eMedicine Specialties > Radiology > Breast

Breast Cancer, Mammography

Author: Nagwa Dongola, MD, FRCR, Clinical Director, Associate Professor, Department of Radiology, Soba University Hospital
Contributor Information and Disclosures

Updated: May 16, 2008

Background

Because of early detection, intervention, and postoperative treatment, breast cancer mortality has been decreasing. The use of mammography for screening has largely contributed to early detection, although its use has resulted in a minor increase in the number of in situ cancers detected.

For excellent patient education resources, visit eMedicine's Imaging Center, Cancer and Tumors Center, and Women's Health Center. Also, see eMedicine's patient education articles Mammogram, Breast Cancer, Breast Lumps and Pain, Breast Self-Exam, and Mastectomy.

Related eMedicine topics:

Magnetic Resonance Mammography

Mammography - Computer-Aided Detection

Breast Cancer Evaluation

Breast Cancer

Pathophysiology

Risk factors

Important risk factors for female breast cancer include early age at onset of menarche, late age at onset of menopause, a first full-term pregnancy after the age of 30 years, a history of premenopausal breast cancer for a mother and a sister, and a personal history of breast cancer or benign proliferative breast disease. Obesity, nulliparity, and urban residence have also been associated with an increased risk of breast cancer.

Classification

Breast cancer is a heterogeneous disease in terms of its clinical course, gross and microscopic pathology, and imaging characteristics.

Several histologic classifications exist. One example is the World Health Organization (WHO) classification, which divides breast cancers into noninvasive type, (in situ), invasive type, and Paget disease of the nipple.

In situ carcinoma is characterized by growth within the ducts without penetration of the basement membrane. In situ carcinoma is subdivided into ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS).

Invasive carcinoma denotes neoplastic penetration of the basement membrane of a duct containing DCIS and extension of neoplastic cell aggregates into the mammary stroma. It is further subdivided into the following: ductal, which accounts for about 75% of all invasive breast cancers; medullary; mucinous, or colloid; papillary; tubular; adenoid cystic carcinoma; and carcinoma with metaplasia.

Paget disease of the nipple is a type of breast cancer that starts in the breast ducts and spreads to the skin of the nipple and then to the areola. It is rare, accounting for only 1% of all breast cancers. Paget disease may be associated with in situ carcinoma or with infiltrating breast carcinoma. If no lump can be felt in the breast tissue and if the biopsy shows DCIS but no invasive cancer, the prognosis is excellent.

Related conditions

Two other entities also need consideration: inflammatory breast cancer and phyllodes tumor.

Inflammatory breast cancer is the appearance of inflamed breasts with peau d'orange (skin dimples) caused by the infiltration of tumor cells into the lymphatics. This disease can sometimes be difficult to distinguish between benign (noncancerous) conditions (eg, mastitis) and inflammatory malignancy (cancerous conditions). Though rare, inflammatory breast cancer may spread quickly to other parts of the body. It is considered stage IIIB or IV.

Phyllodes tumor is a rare breast tumor that develops in the stroma of the breast in contrast to carcinomas, which develop in the ducts or lobules. Phyllodes tumors are usually benign, but on rare occasions, they may be malignant.

Breast cancer staging

To stage cancer, the American Joint Committee on Cancer first places the cancer in a letter category using the tumor, nodes, metastasis (TNM) classification system. The stage of a breast cancer describes its size and the extent to which it has spread. The staging system ranges from stage 0 to stage IV according to tumor size, lymph nodes involved, and distant metastasis.

• T indicates tumor size. The letter T is followed by a number from 0 to 4, which describes the size of the tumor and whether it has spread to the skin or chest wall under the breast. Higher T numbers indicate a larger tumor and/or more extensive spread to tissues surrounding the breast.
  • TX: The tumor cannot be assessed.
  • T0: No evidence of a tumor is present.
  • Tis: The cancer may be LCIS, DCIS, or Paget disease.
  • T1: The tumor is 2 cm or smaller in diameter.
  • T2: The tumor is 2-5 cm in diameter.
  • T3: The tumor is more than 5 cm in diameter.
  • T4: The tumor is any size, and it has attached itself to the chest wall and spread to the pectoral (chest) lymph nodes.
• N indicates palpable nodes. The letter N is followed by a number from 0 to 3, which indicates whether the cancer has spread to lymph nodes near the breast and, if so, whether the affected nodes are fixed to other structures under the arm.
  • NX: Lymph nodes cannot be assessed (eg, lymph nodes were previously removed).
  • N0: Cancer has not spread to lymph nodes.
  • N1: Cancer has spread to the movable ipsilateral axillary lymph nodes (underarm lymph nodes on the same side as the breast cancer).
  • N2: Cancer has spread to ipsilateral lymph nodes (on the same side of the body as the breast cancer), fixed to one another or to other structures under the arm.
  • N3: Cancer has spread to the ipsilateral mammary lymph nodes or the ipsilateral supraclavicular lymph nodes (on the same side of the body as the breast cancer).
• M indicates metastasis. The letter M is followed by a 0 or 1, which indicates whether the cancer has metastasized (spread) to distant organs (eg, lungs or bones) or to lymph nodes that are not next to the breast, such as those above the collarbone.
  • MX: Metastasis cannot be assessed.
  • M0: No distant metastasis to other organs is present.
  • M1: Distant metastasis to other organs has occurred.

Frequency

United States

For white females, breast cancer has the highest incidence of any primary cancer, and breast cancer rates in the United States are among the highest in the world. Breast cancer is the most common nonskin malignant neoplasm in women, accounting for nearly 30% of all female cancers.

An estimated 182,460 new cases of invasive breast cancer will be diagnosed in 2008 among women in the United States. At this time, approximately 2.5 million women living in the United States have been diagnosed with and treated for breast cancer.¹

Carcinoma in situ (CIS) will account for approximately 67,770 new cases in 2008. CIS is noninvasive and is the earliest form of breast cancer. Breast cancer also occurs in men. An estimated 1990 cases will be diagnosed in men in 2008.¹

Geographic variations have also been noted in the United States. White women in the San Francisco Bay area experienced the highest incidence among 162 areas reporting incidence data to the International Agency for Research on Cancer (IARC), with an annual rate of 104.2 per 100,000 women, adjusted to the world standard population.

International

Breast cancer is the second leading cause of cancer deaths in women today (after lung cancer) and the most common cancer among women, excluding nonmelanoma skin cancers. According to the WHO, an estimated 1.2 million people worldwide were diagnosed with breast cancer in 2004. Estimates indicated that in another 46,400 women, ductal DCIS, a noninvasive breast cancer, were diagnosed.

The incidence of breast cancer increased by approximately 4% during the 1980s but leveled off to 100.6 cases per 100,000 women in the 1990s.

Striking differences are noted in the prevalence of breast cancer in different geographic locations. Breast cancer accounts for 28.4 deaths per 100,000 persons in England and Wales, but for only 19.2 deaths per 100,000 persons in France and 5.8 deaths per 100,000 persons in Japan. Possible reasons for these differences include climate, diet, genetic inheritance, environmental toxins, patterns of birth control or breast-feeding, and age at first pregnancy. Women who move from low- to high-prevalence countries seem to acquire the higher risk of their new country.

Mortality and morbidity

Reversing a 60-year trend, the overall cancer mortality rate decreased by 6.8% from 1989 to 1993. Similarly, the National Cancer Institute reported a 4.7% decrease in the mortality rate from 1992 to 1996, with the largest decreases among younger women. It also reported a 3.4% decrease from 1995 to 1998.

From 1930 to 1990, the annual age-adjusted mortality rate was 27 to 28 deaths per 100,000 women. Furthermore, from 1987-2000, breast cancer rates increased only in persons aged 50 years or older. Medical experts attribute the decline in breast cancer deaths to earlier detection and more effective treatment.

Breast cancer is the second leading cause of cancer death in women, exceeded only by lung cancer. The chance that breast cancer will be responsible for a woman's death is approximately 1 in 35 (3%). In 2008, approximately 40,480 women and 450 men will die of breast cancer in the United States. Death rates from breast cancer have been declining.

The 5-year survival rate depends on the stage at the time of diagnosis and ranges from 100% for stage 0 to 16% for stage IV. Other medical concomitant medical conditions also influence the survival rate.

Race

For black females, breast cancer has the highest incidence of any primary cancer. According to the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, white, Hawaiian, and African-American women have the highest incidence of invasive breast cancer in the United States (approximately 4 times higher than the lowest group). Korean, Native American, and Vietnamese women have the lowest incidence of invasive breast cancer in the United States.

African-American women have the highest death rate from breast cancer, and disease in this group is more likely to be diagnosed at a later stage, as compared with breast cancer in white women.

In the age groups of 30-54 and 55-69 years, African-American women have the highest death rate from breast cancer, followed by Hawaiian women and white non-Hispanic women. However, in the 70-year-old age group, the death rate from breast cancer for white women is higher than that for African American women.

Sex

Although breast cancer is primarily a disease of females, it can affect males as well. Breast cancer in men accounts for less than 1% of all breast cancers. Klinefelter syndrome and treatment with estrogenic hormones have been shown to be special risk factors for male breast cancer. When the stage is considered, most data indicate that the pathology, clinical course, and prognosis are similar for female and male breast cancers.

Age

The incidence of breast cancer increases dramatically with age. Although the rate of increase is greatest in women younger than 50 years, most cases (approximately 80% of invasive cases) occur after age 50 years. Breast cancer commonly affects women older than 40 years of age; however, younger women can also be affected, especially those with a genetic predisposition.

Incidence rates in women younger than 45 years are higher among black women. After the age of 45 years, rates are higher for white women. Although breast cancer is less common in young women (eg, those in their 30s), younger women tend to have more aggressive breast cancers; this finding may explain why survival rates are lower among younger women.

Routine mammography for women 80 years of age or older may be beneficial, according to some studies.^2,3

Anatomy

The breasts of an adult woman are milk-producing glands situated on the front of the chest wall. They rest on the pectoralis major muscle and are supported by and attached to the front of the chest wall on either side of the sternum by ligaments. Each breast contains 15-20 lobes arranged in a circular fashion. The fat that covers the lobes gives the breast its size and shape. Each lobe comprises many lobules, at the end of which are glands where milk is produced in response to hormones (see Image below and Image 1 in Multimedia).

Clinical details

The earliest sign of breast cancer is an abnormality depicted on a mammogram, before it can be felt by the woman or her physician. When breast cancer has grown to the point where physical signs and symptoms appear, the patient feels a breast lump (usually painless).

Other presentations include tenderness; skin irritation or dimpling; and nipple discharge and/or pain, scaliness, ulceration, or retraction. Breast pain is commonly due to benign conditions and is not usually the first symptom of breast cancer.

In Paget disease, the skin of the nipple and areola often appears crusted, scaly, and red, with areas of bleeding or oozing. A few women may present with nipple discharge, which may be bloody, serous, blue, green, brown, yellow, watery, or milky. Bloody and (infrequently) serous discharge may be associated with breast cancer and intraductal papilloma. Approximately 10-30% of bloody discharges are associated with breast cancer. The other types of discharge are either normal physiologic phenomena or associated with fibrocystic changes.

Preferred examination

Mammography is the preferred examination for breast cancer especially in women older than 40 years, the age group with the highest incidence. Some studies have shown that mammography may be particularly beneficial for women who are 80 years of age and older.^2,3 Ultrasonography, CT, nuclear medicine study, and MRI have adjuvant roles. In younger patients, due to increased breast density, which may mask small cancers, additional tests such as ultrasonography, nuclear medicine study, and MRI may be useful.

Limitations of techniques

Mammographic sensitivity for breast cancer declines significantly with increasing breast density and is independently higher in older women with dense breasts. Hormonal status has no significant effect on the effectiveness of screening independent of breast density.

Differential Diagnosis

For circumscribed lesions, the differential diagnosis includes benign breast disease (eg, fibroadenomas, cysts), breast cancer, breast lymphoma, and metastasis to the breast from other primary sites.

For skin thickening, the differential diagnosis includes inflammatory carcinoma and mastitis.

For stellate lesions, the differential diagnosis includes breast cancer, traumatic fat necrosis, a radial scar, and a hyalinized fibroadenoma.

For dilated ducts with or without nipple discharge, the differential diagnosis includes papilloma, ductal carcinoma, duct ectasia, and fibrocystic disease.

X-ray Mammography

Mammography is a special type of X-ray imaging used to create detailed images of the breast. It is estimated that 48 million mammograms are performed each year in the US. Mammography uses low dose X-rays, achieved by using targets made of low atomic weight alloys (eg, molybdenum and rhodium). Filters made of aluminum, molybdenum, beryllium, rhodium, or palladium are used. It uses high-contrast, high-resolution (with single-sided emulsion) film to demonstrate microcalcifications smaller than 100 µm.

Mammography plays a major role in early detection of breast cancers, detecting about 75% of cancers at least a year before they can be felt. Mammography uses low-dose ionizing radiation, which may be harmful to the patient. Nevertheless, the benefits of mammography far outweigh the risks and inconvenience.

Chest radiography may also be used to look for lung or chest-wall metastasis or to assess the effects of radiation therapy on bones. Radiography of various bones (eg, the spine) may be performed to find evidence of metastasis.

Screening and diagnostic x-ray mammography

There are 2 types of mammography examinations: screening and diagnostic. Screening mammography is done in asymptomatic women. Early detection of small breast cancers by screening mammography greatly improves a woman's chances for successful treatment.

Screening mammography is recommended every 1-2 years for women once they reach 40 years of age and every year once they reach 50 years of age. In some instances, physicians may recommend beginning screening mammography before age 40 (eg, if the woman has a strong family history of breast cancer). Studies have shown that regular mammograms may decrease the risk of late-stage breast cancer in women 80 years of age and older.^2,3

Diagnostic mammography is performed in symptomatic women—for example, when a breast lump or nipple discharge is found during self-examination or an abnormality is found during screening mammography. Diagnostic mammography is more involved and time-consuming than screening mammography and is used to determine exact size and location of breast abnormalities and to image the surrounding tissue and lymph nodes. Typically, several additional views of the breast are imaged and interpreted during diagnostic mammography. Thus, diagnostic mammography is more expensive than screening mammography. Women with breast implants or a personal history of breast cancer will usually require the additional views used in diagnostic mammography.

For screening mammography, each breast is imaged separately, typically in both the cranial-caudal (CC) and medio-lateral-oblique (MLO) views. For diagnostic mammography, each breast is imaged separately in CC, MLO, and supplemental views tailored to the specific problem. These supplemental views can include latero-medial (LM) and medio-lateral (ML) views, exaggerated CC views, magnification views, spot compression views, and others. Special skin markers are sometimes used to identify certain lesions, skin abnormalities, the nipple, and other areas.

Breast compression is necessary to flatten the breast so that the maximum amount of tissue can be imaged and examined. It also allows for a lower X-ray dose and immobilization of the breast to reduce motion blur. Compression also reduces X-ray scatter, which may degrade the image. Breast compression may cause some discomfort, but it should not cause any significant pain.

American College of Radiology Breast Imaging Reporting and Data System

The American College of Radiology (ACR) has established the Breast Imaging Reporting and Data System (BI-RADS) to guide the breast cancer diagnostic routine. BI-RADS is the product of a collaborative effort between members of various committees of the ACR with cooperation from the National Cancer Institute, the Centers for Disease Control and Prevention, the FDA, the American Medical Association, the American College of Surgeons, and the American College of Pathologists.⁴

According to the ACR, the BI-RADS system is intended to guide radiologists and referring physicians in the breast cancer decision-making process that facilitates patient care.

BI-RADS categories or levels are used to standardize interpretation of mammograms among radiologists. They are useful for statistical analysis of mammography practice, and BI-RADS results are compiled on a nationwide basis in the US to help refine mammographic procedures everywhere.

Interpretation of mammograms

The quality of the mammograms should be assessed, and if not optimal, repeat examinations may be ordered. Mammograms of the right and left breasts are first placed back to back (mirror images) for comparable projections. Lighting should be homogeneous, and adequate viewing conditions should be maintained. The mammograms are inspected carefully. The search is done systematically through similar areas in both breasts.

First, breast symmetry, size, general density, and glandular distribution are observed. Next, a search for masses, densities, calcifications, architectural distortions, and associated findings is performed. For masses, the shape, margins, and density are analyzed. Malignant lesions tend to have irregular and (usually) spiculated margins. Malignancies, especially scirrhous cancers, also tend to have density greater than that of the normal breast tissue. Very low density, such as that of fat, is seen in benign lesions (eg, oil cyst, lipomas, galactoceles, hamartomas).

Benign calcifications are usually larger than calcifications associated with malignancy. They are usually coarser, often round with smooth margins, and more easily seen. Benign calcifications tend to have specific shapes: eggshell calcifications in cyst walls, tramlike in arterial walls, popcorn type in fibroadenomas, large and rodlike with possible branching in ectatic ducts, and small calcifications with a lucent center in the skin.

Calcifications associated with malignancy are usually small (<0.5 mm) and often require the use of a magnifying glass to see them well. They tend to have a pleomorphic or heterogeneous shape or a fine granular, fine linear, or branching (casting) shape.

The distribution of the calcification should be specified as grouped (clustered), linear, segmental, regional, or diffuse.

Special findings may be encountered, such as a linear density that might represent a duct filled with secretions or reniform shape of intramammary lymph nodes (with a radiolucent center).

Associated findings are then taken into account. These include skin or nipple retraction, skin thickening (which may be focal or diffuse), trabecular thickening, skin lesions, axillary adenopathy, and architectural distortion.

The lesion seen is located by using the views to either of the inner or outer or the lower or upper quadrants. It may also be central or retroareolar. The lesion can be described in a clock-shape position. The breast is viewed as the face of a clock with the patient facing the observer. The depth of the lesion is assigned to the anterior, middle, or posterior third of the breast.

If previous examination results are available, their comparison is useful in assessing disease progress.

All of these findings are considered together, a final impression is formed, and a BI-RADS category is assigned.

Summary of BI-RADS assessment categories

BI-RADS assessment categories can be summarized as follows:

• Category 0 - Need additional imaging evaluation
• Category 1 - Negative
• Category 2 - Benign finding, noncancerous
• Category 3 - Probably benign finding, short-interval follow-up suggested
• Category 4 - Suspicious abnormality, biopsy considered
• Category 5 - Highly suggestive of malignancy, appropriate action needed

Category 0 is a temporary category that means additional imaging is needed before assigning a permanent BI-RADS assessment category. Most category 0 findings are shown to be benign after additional imaging is completed.

Treatment by BI-RADS category

Each BI-RADS level has an appropriate management or follow-up plan associated with it. For example, if a referring doctor sees a mammogram report with a category 3 assigned to it, he or she knows the recommendation is for the woman to undergo follow-up mammography in 6 months.

If used correctly and consistently, each BI-RADS category has the risks of malignancy and the associated plan of management or follow-up shown in the Table below.

Risk of malignancy and care plan by BI-RADS category

Open table in new window

Recommendations for screening mammography

Screening mammography is now recommended for all women older than 40 years. In this group, mammography should be performed every 1-2 years and then every year after the age of 50 years.

Of all of the screening mammograms performed annually, approximately 90% show no evidence of cancer (BI-RADS category 1), and 10% show abnormalities that require further diagnostic testing, which typically includes the acquisition of spot compression or magnification mammographic views and/or sonography (BI-RADS category 0).

On additional imaging, about 85% of all cases are determined to be normal (BI-RADS category 1) or involve benign findings (BI-RADS category 2) that do not require further evaluation. About 15% (approximately 2% of all screening mammograms) are shown to be abnormal and require biopsy (BI-RADS category 4 or 5).

Among cases referred for biopsy, approximately 80% of the abnormalities are shown to be benign, and 20% of the abnormalities are shown to be cancerous.

Postoperative mammograms

Women who had previous surgery for breast cancer may still require breast cancer screening with mammography. If a woman had a total mastectomy, then the other breast requires yearly follow-up because she is still at higher risk of developing cancer in the remaining breast. If she had subcutaneous mastectomy or partial mastectomy or lumpectomy, then the breast itself requires follow-up mammography. The first mammogram is best performed 6 months postoperatively to provide a baseline for the new postoperative and radiation changes. Thereafter, the mammogram may be performed every 6-12 months for screening and follow-up.

Women with breasts augmented by implants may be a special challenge. Special 4-view mammograms may be performed to evaluate the breasts; the implant must be pulled aside so the underlying breast tissue can be imaged. MRI may be especially useful for detecting breast cancer and silicon implant rupture in this group of patients.

False-positive and false-negative results

False-positive results may arise when benign microcalcifications are regarded as malignant. Tissue summation shadows may appear as local parenchymal distortion; this may be erroneously called malignant tissue. A benign circumscribed lesion may show signs suggestive of malignancy, along with other findings, such as an irregular border and no halo sign.

According to data from the Breast Cancer Detection Demonstration Project, the false-negative rate of mammography is approximately 8-10%. Approximately 1-3% of women with a clinically suspicious abnormality, a negative mammogram, and a negative sonogram may still have breast cancer.

Possible causes for missed breast cancers include dense parenchyma obscuring a lesion, poor positioning or technique, perception error, incorrect interpretation of a suspect finding, subtle features of malignancy, and slow growth of a lesion.

Birdwell et al performed a multicenter study and found that, on prior mammograms with missed cancers, 30% of the lesions were calcifications, with 17 of 49% clustered or pleomorphic. Approximately 70% were mass lesions, with 40% spiculated or irregular. For calcifications and masses, the most frequently suggested reasons for possible miss were dense breasts (34%) and distracting lesions (44%).⁵

Some cancers (eg, mucinous carcinomas) may have well-defined borders and mammographic features suggestive of benignancy.

Other uses of radiography in breast cancer

A ductogram, or galactogram, is sometimes helpful for determining the cause of nipple discharge. In this x-ray procedure, a fine plastic tube is placed into the opening of the duct in the nipple. A small amount of contrast medium is injected, which outlines the shape of the duct on an x-ray image and shows whether a mass is present inside the duct.

CT and MRI

Computed tomography

Spiral CT is useful for elucidating problems in the diagnosis of breast lesions. Its advantages are the speed of the method, comfort for the patient, absence of movement artifacts, easy standardization, and wide applicability. Dynamic contrast-enhanced CT of the breast has been found to be effective for the detection of intraductal extension of breast carcinoma and is thought to be useful in the preoperative assessment of indications of breast-conserving surgery. The lesions appear attenuating compared with fatty background, and they show early enhancement on arterial phase on dynamic contrast-enhanced CT.^6,7

CT is usually not the first modality to be used in imaging breast cancer, but it may be used as an adjuvant for monitoring spread. Although it involves some exposure to radiation, it should be considered in patients in whom MRI is contraindicated. Three-dimensional (3D) helical CT can provide good information about the spread of breast cancer and could be an alternative to 3D MRI for preoperative examination of breast cancer. In vitro high-resolution helical CT can depict the internal structure of small nodes. Morphologic changes detected on helical CT help distinguish benign from malignant nodes. Tumors appear as dense lesions on CT and usually show early contrast enhancement similar to that seen with dynamic MRI. CT is less sensitive than mammography for detecting microcalcification when it is the sole manifestation of early cancer.

In one study, 3D CT depicted nearly all of the tumors and defined the correct tumor extent in most patients. Its sensitivity, specificity, and accuracy in diagnosing muscular invasion of breast cancer were 100%, 99%, and 99%, respectively. Its sensitivity, specificity, and accuracy in diagnosing skin invasion of breast cancer were 84%, 93%, and 91%, respectively. The sensitivity, specificity, and accuracy in detecting intraductal spread or DCIS were 71.9%, 83.3%, and 76.0%, respectively, for 3D CT and 87.5%, 61.1%, and 78.0%, respectively, for 3D MRI. The sensitivity rate for microcalcifications was about 59%.^6,7

Magnetic resonance imaging

High-resolution contrast-enhanced MRI of the breast has recently emerged as a sensitive instrument for the detection of breast cancer. The sensitivity of MRI makes it an excellent tool in specific clinical situations, such as the detection of local recurrence in patients who have received breast-conservation therapy and augmented breasts with implants. Furthermore, MRI of the breast has the potential to be a powerful aid in presurgical planning (multifocal cancer detection) and to be a useful adjunct to mammography in selected patients.⁶

MRI, however, has a significant false-positive rate, it is not readily available in all areas, and it is more expensive than mammography and sonography. Other limitations are the use of gadolinium-based contrast agent, problems with claustrophobia, and longer imaging times. It also remains unclear if alterations in management plans based on MRI findings actually benefit patients.

Breast cancer appears bright on T2-weighted images and usually enhances on T1-weighted images after gadolinium enhancement. The lesions are best imaged with fat-suppression techniques to eliminate the high signal intensity from fat on T1-weighted sequences. Two-dimensional (2D) or 3D techniques with gradient-echo sequences are time efficient and now largely used.

MRI may prove useful in screening younger women with dense breasts who are at a special high risk of developing breast cancer (eg, strong family history). Its low specificity means that special techniques are needed to develop MRI guidance to biopsy performance, as some lesions visible on MRI are not seen by other imaging modalities.

MRI has high sensitivity approaching 98%, but it has moderately low specificity. MRIs may depict many abnormalities that are later proved not to be cancer.

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans.

As of late December 2006, the FDA had received reports of 90 such cases of NSF/NFD. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

Ultrasound

Benign solid lesions with smooth or lobulated margins that are sharply defined, with homogeneous hypoechoic contents and a horizontal orientation, are assumed to be fibroadenoma and are classified as probably benign. Solid, hypoechoic lesions with irregular margins and an indeterminate or horizontal orientation but without a definite probability of being malignant or benign are classified as equivocal.

The role of ultrasonography in breast imaging is a subject of ongoing discussion. Sonography is generally accepted as the method of choice for the differentiation of cysts from solid masses and for guidance in interventional procedures.

Studies performed to evaluate sonography as a screening modality have failed to establish its efficacy, and it has been concluded that sonography should not be used as a screening tool. However, the use of sonography as an adjuvant to mammography may increase accuracy by up to 7.4%.¹⁰

Some cancers can mimic benign tumors and appear well defined. A normal sonogram does not exclude breast cancer, especially in the early stages.

Nuclear Medicine and Other Screening Modalities

Currently, 3 radiotracers are commonly used for breast imaging or scintimammography in either clinical practice or research: technetium-99m (^99m Tc) sestamibi,^99m Tc-tetrofosmin (2 agents used for myocardial perfusion imaging), and^99m Tc–methylene diphosphonate (MDP, used for bone scintigraphy).^99m Tc sestamibi was the first radiopharmaceutical to be approved by the FDA for use in scintimammography.¹²

Although not indicated as a screening procedure for the detection of breast cancer, scintimammography may play a useful and significant role in various specific clinical indications, as in cases of nondiagnostic or difficult mammography and in the evaluation of high-risk patients, tumor response to chemotherapy, and metastatic involvement of axillary lymph nodes.

In several prospective studies, overall sensitivity of^99m Tc-sestamibi scintimammography in the detection of breast cancer was 85%, specificity was 89%, and positive and negative predictive values were 89% and 84%, respectively. Similar numbers have been demonstrated for^99m Tc-tetrofosmin and^99m Tc-MDP scintimammography.¹²

Other tests used for breast cancer

Electrical impedance imaging (T-scan)

Electrical impedance imaging scans the breast for electrical conductivity, based on the idea that breast cancer cells conduct electricity better. It involves passing a very small electrical current through the body and detecting it on the skin of the breast with a small probe (similar to an ultrasound probe). The test does not use radiation and does not require breast compression. This test has received approval by the US Food and Drug Administration to be used as a diagnostic aid to mammography. However, it has not undergone enough clinical testing to recommend its use in breast cancer screening.

Other tests under investigation include the following:

• Thermography (thermal imaging) and computerized thermal imaging: These depend on mapping heat radiating from the breast, with the assumption that cancerous tissue produces more heat than normal breast tissue. It is not approved as a screening tool for breast cancer.
• Computed tomography laser mammograms: This is an experimental test that uses a laser to produce a 3-dimensional view of the breast. It has not yet been approved for clinical use.

Ductal lavage

During ductal lavage, breast cells are removed from a milk duct through a small flexible tube inserted into one of the ducts in the nipple. The sample is examined under a microscope to determine whether abnormal cells are present in the duct. It may be useful for screening in conjunction with mammography for women at high risk of developing breast cancer.

Intervention, Medical/Legal Pitfalls, and Special Concerns

Intervention

Intervention is usually used to further evaluate lesions detected on screening or diagnostic mammography. The procedures used are cyst aspiration (for diagnostic or therapeutic purposes), biopsy under sonographic or mammographic guidance (manual or computer aided) or galactography, which is done to evaluate nipple discharge or dilated ducts. Some nonpalpable lesions may be localized for subsequent surgery by introducing a special wire under mammographic screening.

Medical/legal pitfalls

Mammography is known to a have a certain false-positive and false-negative rates. Approximately 1-3% cancers may be missed on both screening mammography and ultrasonography. This rate should not be considered as a legal pitfall, as it is an inherent fault of the technique. In some cases, lesions might be visible when reviewed in retrospect, but the element of the human error remains.

Special concerns

From 1973 to 1991, the incidence of invasive breast cancer in the US increased 25.8% in whites and 30.3% in blacks, or roughly 2% per year. The reason for the increase in breast cancer incidence is not clearly understood but may be partly explained by a 75% increase in use of mammography because much of the increase in invasive breast cancer has been for the lowest-stage tumors.^13,14

Multimedia

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Media file 1: (Click Image to enlarge.) Anatomy of the breast.

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Media file 2: Normal mammograms in a 40-year-old woman show dense breast parenchyma.

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Media file 3: Screening mammogram depicts malignant ductal-type microcalcifications.

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Media file 4: Image shows a malignant-type lesion: an invasive ductal carcinoma. This stellate (spiculated) lesion has ductal-type microcalcifications.

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Media file 5: Image shows a benign lesion: a fibroadenoma with well-defined edges and a halo sign.

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Media file 6: Ultrasonogram shows a benign lesion (fibroadenoma in this case) in the same patient as in Multimedia Image 5.

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Media file 7: Benign microcalcifications: cystic hyperplasia.

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Media file 8: Breast cancer, mammography. Bilateral mammogram shows diffuse inflammatory carcinoma of the left breast.

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Media file 9: Traumatic fat necrosis. Mammogram shows traumatic fat necrosis following removal of a lesion. The stellate lesion has a halo center.

Keywords

breast cancer, breast carcinoma, breast cancer imaging, breast cancer screening, X-ray mammography, BI-RADS, Breast Imaging Reporting and Data System

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