells break through the basement membrane where the invading cells have access to the vascular and lymphatic channels of the breast. Common sites for metastasis include the: opposite breast, the axillary Lymph Nodes, liver, skin, lungs and bone. A common feature of invasive malignancies is the production of a mass or localized architectural distortion.

Figure 7: Invasive Malignancy. Courtesy of Mammography for Radiologic Technologists, 2nd Edition, Gini Wentz, McGraw-Hill, 19979

Other types of breast carcinomas include: inflammatory, medullary, colloid comedo, tubular, mucinous, papillary, and Paget’s disease. These types of carcinomas account for less than 10% of the total breast cancer cases. Paget’s disease of the breast (first described y Jean Paget in 1874) is a special form of ductal carcinoma associated with eczematous changes of the nipple. It presents as a malignant nipple lesion and accounts for 2-5% of breast cancers.

The seriousness of invasive breast cancer is influenced by the stage of the disease, or the spread of the cancer, when it is first diagnosed. There are two main staging systems for cancer. The first, developed by the American Joint Committee on Cancer (AJCC), uses the following information: tumor size (T), lymph node involvement (N), and presence or absence of metastases (M). Once the T, N and M are determined, a stage of I-IV is assigned, with stage I being an early stage and stage IV being the most advanced. The second, a broader system used for staging, is known as the SEER Summary Stage system, which defines breast cancers as:

• Local-stage tumors confined to the breast
• Regional-stage tumors which have spread to surrounding tissue or nearby lymph nodes
• Distant-stage cancers which have metastasized to distant organs

BREAST CANCER RISK FACTORS

There are a variety of risk factors that may contribute to the development of breast cancer. Risk factors can be categorized as major, minor and inconclusive. The major risk factors for developing breast cancer include: gender, age, genetics, family history and personal history of breast cancer. The first two risk factors are the most important. It is important to emphasize prior to reviewing the major risk factors that 85% of women who develop breast cancer have no other risk factors than being female and aging.¹⁰

GENDER:

The biggest risk factor for developing breast cancer is gender. The lifetime risk for women developing breast cancer is 1 in 8. Approximately half of all women who develop breast cancer have no identifiable risk factor other than being female. Breast cancer is second to Lung Cancer as the leading cause of death for women of all ages. Men are generally at low risk for developing breast cancer, accounting for less than 1% of breast cancer cases in the U.S. during a period from 1975 to 2002 ¹¹. However, the incidence of male breast cancer has increased annually. The reasons for this are unknown and are not attributable to increased detection, as is generally the case for female breast cancer. It is known that men are more likely than women to be diagnosed with an advanced form of the disease and have a poor mortality rate than women. Risk factors for male breast cancer include: family history of male or female breast cancer, BRCA gene mutations, a chromosomal disorder called Klinefelter syndrome and testicular disorders. It is more common in Jewish men of European ancestry.

AGE:

Besides being female, the second greatest risk factor for developing breast cancer is age. Older women are much more likely to get breast cancer. As indicated in the chart below, breast cancer is much less frequent among younger women, with the earliest diagnoses usually being made at around 25 years.

Figure 8: Courtesy of American Cancer Society, Breast Cancer Facts & Figures 2005-2006.12

According to findings in the 1974-2002 SEER Cancer Statistics Review from the National Cancer Institute, the median age at the time of breast cancer diagnosis is 61 years.¹³ This means that 50% of women who developed breast cancer are age 61 or younger and 50% are older than age 61 when diagnosed.

GENETICS:

About 5-10% of breast cancer cases are hereditary, the third greatest risk factor. This is thought to be because of the cyclical changes that occur in the breast during a woman’s lifetime. Due to the influence of reproductive hormones (estrogen and progesterone), breast cells are constantly going through rapid cell growth and division. This raises the odds that mutations in DNA are the origin of breast cancer in women. Women with a hereditary risk for factor for breast cancer carry the BRCA 1 or BRCA 2 genes. The identified breast cancer genes (BRCA 1 and BRCA 2) are located on Chromosome 17. Women who carry the BRCA 1 and BRCA2 have up to an 85% chance of developing breast cancer in their lifetime. These mutations are present in far less than 1% of the general population.¹⁴

The American Society of Clinical Oncology recommends the following criteria to identify a candidate for genetic testing for the presence of the BRCA 1 and BRCA 2 genes:

• Being a member of a family with more than two breast cancer cases and one or more ovarian cancer cases diagnosed at any age.
• Being a member of a family with more than three breast cancer cases diagnosed before age 50.
• Having sisters with two breast and/or ovarian cancers diagnosed before 50 years of age.
• Being an individual with breast cancer diagnosed before age 30.

The drug tamoxifen has been used for many years as a treatment for some breast cancers and also used to reduce the risk of developing breast cancer in women at high risk of developing the disease. Reports have also indicated that administration of tamoxifen resulted in some risk for developing endometrial cancer.

Woman at very high risk of breast cancer may elect to have preventive (prophylactic) mastectomy. This operation removes one or both breasts before breast cancer has been discovered. A recent study reported a greater than 90% reduction in risk of breast cancer in high-risk women with a family history who received prophylactic mastectomy. Subsequent studies confirmed the benefit of surgery in genetically susceptible women (a woman with a BRCA1 or BRCA2 mutation). While the operation reduces the risk of breast cancer, it does not guarantee that cancer won’t develop in the small amount of breast tissue that remains after the operation. Prophylactic oophorectomy (surgical removal of the ovaries) also appears to reduce the risk of breast cancer, as well as ovarian cancer, in carriers of the BRCA mutations. It is important to note, however, that most breast cancers (80%) occur in women over 50 who do not have the defective BRCA genes.

FAMILY HISTORY:

The fourth major risk factor for developing breast cancer is family history. Breast cancer risk is higher among women whose close blood relatives have this disease (mother, sister or daughter). A blood relative can be from either the mother’s or the father’s side of the family, but the closer the relative, the higher the risk factor. The more first-degree relatives a person has with the disease, the greater the risk. Women are also at a higher risk if the breast cancer occurs in a relative before age 50.

PERSONAL HISTORY:

MINOR RISK FACTORS

Many minor risk factors for developing breast cancer are associated with hormonal changes in the woman’s body. Reproductive hormones (estrogen / progesterone) are thought to influence breast cancer risk through their effects on cell proliferation and DNA damage, as well as promotion of cancer growth. The minor risk factors related to hormonal factors include:

• Childbearing Age
• Menstrual History
• Use of Hormone Replacement Therapy (HRT)

CHILDBEARING:

Never having children increases the risk of breast cancer twice over women who have had at least one baby. Also, having children later in life (over the age of 30) increases the risk of developing breast cancer. Also breast feeding has consistently been shown to decrease a woman’s risk of breast cancer slightly, with greater benefit associated with longer duration.

MENSTRUAL HISTORY:

Women who start menstruating at an early age (early menarche - before age 12) or who went through menopause at a late age (after age 55) are at an increased risk for breast cancer. As long as a woman is menstruating, there is a greater risk of mutating genetic material. The greater the number of menstrual cycles in the woman’s lifetime, the greater the risk of breast cancer.

HORMONE REPLACEMENT THERAPY:

Estrogen and progesterone, produced in the ovaries are important hormones used to regulate the menstrual cycle and pregnancy. As a woman ages, the ovaries begin to shrink and the levels of estrogen and progesterone in the body fluctuate – called peri-menopause, which can last for many years. HRT was approved in 1945 to relieve the symptoms caused by peri-menopause.

In the 1980’s, there was data that supported the long-term use of HRT as a preventative measure for heart disease, stroke and other health problems in older women, even though its use increased the risk of breast and uterine cancers. Most physicians thought the benefits outweighed the risks in women who had few major risk factors for developing breast cancer.

Today new studies continue to find negative results on the long-term effects of HRT. Recent studies have linked HRT with an increased risk of heart attacks, strokes and blood clots. A study in the summer of 2002 found increased risk of developing breast cancer in women taking HRT. An added disadvantage to the use of HRT is that its use increases the proliferation of dense glandular tissue in the breast, which reduces the effectiveness of mammography.

INCONCLUSIVE RISK FACTORS

There are a number of inconclusive risk factors for developing breast cancer which include the following:

• Obesity
• Alcohol consumption
• Higher Socioeconomic Status
• Cultural Origin

OBESITY:

Some studies suggest that obesity increases the risk for postmenopausal, but not pre-menopausal, breast cancer. In postmenopausal women, circulating estrogen is primarily produced in adipose tissue. Thus, having more adipose tissue can increase estrogen levels and the likelihood of developing breast cancer. A large American Cancer Society study showed that overweight women (BMI>25) are 1.3 to 2.1 times more likely to die from breast cancer compared to women with normal weight (BMI=18.5-24.9).¹⁵ Body Mass Index (BMI) is determined by {Weight (lbs.) / Height (in.)²}x703.

ALCOHOL CONSUMPTION:

Alcohol is consistently associated with increased breast cancer risk (the equivalent of two drinks a day may increase breast cancer risk by 21%). A recent review concluded that the most likely mechanism by which alcohol increases risk of breast cancer is by increasing estrogen and androgen levels.¹⁶

HIGHER SOCIOECONOIC STATUS:

Women with incomes in the upper 2/3^rds of the U.S. population get breast cancer more often than those in the lower 1/3^rd income bracket. ¹⁷ One of the theories behind this statistic is that women with higher incomes have greater access of health care than those of lower socioeconomic status.

CULTURAL ORIGIN:

The American Cancer Surveillance Survey, 2005, reported that women of North American / European Ancestry are at a higher risk for developing breast cancer than women of Asian and African Ancestry.¹⁸ However, the report also suggests that African American women who develop breast cancer have a greater mortality rate per incidence of cancer and are more likely to die from the disease. This has been attributed to finding cancers at a later stage, limited treatment options and discrimination.

Figure 9: Courtesy of American Cancer Society. Breast Cancer Facts & Figures 2005-2006.19

BREAST CANCER MYTHS

There are many myths and misconceptions surrounding breast cancer and mammography. The following discussion addresses these myths and the facts that disprove them.

MYTH: Young women (under 35) do not get breast cancer.

It is a fact that breast cancer is more likely to develop in women over age 35, but it can occur in very young women. A breast lump, at any age, that remains longer than a month, needs evaluation by a physician.

MYTH: Women with high risk factors (family history, no children, early menstruation, and late menopause) are usually the ones that get breast cancer.

The facts concerning breast cancer are these: 85% of women diagnosed with breast cancer had no family history which means that all women are at risk.²⁰ The biggest risk factor for developing breast cancer is gender. The second greatest risk factor for breast cancer is aging.

MYTH: Breast Cancer is strictly a woman’s disease

It is a fact that women have much greater risk of developing breast cancer. However, both men and women have breast tissue. Male breast tissue is considered similar to preadolescent female breast tissue. As previously discussed, about 1% of the total male population in the U.S. is diagnosed with breast cancer each year.

MYTH: A cancerous breast lump is not painful. Fibrocystic changes in the breast are what cause breast pain

Pain in a breast lump is a generally thought to be a "Good Sign". Breast Cancer is usually not associated with pain. However 11% of women diagnosed with breast cancer experienced pain as a symptom.²¹ Any pain in the breast, longer than several weeks, needs evaluation by a physician.

MYTH: Fibrocystic changes in the breast increase the risk for breast cancer.

In the past, fibrocystic changes in the breast were thought to be a breast disease – they are not. Studies have proven conclusively that fibrocystic changes are not cancerous and do not affect a woman’s breast cancer risk.

MYTH: Trauma or injury to the breast increases the risk for breast cancer.

Trauma or injury to the breast has not been proven to cause breast cancer. When breast tissue is injured, fat necrosis can occur and as the body heals a scar can develop. The scar tissue is sometimes mistaken for cancer on the mammogram.

MYTH: Having a silicone or saline implant (augmentation of the breast) increases the risk for breast cancer.

Silicone and Saline implants can cause scarring of breast tissue. However, neither type of implant is linked to any significant increase in breast cancer risks. In the past, breast cancers were missed in the augmented breast because of the limits of technology. Newer mammographic imaging techniques including ultrasound and MRI can be used to complement mammography and are effective in diagnosing cancer in the augmented breast.

MYTH: Using underarm deodorant and/or antiperspirants have shown increased risk for developing breast cancer.

Some research studies have focused on the preservatives used in antiperspirants and deodorants that can be found in breast tumors. In lab tests these preservatives, called parabens, have been shown to act like estrogen in the body. A second theory suggests that antiperspirants inhibit the sweat glands, therefore preventing toxins from leaving the body which could increase breast cancer risks. In 2002, the results of a study looking for a relationship between breast cancer and underarm antiperspirants/deodorants did not show an increased risk for breast cancer.²² The National Cancer Institute (NCI) and the U.S. Food and Drug Administration, which regulates food, cosmetics, medicines and medical devices, do not have any evidence in the research data to suggest that ingredients in antiperspirants/deodorants cause cancer.

MYTH: Having a mammogram increases the chance for developing breast cancer due to the radiation exposure.

There are no reported cases of breast cancer developing as a result of mammography. In the early days of breast imaging, the radiation dose was many times higher than those used at current levels. However, long term studies have conclusively shown that regular mammography screening results in 30% reduction in breast cancer deaths.²³

MYTH: A mammogram that is without signs of cancer insures that no cancer is present.

Mammography is the single most effective tool in early breast cancer detection; however it is not 100% accurate. 10% of breast cancers never form a lump that can be felt or seen on mammography.²⁴ Self breast examination and clinical exam by a physician must be performed in conjunction with mammography to insure that a woman receives every method of early detection available.

SCREENING GUIDELINES

In the past there was much controversy regarding the age a woman should begin screening mammograms and whether they should be yearly. The battle of the 1990’s was what to do with women in their 40’s. There was disagreement among the National Cancer Institute (NCI) and the American Cancer Society (ACS), American College of Radiology (ACR) and the American Medical Association (AMA). The cartoon below depicts the confusion that occurred for many years regarding the use of mammography as a screening tool for breast cancer.

Figure 10 Courtesy of Mammographic Imaging, 2nd Edition, Valerie Andolina, Lippincott, 200125

Today, the National Cancer Institute and American Cancer Society recommendations for breast cancer screening include:

Today mammography is still considered the most effective means for detecting occult breast cancer. Incident rates of in situ breast cancer have increased rapidly since the 1980’s due in large part to screening mammography, followed by a decline in mortality deaths because of the emphasis on early detection. Most cases of ductal carcinoma in situ (DCIS) are detectable only through mammography and the large increases in DCIS incidence rates since 1982 are a direct result of mammography’s ability to detect cancers that cannot be felt.²⁶

However mammography cannot detect all breast cancers – it is not 100% effective. Cancer on a mammogram is generally visualized as a white area within the background density of the breast. If the background density is “black” as in fatty tissue (image below), the cancer will be easily seen. As a woman ages and fatty tissue replaces glandular tissue in the breast, the density of the breast generally decreases and the sensitivity of the mammogram increases.

Figure 11: Mammogram with a predominance of adipose tissue. Courtesy of Mammography for Radiologic Technologists, 2nd Edition, Gini Wentz, McGraw-Hill, 199727

In a breast that has a large amount of glandular tissue, the background density is “white” as in the image below. This makes a cancer harder to detect. Mammography is less effective when used to evaluate dense, glandular breasts. This type of breast is typical in younger women and women who are taking HRT. Lesions may be concealed in the dense glandular tissue.

Figure 12: Mammogram with a predominance of glandular tissue. Courtesy of Mammography for Radiologic Technologists, 2nd Edition, Gini Wentz, McGraw-Hill, 199728

Therefore, the sensitivity of the mammogram will be dependent upon: breast composition, age of the patient and hormone status. Other disadvantages of mammography include:

• It is not always diagnostically specific. Benign / malignant processes can appear similar on a mammogram.
• It tends to understate the multi-focality of a lesion.
• Some breast cancers do not produce a recognizable change in the mammographic image. Palpable cancers are not always visible on the mammogram and visible cancers are not always palpable.
• It is prone to technical inadequacies / errors in interpretation by radiologist.

Because of all these disadvantages, mammographic screening is generally acknowledged to have a 10-15% miss rate.²⁹ The only sure method to confirm a diagnosis of breast cancer is to perform a biopsy on the questionable tissue. Less than one half of all recommended biopsies after mammography, even when supplemented by ultrasound imaging, reveal malignant disease.

MAMMOGRAPHY APPLICATIONS

Mammography has two applications: screening for breast cancer and diagnostic for work-up of abnormalities. The first screening mammogram performed on a woman is referred to as the baseline mammogram. After the initial mammogram is performed, it is compared to those that follow to identify subtle changes that may have occurred. After a few years of screening, sensitivity in detection increases since only mammographic changes will require evaluation. A screening mammogram should always be repeated if changes have taken place within the breast, such as breast reduction surgery or breast augmentation. Screening mammography is not performed on the following individuals:

• Pregnant and Lactating Patients - Due to physiologically altered breasts, the breast tissue is too dense to image radiographically.
• Women less than 35 years because the incidence of breast cancer is rare and the breasts have a higher sensitivity to the effects of radiation.
• Males - Because of the rarity of the disease – only 1% of symptomatic male patients have breast cancer.

A diagnostic mammogram is performed on the symptomatic patient or when the diagnosis on the screening mammogram is inconclusive for the presence of an abnormality of the breast. A breast biopsy is never recommended on the basis of a screening mammogram. The patient is always called back for a diagnostic work-up.

CLINICAL BREAST FINDINGS

When a mammogram is performed, the radiologist will depend partly on clinical and physical information to make a diagnosis (and/or recommendation for biopsy). Physical signs can often indicate both benign and malignant processes and include:

• Skin erythema
• Edema (skin thickening)
• Nipple changes
• Nipple discharge
• Breast contour changes

Skin erythema or redness can be extensive, including a large part or the entire breast. The causes of skin erythema include both benign and malignant disease processes. Redness is possible with benign processes, such as a large tension cyst, infection or an abscess. Inflammatory carcinoma may present with redness of the skin or as a result of radiation therapy for breast cancer.

Edema is the development of fluid within the skin and interstitial spaces, causing skin thickening and is generally a result of lymphedema. The skin develops prominent pores which take on the appearance of an orange peel (“peau d’orange”). Skin thickening may be caused by either benign mastitis or carcinoma.

Nipple changes include a sudden nipple inversion, which can indicate the presence of a tumor pulling the nipple inward. The nipple can also display eczematous changes, but this is most often due to benign conditions, such as skin allergies to cosmetics. However, reddening, flaking and crusting of the nipple can be symptoms of Paget’s disease. Nipple discharge is commonly a benign finding. The color of discharge is less important than its occurrence in one or both breasts and whether the discharge occurs spontaneously or is expressed. An expressed or bilateral discharge is most often due to hormone imbalance. A spontaneous, unilateral discharge always requires further evaluation by performing a Ductogram. Discharges can vary in color. A yellow, white, green or brownish discharge is normally an indication of fibrocystic changes or hormonal fluctuations. Bloody or clear watery discharge is most indicative of a papilloma (benign tumor) but a carcinoma can’t be ruled out. Clear watery discharge is more an indication of carcinoma than any other color.

The contour or shape of both breasts should be symmetrical, with minor variations. Bulging, dimpling or retraction of the skin can indicate an underlying process, either benign or malignant. Retraction of the skin may be due to fibrosis and/or shortening of the Cooper’s Ligaments. The skin looses its convex border and becomes flat or concave. This can be present in both benign and malignant tissue, a result of an infection or mastitis or suggestive of locally advanced carcinoma.

MAMMOGRAPHIC BREAST FINDINGS

When a mammogram is performed, the radiologist will compare the baseline mammogram to the present screening mammogram to look for any changes that correlate with any physical and mammographic findings. If the patient has had routine screening mammogram for years, the radiologist will generally compare the new mammogram to one taken two years prior to look for any subtle changes. On the screening mammogram, the radiologist will look for signs of:

• Asymmetry
• Architectural Distortion
• Abnormal Ductal Patterns
• Increased Vascularity
• Lymphadenopathy
• Signs of Benign Disease
• Signs of Malignant Disease

Asymmetry is the radiologist’s greatest aid in determining abnormalities both benign and malignant. The breasts are mirror images and the distribution of glandular tissue should appear the same.

A localized change in appearance of breast parenchyma is known as architectural distortion. It is an interruption of the ductal pattern and may be present with both benign and malignant disease processes. However, architectural distortion is usually a strong indicator of malignancy.

Figure 13: Normal Mammogram. Arrow is pointing to an asymmetric area that is a normal variant. Courtesy of Mammographic Imaging, 2nd Edition, Valerie Andolina, Lippincott, 200130

An abnormal ductal pattern can be visualized as an overall pattern where the ducts are shortened or distorted or it can involve a single duct that is dilated. This would be indicative of something growing within duct causing it to expand. Carcinoma of the breast is often associated with increase in size and number of veins in the breast. This is of limited significance because enlarged veins can also be associated with inflammatory conditions and the size of vein may be enlarged due to compression of the breast during imaging.

Lymphadenopathy can be defined as an increase in the number, density and size of axillary lymph nodes and is suspicious for a breast malignancy. Lymph nodes on a mammogram appear as smoothly outlined, sometimes lobulated densities with a zone of radiolucency in the center. Both axillary and intramammary lymph nodes can appear on a mammogram; however axillary lymph nodes are usually larger in size. Abnormal lymph nodes are ovoid, lack a normal fatty hilum and are closely packed.

Figure 14: Normal appearance of a lymph node on a mammogram. Courtesy of Mammographic Imaging, 2nd Edition, Valerie Andolina, Lippincott, 200131

The mammographic appearance of abnormalities in the breast is separated into two classifications:

• Benign
• Malignan

Pathology may appear on a mammogram as: a mass or lump, calcifications and/or diffuse accentuation of glandular tissue.

BREAST MASSES / LUMPS

Generally most breast abnormalities will show up on a mammogram as a mass density. The density of the mass refers to the x-ray attenuation of the lesion relative to the expected attenuation of an equal amount of fibroglandular breast tissue. A breast mass or lump appears as a 3-Dimensional tissue structure sufficiently different from surrounding tissue. It may be palpable or only detected by mammography or ultrasound. A mass density is evaluated for its borders or margins and its shape.

The borders or margins of breast masses may be circumscribed, microlobulated, obscured, ill-defined or spiculated. Circumscribed lesions are rarely malignant and a lesion with a “halo sign” usually indicates the presence of a benign lesion.

Figure 15: Borders of typical breast masses. Courtesy of Mammography & Breast Imaging: Just the Facts, Olive Peart, McGraw-Hill, 200532

Figure 16: Halo sign surrounding a lesion on a mammogram. Courtesy of Mammography & Breast Imaging: Just the Facts, Olive Peart, McGraw-Hill, 200533

The shape of a breast mass or lump can be round, oval, lobulated or irregular. The most common benign circular or oval abnormalities are breast cysts or fibroadenomas.

Figure 17: Shapes of typical breast masses. Courtesy of Mammography & Breast Imaging: Just the Facts, Olive Peart, McGraw-Hill, 200534

Masses can also be classified as cystic or solid. Cysts are the most common cause of breast lumps in women between 30-50 years of age and do not represent an increased risk for developing breast cancer. These represent fibrocystic changes that may also be referred to as chronic cystic mastitis or mammary dysplasia. The cause of fibrocystic changes in the breast is related to cyclical changes in estrogen / progesterone levels in the breast. Hormonal stimulation of breast tissue causes blood vessels to swell, lobes and ducts to enlarge and breast tissue to retain water. The result of the hormonal stimulation is a firmness of the breast tissue, in which pockets of fluid (cysts) form in obstructed or enlarged ducts.

Figure 18: Mammographic representation of a large cyst. Courtesy of Mammographic Imaging, 2nd Edition, Valerie Andolina, Lippincott, 200135

Ultrasound is the only way to determine if a mass is cystic or solid. A true cyst on an ultrasound appears as a structure that has no internal echoes, sharply defined margins, fluid filled, with thin walls and distal acoustic enhancement (shadowing). Complex cysts have irregularities like wall thickening, internal debris, separation or inartistic masses.

Figure 19: Ultrasound of a breast cyst. Courtesy of Mammographic Imaging, 2nd Edition, Valerie Andolina, Lippincott, 200136

Another benign breast mass is a fibroadenoma. It is a single, firm, moveable lump that is a benign overgrowth of the fibrous tissue of the lobule. Fibroadenomas are the most common lump found in women under the age of 25. A Fibroadenoma’s density is normally that of the surrounding glandular tissue. It can be lobulated and may exhibit a halo sign. Characteristics of a fibroadenoma on mammography include:

• Smooth margins that are sharply defined
• Encapsulated – a thin curved radiopaque line surrounding the mass
• Low Density – surrounding parenchymal structures can be seen through the lesion
• Internal calcifications

Figure 20: A fibroadenoma on a CC view of the breast. Courtesy of Mammographic Imaging, 2nd Edition, Valerie Andolina, Lippincott, 200137

Other benign breast masses / lumps include: lipomas, hamartomas and papillomas. Generally, benign lesions will not change much in size or shape, whereas malignant lesions can grow significantly over a 1 year period. However, the use of HRT is known to promote enlargement of cysts and fibroadenomas. The combination of estrogen and progesterone are often associated with diffuse increasing densities in the breast that can mimic carcinoma.

Premenopausal women breast changes are common because of fluctuating hormones. However, the appearance of a new focal density on a screening mammogram should be followed with a diagnostic workup. If any benign appearing mass develops new calcifications or changes significantly, it should be considered suspicious for malignancy especially in postmenopausal women. Due to involution of the breast (fat replacing glandular tissue) in postmenopausal women, a new density is more suggestive of carcinoma.

A spiculated border is a strong indication for malignancy. Spiculated or stellate lesions have a solid central tumor, with radiating extensions. If the spicules reach the skin, muscle or areola region, it results in retraction and localized skin thickening. The “silhouette sign” can help to determine if a lesion has a true spiculated border.

Figure 21: The silhouette sign. Courtesy of Mammographic Imaging, 2nd Edition, Valerie Andolina, Lippincott, 200138

If a mass is truly spiculated, the lines radiating from it will disappear in the middle of the abnormality. If lines can be followed into, through and out of the mass, then these lines represent silhouetted structures in front of or behind the mass.

Figure 22: A spiculated mass with nipple retraction. Courtesy of Mammography & Breast Imaging: Just the Facts, Olive Peart, McGraw-Hill, 200539

Characteristics of a suspicious breast lump / mass include irregular margins that are stellate or star-burst shaped, with extensions radiating in all directions.

The following table summarizes the differences between benign and malignant breast lumps:

It is important to note, however, that both benign and malignant breast abnormalities can have similar morphologic changes.

BREAST CALCIFICATIONS

Calcifications within the breast can occur with both benign and malignant processes. 80% of breast carcinomas have calcifications - with only 55% visible on mammogram. 20% of breast cancers present only as microcalcifications with no associated mass. The exact cause of calcifications is unknown; however the theory is they result from mineralization of necrotic debris. Evaluation of microcalcifications on a mammogram is performed using magnification.

When calcifications are present on the mammogram, the radiologist will classify the calcifications appearance as: benign, malignant or indeterminate. They are also analyzed on the basis of their: size, number, distribution and morphology.

There are several types of benign microcalcifications, which include:

• Milk of Calcium
• Secretory
• Involution
• Arterial
• Skin

Milk of Calcium is benign microcalcifications that are formed by fine calcium precipitates in fluid which settle to the bottom of cysts. They are demonstrated on a 90 Degree Mediolateral Lateral Projection to layer the calcifications. Milk of Calcium calcification will be having a crescent shaped appearance, resembling a “tea-cup” on a mammogram.

Figure 23: Magnification view demonstrating “Tea Cup” appearance of Milk of Calcium calcifications. Courtesy of Mammographic Imaging, 2nd Edition, Valerie Andolina, Lippincott, 200140

Secretory microcalcifications are solidified secretions shaped like a duct. Because the microcalcifications are within the ducts, they are linear and fragmental, pointing toward the nipple and are often found bilaterally.

Figure 24: Secretory calcifications. Courtesy of Mammography & Breast Imaging: Just the Facts, Olive Peart, McGraw-Hill, 200541

Involutional microcalcifications are uniform, round forms scattered throughout the breast. Calcium becomes trapped in a shrunken TDLUs and form as a result of an involuting fibroadenoma. They appear as large, dense popcorn-like microcalcifications on a mammogram.

Arterial calcifications result from arterial arteriosclerosis. Vascular calcifications follow arterial walls and form parallel tracks. If arterial calcification is evident on a mammogram, new studies suggest the woman could be suffering from coronary artery disease (CAD).

Figure 25: Arterial calcifications as indicated by arrows. Courtesy of Mammographic Imaging, 2nd Edition, Valerie Andolina, Lippincott, 200142

Skin calcifications characteristically are smooth in outline with radiolucent centers. They are usually scattered throughout the medial half of the breast.