Indications for Breast MRI: Case-Based Review

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1 AJR Integrative Imaging LIFELONG LEARNING FOR RADIOLOGY Indications for Breast MRI: Case-Based Review Amy Argus 1, Mary C. Mahoney Objective The educational objectives of this continuing medical education self-assessment activity are for the reader to be able to identify the appropriate indications for breast MRI and to improve his or her skills in the evaluation of breast imaging, particularly MRI. The indications for breast MRI illustrated in this article include determination of the stage and extent of disease in a patient with newly diagnosed breast cancer, evaluation of a patient with an unknown primary tumor, evaluation of a patient with positive surgical margins after breast conservation surgery, monitoring of a patient undergoing neoadjuvant chemotherapy, evaluation of breast implant integrity, screening for breast cancer in a woman at very high risk for the disease, and use as a problem-solving tool for a woman with equivocal mammographic findings. Scenario 1 A 42-year-old woman presented for annual screening mammography, which showed an abnormal left axillary lymph node and no abnormality in the breast. Ultrasoundguided fine-needle aspiration of the lymph node revealed adenocarcinoma. Breast MRI was then performed. Mammography of the left breast shows heterogeneously dense parenchyma (Figs. 1A and 1B). The appearance of the left breast is similar to that of the contralateral breast. No masses, microcalcifications, or architectural distortions are present. An abnormally enlarged left axillary lymph node is seen. MRI shows a 1.5-cm, rapidly enhancing, irregular mass with spiculated margins and washout kinetics (Fig. 1C). Patients presenting with isolated metastatic adenocarcinoma involving axillary lymph nodes without evidence of breast cancer on mammography or physical examination are assumed to have occult ipsilateral breast cancer [1]. The primary role of breast MRI in this setting is to identify a primary malignancy in the breast to confirm the diagnosis and plan treatment. When the primary carcinoma is identified by MRI and the extent of disease is found to be localized, the patient may be treated with breast conservation therapy. Most occult tumors identified on MRI are less than 2 cm [2]. When histology from the primary tumor can be obtained, targeted hormonal and chemotherapeutic treatments may be provided. The number of axillary lymph nodes involved with metastatic disease can not be accurately determined by MRI. MRI does not provide sufficient sensitivity to exclude metastatic involvement of lymph nodes [2]. When imaging-guided sampling or surgical excision identifies breast cancer metastasis in one or more axillary lymph nodes, the number of axillary lymph nodes involved is then determined by surgical removal of the remaining lymph nodes. In this case, a diagnosis of lymph node metastasis has already been made. The number of axillary lymph nodes involved will then be determined by surgical removal of the remaining lymph nodes regardless of their imaging appearance. A high percentage of patients with unilateral metastatic axillary lymphadenopathy treated with axillary lymph node dissection without breast intervention were found to subsequently develop ipsilateral breast cancer [3]. Thus, clinical and imaging observation of the breast is no longer an option in that setting [3]. When lymph node histology results in these cases suggest adenocarcinoma, undifferentiated carcinoma, or unclassified carcinoma, a diagnostic workup to identify the primary malignancy is typically performed. This workup includes breast MRI. If the primary tumor is not identified, the most likely occult malignancy is an ipsilateral breast cancer [4 6]. These patients are most commonly treated with modified radical mastectomy and axillary lymph node dissection. However, in one third of the cases, no primary tumor is identified in the mastectomy specimen, which is presumed to be due to exclusion of small tumors from the serial pathologic sections. The long-term survival of patients treated this way is comparable to that of patients treated for stage II breast cancer detected by conventional methods [3]. The option of whole-breast irradiation accompanied by axillary lymph node dissection rather than mastectomy remains controversial. Increased recurrence rates without a significant differ- Keywords: breast cancer, breast imaging, breast MRI, MRI, women s imaging DOI: /AJR Received October 27, 2009; accepted after revision August 4, Both authors: Department of Radiology, Breast Imaging, University of Cincinnati Medical Center, 234 Goodman St., Cincinnati, OH Address correspondence to A. Argus (amy.argus@healthall.com). AJR 2011;196:WS1 WS X/11/1963 S1 American Roentgen Ray Society AJR:196, March 2011 WS1

2 Argus and Mahoney ence in overall 5-year survival rates have been found in patients undergoing irradiation rather than mastectomy [4]. However, MRI was not performed in the workups of all of those patients [4], so how the addition of MRI may alter results under similar conditions in the future is not known. Multiple studies using MRI have shown detection rates ranging from 62% to 86% for identifying an occult primary breast cancer in patients presenting with axillary lymph node metastases [2, 7]. A Fig year-old woman with history of benign left breast biopsy now presenting for screening mammography. A and B, Mediolateral oblique (A) and craniocaudal (B) views of left breast from digital mammography show heterogeneously dense parenchyma. Appearance is similar to that of contralateral breast, which is not shown. No masses, microcalcifications, or architectural distortions are present. Left axillary lymph node (arrow, A) is abnormally enlarged. C, Contrast-enhanced sagittal fat-suppressed T1-weighted image of medial aspect of left breast shows 1.5-cm, rapidly enhancing, irregular mass (arrow) with spiculated margins and washout kinetics. Scenario 2 A 52-year-old woman presented with a palpable mass in the upper outer right breast. Mammography and ultrasound were performed. She later underwent surgical excisional biopsy of the palpable mass. Pathology results revealed invasive lobular carcinoma with diffusely positive margins. Breast MRI was performed. Breast MRI performed 1 month after lumpectomy shows nodular enhancement of the anterior and inferior margins B Breast MRI is indicated for the evaluation of unilateral metastatic axillary lymphadenopathy with an unknown primary malignancy. MRI used in these instances is able to identify a primary breast malignancy in 62 86% of patients, allowing targeted systemic therapies and often breast conservation. of the postoperative seroma cavity corresponding to areas of residual malignancy found after reexcision (Fig. 2). MRI is more accurate than mammography and ultrasound in evaluating tumor size and the extent of disease for invasive lobular carcinoma. Clinical breast examination, mammography, and ultrasound tend to underestimate the tumor size of invasive lobular carcinoma in up to 50%, 70%, and 80% of cases, respectively [8, 9]. Rodenko et al. [10] found a correlation between the overall extent of disease detected on MRI with the pathologic specimens in 85% of cases versus a 32% correlation for disease detected by mammography. Sensitivities of 93 96% are reported for the detection of invasive C WS2 AJR:196, March 2011

3 Indications for Breast MRI Fig year-old woman with positive surgical margins after lumpectomy for invasive lobular carcinoma. Breast MRI was performed 1 month after lumpectomy. Sagittal subtraction MR image created from first dynamic series obtained 90 seconds after contrast administration shows nodular enhancement (arrows) of anterior and inferior margins of postoperative seroma cavity corresponding to areas of residual malignancy found after reexcision. lobular carcinoma using MRI, which is consistent with the overall sensitivity of MRI in detecting all invasive cancers [11, 12]. This is in contrast to mammographic sensitivity, which is inversely related to mammographic density and reported to range from 34% to 81% [8, 12]. Invasive lobular carcinoma also has a higher incidence of presenting with multifocal, multicentric, or contralateral tumor versus invasive ductal carcinoma, and MRI is more sensitive for detecting additional disease. Contralateral carcinoma visible only on MRI has been detected in up to 7% of cases and additional ipsilateral tumor in up to 32% of cases of invasive lobular carcinoma [12]. Obtaining clear surgical margins after breast conservation therapy for invasive lobular carcinoma is more difficult than for invasive ductal carcinoma. This difficulty is related to the infiltrative growth pattern and tendency for multifocal and multicentric tumor growth seen in invasive lobular carcinoma combined with the general underestimation of disease by mammography. Positive surgical margins, defined as cancer present in the tissue specimen within 2 mm of the margin, occurs in up to 50% of patients with invasive lobular carcinoma who are treated with breast conservation surgery and who did not undergo preoperative MRI. This is compared with up to 25% of patients with invasive ductal carcinoma showing positive surgical margins after surgery without preoperative MRI [9]. Invasive ductal carcinoma most often presents in the not otherwise specified form. However, it may also present as one of several differentiated subtypes. Examples include medullary carcinoma, which typically presents as a mass with circumscribed margins, and tubular carcinoma, which typically presents as a slow growing mass with spiculated margins. All types of invasive ductal carcinoma in general are less likely to have positive surgical margins than invasive lobular carcinoma. In cases of breast conservation therapy with positive surgical margins, MRI is helpful in differentiating whether the patient would be better served by mastectomy than reexcision. It is not the role of MRI to detect microscopic residual disease directly at the lumpectomy site. This information is determined on the basis of the pathologic margins, and surgical reexcision should be performed regardless of MRI findings. One purpose of MRI is to detect bulky residual disease at the lumpectomy site to provide a road map for directed reexcision. MRI has been reported to have a sensitivity ranging from 61% to 86% for detecting residual tumors [13 15]. However, normal granulation tissue can enhance during the early postoperative period, which limits the MRI evaluation. Frei and colleagues [16] determined that the fewest numbers of false-positive results caused by enhancement of postsurgical changes occur when MRI is performed between 35 and 42 days after surgery. Patients may be apprehensive to wait this length of time for reexcision. Some physicians advocate performing MRI during the first postoperative week, proposing that a distended postoperative seroma cavity aids in the evaluation of the surgical bed [17]. Another role of MRI in this setting is to detect multicentric breast cancer, in which separate foci of cancer are present involving different quadrants of the breast. This typically requires a mastectomy. MRI is also useful in this setting to detect multifocal breast cancer, in which separate foci of cancer are present involving the same quadrant. MRI can be used to direct reexcision when the extent of tumor is still amenable to breast conservation and may identify those who would be better served by mastectomy. This mainly applies to patients who did not undergo preoperative breast MRI. MRI is more accurate than conventional imaging in depicting the extent of disease of invasive lobular carcinoma in the ipsilateral breast and for identifying synchronous contralateral malignancy, the latter of which occurs more often with invasive lobular carcinoma than with invasive ductal carcinoma. Preoperative staging MRI for patients with invasive lobular carcinoma results in fewer cases of positive surgical margins; thus, MRI is strongly indicated AJR:196, March 2011 WS3

4 Argus and Mahoney when the patient desires breast conservation. When positive surgical margins occur, MRI is indicated to identify bulky residual disease at the surgical site as well as to identify multifocal disease and multicentric disease. Scenario 3 A 35-year-old woman presented with a palpable mass in her left breast. A bilateral mammogram showed an irregular mass in her lower medial left breast. A corresponding suspicious mass was identified with ultrasound, and an ultrasound-guided biopsy was performed, which revealed invasive ductal carcinoma. The patient desired breast conservation, and preoperative breast MRI was performed. Mediolateral oblique (MLO) views of both breasts show that the breast parenchyma is heterogeneously dense bilaterally (Figs. 3A and 3B). A BB was placed over the palpable lump in the lower left breast. An irregular mass is present near the BB marker. This mass is also visible on the craniocaudal view of the left breast. No abnormalities were shown in the right breast. Preoperative breast MRI was performed after ultrasoundguided biopsy of the left breast mass (Fig. 3C). A sagittal maximum-intensity-projection (MIP) contrast-enhanced image of the left breast shows the index mass in the lower medial left breast as a 1.2-cm, irregular, rapidly enhancing mass with plateau and washout kinetics. These findings are consistent with the diagnosis of invasive ductal carcinoma obtained by ultrasound-guided biopsy. A 6-mm, irregular, rapidly enhancing mass is also identified in the lateral left breast. This mass was subsequently identified with ultrasound and was diagnosed as invasive ductal carcinoma by ultrasound-guided biopsy. A sagittal contrast-enhanced subtraction MIP image of the right breast (Fig. 3D) showed three irregularly shaped, rapidly enhancing masses and an adjacent nonmasslike enhancement at the 12-o clock position. These findings were unsuspected based on mammography, and the diagnosis of invasive ductal carcinoma was made by ultrasound-guided biopsy. The patient was treated with bilateral mastectomies and was also found to carry a BRCA1 gene mutation. The prognosis and treatment options for patients with newly diagnosed breast cancer are based on staging. Compared with mammography and ultrasound, breast MRI provides the highest diagnostic accuracy for detecting breast cancer [12]. A high sensitivity of 99% for the preoperative assessment of the local extent of disease in patients with newly diagnosed breast cancer has been found using a combination of breast MRI, mammography, and clinical breast examination [12]. This is compared with sensitivities of 50% for clinical breast examination, 68% for mammography, 83% for ultrasound, and 94% for MRI alone [12]. MRI also depicts tumor size more accurately than mammography when correlated with pathologic specimens [18, 19]. In patients with newly diagnosed breast cancer and otherwise negative findings on conventional imaging, MRI detects additional tumors that are occult on conventional imaging in up to 27% of patients [20]. These data are applicable for multifocal disease (i.e., the presence of multiple sites of tumor in the same quadrant of the breast) and multicentric disease (i.e., the presence of multiple sites of tumor in separate quadrants of the breast). Synchronous contralateral breast cancer is reported as having an overall incidence of 4 5%. Corresponding closely to this known incidence rate, the American College of Radiology Imaging Network 6667 Trial [21] found MRI to detect unsuspected contralateral tumors in 3% of patients with newly diagnosed breast cancer. Also, a 99.8% negative predictive value for MRI was found. Although false-positive findings on MRI may require biopsy initially, these data combined create a strong case for being cautious to avoid unnecessary contralateral mastectomies [21]. Metastatic involvement of axillary lymph nodes is an important prognostic factor used in the staging of breast cancer. Unfortunately, no imaging techniques provide adequate sensitivity to detect lymph node involvement. The maximum sensitivity reported for MRI is up to 90%, which is not adequate to obviate sentinel lymph node biopsy [22]. Grossly abnormal lymph node morphology can be identified with MRI, most commonly seen as obliteration of the normal fatty hilum, thickened cortex, or irregular margins. Certainly when abnormal lymph nodes are identified, ultrasound-guided lymph node sampling should be performed. This may spare the patient a surgical sentinel lymph node biopsy when positive results are obtained. However, because of the limited sensitivity of both imaging and fine-needle aspiration, patients with negative results still require sentinel lymph node biopsy to be followed by complete axillary lymph node dissection when positive results are obtained. Breast MRI is helpful for evaluating the extent of disease in the ipsilateral and contralateral breasts in patients with newly diagnosed breast cancer. When abnormal axillary lymph node morphology is identified by MRI, ultrasoundguided sampling should be performed. However, MRI does not have sufficient sensitivity to detect lymph node metastasis; therefore, sentinel lymph node biopsy is still required when imaging of the axilla is negative. WS4 AJR:196, March 2011

5 Indications for Breast MRI Scenario 4 A 61-year-old woman presented with complaints of a palpable mass in her upper outer left breast. Bilateral diagnostic mammography was performed, which showed only heterogeneously dense breast tissue and no suspicious abnormality. Ultrasound of the palpable area showed a vague area of ill-defined hypoechogenicity without a discrete A Fig year-old woman with palpable lump in lower medial left breast. A and B, Bilateral mediolateral oblique views from digital mammogram show that breast parenchyma is heterogeneously dense bilaterally. BB marker was placed over palpable lump in lower left breast. Irregular mass (arrow, A) is present near BB marker. This mass was also visible on craniocaudal view of left breast, which is not shown. No abnormalities are shown in right breast. C, Sagittal subtraction maximum-intensity-projection (MIP) image of left breast created from first dynamic series obtained 90 seconds after contrast administration. Examination was performed after ultrasound-guided biopsy of left breast mass. Index mass (arrow) in lower medial left breast is identified as 1.2-cm, irregular, rapidly enhancing mass with plateau and washout kinetics. These MR findings are consistent with diagnosis of invasive ductal carcinoma obtained by ultrasound-guided biopsy. In lateral left breast, 6-mm, irregular, rapidly enhancing mass (arrowhead) was also identified. This mass was subsequently identified with ultrasound and was diagnosed as invasive ductal carcinoma by ultrasound-guided biopsy. D, Sagittal subtraction MIP image of right breast created from first dynamic series obtained 90 seconds after contrast administration shows three irregularly shaped, rapidly enhancing masses and adjacent nonmasslike enhancement (arrow) at 12-o clock position of right breast. These findings were unsuspected based on mammography. Diagnosis of invasive ductal carcinoma was made by ultrasound-guided biopsy. Patient was treated with bilateral mastectomies and was also found to carry BRCA1 gene mutation. B mass. A biopsy of the palpable mass was performed, yielding results of invasive lobular carcinoma. Breast MRI was then performed to evaluate the extent of disease, which was not evident on mammography or ultrasound. Digital MLO and craniocaudal views of the left breast were obtained with a BB placed on the skin over the site C D AJR:196, March 2011 WS5

6 Argus and Mahoney where the patient pointed out a palpable mass (Figs. 4A and 4B). The breast parenchyma is heterogeneously dense. No mammographic abnormality is evident. A sagittal contrast-enhanced subtraction image of the left breast shows a large irregular mass measuring 4 cm in maximum dimension (Fig. 4C). The mass contains areas of rapid enhancement with washout kinetics. Linear nonmasslike enhancement is also seen extending an additional 2 cm anterior to the mass. Several small satellite masses surround the dominant mass. Dense breast tissue is known to limit the sensitivity of mammography to detect cancer [12]. When a cancer is identified, dense breast tissue limits the ability to visualize the borders of the tumor and to detect possible additional disease. The sensitivity of breast MRI to detect breast cancer and evaluate the extent of disease, however, is not affected by breast density [7, 12]. MRI is useful in evaluating the extent of local and regional disease for the purpose of staging and surgical treatment planning. Patients with known distant metastatic disease are considered to have stage IV disease, which is treated systemically. Thus, breast MRI is usually not indicated for these patients. Invasive lobular carcinoma is often subtle or is not even visible on mammography; even when diagnosed, the extent of disease is often underestimated. MRI has been shown to be superior to mammography in accurately detecting the extent of disease of invasive lobular carcinoma [10, 12]. Patients with invasive ductal carcinoma who also have a large component of ductal carcinoma in situ (DCIS) that is, making up greater than 25% of the disease extent are considered to have an extensive intraductal component. Assessing tumor size in these patients is also difficult and MRI is superior to mammography in detecting unsuspected DCIS [12, 23, 24]. Patients with tumors larger than 5 cm are considered to have locally advanced disease. The borders of large tumors can be difficult to accurately determine with mammography and physical examination because of a fibrotic response of the tissue surrounding the tumor. MRI, however, is more accurate in depicting the true tumor size. Also, patients with locally advanced breast cancer are usually treated initially with neoadjuvant chemotherapy. MRI serves two roles for women undergoing neoadjuvant chemotherapy: monitoring response during treatment and identifying any residual tumor at the completion of treatment [14]. Breast MRI for preoperative staging is useful in most patients with newly diagnosed breast cancer. It is particularly useful in the following three scenarios: patients with dense breast tissue, patients with tumors known to be difficult to detect on imaging including invasive lobular carcinoma and invasive ductal carcinoma with an extensive intraductal component, and patients with large tumors. A Fig year-old woman with palpable mass in upper outer left breast. A and B, Digital mammograms, mediolateral oblique (A) and craniocaudal (B) views, of left breast obtained with BB placed on skin over site where patient pointed out palpable mass show breast parenchyma is heterogeneously dense. No mammographic abnormality is evident. C, Sagittal subtraction maximum-intensity-projection image of left breast created from first dynamic series obtained 90 seconds after contrast administration shows large irregular mass measuring 4 cm in maximum dimension. Mass contains areas of rapid enhancement with washout kinetics. There is also linear nonmasslike enhancement (arrow) extending additional 2 cm anterior to mass. Several small satellite masses (arrowheads) also surround dominant mass. B C WS6 AJR:196, March 2011

7 Indications for Breast MRI Scenario 5 A 65-year-old woman presented with complaints of a palpable mass in her right breast. Diagnostic bilateral mammography and right breast ultrasound were performed, which identified a suspicious mass in the inferior medial posterior right breast. Ultrasound-guided biopsy revealed invasive ductal carcinoma. Preoperative breast MRI was then performed. Fig year-old woman with palpable mass in lower medial right breast. A, Digital mammogram, right mediolateral oblique view, obtained with BB marker on skin of inferior breast to indicate palpable abnormality pointed out by patient shows partially obscured mass (arrow) in posterior breast. Mass is not completely included on image because of its posterior location in breast. B, Contrast-enhanced fat-suppressed T1 sagittal image of right breast from MRI performed for preoperative staging shows irregular mass with rim enhancement in posterior breast corresponding to biopsy-proven malignancy. Mass extends into pectoral muscle, and ill-defined enhancement (arrow) extends from superior margin of mass into pectoral muscle. Mass was invasive ductal carcinoma by ultrasound-guided biopsy. The MLO view of the right breast from a digital mammogram is shown in Figure 5A. A BB marker is present on the skin of the inferior breast to indicate the palpable abnormality pointed out by the patient. A partially obscured mass is present in the posterior breast. The mass is not completely included on the image because of its posterior location in the breast. A sagittal contrast-enhanced fat-suppressed T1-weighted image of the right breast shows an irregular mass with rim enhancement in the posterior breast (Fig. 5B) corresponding to the biopsy-proven malignancy. This mass extends into the pectoral muscle, and ill-defined enhancement extends from the superior margin of the mass into the pectoral muscle. Breast MRI has been shown to accurately identify pectoral muscle and chest wall tumor invasion. The only MRI finding to reliably indicate tumor muscle invasion is that of muscle enhancement. Morris et al. [25] described two patterns of muscle enhancement: diffuse infiltrating muscle enhancement without mass effect, with preservation of the muscular architecture; and masslike enhancement expanding the pectoralis muscle and showing loss of the muscle striations. Muscle enhancement was seen to be temporally related to the enhancement of the adjacent tumor mass. Additional findings that may seem suspicious for muscle invasion, including a small distance between the tumor and muscle and loss of fat planes between the tumor mass and muscle, do not indicate invasion. Prominent vascular structures posterior to the mass are often seen as serpiginous smooth enhancing structures that may travel through the muscle. These also do not indicate muscle invasion and are often readily differentiated from the more ill-defined or masslike muscle enhancement caused by tumor invasion. Whether a breast cancer tumor has extended into the chest wall is an important factor for use in staging and treatment planning. Tumor invasion of the pectoralis muscle alone does not affect the cancer stage but does require further surgical intervention to obtain clear margins. If a tumor superficially invades the pectoralis major muscle, a portion of the muscle will be removed. However, if a large portion of the underlying pectoralis major muscle is involved, radical mastectomy may be required. A tumor involving the chest wall including the ribs, intercostal muscles, and serratus anterior muscle has a worse prognosis than one without chest wall involvement. A patient with this level of disease may be treated with preoperative che- A B AJR:196, March 2011 WS7

8 Argus and Mahoney motherapy and radiation therapy, possibly followed by chest wall resection. Thus, it is essential to define the extent of disease before surgery so that appropriate surgical and medical treatment may be planned. The evaluation of posterior tumors by mammography is limited. Mammography may not completely image the Scenario 6 A 39-year-old woman with increased risk for breast cancer presented for screening breast MRI. Bilateral mammography was also performed, which was negative. A sagittal contrast-enhanced MIP image of the left breast shows a focal area of clumped, nonmasslike enhancement with a linear distribution in the lower breast (Fig. 6A). This finding is suspicious for DCIS, which was confirmed by MRI-guided biopsy. An acceptable screening test requires low false-positive and false-negative rates along with cost effectiveness. To achieve these goals in light of the limited specificity and the high cost of breast MRI, a screening population must have a high prevalence of disease. Therefore, the American Cancer Society (ACS) guidelines currently recommend annual screening with breast MRI as an adjunct to mammography only for women with a very high risk for breast cancer [26]. This group includes those with known BRCA1 and BRCA2 mutations and their untested first-degree relatives; women with prior irradiation to the chest between the ages of 10 and 30 years; and women with Li-Fraumeni, Cowden, and Bannayan-Riley-Ruvalcaba syndromes and their first-degree relatives. The National Cancer Comprehensive Network also posterior aspect of the breast and is particularly limited in patients with posterior tumors affixed to the chest wall. MRI does image the entire breast and can identify pectoral muscle and chest wall tumor muscle invasion. Muscle enhancement is the only reliable MRI finding to indicate tumor invasion. recommends MRI screening in women with a history of lobular carcinoma in situ [27]. Women with a lifetime risk for breast cancer of 20 25% or greater, as defined by risk models based mostly on family history (BRCAPRO [Exeter Software], breast and ovarian analysis of disease incidence and carrier estimation algorithm [BOADICEA], or Tyrer-Cuzick models), are also included in the ACS recommendation for annual screening with breast MRI and mammography. These recommendations are based on compelling evidence in support of screening MRI for high-risk women. In an analysis of nine separate series involving 4,485 veryhigh-risk women, 178 of 192 cancers were identified by MRI combined with mammography, whereas only 70 of the 192 cancers were identified with mammography alone [27]. Furthermore, cancers identified by MRI tended to be smaller (< 10 mm) and node-negative than those identified by mammography [28]. Unfortunately there is limited information regarding the cost-effectiveness of screening breast MRI. A large Canadian study identified MRI to be most cost-effective for BRCA gene mutation carriers [29]. Performing breast MRI screening in women with moderately increased risk for breast cancer remains debatable. The lower prevalence of disease in this group of women results in lower cost-effectiveness and higher false-positive rates with MRI use. The ACS considers the following women to be at intermediate risk: lifetime risk of 15 20% Fig. 6 Screening breast MRI of 39-year-old woman with increased risk for breast cancer. Sagittal subtraction maximum-intensity-projection image created from first dynamic series obtained 90 seconds after contrast administration shows focal area of clumped, nonmasslike enhancement (arrow) with linear distribution in lower breast. This finding is suspicious for ductal carcinoma in situ, which was confirmed by MRI-guided biopsy. WS8 AJR:196, March 2011

9 Indications for Breast MRI as defined by risk models; prior diagnosis of lobular carcinoma in situ, atypical lobular hyperplasia, or atypical ductal hyperplasia; heterogeneously or extremely dense breasts on mammography; or personal history of breast cancer including DCIS. The guidelines indicate that there is insufficient evidence to recommend for or against MRI screening in these women and that screening decisions should be made on a case-by-case basis. The ACS recommends against screening MRI in women with a lifetime risk for breast cancer of less than 15% [26]. Annual screening mammography remains the only imaging technique proven to decrease breast cancer mortality Scenario 7 A 46-year-old woman with bilateral silicone breast implants presented with concern for implant rupture. Bilateral mammography, including implant inclusion and implant-displaced views, was performed. No findings to indicate implant rupture were identified. Bilateral breast MRI was then performed. Bilateral mammography was performed (Fig. 7A). A prepectoral-retroglandular implant is present. No densities are seen separate from the implant to indicate extracapsular rupture of the implant. Breast MRI was then performed. A sagittal unenhanced silicone-hyperintense, inversion recovery sequence of the left breast is shown in Figure 7B. Silicone inside the implant is hyperintense. The linguine sign is seen as a dark curvilinear line within the silicone, indicating intracapsular implant rupture. There is no silicone outside the implant to indicate extracapsular implant rupture. Axial bilateral unenhanced silicone-hyperintense inversion recovery sequence shows the keyhole sign in the left breast (Fig. 7C), which indicates intracapsular implant rupture. Normal radial folds are shown in the right breast. Radial folds are a normal finding seen on MRI. In-folding of the implant capsule results in short dark lines extending into the implant lumen. This finding should not be confused with the keyhole sign, in which a loop of the implant envelope protrudes into the implant material, with silicone visualized on both sides of the dark line of the implant envelope. The keyhole sign indicates partial intracapsular rupture. The linguine sign seen on MRI is a sensitive indicator of complete intracapsular rupture. Dark, curvy, linear lines are seen within the implant, representing the collapsed implant envelope floating in silicone within the fibrous capsule. Reported sensitivities for the detection of implant rupture using MRI range from 78% to 100% versus 28% for mammography and 59% for ultrasound. The specificity of MRI ranges for the general population. The addition of contrast-enhanced breast MRI to mammography has been shown to increase the rate of detection of small node-negative cancers in high-risk women [28]. Screening breast MRI has been shown to be most appropriate and is recommended by the ACS for women at very high risk for breast cancer. The decision for screening MRI should be made on a case-bycase basis for women at intermediate risk and it is not recommended for women at average risk. from 63% to 91% [30 33]. False-negative results for intracapsular rupture with MRI may be due to a ruptured, noncollapsed implant envelope that has adhered to the fibrous capsule. Complex radial folds can be a source of false-positive diagnosis of intracapsular rupture with MRI. Signs of implant rupture visible on ultrasound include the stepladder sign and the snowstorm sign. The stepladder sign may be seen on ultrasound when intracapsular implant rupture is present. This sign consists of multiple parallel linear echoes identified in the lumen of the implant. This finding is neither sensitive nor specific for implant rupture [30]. The snowstorm sign is seen as echogenic noise on ultrasound, which represents silicone gel in the breast parenchyma resulting from extracapsular implant rupture. This finding is not very sensitive, but it is highly specific for extracapsular rupture [30]. Similarly, the finding of increased density outside the implant or within axillary lymph nodes seen on mammography is specific but not sensitive for extracapsular rupture [30]. Visualization of silicone outside the fibrous capsule on MRI is diagnostic of extracapsular rupture. However, distal migration of silicone within a herniation of the implant shell can be a cause of false-positive results on MRI [30]. When silicone gel implants are inserted into the breast, the body forms a fibrous capsule around the prosthesis. Most cases of implant rupture are intracapsular: The implant envelope degrades but the silicone remains contained within the fibrous capsule [34]. Extracapsular rupture that is, rupture of both the implant envelope and the surrounding fibrous capsule that results in free silicone in the breast or axilla occurs much less often. Unenhanced breast MRI using silicone-hyperintense inversion recovery sequences allows visualization of the internal architecture of the implant and identification of extracapsular silicone. The linguine and keyhole signs are sensitive indicators of intracapsular implant rupture on MRI. AJR:196, March 2011 WS9

10 Argus and Mahoney Scenario 8 A 43-year-old woman with a new diagnosis of breast cancer and metastatic axillary lymphadenopathy was treated with neoadjuvant chemotherapy. Breast MRI was performed before chemotherapy and then again 4 months later after completion of chemotherapy. She was then treated with lumpectomy. The pathologic specimen from lumpectomy yielded only a 6-mm focus of residual tumor. The baseline MRI shows a large enhancing mass (Fig. 8A) that corresponds to the biopsy-proven invasive ductal cancer. After the patient completed chemotherapy, the tumor was no longer visible by MRI. Only susceptibility artifact from the biopsy marker clip remained at the site of the original mass. MRI provides an accurate method to depict residual disease after the completion of neoadjuvant chemotherapy. MRI findings have been shown to correlate with pathologic response better than conventional imaging and clinical examination do. The accuracy of MRI is in the range of 71 90%, versus 19 A C B Fig year-old woman with bilateral silicone breast implants who presented for bilateral mammography because of clinical concern for implant rupture. A, Left mediolateral oblique breast implant inclusion view from digital mammogram shows prepectoral-retroglandular implant. No densities are seen separate from implant to indicate extracapsular rupture of implant. B, Sagittal unenhanced silicone-hyperintense inversion recovery MR image of left breast shows silicone inside implant is hyperintense. Linguine sign (arrow) is seen as dark curvilinear line within silicone, indicating intracapsular implant rupture. There is no silicone outside implant to indicate extracapsular implant rupture. C, Axial unenhanced silicone-hyperintense inversion recovery MR image of both breasts shows keyhole sign (solid arrow) in left breast, which indicates intracapsular implant rupture. Normal radial folds (dashed arrow) are shown in right breast. 60%, 35 75%, and 26 70% for clinical examination, ultrasound, and mammography, respectively [35 38]. However, both overestimation and underestimation of residual disease have been found on MRI. A prospective study including 41 patients identified overestimation of residual disease in two patients. It is not known why this occurs. Some authors propose that the presence of enhancement in areas lacking tumor may be due to reactive inflammation caused by tumor response and healing or by increased capillary permeability caused by chemotherapy [35]. Underestimation of residual disease has been reported in up to 23 26% of the cases and is suspected to result from chemotherapy-induced decreased vascular supply to the tumor that, in turn, causes less visible tumor enhancement on MRI [35, 39]. Tumor biology and various chemotherapeutic agents affect the accuracy of MRI as well. A recent prospective study of 51 patients found MRI to be highly accurate in predicting a pathologic complete response in patients with HER2-positive tumors [39]. However, the authors of that study identified a high false-negative rate for predicting a pathologic complete response in patients treated with the antiangiogenic agent be- WS10 AJR:196, March 2011

11 Indications for Breast MRI Fig year-old woman with newly diagnosed breast cancer. A, Baseline contrast-enhanced sagittal fatsuppressed T1-weighted image of right breast shows large enhancing mass (arrow). This mass corresponds to biopsy-proven invasive ductal cancer. B, Obtained after patient had completed neoadjuvant chemotherapy, contrast-enhanced sagittal fatsuppressed T1-weighted image of right breast reveals that tumor is no longer visible by MRI. Only susceptibility artifact from biopsy marker clip (arrow) remains at site of original mass. vacizumab and in patients with HER2-negative tumors [39]. Occult residual disease often presented as scattered tumor cells or foci [39]. Thus, MRI cannot definitively exclude the presence of residual disease and surgery is still indicated. For this reason, it is important to place a marker clip within the tumor bed before administering neoadjuvant chemotherapy so that accurate preoperative localization can be achieved in patients who undergo breast conservation therapy. The emphasis on providing breast conservation therapy for women with breast cancer has led to the increasing use of neoadjuvant chemotherapy, in which an attempt is made to decrease the size of locally advanced tumors before surgery. This treatment may allow the option of breast conservation therapy rather than mastectomy. Also, a pathologic complete response that is, when no residual tumor can be found in the surgical pathology specimen has been found to correlate with improved overall survival [40]. It is important to identify those patients who will respond to the specific neoadjuvant treatment early in the course of chemotherapy so that treatment modifications can be made if needed, with the goal of obtaining a pathologic complete response. This Scenario 9 A 60-year-old woman presented for screening mammography. Architectural distortion was questioned in the lateral breast on the craniocaudal view. Diagnostic mammography was then performed. Architectural distortion persisted on a spot compression craniocaudal view but was not seen on rolled craniocaudal views, and no corresponding finding could be identified on the MLO or true lateral views. Breast MRI was then performed. A also prevents the patient from being exposed to the toxicity and side effects of an ineffective chemotherapy regimen. Although it is not perfect, breast MRI is more accurate than conventional imaging and clinical examination for the measurement of residual disease after neoadjuvant chemotherapy. Emerging research is identifying factors, such as tumor biology and various chemotherapeutic treatments, that are likely to affect the sensitivity of the test and that may aid in the ability to target the examination appropriately for various patient populations. Exciting research is also under way to evaluate the use of MRI in predicting early tumor response to neoadjuvant treatment and its role in predicting disease-free survival. ACRIN (American College of Radiology Imaging Network) is currently sponsoring a multiinstitutional prospective clinical trial (ACRIN Trial 6657) to assess the role of MRI for the evaluation of patients undergoing neoadjuvant treatment, including whether MRI measurements of treatment response can predict 3-year disease-free survival and whether an early prediction of response can be made after one cycle of treatment. The protocol was also amended to add MR spectroscopy and was reopened in 2007 to evaluate whether choline concentration corresponds to tumor response after one cycle of chemotherapy. A digital mammogram, craniocaudal view, of the right breast shows architectural distortion in the lateral breast (Fig. 9A). A corresponding area of architectural distortion is not seen on the MLO view of the right breast (Fig. 9B). A contrast-enhanced axial MR image shows an irregular enhancing mass with spiculated margins at the 9-o clock location of the right breast (Fig. 9C). This mass was subsequently identified on targeted ultrasound, and ultrasound-guided biopsy was performed. B AJR:196, March 2011 WS11

12 Argus and Mahoney When suspicious or indeterminate findings are identified by mammography, sonography, or clinical breast examination, a negative breast MRI does not exclude the need for a biopsy. The negative predictive value of MRI in this setting is only 85%, which is not high enough to obviate biopsy [41]. This is particularly true given the accepted standard that a lesion considered to have a 3% or greater probability of malignancy should undergo biopsy. Also, stereotactic and ultrasound-guided biopsies are safe and widely available. For example, a mammographic mass that is new when compared with prior mammograms is a suspicious finding. Even if the mass shows circumscribed margins on mammographic views, if it cannot be identified as a cyst by ultrasound, it should be assumed to be solid and a stereotactic biopsy should performed. MRI is not appropriate in this situation. Also, a focal asymmetry that is new compared with a prior mammogram is suspicious for malignancy. This finding should be further evaluated with tissue sampling. A negative MRI would not obviate biopsy in this case. Indeterminate microcalcifications should be further evaluated with tissue sampling. An even lower negative predictive value for MRI of 76% has been reported in the evaluation of calcifications as an isolated mammographic finding [42]. Calcifications are typically amenable to localization for stereotactic biopsy. Thus, MRI has no role in the determination for or against biopsy of calcifications. However, when a diagnosis of DCIS is made, MRI may be helpful in determining the extent of disease and in identifying a possible invasive component. A final decision regarding the management of mammographic findings may be made after a complete diagnostic mammographic and sonographic evaluation in nearly all cases. At times, mammographic findings remain equivocal and uncertainty remains as to whether a true lesion exists and the 3D location of the finding is unknown. MRI can be useful as a problem-solving tool during these very infrequent circumstances. Performing stereotactic biopsy for a finding seen in only one view carries a degree of uncertainty when negative results are obtained because of the risk of false-neg- A Fig year-old woman who presented for screening mammography. A, Craniocaudal view of right breast from digital mammogram shows architectural distortion (arrow) in lateral breast. B, Mediolateral oblique view of right breast from digital mammogram does not show area corresponding to architectural distortion shown in A. C, Axial contrast-enhanced fat-suppressed T1 image shows irregular enhancing mass (arrow) with spiculated margins at 9-o clock location of right breast. This mass was subsequently identified on targeted ultrasound, and ultrasound-guided biopsy was performed. B C WS12 AJR:196, March 2011

13 Indications for Breast MRI ative biopsy results. A recent single-site study of 115 patients who underwent MRI because of equivocal mammographic findings after a conventional diagnostic workup found MRI to have 100% sensitivity (0 false-negatives results) and 92% specificity [43]. The indications for MRI in that study included asymmetries, both one- and two-view findings, presenting without microcalcifications (n = 98); architectural distortion (n = 12); and possible change in the appearance of a prior benign biopsy site (n = 5). Fifteen enhancing masses corresponding to the mammographic abnormality in question were identified, six of which were malignant, and four of those were identified only on a single mammographic view. Also, all of the identified lesions could be localized for biopsy. These results suggest that in carefully selected and infrequent cases, a negative MRI may add reassurance that an equivocal mammographic finding likely represents summation artifact or normal fibroglandular tissue, allowing increased confidence in the option of close mammographic follow-up. Also, MRI can provide localization of the abnormalities identified to facilitate accurate biopsy targeting. A final decision regarding the management of mammographic findings may be made after a complete diagnostic mammographic and sonographic evaluation in nearly all cases. Problem-solving MRI should not be used as an alternative to a thorough conventional imaging workup. After a conventional workup, it is not appropriate to use MRI as an alternative to biopsy for indeterminate calcifications or for suspicious findings. 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