Ultrasonography in Breast Cancer
- Author: Paul R Fisher, MD; Chief Editor: Eugene C Lin, MD more...
Ultrasonography (US) has been playing an increasingly important role in the evaluation of breast cancer. US is useful in the evaluation of palpable masses that are mammographically occult, in the evaluation of clinically suspected breast lesions in women younger than 30 years of age, and in the evaluation of many abnormalities seen on mammograms. Some breast imagers believe that US is the primary modality for the evaluation of palpable masses in women 30 years of age and older and that mammography plays an adjunctive technique. US is also useful in the guidance of biopsies and therapeutic procedures; research is currently under way to evaluate its role in cancer screening. See the image below.
See Breast Lumps in Young Women: Diagnostic Approaches, a Critical Images slideshow, to help manage palpable breast lumps in young women.
Originally, ultrasonography was primarily used as a relatively inexpensive and effective method of differentiating cystic breast masses from solid breast masses. However, it is now well established that US also provides valuable information about the nature and extent of solid masses and other breast lesions.
Ultrasonography does not expose a patient to ionizing radiation — a factor that is particularly important for pregnant patients and young patients. It is believed that in these patients, the breast is more sensitive to radiation; this would mean that in comparison with US, mammography would be associated with a slight increase in the small risk of acquiring radiation-induced neoplasm. Furthermore, young women's breasts tend to appear dense on mammograms — a factor that reduces the diagnostic sensitivity of mammography in this group. In addition, breast US is superior to mammography in the evaluation of breast abscesses.[1, 2, 3]
The role of US in the screening of specific groups of patients, such as those with mammographically dense breasts and those at high risk for breast carcinoma, is under investigation. The role of breast magnetic resonance imaging is also expanding and is under study.
Role of Ultrasonography in Screening
Although mammography is an effective screening tool, data suggest that it is often less sensitive in detecting cancer in mammographically dense breast tissue. The use of US for screening for breast disease has not been generally recommended for high-risk women with dense breasts.
Although some research projects have reported reasonable results from US breast screening, a number of serious issues need to be solved before the practice is recommended for general application. Factors include interobserver variability, intraobserver variability, unknown sensitivity, and low specificity (leading to numerous biopsy evaluations of benign lesions).[4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28] Kolb et al and Buchberger et al found that, when performed carefully, ultrasonography may be useful in detecting occult breast cancer in dense breasts.[29, 30]
US is generally acknowledged to be a highly operator dependent modality that requires a skilled practitioner, high-quality examinations, and state-of-the-art equipment. Currently, it is recommended that the use of US in screening for breast disease be reserved for special situations, such as for highly anxious patients who request it and for women who have a history of mammographically occult carcinoma.
In view of the results of these studies, a prospective, multicenter study was carried out to examine the role of US in breast cancer screening. A large multicenter study supported by the Avon Foundation and the National Institutes of Health was created through the American College of Radiology Imaging Network (ACRIN). In this project, a protocol to assess the efficacy of screening breast US was implemented in 14 imaging centers to better define the role of US in breast cancer screening. The study reported higher cancer detection in high-risk women that underwent annual ultrasound screening in addition to mammography compared to those that underwent mammography alone. (More information is available on the ACRIN Web site.) In September 2012, the U.S. Food and Drug Administration approved the first ultrasound system, the somo-v Automated Breast Ultrasound System (ABUS), for breast cancer screening in combination with standard mammographyspecificallyforwomenwith dense breast tissue. ABUS is indicated for women with a negative mammogram, no breast cancer symptoms and no previous breast intervention such as surgery or biopsy.
See the images below of ultrasonography for breast cancer.
A study of the positive predictive value (PPV) of bilateral whole-breast ultrasonography (BWBU) for detection of synchronous breast lesions on initial diagnosis of breast cancer found that BWBU can detect additional synchronous malignancy with a relatively high PPV, especially when mammography findings are correlated with ultrasound findings. In 75 patients who had synchronous lesions, PPV for additional biopsy was 25.7% (18 of 70). The PPV for synchronous lesions detected both on mammography and BWBU was 76.9% (10 of 13) and detected only on BWBU was 14.3% (7 of 49). A mass with calcification on mammography presentation (P < 0.01), presence of calcification among the ultrasonography findings (P < 0.01), and high Breast Imaging Reporting and Data System final assessment (P< 0.01) were imaging factors that were associated with malignancy in the additional synchronous lesion.
In a retrospective study of women younger than 40 years identified with invasive cancer (N = 27) or ductal carcinoma in situ (N = 3), ultrasonography was found to be reliable as the primary imaging modality. Of the 30 women, 28 underwent mammography (graded as uncertain, suspicious, or malignant in the majority), and malignancy was missed in one patient. All 30 patients underwent ultrasonography (reported as uncertain, suspicious, or malignant, an indication for diagnostic core biopsy), and ultrasonography alone did not miss any cancers but did fail to detect multifocal disease in one patient.
Breast Imaging Reporting and Data System
As mentioned, ultrasonography is highly operator dependent. Therefore, its efficacy depends on obtaining images that are of high technical quality, on interpreting those images correctly, and on clearly reporting the results.
Baker et al and Rahbar et al demonstrated that observer variability varies considerably in the description and assessment of solid masses demonstrated on sonograms.[36, 37] More uniform and more clearly understandable examination reports are needed to improve patient care and to facilitate research in the use of breast US.
Mendelsohn et al published the results of their initial work in creating a standardized breast US lexicon, and the American College of Radiology (ACR) published the Breast Imaging Reporting and Data System (BI-RADS) Atlas. This latter document is an extended version of the Third Edition of the BI-RADS lexicon used in mammography. The BI-RADS Atlas includes new sections on breast US (ACR BI-RADS–US) and MRI (ACR BI-RADS–MRI). ACR BI-RADS–US may help standardize the terms used for characterizing and reporting lesions, thereby facilitating patient care, the characterization of lesions, and the development of possible screening applications.
ACR BI-RADS–US provides terms that describe the following features or findings on breast US examinations: shape, orientation, margin, boundary, echo pattern, posterior acoustic features, and surrounding tissue for masses; breast calcifications (which are poorly characterized by US); special cases, such as complicated cysts and intramammary lymph nodes; vascularity; and assessment categories.
ACR BI-RADS–US describes 7 assessment categories. One category is for lesions that are incompletely characterized and for which further imaging is needed for final assessment. The 6 other assessment categories have implications on patient care.
Distinguishing Benign Masses from Malignant Masses
Originally, ultrasonography was primarily used to distinguish simple cysts, which did not require sampling, from solid masses that were usually examined with biopsy. In many cases, the results of these biopsies were benign. Improving equipment and scanning techniques have helped expand the applications of breast US. Linear-array high-frequency (7.5 MHz or higher center frequency) transducers are generally used.
Recent innovations include electronically steered compound imaging and tissue harmonic imaging. Contrast-enhanced Doppler US and 3-dimensional imaging are experimental techniques that are under investigation.[41, 42, 43, 44]
Benign, Indeterminate, and Malignant Nodules
In a landmark study, Stavros et al established US criteria for characterizing solid breast masses. This work was facilitated by evolving technical improvements in US equipment that provided better resolution and images. They demonstrated that US may be used to accurately classify some solid lesions as benign, allowing follow-up with imaging rather than biopsy. They used high-resolution transducers, which were state-of-the-art at that time, and performed examinations in both radial and antiradial planes. The investigators also focused on the evaluation of suspected areas in the transverse and longitudinal planes.
Stavros et al proposed a US scheme for prospectively classifying breast nodules into 1 of 3 categories :
To be classified as benign, a nodule had to have no malignant characteristics. In addition, 1 of the following 3 combinations of benign characteristics had to be demonstrated:
Intense uniform hyperechogenicity
Ellipsoid or wider-than-tall (parallel) orientation, along with a thin, echogenic capsule
2 or 3 gentle lobulations and a thin, echogenic capsule
A nodule was classified as indeterminate by default if it had no malignant characteristics and none of the 3 benign characteristic combinations listed above.
To be classified as malignant, a mass needed to have any of the following characteristics:
Taller-than-wide (not parallel) orientation
Posterior acoustic shadowing
Of the 424 lesions that Stavros et al prospectively classified as benign by means of US, only 2 were found to be malignant at biopsy, resulting in a negative predictive value of 99.5% in a population with a cancer prevalence of 16.7%. Of the 125 lesions found to be malignant at biopsy, 123 were classified as malignant or indeterminate with US, yielding a sensitivity of 98.4%. Biopsy is indicated for nodules that are classified on US as either malignant or indeterminate.
Skaane et al found that US could distinguish fibroadenomas from invasive ductal carcinoma. Others who have studied the characteristics of benign and malignant masses by US examination include Zonderland et al and Rahbar et al.[47, 37]
Typical US Patterns of Specific Types of Breast Carcinomas
The appearance of specific types of breast carcinoma have been studied. Although appearances vary greatly, some patterns are typical.
Mucin-containing carcinomas are often circumscribed but may have irregular margins. These lesions may be either hypoechoic or isoechoic relative to subcutaneous fat. In a study of these carcinomas by Conant et al involving 8 patients, US showed hypoechoic, solid masses in all of their cases. The lesions demonstrated acoustic shadowing or increased acoustic enhancement. Some lesions had circumscribed margins, and some were not circumscribed.
Tubular carcinoma is usually hypoechoic but is without circumscribed margins and acoustic posterior shadowing. Invasive ductal carcinoma typically appears as an irregularly shaped mass with spiculated margins with shadowing and architectural distortion of adjacent breast tissue. This lesion may contain malignant microcalcifications.
Invasive lobular carcinoma often does not cause a desmoplastic reaction. This type is frequently missed on mammography and may be difficult to see on sonograms. Butler et al reported that these lesions were ultrasonographically occult in 12% of their cases. In approximately 60% of cases, it appeared as a heterogeneous, hypoechoic mass with angular or ill-defined margins and posterior acoustic shadowing. In 15% of cases, US demonstrated focal shadowing without a discrete mass; in 12% of cases, US showed a lobulated, circumscribed mass.
Medullary carcinoma often appears as a hypoechoic mass with acoustic enhancement (increased through transmission). It may be mistaken for a cyst on US.
Soo et al studied papillary carcinoma of the breast; they found that the cystic in situ form may appear as either a solid mass or a complex cystic mass with an internal solid component. In both types, acoustic enhancement tends to be increased. Doppler study may demonstrate intratumoral blood flow. Invasive papillary carcinoma usually appears as a solid mass, although it may also appear as a complex cystic and solid mass.
Ductal carcinoma in situ of the breast often appears as suggestive microcalcifications on mammography. However, it may occasionally appear as a solid mass on ultrasound.
Characteristic Benign Masses
Many masses that are demonstrated on mammograms require biopsy to determine whether they are benign. Taylor et al reported that the use of US in conjunction with mammography increased specificity from 51% to 66% in a population with a malignancy prevalence of 31%. This improvement could significantly reduce the biopsy rate of benign lesions. Breast US often reveals unexpected benign lesions.
Many benign breast conditions have a nonspecific appearance on US. However, some masses, such as simple cysts, sebaceous cysts, and intramammary lymph nodes, have a characteristic appearance that suggests a specific diagnosis. Almost all highly echogenic masses are benign.
If color Doppler imaging demonstrates blood flow within the contents of a complex cyst or dilated duct, then these contents consist of solid tissue rather then just debris, blood clot, or echogenic fluid. However, we have seen solid tumors that lack demonstrable blood flow on color Doppler imaging. Several investigators reviewed the ability of color Doppler US or contrast-enhanced Doppler US to distinguish benign from malignant lesions. The results were variable; Doppler US is not generally used to distinguish benign from malignant solid breast masses.
Ultrasound-Guided Procedures and Treatments
Ultrasonography is used to guide procedures such as cyst aspiration, percutaneous biopsy, needle localization of masses for surgical excision, abscess drainage in selected cases, and therapeutic radiofrequency or cryoablation.
Ultrasonography is highly accurate in diagnosing a simple cyst, and it is helpful in evaluating some complex cysts. Usually, a simple cyst is not aspirated unless they it is symptomatic or the patient has persistent psychological concerns about it. Complex cysts or suspected abscesses may be aspirated.
Berg et al reviewed their experience with the US-pathologic correlation of cystic lesions and found that all clustered microcysts were benign, but they cautioned that further study is required. They recommended that biopsy be performed in cases involving (1) cystic lesions with thick, indistinct walls and/or thick septations (0.5 mm); (2) intracystic masses; and (3) predominantly solid masses with eccentric cystic foci. These recommendations were based on the fact that, in their series, 18 of 79 of such complex cystic lesions proved to be malignant.
If it is uncertain whether a nodule seen on US is a complex cyst or solid mass, US-guided aspiration of the cyst is often performed. This procedure is also performed if the appearance of a complex cyst on US is of concern. The aspirate may be sent for cytologic evaluation, though there is no general consensus about the indications for cytology. Some clinicians send only the fluid for analysis if it is bloody.
Parker et al reported excellent concordance between the results of US-guided automated core biopsy with a 14-gauge needle and surgical resection in 49 lesions. US provides effective guidance for percutaneous breast biopsy without ionizing radiation. It also offers the advantages of real-time visualization of the needle and target lesion, multidirectional imaging, and low cost. With US, the patient does not need to undergo mammographic compression; in addition, with US, the examination may usually be performed with the patient recumbent rather than sitting, as is often the case with procedures involving mammographic guidance. However, US is not appropriate for guidance in all situations. For instance, microcalcifications often cannot be localized with US; in addition, not all masses seen on mammography can be seen with US.
Other biopsy devices, such as vacuum-assisted devices, have been developed for use with US guidance. Occasionally, it may be difficult to find the area in the breast where core biopsy was previously performed. This may be a problem if the pathologic results from the biopsy sample and other factors indicate that excisional biopsy or lumpectomy is needed. After a patient receives preoperative neoadjuvant chemotherapy, the tumor may become occult, making it difficult to localize for lumpectomy. For these reasons, various US techniques to mark the biopsy or tumor site have been developed. These include the deployment of coils, clips, or wires.
US-guided fine-needle aspiration biopsy (FNAB) of solid nodules has been used at many centers. Some advantages are that it is relatively easy for a skilled practitioner to perform and that the results are quickly obtained if a cytopathologist is available. For good results, the person performing the FNAB and the cytopathologist must be skilled. Some groups have achieved excellent results. However, in a study by Pisano et al involving 18 institutions, US-guided or stereotactically guided FNAB yielded a 10% insufficient-sample rate for US-guided FNAB of masses. This finding does not compare favorably with results of US-guided core biopsy or US-guided needle localization.[55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68]
Several investigators have presented preliminary reports on the use of US-guided therapeutic radiofrequency ablation or cryoablation of invasive breast carcinoma.[69, 70, 71]
Treatment Planning, Surgery, and Posttreatment Follow-up
Berg et al showed the possible benefit of combining preoperative whole-breast US with mammography when breast-conservation surgery is planned. US demonstrated additional sites of multifocal and multicentric carcinoma, facilitating preoperative planning.
Several investigators have studied the role of US in the assessment of axillary lymph nodes for tumor involvement. Normal lymph nodes usually have a prominent echogenic fatty hilum and a thin hypoechoic cortex. Lymph nodes that lack a fatty echogenic hilum or are heterogeneous are considered suspicious. The appearances on US of benign and malignant lymph nodes overlap; therefore, US-guided fine-needle aspiration biopsy (FNAB) of suspicious lymph nodes has been advocated. Krishnamurthy et al found that in approximately 12% of cases, false-negative results occur with US-guided axillary lymph node FNAB.
Deurloo et al showed that US-guided axillary lymph node FNAB reduces the number of the more time-consuming sentinel-node biopsy procedures that are needed.
Intraoperative US may be used to localize breast masses. It obviates the need for preoperative needle localization, offers more flexibility in choosing the incision site than preoperative needle localization, and may allow assessment of the tumor's extent. However, intraoperative US is operator dependent, and as with breast needle localization, it may not help in localizing the carcinoma.[74, 75, 76, 77, 78]
US plays a role in the postoperative assessment of patients with breast cancer. It may be helpful in evaluating both postoperative breast masses and breast infections. Edeiken et al showed that US offers a benefit in the detection of recurrent cancer on breasts reconstructed with autogenous myocutaneous flaps.
Ultrasonography may be helpful under certain circumstances, such as breast implant rupture, identifying benign breast masses in men, and characterizing lesions in children.
Although MRI is accurate in evaluating silicone implants for rupture, MRI is not readily available or cannot be used in a number of circumstances. For instance, rupture of implants may be evaluated with ultrasonography. On US, an intact implant has an echogenic wall, and its contents are anechoic. Normal folds in the implant wall may be seen. US may demonstrate the stepladder sign, consisting of multiple lines in the implant when an intracapsular rupture occurs or when an extracapsular rupture occurs, producing the snowstorm sign of increased echogenicity. US can provide additional information about implants, and it may also help in evaluating breast masses that are unrelated to the implant.
Male Breast Masses
In the male patient, US may help in distinguishing benign conditions, such as gynecomastia, from breast carcinoma. Many believe that the addition of US to mammography increases diagnostic accuracy. However, US findings of malignancy in the male breast may be subtle, and the appearances of benign disease and malignant disease overlap.
Pediatric Breast Masses
US is particularly helpful in characterizing cystic, inflammatory, and neoplastic lesions in children. Fibroadenomas are the most common breast tumors in adolescent girls and may become large. Although most masses that occur in the pediatric breast are benign, phyllodes tumors may be benign or malignant. In adolescents, cystosarcoma phyllodes are rare, but they are still the most common malignant breast tumors. Phyllodes tumors are usually well-circumscribed, oval, or lobulated tumors, and they may have cystic areas. In a study involving female adolescents, Kronemer et al found that sonograms demonstrated 36 fibroadenomas, 12 cysts, 7 abscesses, 1 lactating adenoma, and 1 phyllodes tumor.
After using US to evaluate breast masses in pediatric and adolescent patients, Weinstein et al reported findings on gynecomastia, cyst, fibroadenoma, lymph node, galactocele, duct ectasia, and infection. They had no patients with malignancy, but they cautioned that, in rare cases, rhabdomyosarcoma, non-Hodgkin lymphoma, and leukemia may metastasize to the breast; they also reported that in patients of this age group, these diseases are more likely to be found than a primary breast cancer.
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