Friday, December 8, 2023
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Note: This activity includes discussion of gadolinium-based contrast media for breast MRI. This application is considered off-label.
Except for skin cancer, breast cancer is the most frequently diagnosed cancer in women, accounting for an estimated 1.38 million (23%) new cancer cases and 458,400 (14%) deaths worldwide in 2008.[1] The combination of earlier detection by screening mammography and more effective treatment has resulted in significant reductions in breast cancer death in developed countries. Thirty years of experience with population-based mammography screening has taught us that screening for breast cancer can prevent death from the disease.[2-4] Breast cancer is a progressive disease, but progression can be arrested by early detection and treatment. The most important factor in determining final patient outcome is the timing of treatment relative to the natural history of the disease.
Population-based mammography screening has provided high-quality evidence from several randomized controlled trials in the United States and Europe that screening is beneficial. Nearly 500,000 women were screened in these trials and all but one showed a mortality benefit among those invited for screening.[5,6] None of these trials, however, were specifically designed to show a benefit of mammography screening among high-risk women.
For many years, physicians have relied on mammography screening to identify breast cancer at a preclinical stage. For the general female population, mammography screening remains the best method for early detection. Radiologists have long experience and familiarity with the modality, which has been shown to be effective, widely available, and reasonably priced. Randomized clinical trials have demonstrated a 63% reduction in breast cancer mortality in women 40 to 69 years of age who are screened annually or biennially with mammography, and subsequent service screening has similarly demonstrated a mortality benefit for this age group.[5] Analysis of the Swedish screening mammography trial of women ages 40 to 49, with 16 years of follow-up, revealed 803 breast cancer deaths in the study group of 7.3 million person years and 1238 breast cancer deaths in the control group of 8.8 million person years. The estimated relative risk (RR) for women who were invited to be screened was 0.74 (95% CI, 0.66-0.83), and the RR for women who attended screenings was 0.71 (95% CI, 0.62-0.80).[6]
Digital mammography has generally replaced film/screen analog technique in the United States. Special training for both radiologists and technologists is necessary to achieve optimal patient outcomes from screening.[7] The American College of Radiology Imaging Network (ACRIN) conducted a large mammographic Imaging Screening Trial (DMIST) in the United States (49,528 women) comparing digital and analog technique. This trial demonstrated improved performance for digital mammography with detection rates of up to approximately 27% more cancers than screen-film mammography in women 50 and younger, approximately 21% more cancers in premenopausal and perimenopausal women, and approximately 15% more cancers in women with dense breasts.[8]
Mammography remains the first line of defense in detecting breast cancer; however, it poses some challenges that make it inadequate as a single modality solution for all women, particularly those with dense breast tissue, where overlying breast parenchyma may obscure cancers. New imaging methods such as tomosynthesis, now available in many breast centers, offer the possibility of improved cancer detection.[9] This technique aims to enhance lesion visibility by using a method which obtains multiple slices through the breast instead of only a standard 2-dimensional-view mammogram, thus achieving increased cancer conspicuity for lesions otherwise obscured within normal breast tissue.
Ultrasound, either hand-held or automated, has gained acceptance as supplemental screening, aimed primarily for high-risk women and those with dense breasts inadequately visualized with mammography. A recent report from the ACRIN 6666 screening ultrasound trial reported that a supplemental incidence-screening ultrasound identified 32 (29 %) cancers seen only by the supplemental ultrasound, for an average added annual cancer detection rate due to ultrasound of 4.3 cancers per 1000 screens,[10] in a predominantly high-risk population. It is likely that ultrasound screening will be increasingly be used in radiology practices in the future, partly influenced by legislation. In 2009, for example, a law was passed in Connecticut requiring that women with dense breast tissue be notified of their status and advised of the utility of supplemental screening methods. Other states (Texas, New York, Virginia, California) have since passed similar legislation. Radiology practices across the country are now considering various approaches to implementing ultrasound screening.
The use of magnetic resonance imaging (MRI) for screening high-risk patients is now recommended by almost all major medical societies and is generally reimbursed by most insurers, provided the guidelines for high-risk eligibility are met.[11] Cancers in the high-risk population generally present at a younger age and screening with both mammography and MRI is recommended beginning at age 30. During the past 2 decades, extensive research has clearly shown the value of MRI for improved screening in this patient cohort, and sensitivities for ultrasound and mammography are lower in high-risk women than in the general population. Breast MRI is clearly the most sensitive method for breast cancer detection and specificities are comparable if not superior to other breast imaging methods (Table 1). The technical advantages of MR imaging of the breast include excellent 3-dimentional spatial resolution with superior soft-tissue contrast. The absence of ionizing radiation provides a safe, ideal imaging method for breast cancer imaging.
Table 1. High-Risk MRI Screening Studies
| Investigators | Cancers/n | Mammography | MRI Only |
|---|---|---|---|
| Tilanus-Linthorst, 2000 (Netherlands) | 2.8% (3/109) | 0% (0) | 2.8% (3) |
| Podo, et al, 2002 (Italy) | 7.6% (8/105) | 1.0% (1) | 6.7% (7) |
| Morris, et al, 2003 (United States) | 3.8% (14/367) | 0% (0) | 3.8% (14) |
| Kriege, et al, 2004 (Netherlands) | 2.4% (45/1909) | 0.9% (18) | 1.2% (22) |
| Warner, et al, 2004 (Canada) | 9.3% (22/236) | 3.4% (8) | 3.0% (7) |
| Kuhl, et al, 2005 (Germany) | 8.1% (43/529) | 2.6% (14) | 3.6% (19) |
| Leach, et al, 2005 (United Kingdom) | 5.1% (33/649) | 2.2% (14) | 2.9% (19) |
| Lehman, et al, 2005 (IBMC) | 1.1% (4/367) | 0.3% (1) | 0.8% (3) |
| Lehman, et al, 2005 (IBMC/CGN) | 3.5% (6/171) | 1.2% (2) | 2.3% (4) |
| TOTAL | 4.0%
(178/4442) |
1.3% (58/4442) | 2.2% (98/4442) |
CGN = Cancer Genetics Network; IBMC = International Breast MRI Consortium.
Courtesy of Constance D. Lehman, MD.
MRI sensitivities for high-risk screening result in increased cancer yield, above and beyond the sensitivities of mammography and ultrasound. A review of many screening studies using MR imaging for high-risk women demonstrate a high sensitivity for MRI (71% to 100%) vs a much lower sensitivity for mammography (16% to 49%).[12-19] Detection of cancer at the pre-invasive stage is considered an important goal. In the pre-mammography era, ductal carcinoma in situ (DCIS) was a very rare diagnosis accounting for fewer than 4% of breast cancers. The current increased rate of DCIS diagnosis (20% to 35%) in the United States is strongly associated with the concurrent increase in rates of mammography screening and is similar to the increasing incidence of DCIS in other developed countries where breast screening programs are conducted. DCIS incidence in the United States increased sevenfold from 1973 through the late 1990s, with the most rapid increases found among women older than 50 years of age. The current age-adjusted incidence rate of DCIS in the United States is 32.5 per 100,000 women; at ages 50 to 64 years the incidence is approximately 88 per 100,000.[20] As of January 1, 2005, an estimated 500,000 women were living with a diagnosis of DCIS in the United States, a number expected to grow to more than 1 million by 2020.[21] Mammographic detection of small or nonpalpable DCIS lesions, on average 10 to 20 mm in size, allowed for breast conservation surgery to emerge as a treatment option. MRI can provide an accurate depiction of in situ cancer extent and indeed is often detected at MRI screening. Unlike mammography, where DCIS can be underestimated due to noncalcified regions, most studies show that MRI provides an accurate assessment or overestimation of disease extent in more than 80% of DCIS lesions and is often found to be more accurate than mammography.[22-24]
Breast MRI is recommended by the American Cancer Society (ACS) as an adjunctive screening tool to mammography[11] for patients with a BRCA mutation, a nontested first-degree relative who is a BRCA carrier, an estimated lifetime risk of 20% to 25%, or patients who received radiation therapy to the chest between the ages of 10 and 30 years. ACS also recommends MRI screening for patients who have Li-Fraumeni, Cowden, or Bannayan-Riley-Ruvalcaba syndrome, as well as first-degree relatives of individuals with those syndromes. In addition to detecting cancers occult at mammography and ultrasound, cancers detected at an earlier stage in the MRI screening group can result in more than a 50% decrease in positive nodes compared with the control group (21.4% vs 52.4%).[13] In clinical practice for high-risk MRI screening/surveillance, the expected cancer yield at the initial exam should be approximately 14.9/1000 women.[25]
The American Cancer society does not recommend for or against screening of women with a personal history of breast cancer; however, for women with newly diagnosed breast cancer, there is evidence that a single round of MRI screening of the contralateral breast at the time of diagnosis will detect otherwise occult malignancy in approximately 3% to 9% of these women.[26-28] Additionally, a surveillance study using MRI for follow-up of patients with a personal history of breast cancer yielded a cancer detection rate of 12%.[29]
Patients may occasionally present with metastatic cancer of unknown primary site (CUP syndrome). These women are often diagnosed with axillary lymph node metastases suspicious for breast origin, with negative mammography and ultrasound imaging of the ipsilateral breast. In this situation MRI should be the standard imaging care because positive identification of the index cancer has been achieved in more than 75% patients.[30-32]
Modern breast MR techniques, developed over the past 5 to 10 years, allow protocols combining moderately high temporal and spatial resolution in the same acquisition. In the past, compromises between spatial and temporal resolution were necessary because of technical limitations. Investigators tended toward either a high spatial resolution, the "morphology camp," or an alternative high temporal resolution, the "kinetic camp," resulting in the development of distinctly different approaches to image acquisition. These distinctions are no longer necessary because parallel imaging, higher field-strength magnets (1.5 and 3T), and breast coils with 7 to 16 channels have all contributed to improved image quality.
A major strength of breast MRI is that virtually every invasive cancer enhances following contrast injection, allowing detection of small cancers (less than 5 mm). MRI has a negative predictive value of greater than 95% for invasive cancer. Unlike mammography, MRI sensitivity is not impaired by increased breast density, implants, or postsurgical changes. Imaging at 3T facilitates improved spatial and temporal imaging, allowing isotropic sub-millimeter voxels and high-resolution multiplanar reconstruction (MPR). The 3-dimensional data can be reformatted in the sagittal and coronal planes without loss of spatial resolution. Additionally, high spatial and contrast resolution allows for improved visualization of foci (less than 5mm), ductal structures, and the internal enhancement characteristics of benign and malignant lesions.
Consistent application of standardized protocols are essential for optimal imaging results. Considerable variation exists in the selection of imaging protocols across practices in the United States, but most sites perform bilateral imaging in the axial plane with at least 1 T2-weighted sequence and 1 nonfat-suppressed sequence, both obtained precontrast, followed by a dynamic acquisition with injection of a gadolinium-based contrast agent.
Precontrast acquisition. Most radiologists agree that a T2W acquisition is needed in conjunction with a sequence without fat suppression (fat as a reference tissue). Many sites perform 2 separate sequences, 1 T2-weighted sequence with fat suppression and a second T1 sequence without fat suppression. T2W fat-suppressed acquisitions need a longer time than nonfat-suppressed imaging and thus thicker image slices are usually acquired. A simpler option would be to perform 1 T2W nonfat-suppressed acquisition combining these 2 requirements into 1 sequence. The advantage of this combined approach is not only convenience and shorter imaging time but also the ability to acquire images with the same spatial resolution as the subsequent dynamic sequence (Figure 1).
Figure 1. The acquisition parameters currently used at the University of Chicago for a standard screening breast MR examination are shown in A. The entire acquisition involves about 15 minutes of scanning time. The timing for each dynamic sequence is 75 seconds. B shows an invasive cancer, 7 mm in size, on the T2W nonfat-suppressed sequence as an intermediate signal mass. C demonstrates the mass on a T1 precontrast sequence, which enhances on the next postcontrast source image (D). Note the matching slice resolution on the T1 and T2 sequences.
Dynamic contrast-enhanced acquisition. Dynamic contrast-enhanced MRI (DCE-MRI), consisting of rapid imaging obtained before and after contrast administration, is essential for cancer diagnosis. Although protocols vary across imaging sites, within each center imagers need to agree on acquisition timing for the DCE-MRI sequence, in addition to issues such as contrast dose and threshold settings for the computerized analysis software systems that are frequently used for interpretation. Most contrast material injected for clinical breast MRI examinations is currently used off-label. The standard dose recommended for breast MRI (ie, ACR breast MRI accreditation requirements)[33] is 0.1mmol/kg of body weight. Thus each patient should receive a titrated dose rather than a fixed dose, such as a 20-cc dose for everyone.[34] Higher magnetic relaxivity agents are also now available. It is also important to standardize the contrast delivery. Most sites inject at 2 cc per second and deliver an immediate postinjection flush of saline to ensure prompt delivery to the cardiovascular system. A power injector is helpful. Although breast size may vary considerably in clinical practice, slice thickness can be altered as needed so that the temporal resolution can remain the same.
Care should be taken to ensure proper placement of the patients' breasts within the coil. Ideally the breasts should be pulled down symmetrically into the coil wells so that the nipples are in profile and the breast tissue is free of folds. Skin markers containing commercially available, vitamin E-based skin markers can be easily seen on T2W and nonsubtracted sequences and can be used to mark the nipples, areas of prior surgery, and any palpable masses that may be present.
The 2008 ACR Practice Guideline for the Performance of Contrast-Enhanced Magnetic Resonance Imaging (MRI) of the Breast [33] provides guidelines and basic standards for breast imaging technique.
Precontrast Imaging. The forthcoming second edition of the ACR MRI lexicon[35] includes a new section on precontrast imaging. The section includes the following characterizations: (a) high contrast on precontrast series in a duct, (b) simple cyst, (c) nonsimple cyst, (d) hematoma/seroma, (e) edema, (f) nonenhancing mass, (g) dilated ducts, (h) skin thickening, (i) architectural distortion, (j) signal void from clips, and (k) foreign bodies.
In general, it is easier to see fluid and long-T2 tissue on a T2W sequence with fat suppression (although the images may be confusing if the fat suppression is nonhomogeneous). Cysts, edema, seromata, and lymph nodes appear very bright on these sequences, although spatial resolution is limited. A nonfat-suppressed additional T1W sequence satisfies the requirement for a sequence with fat as a reference tissue. Alternatively, T2W nonfat-suppressed sequences allow high spatial resolution and enhanced depiction of normal tissues and lesion morphology precontrast. The shorter imaging time needed to acquire this data allows acquisition at the same spatial resolution as the dynamic T1 acquisition that follows. Thus, exact comparison of the T2 and TI data and direct lesion evaluation slice by slice is possible and advantageous for diagnosis (Figure 2). This T2W sequence is excellent for visualization of cysts, postoperative changes including scar tissue and seromata (skin thickening), and evaluation of axillary nodes (all planes) and internal mammary lymph nodes (coronal plane). Masses may also be visible.
Figure 2. These images illustrate the acquisition parameters currently used at the University of Chicago for a standard breast MR examination at 3T with a 16-channel coil. The entire acquisition involves about 12 to 15 minutes of scanning time. A, Protocol: T2-weighted turbo spin echo (TSE); 3-dimensional 200 axial slices; 1-mm thick; matrix: 472 x 473; resolution: 0.8 x 0.8 x 0.8 mm. Approximate time: 4 minutes. B, Protocol: dynamic sequence, pre- and postcontrast. The timing of each dynamic sequence is 75 seconds. Bolus injection of contrast agent: 75-second temporal resolution; 0.8 x 08 x 0.8-mm in-plane resolution; matched spatial resolution T2 and T1. Approximate time: 7 minutes. Both images show an 18-mm invasive cancer (arrows) on the T2W nonfat-suppressed sequence as a low signal mass on the T2 image.
The new lexicon adds a new category, "parenchymal volume," and distinguishes between normal breast parenchymal tissue volume and breast parenchymal enhancement (BPE). Parenchymal volume on MRI mirrors the density assessment on mammography with Breast Imaging-Reporting and Data System (BI-RADS) assessment of fibroglandular tissue volume by the radiologist. The volume measures are divided into approximate quartiles, categories 1 to 4. Background BPE indicates a qualitative assessment of enhancement with the following categories: (a) none, (b) minimal, (c) mild, (d) moderate, and (e) marked, as assessed by the interpreting radiologist (Figure 3).
Figure 3. These images demonstrate examples of parenchymal enhancement categories. All are axial maximum intensity projection (MIP) T1 images obtained at the first postcontrast time point (75 seconds). A, Minimal enhancement is shown. B, Mild enhancement is shown. C, Moderate enhancement is shown. D, Marked enhancement is shown.
Normal enhancement of breast tissue following contrast administration is variable and related to estrogen levels, which cause breast hyperemia. This enhancement may limit the sensitivity of the MR examination and may obscure small enhancing lesions. Pregnancy, lactation, exogenous hormone therapy, and normal fluctuation during the menstrual cycle affect the degree of enhancement of normal breast tissue. Imaging during week 2 of the menstrual cycle -- the proliferative phase -- is preferable and recommended to minimize this enhancement effect. Imaging during the premenstrual phase -- week 4 -- should be avoided whenever possible. In clinical practice, menstrual cycle scheduling for screening examinations is usually achieved, whereas for cancer staging examinations this is usually not possible because of the requirement for rapid imaging work-up and biopsy prior to definitive treatment. High temporal resolution is helpful for lesion detection, particularly for women with marked BPE, as small lesions are sometimes only visible on the first postcontrast acquisition and may be obscured later by overlying parenchymal enhancement.
"Foci" are defined as small enhancing lesions less than 5 mm in size whose further characterization is limited because of their small size. Many enhancing foci, when multiple and scattered bilaterally, represent normal enhancing breast tissue. At 3T, however, improved resolution does allow better delineation of margins and internal enhancement features, improving diagnostic capability.
"Masses" are given only 3 categories of descriptors in the new lexicon: shape, margin, and internal enhancement characteristics. Mass shape includes (a) round, (b) oval (including lobulated), or (c) irregular. Margin descriptors are changed and the terms are now "circumscribed" and "noncircumscribed" (uneven, indistinct, or spiculated). Internal enhancement is characterized as "homogeneous," "heterogeneous," "rim-enhancement," or "nonenhancing internal septations." Some descriptors, not widely used or applicable, have been deleted -- for example, "central enhancement" and "enhancing septations."
This new category no longer includes the word "like," as in "nonmass-like."The descriptors for nonmass enhancement (NME) distribution include "linear" or "linear branching," "segmental," "regional," "multiple regions," and "diffuse." The term "ductal" has been deleted. The internal enhancement categories now include a new descriptor, "clustered ring enhancement," in addition to "clumped," "heterogeneous," and "homogeneous." The term "stippled"has been deleted as this applies to normal BPE.
Some invasive cancers, particularly invasive lobular cancer, present as NME at MRI. Most DCIS lesions also exhibit NME, and the challenge to diagnosticians is to differentiate NME from normal parenchyma -- ie, BPE. Unlike many breast masses, DCIS is not usually visible on T2-weighted sequences, either with or without fat nulling. NME is usually not seen on unenhanced T1-weighted images because the lesions may be indistinguishable from normal breast parenchyma, particularly if the lesion extent is small. The pharmacokinetic characteristics, including signal-intensity time-course curves associated with pure DCIS, are variable. In the initial phase, rapid uptake, greater than the surrounding breast parenchyma, is usually seen; in the delayed phase, persistent, plateau, and washout kinetics vary, as is described in the next section. Given that with current MR protocols as many as 30% of DCIS cases show the least-suspicious pattern,[36] that of persistent enhancement, interpretation considerations are benefited by emphasizing morphology, particularly distribution parameters, rather than kinetic characteristics. The distinctive morphology and variable kinetic patterns of DCIS may prompt some radiologists to suggest that MR acquisitions that emphasize spatial over temporal resolution are more sensitive to DCIS. Although spatial resolution is important, sufficient temporal resolution is also needed to distinguish the more slowly and moderately enhancing pure DCIS lesions from enhancing parenchyma. Normal tissue enhancement is usually slower than lesion contrast uptake and usually increases persistently over time. Creation of thin maximum intensity projection (MIP) images and multiplanar reconstruction images of areas of questionable NME at the physician-interpretation workstation, rather than reading planar stacks of images, may accentuate the topography of the enhancement distribution of DCIS and aid in distinguishing in situ lesions from parenchyma (Figure 4). Similarly, simultaneous review of the source (nonsubtracted) datasets, visualizing both the enhancing and nonenhancing parenchyma, may aid the radiologist in distinguishing, for example, segmental distribution of DCIS from patchy parenchymal enhancement. Recognition and understanding of the unique morphology and kinetic characteristics of pure DCIS on MR imaging may improve the detection of early breast cancer.
Figure 4. A 55-year-old woman was referred for staging MR following a stereotaxic biopsy of a 9-mm cluster of pleomorphic calcifications in the lateral inferior right breast yielding DCIS. An axial source T1 image taken at 75 seconds following contrast injection depicts an area of nonmass enhancement in the right breast surrounding the marker clip (arrow). Thin MIP images obtained at 75 seconds in the axial (B), sagittal (C), and coronal (D) planes demonstrate the true extent of the DCIS, (intermediate grade, solid type, measuring 7 cm in the sagittal plane).
The relative enhancement characteristics of cancerous and benign lesions are variable. Enhancement curves depict the kinetic behavior of lesions and are plotted as signal-intensity vs time curves (Figure 5). Computer-aided diagnostic (CAD) systems generate this data automatically and provide tumor measurements and volume data. Initial enhancement is measured as the enhancement at the first postcontrast sequence time point (ie, the percent of increase over background); this is known as the "initial enhancement phase." The "delayed phase" is characterized as the shape of the curve from the first time point onward. Washout of contrast in the delayed phase is seen in many but not all cancers. A plateau enhancement pattern may be seen in both malignant and benign lesions. A slow initial rise and a persistent enhancement in the delayed phase is a typical pattern of benign lesions and normally enhancing parenchyma. High temporal resolution is often helpful, especially the first postcontrast acquisition, in order to identify the slowly enhancing cancers, minimize the degree of parenchymal enhancement, and improve lesion conspicuity. Most invasive cancers enhance in signal intensity at least 90% above background signal intensity, and often more than 150%, following contrast injection.
Figure 5. Figure 5 indicates the effect of image timing/temporal resolution on the shape of the time-intensity curve (TIC). A 1-minute temporal resolution (gray) will capture most effectively the peak enhancement of a cancerous lesion (dark blue). A 2-minute temporal resolution (red) or a 3.5-minute temporal resolution (light blue) will miss the peak enhancement but will capture the delayed phase, which shows washout of contrast. If temporal resolution is very long -- eg, 5 minutes (green) -- then nouseful kinetic information regarding the enhancing lesion will be captured.
Some cancer subtypes, such as invasive lobular carcinoma (ILC), low-grade invasive ductal cancer (IDC), and DCIS, may show a slow initial rise and persistent enhancement in the delayed phase. DCIS is a heterogeneous disease with kinetic behavior that is typically less robust than IDC. As such, DCIS may exhibit kinetic characteristics often associated with benign lesions. Peak enhancement is delayed, often reaching peak at 3 minutes, unlike most invasive cancers, which peak between 60 and 90 seconds. This differential enhancement reflects the differences in underlying tumor biology. The morphologic appearance of DCIS, typically segmental/linear distribution and nonmass clumped enhancement, is the most important differential diagnostic criterion. Both DCIS and ILC may present with nonmass morphology, in contrast to most invasive cancers, which usually present with mass-like morphology.
Multimodal assessment of disease extent is usually performed for cancer staging. Both diagnostic mammography and ultrasound imaging are used. Recent advances in ultrasound have increased its utility for breast imaging. Volume imaging enables 3-dimensional views of breast lesions, while tissue aberration correction for breast transducers compensates for speed of sound variations, resulting in better resolution and conspicuity of lesion details. Ultrasound imaging, however, is highly operator-dependent; more-experienced operators are able to detect and characterize lesions more easily and accurately than less-experienced operators. MRI has been shown to provide the most accurate imaging information with regard to staging of cancer extent in the breast, both invasive and in situ.[22-24]
The American Joint Commission on Cancer (AJCC) breast cancer staging[37] is partitioned as follows: stage 0 = in situ (TIS); stage I = invasive primary cancer 2 cm or less (T1), negative nodes; N0 stage II = T1 with positive nodes or primary tumor 2 to 5 cm (T2) with or without positive nodes; stage IIIA = primary tumor less than 5 cm (T3) or any tumor with fixed nodes; stage IIIB = chest wall/skin involvement/ inflammatory carcinoma; stage IIIC = supra- or infraclavicular nodal metastases; stage IV = distant metastases. Determination of chest wall and pectoral muscle invasion are well demonstrated at MRI but not seen well at mammography and ultrasound. Muscle or chest wall enhancement or both indicates invasion.[38]
The use of breast MRI for cancer staging is variable in the United States. Many oncologists and surgeons recommend staging for all newly diagnosed cancer patients, whereas others restrict its use to patients with a diagnosis of ILC or young women with dense breasts. When staging mammographically detected DCIS, identification of an associated invasive component in addition to assessment of disease extent is critical for optimal patient management. Many studies have shown the comparative efficacy of MRI for staging breast cancer over mammography and ultrasound. Additional ipsilateral malignancies are found in 16% patients.[39] In the ipsilateral breast, sensitivities range from 31% to 62% for mammography, 38% to 79% for ultrasound, and 81% to 100% for MRI.[40-42]
During staging examinations, malignancy may be diagnosed not only in the same breast as the index cancer but also in the contralateral breast. Of additional lesions found, 20% are benign, with positive predictive value (PPV) after biopsy of approximately 50%. The incidence of synchronous cancer in the contralateral breast is about 4% (range: 3% to 24%).[43-45] This rate is increased in ILC (7%),[46,47] as well as in patients with a family history of breast cancer[48] and patients with a prior breast biopsy yielding a high-risk lesion such as lobular carcinoma in situ (LCIS), etc, (19%).[49] During follow-up screening (metachronous breast cancer), the rate of cancer detection is 4% for patients without an initial breast MRI and 1.7% for those patients with an initial breast MRI. Overall, for patients with an initial diagnosis of synchronous cancer, there is a trend toward decreased local control and decreased survival.[43,46,48,50] Breast MRI staging should be done if partial breast irradiation is the recommended treatment[51,52] to avoid cancer excluded from the treatment volume.
In the postsurgical setting, MRI is often used to identify residual tumor when cancer resection yields positive or "close" surgical excision margins for cancer. Imaging may be performed shortly after surgery, as soon as the patient is able to lie prone on the MR table. MR can detect residual tumor following cancer excision and direct the surgeon accordingly for appropriate re-excision of the involved tissue. During the immediate postoperative period, enhancement at the lumpectomy site is a normal finding. Fat in the seroma cavity and rim enhancement are indicators of fat necrosis, a major differential diagnostic problem in some cases. Reliable diagnosis of fat necrosis can be made by identification of fat within a persistent lesion postsurgery, but robust enhancement may lead to biopsy in some cases. A recent paper by Li and colleagues[53] showed that enhancement at the lumpectomy site was present in 37% (82/221) of women in their study. Prior reports have indicated that enhancement at the surgical site is abnormal after 18 to 24 months. Continued enhancement at the seroma or scar was not rare in the Li study; in fact, it was present in 15% of the 60 women examined with MRI performed 5 or more years after treatment. Postoperative seromata may persist for many years. MRI may also demonstrate posttreatment changes in both breasts if the patient has undergone chemotherapy. In particular, BPE and cystic changes usually decrease bilaterally, indicating a systemic influence. Changes due to surgery and radiation therapy -- such as skin thickening, edema, seroma, and focal enhancement -- are seen only in the treated breast. The treated breast generally exhibits less BPE than the contralateral nontreated breast. Posttreatment MRI findings often decrease progressively; however, many findings may persist for years. New enhancement in the treated breast should be evaluated with care, given that the main differential diagnosis is usually recurrent tumor vs fat necrosis. Following cancer treatment, MRI is by far the most accurate method for identifying recurrent tumor because the sensitivity of mammography and ultrasound are limited in this setting.
MRI is widely used to monitor cancer patients undergoing chemotherapy. Neo-adjuvant chemotherapy monitoring is now done routinely, with MRI performed prior to, during, and following completion of chemotherapy. Breast MRI monitoring of treatment effect has been shown to be superior to both mammography and ultrasound imaging for assessment of chemotherapeutic response imaging.[54] Sensitivities for response at MR imaging of 100% (range: 94% to 100%) and specificities of 80% (range: 44% to 97%) have been obtained. However, it should be noted that minimal disease is sometimes underestimated at MR.[55] Active research efforts are underway to evaluate the role of DCE-MRI, spectroscopy, and diffusion-weighted imaging for this application.
Galactography has long been the diagnostic method of choice for patients presenting with significant nipple discharge -- serosanguineous, clear, or bloody -- emanating from a single duct. Today MRI is frequently used to identify the source of discharge for patients when galactography is technically not possible, and MRI may eventually replace the procedure entirely. Papillomata are readily visible on MRI as small enhancing masses with circumscribed margins. Additional ductal lesions, either benign or malignant, may be identified, and detection of coexisting tumors may alter patient management in some cases. Presurgical mapping of papillary disease may allow more accurate surgical excision.
MR-directed ("second-look") ultrasound and mammography are often performed for otherwise-occult lesions found at MRI and is successful for lesion detection about 60% of the time when referred for ultrasound correlation (Table 2).
Table 2. Additional Lesions Found by MR-Directed ("Second-Look") Ultrasound (58.25%)
| Number of Patients |
Indication | Additional Lesions | Ultrasound Visible | ||
|---|---|---|---|---|---|
| Liberman | 2003 | 223 | Breast cancer | 32% | 19% |
| Latrenta | 2003 | 654 | Mixed | NA | 23% |
| Lehman | 2005 | 103 | Breast cancer | 11% | 45% |
| Deurloo | 2005 | 116 | Breast cancer | 41% | 49% |
| Teifke | 2003 | 1273 | Mixed | NA | 57% |
| Berg | 2004 | 111 | Breast cancer | 30% | 68% |
| Furman | 2003 | 76 | Breast cancer | 25% | 69% |
| Schelfout | 2004 | 204 | BI-RADS V | 25% | 87% |
| Beran | 2005 | 191 | Breast cancer | 37% | 89% |
| Camps | 2007 | 358 | Breast cancer | 43% | 90% |
| Demartini | 2009 | 167 | Mixed | NA | 46% |
| Abe | 2010 | 202 | Mixed | NA | 57% |
Although MR-guided biopsy is a reasonable next step following MR examination when an additional enhancing lesion is identified,
it is expensive and time-consuming. Ultrasound sampling, when possible, is preferable, because this method is less expensive,
less uncomfortable, more convenient for the patient, and quicker for the radiologist. Ultrasound, when correlated, may also
provide additional imaging information for further characterization of the target lesion. The evaluation and management of
suspicious breast MRI lesions may vary in clinical practice. In a study by Abe and colleagues,[56] mass lesions identified on MRI were more likely to have a sonographic correlate than NME lesions (65% vs 12%), and malignant-mass
lesions were more likely to show an ultrasound correlation (85%). Malignant lesions detected on MR may be sonographically
nonspecific and subtle, requiring careful MR interpretation -- including size, location, depth, and distance from the nipple
and chest wall -- and meticulous scanning for successful diagnosis. If any doubt regarding absolute correlation exists between
the MRI and ultrasound findings, then MR-guided biopsy is preferable.
MR-guided breast biopsy is an essential part of any breast MR imaging program, and biopsy should be performed for diagnosis of suspicious lesions not correlated with either ultrasound or mammographic findings. The procedure requires special open breast coils allowing breast access and nonferromagnetic tissue acquisition devices. The technical aspects of biopsy are well-developed and widely used in the United States. MR-guided biopsy is needed for most foci and small areas of NME.[57,58] The Breast MRI Accreditation Program established by the American College of Radiology requires that each facility must establish and maintain a medical outcomes audit program to follow up positive assessments and correlate results with the interpreting physicians' findings. The audit must include evaluation of the accuracy of interpretation as well as appropriate clinical indications for the examination. BI-RADS coding must be used for audit and lesion tracking. If the interpreting facility does not perform MR-guided breast interventional procedures, then the correlative pathology must be obtained from an accredited facility within an established referral agreement. Expectations at MR-guided biopsy include positive biopsy yields similar to or better than mammography- or ultrasound-guided biopsy for suspicious lesions. A marker clip should be placed for subsequent presurgical localization and excision.
For optimal patient management, comprehensive evaluation of all pertinent multimodal imaging procedures and related clinical and pathologic data should be readily available for complete reporting and patient management decisions. At present, no good solution exists for the integration breast studies from multiple modalities. Mammography, ultrasound, and MRI all contribute in different ways to breast cancer diagnosis and treatment. Multimodal assessment of breast lesions provides maximum information regarding the nature of each individual lesion and can drive further diagnostic interventions such as image-guided biopsy and appropriate therapy. However, while multimodal approaches continue to gain traction, they create an unwieldy amount of data. Managing this data is 1 of the greatest challenges to the full adoption of multimodal breast cancer diagnosis.
Multimodal assessment increases radiologists' interpretive time simply because of large data sets. Adding to the time burden is the lack of an efficient and easy way to compare studies from different imaging modalities, because each modality is often evaluated on a different workstation. A single workstation that enables viewing of current and prior studies from multiple sources would be helpful, as well as accessing pathology results and surgical and treatment histories. Computer-aided visualization and analysis (CAVA) tools to help radiologists sort through the large amounts of images and focus on those most likely to aid diagnosis would also be useful. Links to the electronic medical record and pathology and genomic data would allow radiologists to provide more meaningful reports. Structured and standardized reporting to aid communication among breast cancer caregivers in different departments, as well as to help patients seeking second opinions or switching care institutions, are also needed. These advances have the potential to simplify breast cancer diagnosis and improve patient care but remain significant challenges in current medical practice.
Image-based criteria, often called "imaging biomarkers," are increasingly used as surrogate end points in clinical trials of therapeutic drugs and devices. Efficient collection of accurate, reproducible, and standardized measures of tumor volumes, kinetics, and prognostic and predictive imaging biomarkers[59] will probably prove to be increasingly important for the assessment of patients with a cancer diagnosis before, during, and following treatment. For example, risk of recurrence used to be predicted based on tumor size and grade. In the postgenetic/genomic era, however, imaging biomarkers and gene expression analysis could also be factored into the analysis, providing more accurate estimates of the likelihood of recurrence as well as the potential benefits of hormonal therapy or chemotherapy. Future endeavors should include development of a breast oncology informatics program and protocols providing standardized methods for reporting of tumor sizes and functional and pathologic data. Such measures could greatly assist cross-institutional collaborative efforts, such as in oncology therapeutic trials. To this end, development of a service-oriented, user-friendly informatics architecture is highly desirable. It could be used throughout the local digital breast-imaging enterprise to improve workflow and enhance the visualization and analysis of multimodal breast-imaging studies. This effort should also be extended to incorporate not just the local breast-imaging program but also the information from the pathology and oncology departments to provide a comprehensive signature file for each patient. The principal value of these workflow improvements would be improved efficiency in managing tasks that are specifically tied to clinical applications where examinations are performed and interpreted. The main goal would be to provide optimal patient care.
MRI of the breast has developed rapidly over the past 20 years and is now firmly established as an important diagnostic tool in breast clinical practices throughout the developed world. MRI as a screening tool for women at high risk is supported by clinical research trials and evidence indicates that MRI in the preoperative setting would identify additional malignancies, reduce the need for re-excision, decrease the recurrence rate, and allow more focal therapy than is currently possible. Further studies on patient outcomes following preoperative staging and neoadjuvant treatment monitoring are currently under investigation. The projected universe of ongoing technical investigations and potential clinical applications has not yet been fully explored. Higher field-strength magnets, new contrast agents, and a plethora of new acquisition techniques -- such as diffusion-weighted and diffusion tensor imaging, MR-spectroscopy, and many other new sequences -- promise major advancement in both imaging and therapeutic capacities in the coming years, all to the benefit of patients with 1 of the most common and potentially curable cancers in the world.
