Breast Mammography: Correlated Ultrasound, MRI, CT, and SPECT-CT
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This article discusses historical aspects of breast imaging, and the rationale for mammography as a pre-screening tool for early detection of breast cancer. Includes stereotactic biopsy, ultrasound, MRI, CT, and other types of breast imaging.
Author: Nicholas Joseph Jr. R.T.(R) B.S. M.S
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According to the American Cancer Society (ACS) breast cancer is the second leading cause of death in women. Lung cancer is the leading cause of death among women. Mammography screening is perhaps the single most important diagnostic tool in the fight against breast cancer. Today there are many improvements in the way we image and diagnose breast cancer. It is imperative that radiologic technologists understand how our profession contributes to the progress in diagnosing and treating breast cancer. Mammography is such an important tool contributing to the decline in breast cancer deaths that an understanding about its benefits cannot be ignored. It was estimated that 230,480 new cases of invasive breast cancer would be seen in women in the United States in 2011. That’s slightly more than one woman every two minutes, and in the same period another 57,650 women would develop a non-invasive type of breast cancer called carcinoma in situ (CIS). In spite of these harsh statistics it is encouraging to know that early detection of breast cancer has a 90 to 98 percent long-term survival rate and survival longevity is increasing. It is heartening to know that in the United States alone there are currently over 2 million survivors of breast cancer. This is due in part to women understanding the risks associated with breast cancer and timely utilizing early screening exams. These statistics prove that our ongoing fight against breast cancer is clearly affected by our ability to detect it early. On the medical forefront are dedicated radiologic technologists who are specially educated in radiological studies that diagnose breast cancer. Today’s medical radiographers performed several studies of the breast including mammography, ultrasound (US), magnetic resonance imaging (MRI), and dedicated nuclear isotope scans. Computed tomography (CT) is also used to help stage cancers and monitor remission and treatments for various types of cancers.
Many women and some men have had a mammogram. Our goal is to help as many as do read this article to understand the benefits of mammography, and to know basically what it is, and to know something about how it is performed. The purpose of this article is to explore modern concepts in breast imaging performed by radiologic technologists. This article will benefit both medical persons and the general public wanting to understand the importance of breast imaging and what it entails. It is also important that those radiographers who do not perform mammography or related studies have a better than basic understanding of breast imaging. Anyone can be a victim of breast cancer, male or female, and age is simply a statistical factor granting immunity to no one. Technological advancements in mammography, ultrasound, and magnetic resonance imaging have strongly tilted the scale so that benefits gained by using ionizing radiation far outweigh radiation risk. Mammography can be simply described as a specialized radiographic examination of the male or female breast to detect cancer. Mammography is such an important study that it is the only x-ray exam that has a medical annual recommendation in appropriate age groups. In spite of its benefits, mammography shares an equal concern over its historically high radiation exposure to vital breast tissue. But when one considers our current knowledge about breast cancer and the many positive outcomes possible with early detection, radiation risk versus patient benefit is well substantiated for mammography.
Screening mammography is recommended based on the reality that currently, there is no known prevention strategy we can employ to combat breast cancer. So unlike heart disease where exercise and diet can be a weapon of prevention, our most important strategy in fighting breast cancer is early detection. Screening mammography for the general at risk population is the main means to reduction in morbidity and mortality caused by breast cancer. Retrospective studies and ongoing new data collection strongly support the observation that mammography is most beneficial when used as an early screening tool. It also has important diagnostic applications when a lesion is discovered at screening, or when a lump is felt in the breast or axilla. The physician should consider mammography whenever a lump is found on breast self exam (BSE), or when an individual experiences localized breast pain. The rational for screening the targeted population is well founded in research literature. The primary reason for recommended screening mammogram by the ACS is that mammography can show breast changes up to two years before even an experienced physician can feel them. Furthermore, it is in this “early time” period that breast cancers are most curable. This is also the time period when those who might opt for a breast-conservative surgical strategy, which is desired by many women is most likely to succeed.
The American Medical Association (AMA), American College of Radiology, and the American Cancer Society all recommend annual screening mammography for all women beginning at age 40. Guidelines from the National Cancer Institute (NCI) recommend those with a family history of breast cancer, or those having known genetic history for breast cancer should ask their physician about how frequent they should have their screening mammogram. Also the appropriate age for beginning screening mammograms in those with family history of breast disease should also be discussed. Generally it is recommended that any woman who has a first degree relative with breast cancer begin screening 10 years from the age of discovery in the relative. The fact is that American women have an 11% (1 in 8) lifetime risk of developing breast cancer. Sadly, breast cancer claims the lives of approximately 50,000 victims each year. Unfortunately, researchers still do not know why women living on the North American continent have the highest rate of breast cancer in the world. This means women in the screening populace should be vigilant about their annual screening. But we have many successful treatments when breast cancer is discovered early. Therefore, the American Medical Association supports a proactive approach that includes early detection and advancement of treatments for breast cancer. The purpose of this paper is to shed light on risk factors associated with breast cancer, discuss breast anatomy and how it is affected by breast cancer, discuss the various types of breast cancers, and discuss various radiologic studies including mammography, and procedures used to diagnose breast cancer.
What is breast cancer?
We hear a lot about cancer these days, like that of the prostate, liver, pancreas, colorectal, and so forth, and especially of the breast. But laypersons and healthcare providers alike are often confused in our understanding about why breast cancer is such a deadly disease. The term cancer is just a general word meaning aberrant disorderly “out of control” growth of cells that can spread outside their normal anatomical boundary. Cell growth is a normal part of the human cell cycle and is the mediator of repair as well as human development. Growth and development begins as an embryo, then through infancy, early childhood, puberty, adulthood, and into old age as a result of cellular changes and growth. Throughout life our cells participate in many bodily repair processes. Do you remember falling as a child and getting an abrasion? Soon it was covered with a scab and later some scar tissue developed. This is what our body is supposed to do to protect itself as part of the normal processes involving growth and repair. But cancer cells do not adhere to normal growth and repair mechanisms, which are highly regulated and limited. Cancer cells continue to grow beyond natural borders invading adjacent tissues and can spread to other organs in the body.
Cancer cells are not all the same, for example, breast cancer cells are vastly different from prostate or lung cancer cells. The behavior of different cancer cells within the same tissue also varies greatly. Just as the many types of cancers have different presentations so is our ability to detect them differently. Likewise there are varying treatments and prognosis associated with a specific type of cancer, even within the same tissue. Aggressive cancers can sometimes seed to a site remote from its primary development. These cancers are said to have metastasized. Breast cancer, for example tends to metastasize through the lymph vessels to the lungs, bone, and ovaries. Sometimes cancer found in one location is indicative of a primary cancer in remote location.
There are two broad classifications of breast cancer: ductal carcinoma and lobular carcinoma. The most common type of breast cancer is ductal carcinoma occurring in slightly over 90% of all cases. Lobular carcinoma affects another 5-10% of women. Ductal carcinoma is further divided into two types: 1) ductal carcinoma in situ (aka: noninvasive intraductal) and 2) invasive (aka: infiltrating) ductal carcinoma. Regardless of the cancer type over 90% of breast carcinomas arise within the ducts. A noninfiltrating intraductal carcinoma is so named because it is confined to the ductal system meaning it does not penetrate the duct’s basement membrane. The cancer is therefore confined to within the duct walls. The term basement membrane applies to the support structure on which membranous epithelial cells are bound. The basement membrane is like the lattice that carpet is built on. It is composed of glycoproteins and a meshwork of collagenous and reticular fibers derived from the underlying connective tissues. The basement membrane is an important structure because cancer must break through it in order to metastasize. The pathogenesis of an in situ carcinoma begins as an atypical proliferation of ductal epithelium that eventually completely fills the duct plugging it up with neoplastic cells. In situ carcinoma has also been called comedocarcinoma because a cheesy tumorous substance can be pressed out of the duct on histological sectioned tissue. The growth pattern of a histological section can be described as cribriform, papillary or lobular progression. A cribriform pattern describes the presence of duct like structures within the primary dilated ducts. Intraductal papilloma generally occurs in women just prior to menopausal age. They appear as a small lesion (sometimes multiple) near the nipple. They may not be obvious or palpable but do get the individual’s attention when there is a bloody discharge from the nipple. Fortunately, discharge from the nipple is a more common finding in benign lesions than malignant ones, and intraductal papilloma is the most common of all causes.
Malignant disease originating in the lobules or ductal system that does not penetrate the basement membrane is designated “in situ.” The reason that it is important to identify a malignant process that transgresses the basement membrane is that invasion signifies a more destructive type of cancer. Invasive cancer must be treated aggressively to prevent spread through adjacent weak capsular boundaries like the mammary apparatus, or through the pectoral fascia into the pectoral muscles and to the anterior chest wall. The goal of mammography screening is to catch cancer in Stage I when is it “in situ,” which is the earliest stage with no spread of the disease. An invasive cancer that penetrates the basement membrane is at least a Stage III cancer. A stage IV cancer is the most advanced disease state with metastasis to other organs distant from the breast.
Lobular carcinoma in situ is a unique lesion that is manifested by proliferation in the terminal ducts or acini. These lesions have loosely spaced large cells. This type of cancer does not usually penetrate through the wall of the lobule, thus its name. However, it is an important type of cancer because it can be present, but not seen in nearly 50% of mammography exams. Lobular carcinoma is mainly seen in breast tissue removed near invasive carcinoma in patients with fibrocystic disease. A finding of lobar carcinoma is followed very closely because it frequently develops into invasive carcinoma. A 24-year study showed the frequency of carcinoma developing in the same or contralateral breast was 30% in a population of patients with lobar carcinoma in situ. This means both breast are at risk when lobar carcinoma in situ is found in either breast. The types of carcinomas that developed in patients with lobular carcinoma were either infiltrating ductal or infiltrating lobular.
Intraductal carcinoma is easier to diagnose and treat because it remains confined to the breast for many years; however, approximately 20-25% of in situ cancers eventually penetrate through the basement membrane to metastasize. The cancer spreads by invading the stromal tissue surrounding the cancerous duct. In some cases it may invade the fascia of the pectoral muscle. Advanced disease may involve invasion of the pectoral muscle itself. There are other types of breast cancers that combined cause less than 10% of breast cancers. These other types have a better treatment and prognosis than either ductal or lobular cancers. These types include colloid comedo, mucinous, infiltrating medullary, papillary and other types of breast cancers.
Breast Cancer Risk Factors
Currently there are no known preventive measures against breast cancer one can adapt, like life style changes associated with heart disease. However, there are known risk factors for breast cancer and just as many myths fostering false beliefs. Risk factors are just that, factors that increase the probability of developing a disease. Like eating lots of fried foods may increase your risk of gaining weight and developing heart disease. You are not guaranteed to get a disease because you have a risk factor for it; however, you would be foolish to accumulate controllable risk factors that can be minimized. For instance, you can get lung cancer without smoking; however, smoking is an added risk factor you can avoid. The point about risk factors is that we should change the ones we can and monitor the ones that we cannot. Risk factors that cannot be changed are those like age, gender, race, and those we can change are diet, exercise, abstinence from smoking, and the like. It is important that we are all familiar with the risk factors associated with breast cancer. Knowing what risk factors one has, getting proper on time clinical screening exams, performing breast self examination, and mammography together have significantly contributed to the reduction in breast cancer deaths. Here are some of the risk factors associated with breast cancer:
Being female is by far the greatest risk factor for breast cancer. Comparatively, about 2,140 males developed breast cancer in 2011 giving women a 100 times greater risk based on gender alone. Of those women who will develop invasive breast cancer, statistically 78% will be over age 50 at diagnosis, whereas 17% will be in their forties. Therefore, aging is the second greatest risk factor. Besides gender and age, several genetic markers have been found over the years; of them the breast cancer genes BRCA1 and BRCA2 are the most significant. The BRCA1 gene is a tumor suppression gene located on chromosome 17, and BRCA2 is a tumor suppression gene located on chromosome 13. These mutated genes are segregated in a small at risk population accounting for 5-10 of breast cancers. Those who inherit these mutated genes carry an 80% chance of getting breast cancer. Other genetic markers are the ATM gene (ataxia-telangiectasia mutation), CHEK-2, and p53 tumor suppressor gene; all have been linked to increased cancer risk. Li-Fraumeni syndrome is an inherited cancer syndrome described by two researchers for whom it is named. This is an extremely rare cause of inherited breast cancer, but is significantly proven for those who have this syndrome. Those with a family history of breast cancer may wish to ask their family physician if they should have genetic testing for breast cancer genes.
A woman’s risk is increased if you have a family member with breast cancer. Approximately 20-30% of new cases have a relative with breast cancer. The risk associated with having a blood relative with breast cancer is:
The discovery of breast cancer in only one breast raises the risk for breast cancer in the other breast even if it is initially disease free; there is a 2 to 4 times increased risk of developing breast cancer in the contralateral breast. Therefore, there is an ongoing mandate to evaluate the opposite breast each year or as determined by the patient’s physician. A new development of breast cancer in the same breast is also statistically significantly high. These issues should be discussed with one’s physician especially when considering surgical breast conservative treatments.
Ethnicity also has a statistical significance for breast cancer. White women have the highest frequency followed by African-American women. However, African-American women are more likely to have aggressive basal type cancer when discovered and therefore have the highest breast cancer death rate. The lowest frequencies of breast cancer and related deaths are found in Asian, Hispanic, and Native-American women.
To complete the assessment of personal risk when a lesion is found on mammography a biopsy of the lesion may be necessary. When these lesions are reported benign it is important the patient understands that some benign breast lesions are more closely linked to cancer than others. These lesions are generally divided into 3 main groups that are related to risk: non-proliferative, proliferative without atypia, and proliferative with atypia. Non-proliferative lesions are diagnostically confusing on mammogram. They must be differentiated because some do and others do not have an associated risk for breast cancer. Benign lesions on mammogram do not present with overgrowth of breast tissue and are considered to have a stable growth pattern. This is why prior mammograms must be compared with any new study, and scheduled follow-up studies are so important. Some benign non-proliferative lesions that are not associated with breast cancer include fibrosis, cysts, mastitis, and simple fibroadenomas. These can present as a lump or with some degree of pain that may cause the patient anxiety.
Some lesions do not involve aberrant growth in the lobules or ducts, but are proliferative; these types of growths are termed proliferative lesions without atypia. The risk of later developing breast cancer for a person diagnosed with a proliferative lesion without atypia is 1 to 2 times normal. Some examples of proliferative atypia lesions are: complex fibroadenoma, sclerosing adenosis, and multiple papillomas. These type proliferations should be followed since they carry an increased risk. By contrast some types of breast lesions display an excessive growth pattern called atypia. Proliferative lesions with atypia are those with excessive growth involving the ducts or lobules. The architecture of aberrant cells diagnosed as atypia means the ducts or lobule lacks the normal appearance. A biopsy finding of proliferative lesion with atypia raises the risk 4 to 5 times normal, especially when there is a family history of breast cancer. So as you can see the final determination of a person’s risk for breast cancer is based on history, mammogram results, and the histological presentation of a biopsied tissue.
Now getting back to risk we should examine what role hormones and hormone replacement plays in breast cancer risk. There seems to be some indications that hormones involved in the menstrual cycle may have an important role in breast cancer risk. The basis for this line of thought is that women who have no children, or have their first child after age 30 have a modestly increased risk. Furthermore, early onset of menstruation (before age 12) and late menopause (past age 55) also has an increased risk. Concurrent supporting data shows that women who have their first pregnancy before age thirty do have a lower risk for breast cancer. Data also shows that having multiple pregnancies also seem to lower risk. Breast-feeding is also shown to reduce risk. In fact, women who have several children and breast feed up to 18 months can possibly reduce their risk by nearly half. It seems that reduced risk is linked to shortened menarche through the childbearing years and menopause. Now having said this, it is important for women to know that this protection is not extended to women who use oral contraceptives. Instead, there is an increased risk associated with oral contraceptive use. The risk incurred due to contraceptive use does not return to normal until one is oral contraceptive use free for 10 years.
A large body of research data has been gathered over the years concluding that postmenopausal hormone therapy (PHT) utilizing both progesterone and estrogen raises the risk for breast cancer and breast cancer related death. We now know that estrogen replacement therapy (ERT) alone does not appear to raise breast cancer risk. However, the rational for adding a PHT regime is based on many factors. Among them is whether or not the person has had a hysterectomy or not. The general scenario is when the uterus is still present at the time of menopause (absence of a hysterectomy) estrogen is sometimes given to reduce the woman’s risk of osteoporosis. Unfortunately estrogen replacement alone has been shown to increase the risk of cancer of the uterus. To counteract estrogenic effect on the uterus the physician may prescribe progesterone. On the contrary, if a hysterectomy has been performed progesterone is not needed and ERT alone can be given. Unfortunately in some patients the need to prevent osteoporosis has to be carefully weighed against the risk associated with combined replacement therapies.
Recent studies conducted by the World Health Organization (WHO) and large scale studies conducted in the United Kingdom showed some rather surprising results on the effects of PHT on mammography. These studies collaborated in concluding that PHT reduces the effectiveness of mammography. Consider the importance of mammography as a screening and diagnostic tool being that it can identify small lesions and can localize them for biopsy. A biopsy result of indeterminate breast lesions along with radiographic imaging is what provides a definitive diagnosis, speed early treatment and a good prognosis for most breast cancers. PHT on the other hand contributes to a significant increase in the number of pseudo-abnormal finding on mammograms and makes diagnosis a chase, which significantly delays treatment. Studies also show that women on PHT therapy are more likely to die from breast cancer when PHT has been used within 5 years of breast cancer discovery. The increased breast cancer risk due to PHT therapy returns to normal within 5 years of ending its use. On the other hand, ERT has not shown an increased risk for breast cancer, but does propose an increased risk for ovarian cancer, and for stroke.
There appears to be some risk to women who received ionizing radiation therapy to the chest area to treat certain types of medical conditions. For example, young females who receive therapeutic irradiation for Hodgkin or non-Hodgkin’s lymphoma have and increased risk of later developing breast cancer. The risk has been associated with patient age at the time if radiation treatment. Adolescence age period seems to be the greatest at risk period for radiation therapy exposure related to later development of breast cancer. The risk for those young females receiving irradiation during adolescence may have an increased risk, which is upwards to 12 times the normal risk.
There are some drugs used in medicine are also known to cause an increased risk for breast cancer. The best example of these drugs is a drug called diethylstilbestrol (DES). Diethylstilbestrol was once thought to reduce the risk of miscarriage when spotting occurred during pregnancy. DES was commonly administered to pregnant women in the 1940s through 1960s. Regrettably, it was not know at the time that DES slightly raises the risk of developing breast cancer. A slight increased risk is also seen in children of these mothers who were exposed in utero. For many years now DES is no longer used to treat spotting during pregnancy. One should always talk to their physician before using any drugs during pregnancy. Now having discussed risk for breast cancer, it is important to understand that 80% of breast cancers occur in women with no risk factors for the disease; therefore, screening women in the target population age group is the best way to detect it.
Decreasing Breast Cancer Risks
Certain lifestyle choices can raise risks while others can reduce risks for breast cancer. Let’s look at how managing lifestyle choices can help reduce a woman’s risk of developing breast cancer. The major known lifestyle choices that can affect breast cancer risk include one’s use of alcohol, exercise, obesity, breast-feeding, and having children. One can choose whether or not to drink excessively, or not to exercise regularly, or not to seek medical help to overcome obesity, and so forth, but understand there are potential consequences of adverse lifestyle choices. Just looking at alcohol use as a lifestyle choice; published studies have altogether provided data linking small doses of alcohol to reduced risk of some types of heart disease. However, having more than one drink a day can increase the risk of breast, esophageal, and oral cancers. Having 2-5 drinks a day clearly increases the risk of breast cancer to about 1.5 times that of a nondrinker. This does not mean you should refrain from all social drinking. It simply means that if you are having too many drinks daily there is an associated risk of breast cancer and other health problems. Moderate drinking has been shown to have moderate health benefits on the cardiovascular system.
Some women have been told that breast-feeding lowers one’s risk of breast cancer. However, the truth is that breast-feeding nurturing as practiced in North America does not provide a significant reduction in breast cancer risk. To see the reduction in breast cancer reported in research literature due to breast feeding it must be continued for 1.5 to 2 years. This is generally longer than most American woman will breast feed an infant. Studies conclude that the mechanism and effect of breast-feeding has the same or similar reduction in risk as having several children. The thought is that breast-feeding may have the same mechanism like pregnancy, late menarche, and early menopause in reducing the total number of hormonal controlled menstrual cycles thereby reducing risk. Sustained breast-feeding combined with having several children could possibly reduce breast cancer risk to half that of the general population.
When we look at studies to determine if a link to obesity and breast cancer risk exists, nearly all concluded that it does. The basis for increased breast cancer risk caused by obesity is related to the production of estrogen by fat cells. Obese postmenopausal women tend to have increased blood estrogen level. It is known that raised estrogen level after menopause is a risk factor in itself. Interestingly, fat in the diet is not currently correlated to risk; however, weight gained as an adult is. This is especially true when weight is gained in the waist as opposed to the thigh or legs. The American Cancer Society recommends a healthy lifestyle in regards to diet and weight. As part of the healthy diet recommendations one should limit their intake of processed foods and red meats. The American Cancer Society Guidelines on Nutrition and Physical Activity also recommends a healthy exercise program. It is recommended that one exercises for at least 45 to 60 minutes 5 or more days each week. This level of exercise will reduce risk by 18%, which is a significant breast cancer risk reduction and will help maintain a healthy body weight.
Breast cancer awareness has been welded into social culture giving much of the attention to the importance of mammography screening for women over 40. Social awareness has also led to the spreading of several myths and rumors about causes of breast cancer. Even today many of these myths are uncertain as to origin, erroneous in most cases, or are unproven by scientific methodology. You may have heard some of these tales like wearing an underwire bra or using antiperspirants can cause breast cancer. One of the most widely believed myths is that breast implants are causative of breast cancer. These tittle-tattles are simply unfounded in scientific studies. Antiperspirants have not been shown to cause breast cancer and are in fact highly tested to determine if there is any carcinogenic effect. The hypothesis behind the tale is that parabens (preservative in antiperspirants) produce an estrogen like effect, but this theory has not been fully tested or proven. Preliminary results from available data show that no such correlation between parabens and breast cancer exist. The notion that wearing underwire bras to support the breast can cause breast cancer is just completely myth. Likewise, breast implants do not cause breast cancer; however, silicone breast implants do cause scarring of breast tissue should silicone escape the implant and infiltrate breast tissue. It is true that sometimes implants can cause breast tissue to be occasionally obscured on some routine mammogram projections; however, the mammogram technologist is skilled at taking “implant displacement views” to properly demonstrate hidden breast tissue. MRI is also very effective in imaging breast tissue when displacement mammography views are limited.
Some women have been improperly informed about intimate health issues such as whether or not breast cancer is related to prenatal loss of a fetus, or by voluntary or spontaneous abortion, or even stillbirth. The truth on this issue is that data reviewed from over 83,000 case studies of women with breast cancer, the National Cancer Institute have concluded that no relationship exist between abortion or stillbirth, and breast cancer. Another important general assumption that is popularly spread to women is the belief that smoking causes breast cancer. Women who smoke regularly often believe that tobacco is a major cause of breast cancer; however, numerous studies have not correlated smoking and breast cancer. It has therefore been concluded that tobacco does not significantly contribute to breast cancer so let’s put this myth to rest. Although the best research to date has not uncovered a link between smoking and breast cancer one should be warned that smoking tobacco is related to lung cancer deaths, which exceeds breast cancer deaths in women. Some experiments were done in which laboratory mice were exposed to exceptionally high concentrations of cigarette smoke. They did develop breast cancer; however, the data could not be extrapolated to humans. Women and men alike should beware, because there are about twenty chemicals found in second hand smoke that have been shown to cause breast cancer in rodents. Many of the chemicals found in tobacco smoke can infiltrate into breast tissue and has been detected in breast milk. So the real issue is why smoke when there are no health benefits to it and we know certainly there are many health risks associated with tobacco use.
Anatomy of the Breast
The evolution of the breast begins in the embryonic stage of gestation and continues throughout life. At the end of the third week of gestation the three primary germ layers (ectoderm, mesoderm, and endoderm) are formed. The ectoderm gives rise to the epidermis and nervous system; the mesoderm will give rise to the smooth muscle, connective tissue, blood cells and vessels, bone marrow, the bony skeleton, reproductive organs, and excretory system. The endoderm gives rise to the epithelial lining of the digestive and respiratory systems. It is also the origin of glandular cells such as hepatocytes (liver cells) and pancreatic cells, salivary glands, etc. The mammary glands are actually modified sweat glands. Their development begins along two embryological tissue lines called the milk lines. Around the twenty-eighth day of gestation mammary ridges (a.k.a. milk ridges or milk lines) can be seen on the ventral surface of the embryo. These milk lines extend bilaterally from the axilla to the groin. The embryological development of the breasts is the same in females and males. Because of their extensive coverage of embryonic breast tissue along the milk lines there can be accessory breast tissue development along its course. The mammary ridges are ectoderm tissue. Ectodermal mammary ridges should persist only in the area of the chest becoming the breasts. Breast tissue that develops anywhere along the milk lines can later manifest as abnormalities of mammary gland tissue.
The mammary glands (breast) are modified sweat glands that start their embryonic development from primary buds at about the sixth week of gestation. These buds are remnants of the mammary ridges that run along the lateral ventral surfaces of the embryo. At this time the epidermis begins to involute into underlying undifferentiated mesenchymal tissue. Each primary bud develops secondary buds, which become the lactiferous ducts and its branches (figures A-D below). Fat and connective tissues of the breast develops from mesenchymal tissue that surrounds these buds. Mammary glands are not developed at birth, only the lactiferous ductal system. Prepubertal growth is slow although mammary ducts are in a growth phase and so is the ductal stroma. At this stage the breast consists of fat and the nipple. Then at puberty under the influence of estrogen, and to a lesser degree progestogens, corticoids, growth hormone, and prolactin the glands enlarge, fat and connective tissues proliferate. As glandular tissue and fat increase the breast enlarges giving the appearance of the female secondary sex characteristics and breast enlargement. The mammary glands are incompletely developed from puberty till pregnancy. The breast in females continues development beyond puberty becoming functionally mature just a few weeks before childbirth. In males the breast is a rudimentary organ having no normal functions at any stage of its development.
During pregnancy estrogen and progesterone levels rise and are sustained to complete the development of the mammary glands. At pregnancy the intralobular ducts of the breast undergo proliferation forming buds that become alveoli. Fat is deposited in the breast giving them an enlarged somewhat spherical shape. The male breast does not normally undergo postnatal development because males have a low estrogen level. There are some conditions were male breast tissue may develop. Some males develop excessive breast tissue, a condition termed gynecomastia (Gr. Gyne, woman, + mastos, breast). A male genetic condition called Klinefelter syndrome in which the individual has a chromosomal complement of 47; XXY (extra “X” chromosome) can have excessive development of male mammary gland tissue.
The fully developed human breasts lie on the anterior chest wall atop the pectoralis major muscle. It extends from about the second rib to seventh bilaterally. The adult breast is composed of adipose, glandular and fibrous tissues. The fibrous and glandular tissues are sometimes called fibroglandular tissue. The breast is a mixture of tissues: blood vessels, secretory structures, lymphatics and fibroglandular tissue. An important anatomical space called the retromammary space lies between the pectoralis muscle and the breast. The space is filled with a layer of fat tissue. Projecting through this fat layer is a deep fascia that extends into the pectoralis muscle. It is this anatomical architecture of deep fascia invaginating into the pectoralis major that contributes to cancer metastases. Because the breast is incompletely isolated due to continuity of deep fascia, even a radical mastectomy cannot guarantee arrest of metastases. This network of connective tissue fascia gives shape and support to the breast parenchyma. This network is commonly called the suspensory ligaments of Cooper. Cooper’s ligaments and epithelial tissue traverse breast adipose tissue which surrounds the lobules and attach the breast to the anterior chest wall. There is no anatomical isolation of breast lobules to protect the breast in disease states. Advanced breast cancer near the chest wall can even penetrate into the pectoral muscles.
When we speak of the breast parenchyma we are referring to the 15-20 independent glandular lobes found in each breast. Each lobe consists of several tubulo-acinar glands arranged bulbously at different depths in the breast. Each lobe has a single lactiferous duct that drains it on the surface of the nipple (mammary papilla). At the nipple each lactiferous duct dilates slightly forming a lactiferous sinus (a.k.a. lactiferous ampulla). Lobes are further organized into smaller lobules each containing alveoli and an intralobular terminal duct. These are the functional units of the breast ending in a terminal unit called the terminal duct lobular unit (TDLU), and its extralobular terminal duct. The terminal duct lobular unit is the site where most lesions of the breast originate and where milk production occurs. During lactation milk is conveyed from the TDLU by way of extralobular terminal ducts to the lactiferous ducts and sinus where a small amount can be stored. About eight mammary ducts open on the surface of the nipple.
The terminal ductal lobular unit consists of the extralobular terminal ducts (ETD) and the intralobular terminal ducts (ITD). The intralobular terminal ducts are at the end of the TDLU and contain the milk-producing acinus. Each lobule can contain up to 100 terminal ductules that contain acini. The terminal duct lobular units increase and decrease with hormonal periods such as menstruation, pregnancy, lactation, oral contraception, and hormone replacement. It is important to understand that most breast cancers originate in the TDLU. When cancer is confined to the TDLU it is called in situ and when it spread out of the TDLU it becomes invasive.
Each mammary gland is supplied blood by thoracic branches of the axillary arteries, and from the internal thoracic and intercostal arteries. Veins that drain the breast are seen along the periphery of the breast but form a complex network deep to the nipple. Drainage of the breast is into the axillary and internal thoracic veins. Lymphatic also drain the breast of excess intercellular fluid into the axillary region. Lymph vessels are found throughout the interlobular connective tissues and walls of the lactiferous ducts. Axillary nodes receive more than 75% of the lymph draining the gland. Most of the remainder of the lymph drains into the parasternal lymph nodes. Axillary nodes can often be seen on mammograms. They are generally kidney bean shaped and less than 2 cm in size. Abnormal nodes on a mammogram could indicate metastasis, lymphoma, even rheumatoid arthritis, or be caused by gold injections given to treat arthritis.
There are natural anatomical barriers that surround and protect the structural components of the breast. The skin, for example provides the outermost covering that protects underlying tissues from the external environment. Likewise the epidermis keeps moisture in and helps shape the breast. Deep to the skin a relatively weak capsule envelops glandular breast tissue to support the lobes and gives the breast its typical conical shape. This capsule has a natural defect in it called the foramen of Langer through which the axillary tail of Spence protrudes. Both lobes and the lobules are well encapsulated protecting the breast at all levels. The pectoral muscle and its fascia provide a posterior barrier for the breast. Loose connective tissue separates the breast from the protective fascia of the pectoral muscle; it is called the retromammary space. By far the strongest architectural barrier is the individual cell membranes of the cells of the breast parenchyma. The basement membrane lining each acinus is an important strong barrier that is not easily breached. Only aggressive cancers are able to breach the basement membrane of acini cells. A cancer that does not breach the basement membrane is called “in situ.”
Breast cancer most often originates in the lobules or in the ducts of the breast. Malignant disease that originates in a lobule or duct is an “in situ” cancer as long as it does not penetrate through the basement membrane. The transgression of the basement membrane is an important microscopic and biological sign that the lesion has evolved into an aggressive entity. To successfully contain the spread of an aggressive cancer an aggressive treatment regime is necessary. If not diagnosed and treated before breaching the basement membrane a malignant lesion will progressively advance through the relatively weak capsular barriers of the lobe and mammary apparatus, and finally through the more resilient barrier of the skin, or posteriorly through the pectoralis fascia into the pectoral muscle. At this stage the cancer is classified as a stage III cancer. Stage I breast disease is the earliest stage with no spread of the disease, while stage IV is the most advanced disease, with widespread involvement of other organs beyond the breast. Cancerous disease is classified according to tumor size (T), chain of lymph nodes involved (N), and whether or not the cancer has spread or metastasized (M). This is called the TNM classification system, which is used to stage a cancerous tumor as stage I, stage II, stage III, or stage IV.
To definitively diagnose breast cancer a biopsy of the lesion is performed. The tissue samples are preserved, stained, and viewed under a microscope by a pathologist who carefully studies the tissue, and if abnormal, assigns the tumor a grade. Grading also gives a more accurate prognosis and staging helps predict survivability. The lower the grade given to breast cancer at discovery the better the survivability, for example, stage I carcinoma in situ has a 98-100% five-year survival rate. Stage IV breast cancer, which implies distant metastasis remote from the breast has a 16% five-year survival. Intermediate stages have a 49 to 98% five-year survival rate. It should be noted that the five year survival is just another way of describing prognosis; it does not mean that one only has five years to live.
For the purpose of describing areas of the breast self-examination (BSE) and mammography imaging each breast is conventionally divided into four quadrants and the axillary tail. But before we describe these zones it is pertinent to discuss the importance of monthly breast self exam (BSE). The purpose of BSE is for a woman to become familiar with normal characteristics of her breast and to detect abnormal changes. But unfortunately many women do not know how to properly perform the self-exam. It is important that women ask their physician how to properly perform the exam. BSE should begin at age 20 and continue monthly throughout life. It should be performed about a week following menstruation when the breasts are not tender. During menstruation, hormonal changes make the breast more lumpy and swollen and may mimic abnormal findings. Postmenopausal women should perform the BSE on the same day each month since hormonal influences will be diminished in the absence of a cycle. For a more consistent comparison, women taking oral contraceptives should perform their BSE each month on the day that the first pill in a new package is taken.
When performing BSE there are several things that should be observed. A new lump or hard knot that does not shrink between menstruations should be noted and discussed with a physician. Skin change such as dimpling (indentation), nipple inversion, or change in the direction in which the nipple points should be noted. Any discharge from the nipple or ongoing tenderness should also be reported to your physician immediately. Some women falsely believe that because they are pregnant, or are getting an annual mammogram they do not need to perform the monthly breast self-exam. It is important to perform a monthly BSE since 10% of breast cancers are not detected on mammography. Likewise, fear of finding a lump is a primary reason some women do not perform BSE. Eighty percent of lumps found on BSE are not cancerous so you should feel at ease about reporting findings to your physician. In addition to the BSE you should have clinical breast exams and mammograms on schedule. Every young woman should be taught how to perform the breast self-exam. Below is a general description of how to do it, but you should check with your health care provider for instruction and a clinical breast exam. When performing the BSE it is important to have a general idea of the relative percents of lesions found in the breast.
The distribution of cancers by region are: posterior to the nipple – 34%; upper outer quadrant – 41%; upper inner quadrant – 14%; lower outer quadrant – 6%; lower inner quadrant – 5%. When performing the breast self-exam the patient should be taught to examine the upper outer quadrant and axillary tail, and the area posterior to the nipple very well since this is where most cancers are found.
When describing the location of a breast lump each breast can be subdivided into four quadrants: the upper outer quadrant (UOQ), upper inner quadrant (UIQ), lower outer quadrant (LOQ), and lower inner quadrant (LIQ). Each quadrant is further subdivided using the clock face model. The 12 o’clock position is above the nipple and the 6 o’clock position below the nipple. Care must be used when describing the location of a lesion in the right vs. the left breast since the 2 o’clock position in the left breast would be in the UOQ, but the 2 o’clock position in the right breast would be in the UIQ.
In addition to the breast self-examination, women over 40 should have an annual clinical breast examination (CBE). A qualified health care professional such as a physician, nurse, physician assistant, or mammographer performs the clinical breast examination. It involves a thorough visual and physical exam of each breast. The visual exam is to look for signs of breast cancer such as skin dimpling or scaliness, nipple discharge, skin irritation or thickening, ulceration, edema, color changes, nipple retraction, moles or keloids, or abnormal asymmetry of the breasts. The visual inspection is performed in good lighting so that color changes can be seen. The purpose of the physical exam is to locate any lumps within the breast. The entire breasts are examined including feeling for reactionary lymph nodes, especially those under the armpit and above the clavicle. Evaluating the lymph nodes is important since breast cancer is known to spread through the lymph nodes, especially those in the axillary region. A health professional is able to determine if lymph nodes are enlarged or firm, which the layperson may not be able to evaluate. If a lump is found it can be determined if it is attached to the skin or underlying tissues. Another important part of the CBE is that the clinician can teach the patient how to properly perform the self-examination. The proper way to physically examine the breast is to use the pads of the fingers in a circular motion from the nipple outward, or use vertical strip movements, or a wedge motion. The examiner will use light, medium and firm pressure during the assessment for lumps. Pressure by squeezing the nipple will reveal any abnormal discharge, and the color of the discharge noted when present.
Preparing for the Screening Mammogram
Unlike a hand x-ray or a chest x-ray, the mammogram preparation begins at scheduling when the patient is given specific instructions for preparing for the examination. It is normal for the breasts to be tender in the premenstrual cycle and following menses as water is retained due to hormonal fluctuations. Postmenstrual scheduling of the mammogram will reduce discomfort that may occur when compressing the breasts. It is best to schedule the mammogram for women who are not menopausal 5 to 7 days past the last day of menstrual flow.
The patient should be given specific instructions about what to wear and what to expect. The patient will need to remove all clothing from the waist up, so it is advisable to wear pants and a removable blouse. This way the patient will not feel completely exposed when the gown is partially removed for the mammogram. Patients should not use deodorant, perfume, or powders before the exam. These items can produce artifacts on the mammogram leading to misinterpretation. You can tell the patient to bring deodorant and perfume for after the exam if they are sensitive to personal body odor. A good patient history should reveal if they have special needs that may cause a longer study, or if they may need additional mammogram views. Any mammograms taken at another institution should be obtained prior to the appointment.
Although mammography has been performed for over thirty years, there are many questions about the procedure asked each day. Even healthcare workers and radiographers who do not perform mammography are often confused about the different mammography procedures. Even less general knowledge about adjunct procedures and test related to breast imaging is ubiquitously known among health professionals. Fear of the unknown causes many women in the screening age to avoid getting mammograms and this in some cases is unfortunate. It should be emphasized that the screening mammogram is used almost exclusively for asymptomatic patients beginning at age 40. Those with a family history of a first degree relative (e.g. mother, sister) should start annual screening beginning 10 years earlier than the age the first-degree relative was diagnosed with breast cancer. The diagnostic mammogram, which we will discuss later, is performed on a symptomatic or abnormal screening mammogram patient. A careful review of the individual’s risk factors and the physical exam performed by the physician is passed on the radiologist along with the mammogram. Most screening mammograms are performed because of age specific recommendation for annual screening. The goal of screening mammogram for an individual is to detect cancer in its early stage, which significantly increases chance of long-term survival. Annual screening finds small tumors in most of the screening population while they are still confined to the breast. Overall, annual screening accounts for about 61% of breast cancer survival statistics.
Approximately 11% of women in the United States who are currently age 20 will get breast cancer if they live to be 85 years of age. The good news is that mammography screening has detected 75% of malignant breast cancer in stage 0 (in situ) or stage 1. Furthermore, in an 18-year study involving 62,000 women there was a 23% lower mortality rate from breast cancer in patients who had a mammogram. About 10% of cancers are not seen with mammography but are palpable during the BSE or clinical breast exam. There are adjunct screening and diagnostic studies that can detect most of these lesions, for example, MRI, ultrasound, and biopsy. According the Breast Cancer Detection Demonstration Program (BCDDP) 20% of cancers were not detected by mammogram or physical exam, and 9% were only detected with physical exam. This means that the mammogram and physical exam are complimentary studies that need guidelines. We have already discussed the need and age specific recommendations for BSE and clinical breast exam.
There are many positive reasons to encourage women in the appropriate age and risk group to get a mammogram. The most important reason to encourage annual mammography is that there is no scientific incite to prevention of breast cancer. Therefore, our only recourse is to detect it early and treat it. We know that early stage breast cancer (stage 1) is locally confined to the breast. This gives treatment options like lumpectomy an advantage towards curing the disease. When we look at prognosis for all types of breast cancer we see that those carcinomas less than 1 cm at the time of diagnosis have a 12-year survival rate of 95%. Mammography, ultrasound, and MR imaging combined can detect nearly all of these lesions. Premenopausal women should begin their screening mammogram at age forty. The basis for this age recommendation is that breast cancer has been shown to grow faster in premenopausal women than in postmenopausal women. Unquestionably mammography has lowered the threshold for adjunct diagnostic testing and for invasive procedures such as biopsy. This in turn has increased the number of definitive diagnoses and early treatments of women with breast cancer and raised the long-term survival rate. Screening a large population of women is important since the larger the screening population the better are the overall statistical results seen. Breast screening has resulted in a 20-40 percent reduction of breast mortality in the 40-49 year old population over study control population.
A statistically significant reduction in breast mortality is related to three types of mammography procedures commonly performed in radiology departments. The most common types of mammograms are: screening mammogram, diagnostic mammogram, and stereotactic biopsy. In addition, ultrasound and magnetic resonance imaging (MRI) of the breast are also performed to increase sensitivity and specificity of breast imaging when needed.
The screening mammogram is a basic radiographic study to demonstrate all of the breast tissue with a minimum radiation dose to the breast. Screening mammogram should not be scheduled during menstruation or during lactation. This is because during these periods blood to glandular tissue is increased, and milk production is also increased. These two conditions cause more glandularity of the breast that reduces the effectiveness of mammography. Glandular tissue is dense and requires more radiation dose to penetrate it, which makes mammography during this time period less than ideal for screening. Glandular tissue predominate the breast of younger women whereas fatty tissue predominates in older women. The ratio of glandular to adipose tissue varies with age, hormonal changes, menopause, pregnancy and lactation. It is important to perform a diagnostic exam on a patient who is lactating or pregnant when the patient is symptomatic. Either an ultrasound or mammogram may provide information that is essential for diagnosis for these patients. An example would be a lump is noted in a mid-aged pregnant woman who has a history of cancer. But keep in mind that mammography is more accurate in postmenopausal women because the breast at menopause is mostly fat. Mammography for all age groups overall detects 90% of breast cancer in asymptomatic women. This may in part be due to the decrease in fibroglandular tissue that is replaced with fatty tissue as a woman ages. Mammography more accurately images the breast when it is fatty rather than heterogeneously dense. In fact, heterogeneously dense breast tissue lowers the sensitivity of mammography, especially in young women.
Two views are normally taken for the screening mammogram: the right and left craniocaudal (CC) views, and the right and left mediolateral oblique (MLO) views. The craniocaudal views are labeled on the radiograph as LCC for the left breast and RCC for the right breast. The mediolateral oblique views are labeled on each radiograph as RMLO for the right breast and LMLO for the left breast. The craniocaudal and mediolateral oblique views are at 90 degrees to each other and together should demonstrate all breast tissue.
Only two views are generally taken for the screening mammogram since the CC and MLO views will show all of the breast tissue. It is also desirable to keep the radiation dose low for screening exams since it is recommended across a large population. The American College of Radiology (ACR) recommends that the average glandular dose to the breast for screening mammogram be no greater than 0.3 rad (300 mrad or 3 mGy) when using a grid. For nongrid breast imaging the ACR recommends glandular dose be less than 0.1 rad (100 mrad or 1 mGy). The average dose to the breasts using modern mammogram equipment is only 0.1 to 0.2 rad per view. This is well within the acceptable limits for universal breast screening.
The Craniocaudal Projection
The craniocaudal projection is taken to demonstrate the medial, subareolar, central, and most of the lateral breast tissue. The primary area of the breast demonstrated by the CC view is the medial breast tissue. The central breast tissues and as much of the lateral tissue as possible should also be included. The pectoralis muscle is minimally demonstrated, and the nipple should be seen in profile. The CC view determines whether a lesion is medial or lateral to the nipple. It also determines a lesion's location relative to the nipple. There are several techniques the technologist use to demonstrate the maximum amount of breast tissue on the craniocaudal view. These include elevating the inframammary fold, pulling breast tissue away from the chest wall, properly compressing the breast, and perform lateral pull to demonstrate most of the lateral breast tissue. The inframammary fold is elevated superiorly towards the fixed border of the breast, and the image receptor is raised to the level of the inframammary fold. This reduces the distance the compression paddle must traverse resulting in less tissue displacement. Care should be taken not to elevate the breast higher than the inframammary fold because this may cause exclusion of inferior and posterior breast tissue, and the chest wall. If the image receptor is too low the superior and posterior tissue may be partially excluded. Next the technologist brings the breast away from the chest wall and lateral tissue towards the center. To pull the breast from the chest wall both hands are used in a technique called the “two-hand” technique. One hand holds the IMF the other hand pulls from across the top of the breast. During compression the hand is brought along the lateral tissue towards the nipple to smooth out any wrinkles that cause skin folds on the mammogram. Another technique to reduce skin folds is to externally rotate the humerus of the breast being imaged as the patient looks at the opposite breast and have the arm relaxed by the patient’s side. Turning the patient’s head towards the opposite breast also helps bring more breast tissue into the field of view. Optimal compression is applied so that the skin is taut. The patient is instructed to hold still and suspend breathing during the exposure. Using these techniques the pectoral muscle is seen in approximately 30 to 40 percent of CC views.
The Mediolateral Oblique Projection
A properly positioned mediolateral oblique (MLO) projection demonstrates from the pectoralis muscle to the nipple, the inframammary fold, and the nipple in profile, and the axillary portion of the breast. The main purpose of the MLO projection is to demonstrate the upper outer breast tissue. Most of the medial tissue is demonstrated; however, the CC view will better demonstrate all medial tissue. The MLO determines if a lesion is superior or inferior to the nipple and its relative distance posterior to the nipple. This view is especially important because it demonstrates more breast tissue than any other projection. When performing the MLO projection the x-ray tube is angled between 30 and 70 degrees directed from superomedially to inferolaterally. Short thick patients require a lesser tube angle, usually between 30 and 40 degrees. Tall thin patients require a steeper angle between 60 and 70 degrees, while for average patients 40-50 degrees is adequate. The tube is aligned parallel with the pectoral muscle and the image receptor. If the image receptor is not parallel to the pectoral muscle less breast tissue will be demonstrated. The inframammary fold should be openly demonstrated. The pectoral muscle should be seen below the posterior nipple line. Misalignment may cause more compression to be applied to the superior breast tissue than to the inferior breast tissue resulting in a more painful examination.
The positioning of each breast for the mammogram is critical especially when we consider that the size of a cancerous lesion at the time of diagnosis is an important prognostic factor. The American College of Radiology and the Food and Drug Administration recognize that the key to finding small lesions is to have consistently high-quality mammography images. Excluding any breast tissue from the composite field of view may eliminate the opportunity for early diagnosis of a curable breast lesion should it occur. It is especially important that the technologist includes the breast tissue close to the chest wall. A key measurement in determining whether or not all breast tissue is included using the MLO and CC views for the screening mammogram is to measure the posterior nipple line (PNL). Assuming a correctly positioned mediolateral oblique view, the first line is drawn along the anterior margin of the pectoral muscle. A second line perpendicular to it is drawn from the nipple to the muscle and measured. To determined if tissue is omitted on the CC view draw a line from the nipple to the back edge of the breast. To assure all breast tissue is included on the CC and MLO screening views the posterior nipple line of the CC view must be within 1cm of the measurement on the MLO view. It is not necessary to see the pectoral muscle on the CC view to make this determination. Remember, to maximally visualize tissue on the CC views the inframammary fold must be lifted and the breast close to the chest wall pulled forward. The MLO projection is slightly distorted showing overlapping of anterior structures of the breast. However, it is the single best projection to demonstrate the entire breast. The mediolateral (ML) view gives a true lateral of the breast, but it poorly demonstrates the posterior and lateral most portions of the breast.
The diagnostic mammogram is performed on a symptomatic patient, or because of an abnormal finding on a screening mammogram. Keep in mind that diagnostic mammography is recommended quite often because of the low sensitivity of screening mammography. Mammography is relatively good at detecting suspicious lesions in fatty breast tissue; however, it is not always accurate in dense breast tissue. Screening mammography is estimated to miss between 10 and 30 percent of cancers. With about 10 million at risk women in the United States between 1 and 3 million women may get a false-negative or false-positive result.
Let’s look at a clinical history that commonly indicates the typical need for a diagnostic mammogram. Case: A 40-year-old woman had her first mammogram 5 months ago, which was normal. She now presents with a focal lump in her right breast but does not experience pain. Her physician explained to her that the best course of action is to follow the lump for 2 or 3 menstrual cycles. Experiencing a lump is not uncommon in the premenopausal period and when found most likely represents a benign cyst. The screening mammogram was normal so the radiologist recommended a diagnostic mammogram at this time with a possible ultrasound of the breast to follow. The diagnostic mammogram was performed only on the symptomatic breast to determine if there is a circumscribed lesion corresponding to the palpated lump. The clinical physician provided a good clinical history to the radiologist to include location and approximate distance of the lump from the nipple (i.e. left breast, 5 o'clock 2 cm from nipple) and its size. A schematic of the breast showing the location of the suspected lesion should be provided to the technologist and the radiologist. All prior mammograms from various institutions should be made available to the institution performing the diagnostic mammogram.
The mammography technologist may conduct a detailed clinical history that will be given to the radiologist along with the imaging study. Some basic questions that may be asked includes how long has the lump been present and is it fixed or mobile? The radiographer may ask whether or not it changes size or texture with the menstrual cycle. Any pain or nipple discharge should also be reported. If the patient is known to have BRCA genes, or a first-degree sibling with breast or ovarian cancer, and other risk factors that information should also be conveyed. Any observed skin change (dimpling, bloody discharge, or nipple retraction) should also be indicated. Based on the clinical finding and risk factors the radiologist may request an ultrasound only, or a diagnostic mammogram and ultrasound. Generally, if the patient is over age 30 a diagnostic mammogram and ultrasound is performed. A patient under the age of 30 without risk factors for breast cancer an ultrasound exam only may be recommended. Some causes of a lump in patients like our example include fibroadenoma, cyst, abscess, hematoma, lipoma, hamartoma, phyllodes, and rare malignancy.
So just what is a diagnostic mammogram? This is basically a dedicated study of the affected breast with some additional imaging. The CC and MLO views are taken, sometimes with a BB placed on the skin over the suspected lump. This helps localize the lesion relative to positioning of the breast during imaging. In addition, spot compression and/or magnification views of a suspicious lesion may be taken. Magnification helps differentiate morphology of microcalcifications, can better show the margins of a mass when present, and to image biopsy specimens to prove the lesion (e.g. microcalcifications) is within the specimen. Magnification views are not used to routinely image the breast because the entire breast is not demonstrated. Also, magnification requires an increase in radiation exposure dose so it is not recommended for dense breast tissue.
Now let’s get back to our example of a patient who now presents with a palpable lump and a normal screening mammogram six months prior. The radiologist needs only to look at the symptomatic breast at this time. A dedicated mammogram of the affected breast will allow the radiologist to determine if the lump can be differentiated on radiographic images. If there is a demarcated lump it will be scrutinized to see if it is circumscribed with smooth margins or irregular with ill-defined or spiculated margins, and whether or not there are associated microcalcifications.
The technologist may make spot compression views of a local area of the breast. Spot compression uses a small compression plate or cone. This increases the effective pressure on the tissue being compressed resulting in better tissue separation to visualize the area. Spot compression shows the borders of a lesion in question better than standard mammogram views. Spot compression can be important in some cases because often questionable areas on standard mammogram images are proven to be normal tissue with spot compression. Likewise, abnormalities become more prominent and the borders of these lesions are better seen with spot compression.
Spot compression can be performed with or without magnification. Magnification gives a better evaluation of the margins and architectural characteristics of a focal mass. It also allows the radiologist to delineate the shape, number, and distribution of calcifications when present. When additional special views are requested following the screening mammogram eighty percent of recalls are subsequently reported benign or “probability” benign. These women are followed with routine screening mammography at 12 or 6-month intervals. Only 10% of recalled screening mammogram cases that need diagnostic mammography and biopsy prove to have cancer.
When the area of question is in the medial edge of the breast the technologist may perform a special view called the cleavage (valley view) view. When imaging each breast separately the medial tissue is pulled out of the field of view. The radiologist may see a questionable are on the MLO view that is not demonstrated on the CC view. The CC view is repeated with both breasts on the imaging plate so that the medial tissues of both breasts are demonstrated.
Sometimes the mammogram cannot definitively determine if a lump is solid or cystic. In such case an ultrasound exam of the mass may be performed to determine whether it is cystic or solid. There are strict criteria for diagnosing a cyst on ultrasound, which include: well-defined barely perceptible borders, completely anechoic, and posterior acoustic enhancement. If a lesion does not meet the criteria for a cyst, the radiologist usually recommends aspiration or core needle biopsy (if solid).
Biopsy of a suspected lesion is recommended in some cases such as when the breast tissue is radiographically dense, even when the mammogram and ultrasound results are negative. This is because about 13% of cancers in dense breast tissue are not seen on mammogram. Ultrasound imaging is an extremely important adjunct study for diagnosing some types of lesions in dense breast tissue. Ultrasound statistically finds about 84% of these cancers missed on mammography alone. Combined mammography and ultrasound is about 99% accurate; however, the risk of breast cancer with negative results following this type of work-up is unfortunately between 1 and 2.4%.
Diagnostic Ultrasound of the Breast
Adjunct studies of the breast include ultrasound, magnetic resonance imaging, computed tomography, and breast biopsy. The need for additional diagnostic work-up is due to the reported sensitivity and specificity for mammography. It is reported that mammography has a sensitivity of 60-90% and specificity of 10-40% owing to its low sensitivity with dense tissue. When mammography identifies a cancerous lesion it often underestimates the extent of disease. Using all known detection and treatments available the average long-term survival with early detection is about 84%; the long-term survival for local carcinoma is about 97%, and for distant metastasis-27%. The goal is to improve detection using adjunct high sensitivity imaging protocols to impact a greater long-term survival. Some breast lumps may be examined with ultrasound as an adjunct to the diagnostic mammogram. Ultrasound is an especially important diagnostic study since it can determine if a mass is a cyst or is a solid tumor. Ultrasound can also determine the presence or absence of those microcalcifications associated with some types of cancers. It is not uncommon to find a cyst on the mammogram and confirm it with ultrasound. Cysts may occur during the menstrual cycle and more often towards the end of the cycle. So mammography is recommended 5-7 days after the last day of menses. In approximately 7-16% of women under the age of 30 simple cysts called fibroadenomas occur. Because cysts are benign it is important to diagnose them using strict ultrasound diagnostic criteria. A cyst will have well-defined hardly perceptible wall and be completely anechoic (no internal echoes); through transmission. Posterior acoustic enhancement is also seen from the cyst. Cysts may be painful, but they usually self-resolve requiring no immediate treatment. Persistent pain from a cyst can be relieved by aspirating the fluid is most cases. When the lesion on ultrasound does not appear to be a cyst, aspiration or core needle biopsy of a solid mass is recommended.
Cysts and solid lesions are difficult to differentiate on mammography alone, especially well-circumscribed mammographic densities. Benign lymph nodes that have fat in the node hilum can produce a characteristic central echogenic center. Oil cysts are hypoechoic and have poor sound transmission. Lymphomas are generally hypoechoic, and lipomas are difficult to differentiate as they provide little to no contrast with surrounding tissue. Mammography along with ultrasound is proven beneficial in individuals over age 30 with a small palpable lump because small calcifications are not easily seen on screening with ultrasound only.
Localized breast ultrasound can be performed on women under the age of thirty to assess for fibroadenoma or abscess. This eliminates radiation exposure of the breast in young women with low probability for malignancy. Fibroadenomas are hypoechoic oval lesions that are well circumscribed. Abscesses are usually seen in lactating women and respond to antibiotic treatment and rare cases may need draining. The ultrasound characteristic of an abscess is a complex hypoechoic and hyperechoic quality image. While ultrasound alone may be a good diagnostic approach to a single painful lump in women under 30 it may not be sufficient for women over 30. A palpable lump in the over 30 age group should have both a diagnostic mammogram (affected breast only) and a targeted ultrasound. This is because the diagnostic differential in the over 30 age group include: abscess, fibroadenoma, cysts, lipoma, hematoma, phyllodes, and malignancy.
Breast biopsy has lead to a significant increase in detecting and diagnosing small and impalpable breast lesions. Breast biopsy is part of the triad of patient care that includes clinical examination, mammogram and adjunct breast screening, and histopathological diagnosis of lesions leading to appropriate treatment planning and patient counseling. The decision to perform a biopsy of a mass can be a frightening experience for the patient; however, it should be noted that biopsy is the only way to get a definitive diagnosis of a suspected malignant mass. According to MGH statistics between 1978 and 1988 for 3,000 biopsies performed, 25% were malignant (positive predictive value of 25%). Biopsy of a breast mass is recommended for certain types of lesions that are seen on mammography, and most solid ultrasound masses. There are four common types of biopsies of that are performed: stereotactic, fine needle aspiration, core biopsy, and excisional biopsy.
Stereotactic breast biopsy refers to using techniques that give spatial localization of the lesion when taking samples of nonpalpable or indistinct breast lesions. Stereotactic techniques evolved in an effort to accommodate breast conservative and minimally invasive surgery strategies. Because of new current biopsy techniques complete surgical excision of normal breast lumps has significantly declined. Imagine having a large surgical breast incision and excision of breast tissue only to discover it is normal. Biopsy techniques such as stereotactic and fine needle aspiration (FNA) have eliminated these procedures. More than a million breast biopsies have been performed in the United States alone; only 30% of these carefully decided biopsies prove malignant. Nearly 70% of these biopsies were spared surgical excision for nonmalignant mammographic abnormalities. Needle biopsy also reduces breast disfigurement and is relatively nontraumatic.
To understand why we get from a screening mammogram to a biopsy let’s look at a case example. This person had a screening mammogram in which both breast were imaged in the MLO and CC projections. A cluster of microcalcifications in the superior right breast was noted and spot magnification views recommended.
The point here is that these microcalcifications must be evaluated and a confident diagnosis made. In this case these microcalcifications are indeterminate and a definitive diagnosis can only be made by histological examination of breast tissue containing the microcalcifications. Stereotactic localization of a breast mass uses computerized stereo equipment to localize and take core or FNA tissue samples. The computer calculates the XYZ coordinates of the lesion so that exact needle placement can be made. Once the lesion is localized fine needle aspiration or core biopsy is performed. Fine needle aspiration withdraws some cellular material from the site in question for cytological analysis. Core biopsy removes a larger sample of affected tissue than does FNA. An 11 to 14 gauge needle is used to take tissue samples. Some types of core biopsy techniques are the Minimally Invasive Breast Biopsy (MIBB, Vacuum Assisted Core Biopsy VACB, and Advanced Breast Biopsy Instrumentation (ABBI).
When placing the localizing needle into a lesion, for biopsy, the parallel approach is commonly used. Using this technique a second needle is placed approaching from parallel to the chest wall. Two views are used to localize the lesion, the CC view to measure the distance from the lesion to the lateral or medial skin surface. Then a second film is made 90 degrees to the CC view (in either the medial or lateral breast surface to the image receptor) to measure the distance from the lesion to the inferior or superior skin surface. So, a lesion seen at the top or bottom of the breast on a 90 degree lateral view is localized using the caudocranial projection. A lesion close to the lateral surface in the CC view is localized in the 90 degree true lateral projection. Orthogonal views are one of the best and most accurate ways to position a needle for preoperative localization.
Breast tissue called a specimen is removed during a biopsy. A radiograph of the specimen is obtained to assure the suspicious tissue is removed and margins are clean. Specimens are stained and examined under a microscope by a pathologist to determine the pathology of the specimen. To reduce tissue thickness and improve contrast compression magnification radiography is used.
Once the specimen is returned to the pathology laboratory it is stained and viewed by a pathologist who will give the definitive diagnosis. This diagnosis is important to treatment planning and prognosis for a newly discovered carcinoma. Some examples of breast pathology will be shown below, but first we should look at the normal presentation of breast tissue.
Excisional/Incisional Surgical Biopsy
Traditional open surgical biopsy is the method that has been used for many years before techniques like vacuum-assisted, Mammotome (MIBB), or core needle biopsy. It remains the gold standard to which other methods of breast biopsies are compared. Excisional and incisional biopsy is a surgical procedure in which an incision of 1 to 2 inch is made in the breast. During the excisional biopsy the surgeon attempts to remove all of the mass and some of the surrounding normal tissue during the procedure. Incisional biopsy only removes a portion of the lesion. These procedures are conservative relative to a mastectomy.
Often the lesion is not palpable and the surgeon will use mammography to help locate it as the radiologist marks the area with a wire marker. This is called “needle” or “wire” localization. During the mammogram the radiologist uses a hook wire system placed in the area of the lesion to localize it for the surgical biopsy. A hook in the distal end of the wire within the breast allows it to stay in place until the surgical procedure is complete. Mammography can be used to place the wire or ultrasound can be used. Consider the following procedure in which a hook wire is placed in the breast close to the lesion so that an excisional biopsy can be performed.
Breast MR imaging (MRI) is now on the forefront of early breast detection. The most important purpose of doing breast MRI is to find breast cancer and to determine its extent. It started in the late 1980’s in the United States and Germany. Then with the silicone breast implant concerns MR breast imaging began to become an important diagnostic tool. Improvements in hardware and software have enabled MR imaging to detect lesions not seen on conventional mammography. Remember, conventional mammography can show up to 90% of breast lesions early. Breast MRI has a sensitivity of 95-100% and specificity of 80-95% for all invasive carcinomas. MRI can differentiate some stages of DCIS demonstrating some 50-90% of cases. The down side is that MRI can sometimes miss lobular carcinoma. The negative predictive value for MRI approaches 100% for lesions 3mm or larger. Another important development for breast screening using MRI is its ability to diagnose breast tissue in the augmented breast (implants). There are some important statistics that are boosting MRI technology into the diagnostic arena and may soon make MRI the new definitive study for detection, treatment, and prognosis prediction. Recent studies overwhelmingly suggest that some occult malignant tumors not seen on conventional mammography can only be detected by magnetic resonance imaging.
One of the most important studies that prompted all this talk about breast MR imaging as the definitive study for breast cancer is a study conducted on some 696 women diagnosed with unilateral breast cancer. This study reported in the March 2007 edition of the New England Journal of medicine discussed a finding of 33 of 969 patients with unilateral breast cancer were found to have bilateral breast cancer as detected by MRI alone. Here’s the important part of the study, all women in the study had no detected lesion in the contralateral breast using conventional mammography. However, magnetic resonance imaging of the contralateral breast of 30 women with unilateral breast cancer were confirmed to have cancerous lesion(s) not previously detected. These finding were cohobated by a study published in Radiology, 2007 of missed occult multifocal or multicentric cancer in 22 of 118 study patients. The sensitivity and specificity for finding occult cancer with MRI in newly diagnosed breast cancer patients is 100, 94 percent respectively (100% negative predictive value). Multicentric breast cancers are multiple cancers that form separately from one another and often develop in different quadrants of the breast. Multifocal breast cancers are more than one tumor from one original source is called multifocal. These are usually found in the same quadrant. This has led to a new recommendation that women with newly discovered unilateral breast lesion with conventional mammography undergo breast MR imaging of the contralateral breast prior to treatment. MRI is superior to mammography and ultrasound in diagnosing multifocal, multicentric, and bilateral disease, and assessing size and extent of breast disease when discovered.
A study was conducted by the American College of Radiology Imaging Network (ACRIN) trial and published in the March 2007 edition of the New England Journal of Medicine to determine the sensitivity and specificity of MRI breast imaging. This was an extensive project covering 25 medical centers. Its primary goal was to accurately determine the sensitivity and specificity of MR breast imaging. The study concluded breast MRI has a sensitivity of 91% and specificity of 88%. These are impressive figures for any diagnostic imaging study and can be attributed to the ability of MR imaging to acquire data at millimeter thin slices. Conventional mammography acquires images in full field bulk beam, sometimes through dense breast tissue. MR also offers features not possible with mammography like contrast enhancement, fat suppression, and 3D imaging.
The main issues with MR imaging of the breast are to: determine clinical parameters that produce maximum MRI effectiveness, recognize technical factors that increase specificity and reduce false-positive scans, and determine what indicators should be standardized for MR imaging. Breast MR imaging has proven to be a superior diagnostic protocol than clinical breast exam and mammography in high risk individuals. There are still many clinical questions that need to be answered before breast MRI can become primary screening tool. Currently it is an adjunct to mammography. One of the main issues with breast MRI is what are the most beneficial results applicable to setting guideline for its use? Certainly, there are false-positives associated with MRI, and this leads to additional imaging and often successive negative biopsies. The false-negative rate for breast MR imaging is currently unknown. It seems MR imaging is setting the pace as an adjunct breast imaging tool because it can help surgeons avoid unnecessary biopsies, or can differentiate cases that may benefit from a lumpectomy vs. mastectomy. Since MR imaging is more sensitive than mammography, biopsy is not needed following a negative MRI study.
In the last two years MRI technology has made drastic improvements and continues to get better. Four important requirements have made MR imaging effective:
It is a standard that MR imaging must likewise identify any lesion seen on conventional mammography. MRI would not be useful if some tumors seen on mammogram were not seen on MRI. There is continuity in diagnosis from mammography to MRI, but not all lesions seen on MRI are identified on mammography, which gives MRI an advantage over mammogram. MRI is used as an adjunct to mammography rather than as a screening tool. MRI breast screening is recommended in some populations, such as young women that are not in the mammogram screening age, yet known to have a high risk for breast cancer. The American Cancer Society recently recommended the breast MRI and mammography be performed on high risk young patients under the recommended screening age. A duel study is recommended because the increased sensitivity of MRI may cause false-positives in these patients. This results in negative biopsy, which could be lowered when mammography is also performed.
Research is currently underway to study the need to perform MRI of the opposite breast of patients with unilateral breast cancer on mammogram. The American Cancer Society now recommends magnetic resonance imaging of the breast and opposite breast when mammogram proves unilateral carcinoma. Because of the sensitivity of MRI it can differentiate a single focus carcinoma on mammogram that is in fact multi-focal. This is important because surgical treatment of multi-focal tumors requires mastectomy (breast removal). Single tumors can in some cases be treated with a lumpectomy, which is a breast conserving surgery. In both cases MR imaging is used to monitor the breast following lumpectomy or mastectomy. Scar tissue or lymph nodes can sometimes be palpated by the patient and raise false alarm as to the recurrence of cancer. MRI can differentiate scar from recurrence of cancer.
MR imaging is also an important tool to determine if breast cancer has spread into the chest wall. Finding a cancer that has breach the breast lobule and traversed the retromammary space to enter the chest wall requires chemotherapy and radiation therapy. In many cases chemotherapy is initiated prior to mastectomy, which is also required to increase survival. If the cancer is discovered to have spread to the chest wall after surgery the patient will need to undergo radiation therapy as well. Another important use of MRI is to better visualize the augmented breast. Breast implants have received a lot of attention over the last 10 or so years about concerns of leakage. In most cases MR imaging can distinguish a leaking implant from surrounding tissue scarring. An additional benefit of MR imaging of the breast with an implant is that breast tissue is also evaluated. Contrast enhancement is not needed to evaluate breast implant integrity. The sensitivity and specificity of MRI for implant leakage is 94 and 97 percent, respectively.
Breast MRI uses intravenous contrast agent gadolinium to image the breast. Using intravenous contrast increases the sensitivity of MRI. Normal breast tissue takes up gadolinium differently than do abnormal breast lesions, and normal and abnormal breast tissues are influenced by estrogen levels. This is related to the menstrual cycle and hormone replacement therapy. Before scheduling a breast MRI the ordering physician should consult with the radiologist. Many factors will influence the effectiveness of the study because gadolinium is used. For example, gadolinium used to image post biopsy or post surgery will linger in the breast up to 1 year, and up to 2 years when radiation therapy has been performed. In pre-biopsy and pre-surgical patients the optimal time to perform breast MRI is between days 5-15 of the menstrual cycle.
Breast MR imaging is performed with the patient prone using dedicated bilateral surface coils. These coils are usually receive only but can be transmit/receive coils. MR images are taken in a variety of formats among them are sagittal fat-suppression T2 weighted images, unenhanced fat-suppressed T1 images, and sagittal fat-suppressed T1 weighted images. Other features of MR imaging include automated functions like image registration, multiplanar reformatting, subtractions, angiogenesis maps, curves, maximum intensity projections (MIPS), and volume summaries. Staging MR imaging is routinely performed on patient’s with known breast cancer to determine the extent of the disease. Let’s look at such a case in the images that follow. On the average one breast MRI study generates 1,000 to 4,000 images, which significantly adds value beyond the 2 view screening mammogram. The radiologist also can use computer aided detection (CAD) software that augments post processing and interpretation of images. CAD is proven to reduce interpretation time, improve interpretation accuracy, help detect small cancers, and reduce false positives associated with widespread MR imaging. MRI can for example detect occult high grade DCIS missed on mammography even though it can present as a benign look alike on scan images.
We hear a lot about CAD in terms of mammography; however, CAD when referenced to MRI is not a computer software system that provides a second reading of the study. What CAD-MRI does is provides the radiologist with additional tools that analyze enhancement kinetics of malignancy. It improves detection in the initial reading of the MRI scan through lesion detection and differentiation and lesion kinetics qualification. One of the most important indicators of malignancy using contrast enhanced breast MR imaging is the “wash in, progression, and wash out times.” Contrast enhancement peaks at about 90-120 seconds, which is the wash in time. How long it takes to disperse or its pattern of dispersal is the washout time.
The function of CAD is to compare image pixel(s) in the pre and post contrast phases and assigning a value. The threshold enhancement is a term meaning pixel value meets the diagnostic criterion of being above minimum 50 or 100 percent threshold. Either 50 or 100 percent threshold can be set by the diagnostician interpreting the study (radiologist). CAD uses color imaging to reflect threshold enhancement. Pixels are colored red when delayed post contrast tumor enhancement decreases by 10% during washout phase. Fast washout is characteristic of malignant cancerous tissues. This because increased vascularity allows contrast to rapidly be removed by the blood causing a rapid decrease in enhancement. If delayed post contrast pixels increase by 10% it is termed “washin” and CAD will color them blue. Delayed post contrast emptying by tissues is normal because the blood vessels draining normal tissue is not increased. Blue is characteristic of benign processes, but keep in mind that at least 6% of malignant tumors exhibit wash in, progression and washout Type I kinetics of benign growth and are colored blue. It is these undifferentiated malignant tumors that have the same enhancement kinetics as benign tissue is what lowers the specificity of MRI. However, the sensitivity is not affected since the tumor is demonstrated, but must be evaluated by its morphology in addition to its kinetics. It is this type of scenario that concludes that the morphology of a lesion must also be considered rather than relying on CAD imagery alone. Some lesions present with a stable pattern of enhancement kinetics that rapidly rise and then reaches a plateau. CAD colors these regions yellow (green on some CAD systems) to indicate they are possibly benign or early malignant, called intermediate or indeterminate. These lesions are indeterminate and are often biopsied or monitored with a follow-up scan at relatively short intervals (3-6 months). The ability to detect breast lesions using CAD is shown in the two tables below:
The statistical ability to detect breast lesions using magnetic resonance imaging with CAD is shown in the two tables below:
CAD is able to locate foci within a lesion when there is significant enhancement as well as detect any suspicious washout curve patterns within foci. It also corrects for motion that may cause artifact in the enhancement curves. The enhancement kinetics of tumors using CAD is as follows: rapid early enhancement that continues to progress exhibit Type I enhancement kinetics and are considered benign. Tissue having Type I kinetics is colored blue with CAD. An area displaying rapid early enhancement that levels off or plateaus has Type II kinetics. The pathology of a Type II lesion is indeterminate; CAD colors these lesions yellow (some CAD programs use green). A tumor or area with Type III kinetics will have rapid “wash in” and rapid washout of contrast. Type III kinetics within a tumor is colored red to indicate an area of cancerous growth. Type III kinetics is seen in 60% of cancers making all Type III tumors suspicious and should be further evaluated with biopsy. Kinetic assessment of tumors seen on MRI is a basic part of the imaging profile along with tumor morphology assessment. Enhancement kinetics alone is not a conclusive standard for evaluating MRI displayed tumors. The basis for this is that at least 6% of malignant tumors display Type I enhancement kinetics. The caution here is for the radiologist to weigh each tumor’s enhancement kinetics against strict morphology standards. About 34% of Type II enhancement kinetic tumors are found to be malignant at biopsy, and 60% of Type III proves malignant at biopsy. What we have learned from using CAD in MR breast imaging diagnosis is that it is not the ultimate diagnostic tool because of the statistical overlap between malignant and benign tumor kinetics. But when buffered with morphological analysis and radiologist experience even what appears to be a benign tumor can be diagnosed when it is small. Diagnosis therefore should error in favor of biopsy or short interval follow-up imaging for morphologically suspicious Type I and Type II tumors. This will help insure the patient suffers no adverse consequence of an under read MRI.
In order to complete an MRI assessment of a lesion both the kinetics of enhancement and morphology of the lesion must be evaluated. The progression of contrast enhancement, plateau, and washout is evaluated. Morphology evaluation considers the shape of the tumor (round, oval, lobulated, irregular, stellate, etc.) and discriminates its architectural margins (smooth vs. speculated). Those lesions that are smooth have a 95% negative predictive value and those that are speculated have a 90% positive predictive value. Remember the negative predictive value of a test is the probability that the patient will not have the disease. The positive predictive value is the probability that the patient has the disease. This leads us to an important point about breast MR imaging. Occasionally a suspicious lesion on mammogram or ultrasound is registered as Type I benign with CAD. It is important to note that MRI does NOT override suspicious findings on mammography in these cases and the lesions must be confirmed by biopsy.
The angiogenesis character of the breast can also be used to evaluate malignant tumors. Most malignant tumors are unable to grow more than 2-3mm without promoting angiogenesis activity to supply blood and nutrients. This allows us to study angiogenesis related to a tumor to help characterize tumors as potentially benign or potentially malignant. In other words, tumor growth is mediated by angiogenesis, which is demonstrated on MR images. Being vascular rich, most malignant tumors show at least a 70% enhancement in the first 1 or 2 minutes. It is this property of high grade tumors (neovascularity) that causes rapid washout we see with CAD. Rapid wash in and rapid washout is one of the main factors that differentiate malignant tumors from benign process.
Another important feature of MR imaging the ability to perform subtraction contrast studies. It is important that subtraction imaging be performed on MR images as part of the protocol for breast imaging. It is preferred that subtraction images are “registered” in the background of the scan parameters to increase accuracy and throughput. Most radiologic technologists are familiar with the concept of subtraction imaging. Subtraction is commonly performed in interventional radiology imaging. MR imaging software is also capable of subtraction; however, it is very important that the software is able to register subtraction images. Registration correction is a process of compensating for image motion resulting from pre and post subtraction images being out of phase. This is important because the final subtraction MR image displayed is the result of subtracting the pre-contrast image from the post-contrast image. To do this effectively the two images must be superimposed much like a subtraction mask in interventional angiographic imaging. The problem for MR imaging is that sometimes patient motion artifact occurs in some slices. A mere 2 mm motion shift creates partial volume artifact between the pre and post contrast scans. When the subtraction is unregistered the resulting image may present artifacts that require the radiologist to some images slowing throughput and reducing diagnostic accuracy (false positives). For example, the size of a tumor may be overestimated, or false skin thickening reported causing the patient unnecessary skin biopsy. It is important that the pre and post contrast images are superimposed even when motion artifact occurs, which is what registration does. Consider the diagram below:
Breast MRI is an excellent modality for imaging the breast. It is currently used to image high risk young patients, and both breasts of those diagnosed with ipsilateral breast cancer. It is better diagnostic study for breast implant leak and breast tissue than conventional mammography with displacement views. Currently there are is not a consensus on when MRI should be used as a screening tool, however, it is being recommended by the American Cancer Society for women below the screening age for mammography with high risk for breast cancer (such as BRCA genes, sibling with breast cancer, etc). There is consensus that when cancer is found in one breast both should be imaged with MRI to evaluate the extent of the disease.
Digital Mammography and Digital Breast Tomosynthesis
It is proposed by many radiologists that the time has come to replace film-screen mammography imaging with digital mammography universally throughout all imaging centers. So it is appropriate to discuss digital mammography in this context. The leading point of view on digital mammography comes from results of the Digital Mammographic Imaging Screening Trial (DMIST). This study accepted some 49,528 women of which 42,760 among 33 centers were included in the analytical data. The lag in requiring all imaging centers to convert to digital mammography is in part due to the findings that there was no difference in the performance of screen-film and digital mammography for the population. The standard was the area under the receiver operating characteristic curve (AUC). The receiver operating characteristic curve uses a binary classifier system while discrimination threshold is varied. But for our purposes it can be understood to mean a graphic plot of true positives rate (TPR) vs. false positive rate (FPR). So in the study there was a comparison of TPR and FPR as the criterion varied. The study compared digital and screen-film mammographic imaging. Part of the argument for raising the mammographic imaging standard to digital mammography only is based on these findings. The DMIST study showed digital mammography is significantly superior in women younger than 50 years of age, pre and post menopausal women, and women with heterogeneously dense breast tissue. It is important to understand that the study showed an improvement in sensitivity within these three subsets, but did not show differences in specificity. The argument either for or against pressing the FDA to adapt digital imaging as the mammography standard requires further investigation beyond the DMIST study. What needs to be included in study data is correlation of DMIST data to show significance in the performance digital vs. film-screen mammography in younger vs. older women. The extended study must address whether there is significance in comparison of dense breast vs. fatty breast tissue. Clearly, studies have been directed towards analysis of digital mammography of dense breast tissue and poor data regarding its performance on fatty breast compared to film imaging. Likewise manufacturers have tried to solve algorithm issues that promote accurate view of dense breast. Improvements are therefore reflected in digital imaging of dense breast. We already know that film screen imaging of dense breast tissue is problematic in some cases.
A new procedure that is currently only performed at research institutions that is a benefit of digital imaging is tomosynthesis. Tomosynthesis is a term used to describe a breast imaging technique that combines digital mammography and tomography. Thin slice (one millimeter) images through the breast are made. This allows the radiologist to view single slice images much like CT or MRI, or view them as a cine loop. Tomosynthesis is to mammography as a chest CT is to a chest x-ray. X-rays are used in tomosynthesis to produce 3-D images of the breast. Its main advantage is its similarity to CT in which slices through breast tissue eliminates the problem with overlying tissue. This is especially important when evaluating a small suspicious lesion typically seen with conventional mammography. Tomosynthesis can provide a look at the lesion in multiple thin slices giving a diagnostic edge to the radiologist. The main advantage of tomosynthesis is its ability to eliminate the problem with overlying tissue that causes uncertainty when viewing suspicious areas for lesions with conventional mammography. Recent research conducted at Dartmouth Hitchcock Medical Center/Dartmouth Medical School in Lebanon, New Hampshire, under the direction of Steven Paplack, M.D. concluded “tomosynthesis may decrease false-positive screening mammography findings by half.” This is great news for radiologists, mammographers, and especially patients, because false-positive screening studies often causes the patient to undergo addition diagnostic imaging, and possibly biopsy. The Dartmouth study is an important study because it looked at 98 women who had been recalled for a diagnostic mammogram because of an abnormal screening mammogram. Within the study population radiologists reported 112 abnormal findings on screening mammograms. The Dartmouth study concluded that 40% of the women would not undergo diagnostic mammography if tomosynthesis alone were used as the initial screening exam. Tomosynthesis was considered superior to the screening mammogram in about 88% of the women. Dr Paplack pointed out that with tomosynthesis radiologists are building on their expertise in reading mammograms while the technology greatly improves initial breast screening. Currently tomosynthesis has not been compared to MRI in the context of adequacy as a screening tool for high risk patients. Look for this imaging tool in the near future as well as digital mammography becoming the FDA standard for screening mammography.
Molecular imaging is of great importance for those diagnosed with metastatic breast cancer. This is because bone is the most common site of breast cancer metastasis. Bone metastasis occurs in up to 70% of patients with advanced breast cancer. In the past bone scintigraphy using technetium-99m-labeled diphosphonates has been the standard. Other adjunct imaging parameters may include plain films, computed tomography, magnetic resonance imaging, and positron emission tomography (PET). Bone imaging related to metastasis is one of the most problematic areas in diagnostic imaging. This is because bone lesions can be osteoblastic, osteolytic, or mixed, as such can be secondary to either benign etiology or to malignancy. Until hybrid single-photon emission computed tomography (SPECT-CT) the diagnosis of bone metastasis was based on direct anatomical correlation using CT, or indirect measurement of bone or tumor metabolism using SPECT, both had poor specificity. Furthermore, the response of bone metastasis to medical treatments using SPECT and CT is difficult to measure accurately. Another problem with bone imaging is that when osteoblastic bone disease is treated successfully nuclear imaging most often shows positive for ongoing osteoblastic disease. The result is that molecular imaging is unreliable and unsuitable for treatment evaluation. This inadequacy is simply devastating for patients because they are often excluded from experimental drugs and therapies approved for clinical trials because measuring outcomes is poor. It is known that the solution is to design a technology that fuses radioisotope scanning and anatomical correlation provided by CT to diagnose and measure remission of solid bone tumors.
The future of molecular medicine is now here in the form of hybrid SPECT-CT technology. SPECT provides functional a functional study where as CT provides the anatomical correlation. Together as a hybrid study (function and anatomy) SPECT and CT are coregistered into high quality diagnostic images. Coregistration provides more information, according to those who use this technology that the two studies separately performed and evaluated. Keep in mind that this technology is so new that clinical diagnostic applications are evolving and terminology related to the discipline. One of the primary reasons to perform a nuclear scan is to determine whether or not metastasis has occurred and to locate secondary sites. SPECT guided CT is an important tool in evaluating foci of increased bone metabolism in breast cancer patients. This is important in the planning of surgical, chemotherapeutic and radiation therapy treatments early. The problem with SPECT scintigraphy alone is that there are many instances when a focus of increased isotope uptake is indeterminate because of inadequate anatomical correlation. One recent study found that SPECT guided CT was able to clarify more than 90% of SPECT studies that were initially indeterminate. The results showed that three specific diagnoses can be given with accuracy: definitely benign, definitely malignant, and indeterminate. Only 4% of the cases were reassigned indeterminate based on SPECT-CT imaging. This considerably lowers the diagnostic and planning time for cancer patients. The specificity of SPECT is low and not sufficiently reliable for diagnosis in all cases. This is because degenerative processes also uptake radioisotope and in tiny areas of bone (for example, facets), can confound the exact location of lesions.
Most breast cancer patients have predominately osteolytic bone lesions ((80-85%), and 15-20% have predominantly osteoblastic lesions. To understand why this is significant it is important to remember that bone formation and bone metabolism are natural parts of human physiology. Think of it this way, bone stores calcium that the body needs and degrades bone to release calcium stores during bone homeostasis. Cells called osteoclast reabsorb bone to release calcium and osteoblast build bone adding calcium to it to help make bone hard. Breast cancer cells produce factors that induce formation of osteoclast. Bone cancer cells also produce factors that suppress the activity of osteoblast. So breast cancer cells promote bone destruction, a lytic process, and suppress bone formation, an osteoblastic process. What breast cancer cells get for this disturbance is growth factors in bone that promote tumor growth. It’s a vicious and difficult cycle to break the tumor burden and to measure progress radiographically. Therefore, molecular imaging is the best current model advancing us towards this goal. Keep in mind that there is a similar mechanism that causes osteoblastic metastasis, and mixture of osteoblastic and osteolytic metastasis. It is beyond the scope of the module to investigate molecular imaging in all of these scenarios.
Computed tomography (CT scans) are not used routinely to evaluate the breast. Occasionally a CT scan is performed along with biopsy of the anterior chest wall or for tissue deep in the axilla. For some large breast cancers it is possible in some cases to assess whether the cancer is removable by mastectomy or inoperable because it has moved into the chest wall. CT is routinely used to evaluate lymph nodes, lungs, liver, brain, spine, or other areas searching for metastatic disease. When metastasis is found, CT scans to include the head, chest, and abdomen can assess the extent of metastatic disease prior to treatment. CT scans are also used periodically during treatment to evaluate response, but are not as effective as hybrid PET/CT imaging. Sometimes a chest or abdomen CT study identifies primary breast cancer. At times, secondary metastasis is seen and the physician must work backwards to find the primary cancer. CT is also useful in staging cancer and evaluating remote organ seeding and lymph node involvement. Now let’s look at some examples of how CT is used in the diagnosis and staging of breast cancer.
Additional Breast Pathologies
Cyst is a term for a fluid filled sac. In the breast these can sometimes become large, tender and painful, usually just before menstruation. Most cysts are benign and are most commonly found in women between the ages of 35-50. A lump that could potentially be a cyst must be differentiated from other causes of lumpiness. When a lump is found on breast self examination or clinical breast examination a mammogram or ultrasound should be performed. A persistent painful cyst can be aspirated (drained) with a needle. This usually relieves pain as the size diminishes.
The term “fibro” implies structural fibrous tissue and “adenoma” means glandular tissue. Being fibrous tissue they are not painful and are usually discovered on breast exam. The physical characteristics of a fibroadenoma are round, solid, rubbery, and movable. They are more common in African-Americans and women in their teens and early twenties and common during pregnancy and lactation. They are benign and do not develop into carcinoma.
A hard painless lump caused by dead degenerating fatty tissue is called fat necrosis. It is believed that this pathology is caused by injury to the breast that can be subtle and not noticed. Sometimes the only indicator of past trauma is a bruise in the skin overlying the lump. This is a benign condition.
Women who breast feed can sometimes get an acute infection, a condition called mastitis. The etiology of the condition is blockage of a duct during lactation; this causes pooling of milk and local inflammation. Progression of infection is due to bacterial invasion and resulting abscess. On touch the breast may be warm, tender, and lumpy.
This is a type of cyst that occurs during lactation. Galactocele can occur as a solitary lesion or as multiple cysts. The duct dilates and is filled with milk, and may present as a tender lump. Sometimes a galactocele may convert to an abscess formation or acute mastitis.
This is a complicated term that is applied to miscellany of conditions of the breast from benign to those with increased risk of carcinoma. The one common factor to the many morphological presentations of this disease is that lumps frequently are found in the breast. The term is applied to lesions composed of cysts, or overgrowth of the fibrous stroma, or lesions containing stromal and epithelial components, and so forth. The classification of fibrocystic changes is usually not clinically significant.
This is a type of fibroadenoma that grows large in size (can reach 15-20 cm). They can be benign or malignant. These tumors distort the breast producing bulges in the skin and can ulcerate. Just because these tumors may fungate through the skin does not make them malignant. Rapid growth is a sign of high probability of malignancy; however, the cytological atypia will determine if it is malignant or benign.
This is a neoplastic papillary growth that occurs within a duct. They occur as a solitary lesion within the principle lactiferous duct or sinus. The patient presents clinically with serous or bloody nipple discharge. Clinically a small subareolar tumor may be felt or in rare conditions a rare retraction of the nipple. In most cases of single intraductal papilloma the duct is excised and this keeps this benign condition from recurring. In multiple occurring papillomas there is an increased risk of developing papillary carcinoma.
The best news about breast cancer is that deaths related to breast cancer is on the decline. This is because screening mammography is having a significant effect on detection and therefore treatment of breast cancer. The recurrence of breast cancer following conservative breast surgery is reported to be 7% at 5 years and 14% at 10 years. We are able to use mammography and adjunct screening like ultrasound, MRI, CT, and SPECT-CT to follow and diagnose these cancers early in the at risk population. The best treatment for discovery of early recurrence is mastectomy. Mastectomy when breast cancer reoccurs has a 5 year survival of 84%. With so many options for patients today it is unfortunate that there is a patient choice trend to have a mastectomy when breast cancer is found rather than opt for breast conservative strategies. New drugs like tamoxifen and just recently Arimidex are found to reduce recurrence of breast cancer and development of breast cancer in the contralateral breast. The fight against breast cancer is not based on diagnostic research and surgical treatments, but on drug therapies and genetic research as well. We are closing in on a prevention strategy that has not been easily forthcoming. Today, a woman that follows screening guidelines and performs BSE, and get regular clinical breast exams can expect to find breast cancer in its early stage. The success of remitting early breast cancer is nearly 100%. We are winning the fight against breast cancer.