Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Imaging of Invasive Breast Cancer biopsy in 9.3% of women (95% confidence interval [CI], 5.8%-14.7%) with PPV for malignancy of 47.9% (95% CI, 31.8%-64.6%). Where reported, 35.1% of MRI-detected cancers were DCIS (mean size = 6.9 mm) and 64.9% were invasive cancers (mean size = 9.3 mm) [58]. MRI can accurately assess tumor size for preoperative planning [50,59-61]. In a study involving 343 tumors, size measurements of cancers on breast MRI were within 5 mm of pathological size in 88% of patients [60]. Still, other studies using mastectomy specimens have shown that MRI underestimates primary tumor size in 21% and overestimates primary tumor size in 24% of cases [62]. MRI also overestimated the number of invasive lesions by 19% and underestimated the number of invasive lesions in 28% in the same study [62]. These data underscore the importance of using biopsy to pathologically confirm MRI findings instead of relying on them to alter surgical planning, especially when the MRI finding is nonmass enhancement [63]. In addition to tumor size assessment, some studies show a reduction in re-excision after preoperative MRI [64-68]. For example, in a study of 991 women, preoperative MRI changed the surgical procedure in 25% (157/626) of cases. In 81% (127/157), MRI benefited some patients, as otherwise occult carcinomas were removed (n = 122) and further biopsy prevented (n = 5) [67]. In this trial, the rate of mastectomy did not differ between patients undergoing preoperative MRI and those who did not. A recent multinational observational study at 27 centers also found that subjects receiving MR as part of routine clinical care had a significantly lower reoperation rate after breast conservation (8.5% versus 11.7%, P < . 001) [69].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. However, other large multicenter studies, such as the comparative effectiveness of MRI in breast cancer (COMICE) trial, showed the addition of MRI to conventional imaging was not significantly associated with a reduced reoperation rate, with 153 (19%) needing reoperation in the MRI group versus 156 (19%) in the non-MRI group (odds ratio [OR], 0.96; 95% CI, 0.75-1.24; P = . 77) [70]. Although the findings are important, limitations from the COMICE trial are also noted, such as its inclusion of patients from several small centers where technical factors and varying degree of experience among interpreting radiologists could have influenced the MRI results. It is also not clear that the data from the MRI was incorporated into surgical planning, and nearly 7% of the group assigned to MRI did not actually have an MR interpreted (analyzed by intention to treat). When all breast cancer subtypes were included, a meta-analysis of 19 studies did not find evidence that MRI impacted the rates of re-excision, reoperation, or positive margins, but MRI was significantly associated with increased odds of receiving contralateral prophylactic mastectomy (OR, 1.91; 95% CI, 1.25-2.91; P = . 003) [71]. This analysis of 85,975 women also showed that preoperative MRI was associated with increased odds of receiving mastectomy (OR, 1.39; 95% CI, 1.23-1.57; P < . 001) [71]. Still, it is unknown whether some of the studies included in that meta-analysis had a bias in randomization (ie, women who were preplanned for mastectomies were more likely to have been referred rather than randomized to the preoperative MRI arm). As an example of this, in the multicenter international prospective analysis cited above [69], mastectomy was already planned based on conventional imaging in 22.4% (MRI group) versus 14.4% (no MRI group) (P < . 001). The data are different for ILC histological subtypes. For ILC, there is strong evidence that MRI improves surgical outcomes [72-81].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. In a study with 70 cases of ILC, preoperative MRI reduced re-excision rates, particularly in young women with dense breasts [82]. In another study with 369 women, preoperative breast MRI was also associated with a reduction in repeat surgery (OR, 0.140; P < . 001), without increasing mastectomy rates [76]. Although MR does lead to increased cancer detection, there is limited evidence that preoperative MRI improves survival or decreases recurrence, including data from multicenter analyses [61,68,83-85]. In 3,180 affected breasts in 3,169 women (median age, 56.2 years), 8-year disease-free survival did not differ between the MRI (97%) and the non-MRI (95%) groups (P = . 87), and the multivariable model showed no significant effect of MRI on disease- free survival: hazard ratio (HR) for MRI (versus non-MRI) was 0.88 (95% CI, 0.52-1.51; P = . 65); age, margin status, and tumor grade were associated with disease-free survival (all P < . 05) [85]. Of the 31,756 patients included in a survival cohort (70% non-MRI and 30% MRI), breast MRI was not significantly associated with overall survival (HR, 0.91; 95% CI, 0.74-1.11, P = . 35) or with disease-free survival (HR, 1.16; 95% CI, 0.81-1.67), even among the different histological subtypes. The lack of survival benefit extends also to patients with ILC, despite improved surgical outcomes in this population as described above [83]. One recent study did show lower recurrences (locoregional, distant and contralateral) in women who received a preoperative MRI, with a nonsignificant trend toward MR improving disease-free survival (P = . 057) [86], and another study of 1,199 subjects did show improved overall survival in the group who received MRI [87]. Given these data, benefits of preoperative MRI for additional cancer detection or delineating extent of disease should be balanced with the possibility of a false-positive diagnosis leading to additional biopsy, unnecessary additional imaging, and potential delays in definitive treatment.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Due to additional cancer detection on a per-patient Imaging of Invasive Breast Cancer level, MRI is considered optional, despite a lack of definitive data supporting classical improved outcomes and continued controversy regarding potential harms. Considering the evidence above, MRI-detected suspicious masses >2 cm from the index malignancy or nonmass enhancement significantly larger than expected from mammographic/sonographic findings should be sampled before using MRI findings to alter surgical planning or change treatment recommendations. MRI Breast Without IV Contrast There is no evidence to support the use of noncontrast breast MRI in evaluating extent of disease. US is the most established noninvasive imaging test for assessing the axilla following a clinically or imaging detected suspicious lymph node. US features associated with a higher likelihood of malignancy include short-axis lymph node size >1 cm, cortical thickness of >0.3 cm, and an absence of a fatty hilum [90-93]. There is a wide range of reported sensitivity and specificity for axillary US, and none of these imaging features are specific enough to avoid the need for histologic sampling. The sensitivity ranges from 26.4% to 94%, and the specificity ranges from 53% to 98% [94-97]. Axillary US alone has a relatively low NPV to rule out metastatic disease [36,98]. A meta-analysis of 21 studies showed that US combined with needle biopsy improved the sensitivity from 61% to 79% [99-101]. US-guided core needle biopsy was superior to US-guided FNA in a meta-analysis of 1,353 patients with newly diagnosed invasive breast carcinoma, with a reported sensitivity of 88% for core biopsy and 74% for FNA [102]. Axillary US and an MRI performed similarly (sensitivity of 99.1% versus 97.4% and specificity 15.4% versus 15.4%, respectively) in evaluating axillary lymph nodes.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Despite this performance, approximately 14% of women with breast cancer and negative imaging for axillary metastasis ultimately have metastatic disease on sentinel lymph node biopsy [103]. US Breast Diagnostic mammography and US together can assess for extent of disease and tumor size. These imaging tests are usually already completed as part of the diagnostic workup (prior to pathological diagnosis). The sensitivity of US for detecting cancer ranges from 79% to 94% [22,25,104,105]. The addition of DBT to US improved sensitivity for detecting both primary breast cancer and multicentric and multifocal disease, from 82.6% (nondense) and 91.6% (dense) with US alone to 97.7% with combined DBT and US [106]. However, DBT and mammography have limited added value over US alone for initial evaluation in women <40 years of age [105]. Although bilateral US use in women with primary breast cancer to evaluate for multicentric and multifocal disease shows a lower sensitivity than MRI (85.1% versus 71.1%), US showed higher accuracy and specificity than MRI (67.6% versus 39.3% and 69.2% versus 60.2%, respectively), suggesting that bilateral US may be an acceptable alternative to MRI for locoregional staging [57]. When compared with DM alone, supplemental US more accurately depicted the extent of disease needing wider excision in 17 of 96 (18%) breasts for which conservation was anticipated, corresponding to 17 of 30 (57%) breasts with mammographically occult disease [22]. Based on mammography/clinical examination, 2% to 3% of patients have synchronous bilateral cancer [107]. This risk for bilateral synchronous cancer is increased in patients less than 55 years of age or in those diagnosed with invasive lobular subtypes [108]. In 1 series with 9% contralateral synchronous malignancy, mammography detected 60%, US detected 80%, and MRI detected 90% (with the remainder detected on follow-up imaging) [22].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. In addition to its role in the initial diagnostic workup, US is important in the secondary evaluation of a suspicious finding on MRI in the setting of evaluation of disease extent. US sensitivity and NPV are higher than those of DBT [109]. Compared with DBT, US showed a lower specificity (98.1% versus 78.9%) and similar PPV (66.7% versus 52.2%). However, a meta-analysis of second-look US following a suspicious finding on MRI showed heterogeneity in US performance, with the detection rate ranging from 22.6% to 82.1% (pooled detection rate 57.5%) and an 87.8% pooled NPV [110]. Therefore, a negative US is insufficient to obviate the need for an MRI biopsy in this setting. There is no evidence supporting US as an accurate method for determining disease extent of those diagnosed with ILC subtype. Conventional imaging with mammography and/or US can significantly underestimate the extent of ILC [26,111-114]. For example, US specifically underestimated ILC tumor size by 27% (95% CI, 17%-37%) in a Imaging of Invasive Breast Cancer study [113], and a different study showed that the greatest discrepancy between tumor size and pathologic size using US measurements was for the ILC subtype [26]. Variant 2: Newly diagnosed. Clinical stage I-IIA (early stage) breast cancer at presentation. Evaluation for distant disease (includes IDC, or ILC, or NOS). It has long been recognized that steroid receptor expression reflects intrinsic biologic diversity in breast cancer with treatment and survival implications, also determining patterns of metastatic spread. Historically, bone is the most likely site of breast cancer metastases (51%), followed by liver/soft tissue (19%), pleura (16%), lung (14%), and brain (4%) [115]. The higher percentage of bone metastases from breast cancer appears to be driven primarily by the majority of primary tumors expressing ER and/or PR.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. In 1 large multidecade study, 82% of patients with breast cancer who developed bone metastases had either ER and PR or ER positivity in the primary tumor [115]. A landmark study 2 decades ago transformed our field by discovering 5 distinct composite molecular portraits using quantitative analysis of breast cancer gene expression patterns; luminal A, luminal B, HER2-enriched, basal-like, and normal-like, providing a new type of disease characterization [116]. The molecular subtypes were linked to pattern and type of metastatic spread, as well as disease-specific survival [117,118]. For example, luminal cancers have a propensity to give rise first to bone metastases, HER2-enriched cancers to liver and lung metastases, and basal type cancers to liver and brain metastases [119,120]. These molecular subtypes share similarities with ER/PR expression and HER2 gene amplification but are not synonymous. Luminal subtypes more commonly have ER expression, HER2-enriched cancers more commonly exhibit HER2 expression, and triple-negative breast cancers are most often the basal breast cancer subtype. Although luminal subtypes have significantly better overall and relapse-free survival [118], they carry a long-term risk of recurrence, especially to bone, whereas basal and HER2 subtypes have a higher rate of recurrence in the first 4 years [121], which can be considered when planning frequency and type of surveillance imaging. Bone Scan Whole Body Bone is the most common site for breast cancer metastasis; up to 70% of women with stage IV disease have bone metastasis, with the predilection for bone metastases not applying to basal-like tumors [117]. Up to 13.6% of women diagnosed with early stage breast cancer will develop bone metastasis within 15 years of diagnosis [122], even if the parent tumor is low grade [123].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Tc-99m bone scans detect early bone metastasis because of the new bone formation occurring at these sites [124] and have a 98% sensitivity for detecting early bone metastasis in symptomatic patients. However, bone scan is not helpful for asymptomatic women with newly diagnosed early stage breast cancer due to the low prevalence of metastasis (<1%) at initial diagnosis [125]. Whole body bone scans are performed in up to 35% of women with newly diagnosed breast cancer despite National Comprehensive Cancer Network (NCCN) guidelines recommending against routine staging in asymptomatic women with early stage breast cancer [125,126]. The unnecessary use of this imaging test and the further evaluation of false-positive findings can result in treatment delay [127]. There is no evidence to use whole body bone scan in the evaluation of distant disease in stage I to IIA breast cancer. CT Chest, Abdomen, and Pelvis With IV Contrast National and international guidelines (American Board of Internal Medicine [ABIM]/ASCO, European Society for Medical Oncology [ESMO], and Spanish Society of Medical Oncology [SEOM]) discourage the use of imaging for staging in asymptomatic patients with newly diagnosed early stage breast cancer [128-130]. NCCN guidelines recommend chest, abdomen, and pelvic CT as an additional test prior to preoperative systemic therapy in clinical stage I to IIA if the tumor is >2 cm, >1 cm and immunohistochemical subtype is triple negative, or HER2+ or any size/subtype with known axillary nodal spread [126]. However, this test is often used in the staging evaluation of low-risk cancers, outside these guidelines, despite a lack of evidence suggesting that it improves detection of metastatic disease or increases survival. There is a lack of evidence demonstrating a benefit for the use of CT in asymptomatic individuals with clinical stage I or II disease outside the guidelines above.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. A survey of NCCN member institutions found that 11% of patients with stage I and 36.2% of patients with stage II received a staging CT of the chest. This resulted in 27% of patients diagnosed with pulmonary nodules requiring a mean 2.34 additional CTs (range 0-16) for follow-up. Of pulmonary nodules detected in asymptomatic women with early stage breast cancer, only 2% of these patients were ultimately diagnosed with pulmonary metastasis [131,132]. Imaging of Invasive Breast Cancer CT Chest, Abdomen, and Pelvis Without and With IV Contrast The majority of clinical questions for abdominal and/or pelvic CT can be appropriately answered with a single- phase study as detailed in the ACR-SABI-SPR practice parameter for the performance of CT of the abdomen and CT of the pelvis [21]. CT Chest, Abdomen, and Pelvis Without IV Contrast There is no evidence to support the use of CT chest, abdomen, and pelvis without IV contrast in identifying distant disease. Digital Breast Tomosynthesis Diagnostic There is no evidence to support the use of DBT to evaluate distant disease. FDG-PET/CT Skull Base to Mid-Thigh According to the ABIM/ASCO, ESMO, and SEOM guidelines, there is insufficient evidence to routinely use FDG- PET/CT to evaluate for distant disease in asymptomatic women with early stage breast cancer [128-130]. NCCN guidelines recommend chest, abdomen, and pelvic CT as an additional test prior to preoperative systemic therapy to evaluate for distant disease if the tumor size is >2 cm (T2) or there are positive lymph nodes, or the tumor size is >1 cm (T1c) and HER2+, or there is triple-negative disease [126]. Although not definitive, and not currently recommended in the guidelines above, there is evidence that PET/CT may be useful in early stage breast cancer [133].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. A recent study of 196 subjects [134] tested the utility of PET/CT in breast cancer and found the overall yield of unsuspected distant metastases was 14% (n = 27), including 0% for stage IIA, 13% for stage IIB (10/79), 22% for stage IIIA (9/41), 17% for stage IIIB (5/30), and 37% for stage IIIC (3/8). In another study of 303 patients, PET/CT demonstrated unknown metastatic disease in 4.9% (15/303), 0.8% in stage IIA, and 9.8% in stage IIB [135]. Finally, Groheux et al [136] performed a prospective study of 254 women with breast cancer, and PET/CT found unsuspected metastatic disease in 2.3% of stage IIA and 10.7% in stage IIB [128]. The performance of PET/CT was independent of cancer subtype, as shown in other studies on stage IIB disease [137]. Finally, a recent meta-analysis of 4,276 patients (29 studies) also found 11% (95% CI, 3%-22%) of patients with stage I and 20% (95% CI, 16%-24%) of patients with stage II breast cancer changed disease stage or management plan (including up or downstaging) with PET/CT [13]. Thus, there is some evidence to consider this test, even in early breast cancer, if the immunohistochemical subtype is HER2+/TN or the disease is locally advanced as described above. Mammography Diagnostic There is no evidence to support the use of diagnostic mammography to evaluate distant disease. Mammography With IV Contrast There is no evidence to support the use of diagnostic mammography with IV contrast to evaluate distant disease. MRI Breast Without and With IV Contrast There is no evidence to support the use of MRI breast to evaluate distant disease. MRI Breast Without IV Contrast There is no evidence to support the use of noncontrast breast MRI in evaluating extent of disease. US Axilla There is no evidence to support the use of US axilla to evaluate distant disease. US Breast There is no evidence to support the use of US breast to evaluate distant disease. Variant 3: Newly diagnosed. Clinical stage IIB-III (late stage) breast cancer at presentation.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Evaluation for locoregional disease (includes IDC, or ILC, or NOS). Bone Scan Whole Body There is no evidence to support the use of bone scan whole body for determining locoregional disease. CT Chest, Abdomen, and Pelvis With IV Contrast Few studies have evaluated the use of CT to determine locoregional disease in breast cancer and so there is limited supporting evidence for this indication. In a study using CT to determine the size of the in-breast malignancy, surgical treatment was changed in 42 of 297 (14.1%) patients. The same study showed that CT failed to show the extent of disease in 10.8% of patients and overestimated the extent of disease in 1% of tumors. Notably, MRI was not included as a comparator [20]. An additional study looking at later stage (at least 2 cm) or higher risk (triple Imaging of Invasive Breast Cancer negative or other biomarkers of risk such as high Ki67 or HER2+) found that CT predicted the N stage correctly in 64 of 80 patients (80%, 95% CI,70.0%-87.3%), with a sensitivity of 61.5% (CI,45.9%-75.1%) and a specificity of 97.6% (CI, 87.4%-99.6%). Despite the higher specificity of CT, MRI has better performance to detect multicentric/multifocal disease and estimate final pathologic size. CT Chest, Abdomen, and Pelvis Without and With IV Contrast The majority of clinical questions for abdominal and/or pelvic CT can be appropriately answered with a single- phase study as detailed in the ACR-SABI-SPR practice parameter for the performance of CT of the abdomen and CT of the pelvis [21]. CT Chest, Abdomen, and Pelvis Without IV Contrast There is no evidence to support the use of CT chest, abdomen, and pelvis without IV contrast for determining locoregional disease and guiding surgical management in late-stage disease. Digital Breast Tomosynthesis Diagnostic Diagnostic mammography and US together can assess for extent of disease and tumor size.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. These imaging tests are usually already completed as part of the diagnostic workup (prior to pathological diagnosis). However, mammography is limited by breast density. In a prospective study of 111 consecutive women with newly diagnosed breast cancer, sensitivity of 2-D mammography for malignancy decreased from 100% in breasts that are almost entirely fatty to 45% in extremely dense breasts [22]. In addition, 2-D mammography was more sensitive than US in detecting DCIS and less sensitive at detecting ILC. DBT shows higher overall sensitivity, compared with 2-D mammography, with similar specificity. Overall sensitivity for DBT was 88.2% compared with 78.3% for 2-D mammography [23]. DBT also has a higher sensitivity for detecting multifocal, multicentric, and contralateral breast cancer [24,25]. The improved diagnostic performance of DBT over 2-D mammography was limited to women with nondense breasts in 1 study [24], but not others [25]. Due to patient positioning constraints, 2-D mammography and DBT have limited value for evaluating the axilla. In a single-institution retrospective study of 3,944 patients with breast cancer, mammography improved the sensitivity over US alone for distinguishing N0 to N1 from N2 and N3, but at a lower specificity [35]. After the ACOSOG Z0011 trial supported the omission of axillary lymph node dissection in women with <3 positive sentinel lymph nodes undergoing breast-conserving surgery and radiation therapy, some providers may request that radiologists not image the axilla in the setting of clinically node-negative disease [36]. Although axillary US is not recommended for every patient [37], axillary abnormality visible on mammography is still considered an appropriate indication for sonographic axillary evaluation. Also, when neoadjuvant chemotherapy is planned, the NCCN recommends consideration of axillary US, with marker placement if a biopsy is performed, in addition to mammography [126].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Mammography Diagnostic Diagnostic mammography and US together can assess for extent of disease and tumor size. These imaging tests are usually already completed as part of the diagnostic workup (prior to pathological diagnosis). However, mammography is limited by breast density. In a prospective study of 111 consecutive women with newly diagnosed breast cancer, the sensitivity of 2-D mammography for malignancy decreased from 100% in breasts that are almost entirely fatty to 45% in extremely dense breasts [22]. In addition, 2-D mammography was more sensitive in detecting DCIS and less sensitive, compared with US, in detecting ILC. DBT shows higher overall sensitivity, compared with 2-D mammography, with similar specificity. Overall sensitivity for DBT was 88.2% compared with 78.3% [23]. DBT has higher sensitivity for detecting multifocal, multicentric, and contralateral breast cancer than 2-D mammography alone [24,25]. The improved diagnostic performance of DBT over 2-D mammography in breast cancer staging was limited to women with nondense breasts in 1 study [24], but not others [25]. Due to patient positioning constraints, 2-D mammography and DBT have limited value for evaluating the axilla. In a single-institution retrospective study of 3,944 patients with breast cancer, mammography improved the sensitivity over US alone for distinguishing N0 to N1 from N2 and N3, but at a lower specificity [35]. After the ACOSOG Z0011 trial supported the omission of axillary lymph node dissection in women with <3 positive sentinel lymph nodes undergoing breast-conserving surgery and radiation therapy, some providers may request that radiologists not image the axilla in the setting of clinically node-negative disease [36]. When neoadjuvant chemotherapy is planned, the NCCN does recommend consideration of axillary US, with marker placement if a biopsy is performed, in addition to mammography [126].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Mammography With IV Contrast Several retrospective studies have compared the sensitivity and specificity of CEM with conventional 2-D and 3-D mammography, US, and MRI. Overall, CEM and MRI are superior to DM and DM/DBT imaging [47]. The sensitivities between CEM and MRI are comparable, with some studies showing improved sensitivities with CEM Imaging of Invasive Breast Cancer [48], and some showing MRI to be superior [49,50]. Overall sensitivities ranged from 92% to 100% [16,49,51-53], including CEM detecting 92.3% of satellite masses and up to 100% of contralateral cancers [28]. CEM and MRI show similar abilities to estimate tumor size (r, 0.72-0.89 versus 0.65-0.84), but studies have shown improved PPV of CEM (52%-93%) compared with MRI (28-60%) [16,49,53]. Despite increased specificity over MR, limitations of contrast mammography in determining disease extent include evaluation of the axilla and other nodal groups as well as chest wall involvement [47], and there is evidence against using CEM to determine disease extent in lobular cancer, due to lower conspicuity [54]. MRI Breast Without and With IV Contrast MRI breast is useful for detecting additional cancers in the ipsilateral and contralateral breast [16,55], particularly in women with dense breasts [23,56,57]. A meta-analysis of 22 studies investigated MRI screening of the contralateral breast in women with newly diagnosed breast cancer. The study reported contralateral malignancies that were detected by MRI in 131 of 3,253 women. Thus, the summary estimate for incremental cancer detection rate was 4.1%. In studies in which pathologic tumor stage was reported, all but 2 tumors were in situ or stage I, and of those 2 tumors, 1 was a node-negative ILC (42 mm). Summary estimates were as follows: MRI-directed additional biopsy in 9.3% of women (95% CI, 5.8%-14.7%) with PPV for malignancy of 47.9% (95% CI, 31.8%- 64.6%).


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Where reported, 35.1% of MRI-detected cancers were DCIS (mean size = 6.9 mm) and 64.9% were invasive cancers (mean size = 9.3 mm) [58]. MRI can accurately assess tumor size for preoperative planning [50,59-61]. In a study involving 343 tumors, size measurements of cancers on breast MRI were within 5 mm of pathological size in 88% of patients [60]. Still, other studies using mastectomy specimens have shown that MRI underestimates primary tumor size in 21% and overestimates primary tumor size in 24% of cases. MRI also overestimated the number of invasive lesions by 19% and underestimated the number of invasive lesions in 28% in the same study [62]. These data underscore the importance of using biopsy to pathologically confirm MRI findings before using them to alter surgical planning, especially when the MRI finding is nonmass enhancement [63]. In addition to tumor size assessment, some studies show a reduction in re-excision after preoperative MRI [64-68]. For example, in a study of 991 women, preoperative MRI changed the surgical procedure in 25% (157/626) of cases. In 81% (127/157), MRI was beneficial for the patients, as otherwise occult carcinomas were removed (n = 122) or further biopsy could be prevented (n = 5) [67]. In this trial, the rate of mastectomy did not differ between patients undergoing preoperative MRI and those who did not. A recent multinational observational study at 27 centers also found that subjects receiving MR as part of routine clinical care had a significantly lower reoperation rate after breast conservation (8.5% versus 11.7%, P < . 001) [69]. However, other large multicenter studies, such as the COMICE trial, showed the addition of MRI to conventional imaging was not significantly associated with a reduced reoperation rate, with 153 (19%) needing reoperation in the MRI group versus 156 (19%) in the non-MRI group, (OR, 0.96; 95% CI, 0.75-1.24; P = . 77) [70].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Although the findings are important, limitations from the COMICE trial are also noted, such as its inclusion of patients from several small centers where technical factors and varying degree of experience among interpreting radiologists could have influenced the MRI results. It is also not clear that the data from the MRI were incorporated into surgical planning, and nearly 7% of the group assigned to MRI did not actually have an MR interpreted (analyzed by intention to treat). When all breast cancer subtypes were included, a meta-analysis of 19 studies did not find evidence that MRI positively impacted the rates of re- excision, reoperation, or positive margins, and MRI was significantly associated with increased odds of receiving contralateral prophylactic mastectomy (OR, 1.91; 95% CI, 1.25-2.91; P = . 003) [71]. Primary analysis of 85,975 women also showed that preoperative MRI was associated with increased odds of receiving mastectomy (OR, 1.39; 95% CI, 1.23-1.57; P < . 001) [71]. Still, it is unknown whether some of the studies included in that meta-analysis had a bias in randomization (ie, women who were preplanned for mastectomies were more likely to have been referred rather than randomized to the preoperative MRI arm). As an example of this, in the multicenter international prospective analysis cited above [69], mastectomy was already planned based on conventional imaging in 22.4% (MRI group) versus 14.4% (no MRI group) P < . 001). The data are different for ILC histological subtypes. For ILC, there is strong evidence that MRI improves surgical outcomes [72-81]. In a study with 70 cases of ILC, preoperative MRI reduced re-excision rates, particularly in young women with dense breasts [82]. In another study with 369 women, preoperative breast MRI was also associated with a reduction in repeat surgery (OR, 0.140; P < . 001), without increasing mastectomy rates [76].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Imaging of Invasive Breast Cancer Still, there is no evidence that preoperative MRI leads to improved survival or decreased recurrence, including data from multicenter analyses [61,68,83-85]. In 3,180 affected breasts in 3,169 women (median age, 56.2 years), 8-year disease-free survival did not differ between the MRI (97%) and the non-MRI (95%) groups (P = . 87), and the multivariable model showed no significant effect of MRI on disease-free survival: HR for MRI (versus non-MRI) was 0.88 (95% CI, 0.52-1.51; P = . 65); age, margin status, and tumor grade were associated with disease-free survival (all P < . 05) [85]. Of the 31,756 patients included in a survival cohort (70% non-MRI and 30% MRI), breast MRI was not significantly associated with overall survival (HR, 0.91; 95% CI, 0.74-1.11, P = . 35) or with disease-free survival (HR, 1.16; 95% CI, 0.81-1.67), even among the different histological subtypes. The lack of survival benefit extends also to patients with ILC, despite improved surgical outcomes in this population as described above [83]. Given these data, benefits of preoperative MRI for additional cancer detection or delineating extent of disease should be balanced with the possibility of a false-positive diagnosis leading to additional biopsy or unnecessary additional imaging. MRI Breast Without IV Contrast There is no evidence to support the use of noncontrast breast MRI in evaluating extent of disease. US is the most established noninvasive imaging test for assessing the axilla following a clinically or imaging detected suspicious lymph node. US features associated with a higher likelihood of malignancy include short-axis lymph node size >1 cm, cortical thickness of >0.3 cm, and absence of a fatty hilum [90-93]. There is a wide range of reported sensitivity and specificity for axillary US, and none of these imaging features are specific enough to avoid the need for histologic sampling.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. The sensitivity ranges from 26.4% to 94%, and the specificity ranges from 53% to 98% [94-97]. Although axillary US alone has a relatively low NPV to rule out metastatic disease [36,98], axillary imaging is significantly more likely to identify metastatic disease in patients with pN2-3 disease compared with low volume burden (ie, those eligible for axillary preservation according to the Z0011 trial). Therefore, detection of nodal disease can help identify patients who would benefit from neoadjuvant systemic therapy to help downstage and de-escalate their axillary surgery and avoid axillary lymph node dissection. However, imaging is less sensitive in detecting invasive lobular cancer metastasis compared with ductal type [140]. A meta-analysis of 21 studies showed that US combined with needle biopsy improved the sensitivity from 61% to 79% [99-101]. US- guided core needle biopsy was superior to US-guided FNA in a meta-analysis of 1,353 patients with newly diagnosed invasive breast carcinoma, with a reported sensitivity of 88% for core biopsy and 74% for FNA [102]. Axillary US and an MRI performed similarly at evaluating axillary lymph nodes in an additional study [103]. In a meta-analysis of 9,232 cases of preoperative axillary staging procedures in 9,212 patients with breast cancer, preoperative axillary US-guided biopsy was able to identify approximately 50% of women with axillary involvement, but the false-negative rate was 25% [141]. An additional meta-analysis reported similar findings [100]. The NCCN does recommend consideration of axillary US, with marker placement if biopsy is performed, prior to preoperative systemic therapy [126]. US Breast Diagnostic mammography and US together can assess for extent of disease and tumor size. These imaging tests are usually already completed as part of the diagnostic workup (prior to pathological diagnosis). The sensitivity of US for detecting cancer ranges from 79% to 94% [22,25,104,105].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. The addition of DBT to US improved sensitivity for detecting both primary breast cancer and multicentric and multifocal disease, from 82.6% (nondense) and 91.6% (dense) with US alone to 97.7% with combined DBT and US [106]. However, DBT and mammography have limited added value over US alone for initial evaluation in women <40 years of age [105]. Although bilateral US use in women with primary breast cancer to evaluate for multicentric and multifocal disease shows lower sensitivity to MRI (85.1% versus 71.1%), US showed higher accuracy and specificity than MRI (67.6% versus 39.3% and 69.2% versus 60.2%, respectively), suggesting that bilateral US may be an acceptable alternative to MRI for locoregional staging [57]. When compared with DM alone, supplemental US more accurately depicted extent of disease needing wider excision in 17 of 96 (18%) breasts for which conservation was anticipated, corresponding to 17 of 30 (57%) breasts with mammographically occult disease [22]. Based on mammography/clinical examination, 2% to 3% of Imaging of Invasive Breast Cancer patients have synchronous bilateral cancer [107]. This risk of synchronous bilateral malignancy is increased for patients less than 55 years of age or those with diagnosis of invasive lobular subtype [108]. In 1 series with 9% contralateral synchronous malignancy, mammography detected 60%, US detected 80%, and MRI detected 90% (with the remainder detected on follow-up imaging) [22]. In addition to its role in the initial diagnostic workup, US is important in the secondary evaluation of a suspicious finding on MRI in the setting of evaluation for disease extent. US sensitivity and NPV are higher than DBT [109]. Compared with DBT, US showed a lower specificity (98.1% versus 78.9%) and a similar PPV (66.7% versus 52.2%).


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. However, a meta-analysis of second-look US following a suspicious finding on MRI showed heterogeneity in US performance, with the detection rate ranging from 22.6% to 82.1% (pooled detection rate 57.5%) and an 87.8% pooled NPV [110]. Therefore, a negative US is insufficient to obviate the need for an MRI biopsy in this setting. There is no evidence supporting US as an accurate method for determining disease extent in those diagnosed with the ILC subtype. Conventional imaging with mammography and/or US can significantly underestimate the span of ILC [26,111-114]. For example, US specifically underestimated ILC tumor size by 27% (95% CI, 17%-37%) in a study [113], and a different study showed that the greatest discrepancy between tumor size and pathologic size using US measurements was for those with the ILC subtype [26]. Variant 4: Newly diagnosed. Clinical stage IIB-III (late stage) breast cancer at presentation. Evaluation for distant disease. IDC or ILC that is ER+/HER2-. It has long been recognized that steroid receptor expression reflects intrinsic biologic diversity in breast cancer with treatment and survival implications, also determining patterns of metastatic spread. The specific response patterns and outcomes associated with ER/PR/HER2 status occur despite the known limitation of pathologic sampling and receptor expression heterogeneity [142]. Historically, bone is the most likely site of breast cancer metastases (51%), followed by liver/soft tissue (19%), pleura (16%), lung (14%), and brain (4%) [115]. The higher percentage of bone metastases from breast cancer appears to be driven primarily by the majority of primary tumors expressing ER and/or PR. In 1 large multidecade study, 82% of patients with breast cancer who developed bone metastases had either ER and PR or ER positivity in the primary tumor [115].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. A landmark study 2 decades ago transformed our field by discovering 5 distinct composite molecular portraits using quantitative analysis of breast cancer gene expression patterns; luminal A, luminal B, HER2-enriched, basal-like, and normal-like, providing a new type of disease characterization [116]. The molecular subtypes were linked to pattern and type of metastatic spread, as well as disease-specific survival [117,118]. For example, luminal cancers have a propensity to give rise first to bone metastases, HER2-enriched cancers to liver and lung metastases, and basal type cancers to liver and brain metastases [119,120]. These molecular subtypes share similarities with ER/PR expression and HER2 gene amplification but are not synonymous. Luminal subtypes more commonly have ER expression, HER2-enriched cancers more commonly exhibit HER2 expression, and triple-negative breast cancers are most often the basal breast cancer subtype. Although luminal subtypes have significantly better overall and relapse-free survival [118], they carry a long-term risk of recurrence, especially to bone, whereas basal and HER2 subtypes have a higher rate of recurrence in the first 4 years [121], which can be considered when planning frequency and type of surveillance imaging. Bone Scan Whole Body Bone is the most common site for breast cancer metastasis; up to 70% of women with stage IV disease have bone metastasis, with the predilection for bone metastases not applying to basal-like tumors [117]. Up to 13.6% of women diagnosed with early stage breast cancer will develop bone metastasis within 15 years of diagnosis [122], even if the parent tumor is low grade [123]. Tc-99m bone scans detect early bone metastasis because of the new bone formation occurring at these sites [124] and have a 98% sensitivity for detecting early bone metastasis in symptomatic patients.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. The sensitivity of whole body bone scans for detecting bone metastases in patients with late-stage breast cancer ranges from 62% to 100%, regardless of tumor subtype [143]. Studies using bone scans to stage women with late- stage disease have shown the prevalence of osseous metastases ranging from 4.7% to 45% [144]. A study by Chu et al [145] on 256 women with N2/N3 disease showed a metastatic workup for asymptomatic patients was only indicated with T3 or T4 primary lesions. For patients with T0, T1, and T2 diseases, the incidence of stage IV disease was 0%, 0%, and 6%, respectively. The incidence increased with higher T stage; 22% for T3 and 36% for T4 tumors. Imaging of Invasive Breast Cancer Several studies comparing bone scan performance with CT and PET have been performed in women presenting with late-stage disease [144]. Some studies have shown up to 17.1% of women with extraosseous metastasis on CT had negative or inconclusive bone scans. One of the benefits of whole body bone scans is the detection of metastasis in the peripheral skeleton, areas not included by CT chest, abdomen, and pelvis with IV contrast. However, the presence of peripheral metastasis almost always (>99%) occurs in the context of extraosseous or central osseous metastasis, and detection of additional peripheral metastases does not typically result in a change in management [144,146]. CT Chest, Abdomen, and Pelvis With IV Contrast Correctly identifying the stage of breast cancer prior to surgery has important prognostic implications, because survival decreases as stage increases [145]. In a study of 1,329 patents with breast cancer, metastatic disease of any type was identified by imaging between 15% to 16% and 22% to 36% based on N2/3 and T3/4 status, respectively [145].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. NCCN guidelines recommend chest, abdomen, and pelvic CT as an additional test prior to preoperative systemic therapy to evaluate for distant disease if the tumor size is >2 cm (T2) or there are positive lymph nodes, or the tumor size is >1 cm (T1c) and HER2+, or there is triple-negative disease [126]. In asymptomatic women with late-stage breast cancer, metastatic disease to the thorax is identified in 5% to 9% of patients [17,132,147]. The false-positive rate requiring additional imaging studies for further evaluation or follow-up ranged from 10% to 33% [17,132,148]. CT Chest, Abdomen, and Pelvis Without and With IV Contrast The majority of clinical questions for abdominal and/or pelvic CT can be appropriately answered with a single- phase study as detailed in the ACR-SABI-SPR practice parameter for the performance of CT of the abdomen and CT of the pelvis [21]. CT Chest, Abdomen, and Pelvis Without IV Contrast There is no evidence to support the use of CT chest, abdomen, and pelvis without IV contrast. Chest CT without IV contrast is often used to evaluate for metastatic disease to the lung. In asymptomatic women with late-stage breast cancer, metastatic disease to the thorax is identified in 5% to 9% of patients [17,132,147]. The false-positive rate requiring additional imaging studies for further evaluation or follow-up ranged from 10% to 33% [17,132,148]. Digital Breast Tomosynthesis Diagnostic There is no evidence to support the use of DBT to evaluate for distant disease. FDG-PET/CT Skull Base to Mid-Thigh There is a large body of evidence that FDG-PET/CT is useful to detect metastatic disease in stage IIB to III breast cancer [136-139,149-158]. This is important because patients with locoregional breast malignancy have 5-year survival rates of 76% to 99%, but for patients with distant metastases, 5-year survival rates decreases to 20% to 28% [159].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. The sensitivity, specificity, PPV, NPV, and accuracy of PET/CT in identifying metastatic disease in this population are 100%, 96%, 80%, 100%, and 97%, respectively [41]. The false-positive rate of PET/CT was 19%. In comparison with CT and other modalities, 80% of patients with distant disease had the metastases exclusively identified on PET/CT [41]. Groheux et al [136] investigated 254 patients and found previously unknown metastases in 1 of 44 (2%) women with stage IIA breast cancer, 6 of 56 (11%) women with stage IIB cancer, 11 of 63 (18%) women with stage IIIA cancer, 27 of 74 (37%) women with stage IIIB cancer, and 8 of 17 (47%) women with stage IIIC cancer. PET/CT has especially high yields in patients newly diagnosed at <40 years of age, revealing distant metastases in 17% of asymptomatic stage IIB [155]. PET/CT modified staging between 14% and 28% of patients with late-stage disease, regardless of tumor receptor status [138,139]. In a study of 163 women, PET/CT and whole body bone scan demonstrated concordance in identifying osseous metastases in 81% of cases. Also, PET/CT had the added benefit of detecting extraosseous metastasis in 62% of patients with osseous metastasis. Of those patients with extraosseous metastases, 6% had equivocal and 42% had negative bone scans [160]. The sensitivity and specificity for PET/CT in the detection of distant metastases is higher than conventional imaging, with a 97% sensitivity and 91% specificity versus an 86% sensitivity and 67% specificity (P = . 009 and P < . 001, respectively) [161]. However, PET/CT has limited sensitivity for ILC [162]. NCCN guidelines recommend FDG-PET/CT as an optional additional test prior to preoperative systemic therapy to evaluate for distant disease if the tumor size is >2 cm (T2) or there are positive lymph nodes, or the tumor size is >1 cm (T1c) and HER2+, or there is triple-negative disease [126].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Mammography Diagnostic There is no evidence to support the use of diagnostic mammography to evaluate for distant disease. Imaging of Invasive Breast Cancer Mammography With IV Contrast There is no evidence to support the use of mammography with IV contrast to evaluate distant disease. MRI Breast Without and With IV Contrast There is no evidence to support the use of MRI breast without and with IV contrast to evaluate for distant disease. MRI Breast Without IV Contrast There is no evidence to support the use of noncontrast breast MRI in evaluating extent of disease. US Axilla There is no evidence to support the use of US axilla to evaluate for distant disease. US Breast There is no evidence to support the use of US breast to evaluate for distant disease. Variant 5: Newly diagnosed. Clinical stage IIB-III (late stage) breast cancer at presentation. Evaluation for distant disease. IDC or ILC that is HER2+ or triple negative (ER, PR, and HER2-). It has long been recognized that steroid receptor expression reflects intrinsic biologic diversity in breast cancer with treatment and survival implications, also determining patterns of metastatic spread. The specific response patterns and outcomes associated with ER/PR/HER2 status occur despite the known limitation of pathologic sampling and receptor expression heterogeneity [142]. Historically, bone is the most likely site of breast cancer metastases (51%), followed by liver/soft tissue (19%), pleura (16%), lung (14%), and brain (4%) [115]. The higher percentage of bone metastases from breast cancer appears to be driven primarily by the majority of primary tumors expressing ER and/or PR. In 1 large multidecade study, 82% of patients with breast cancer who developed bone metastases had either ER and PR or ER positivity in the primary tumor [115].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. A landmark study 2 decades ago transformed our field by discovering 5 distinct composite molecular portraits using quantitative analysis of breast cancer gene expression patterns; luminal A, luminal B, HER2-enriched, basal-like, and normal-like, providing a new type of disease characterization [116]. The molecular subtypes were linked to pattern and type of metastatic spread, as well as disease-specific survival [117,118]. For example, luminal cancers have a propensity to give rise first to bone metastases, HER2-enriched cancers to liver and lung metastases, and basal type cancers to liver and brain metastases [119,120]. These molecular subtypes share similarities with ER/PR expression and HER2 gene amplification but are not synonymous. Luminal subtypes more commonly have ER expression, HER2-enriched cancers more commonly exhibit HER2 expression, and triple-negative breast cancers are most often the basal breast cancer subtype. Although luminal subtypes have significantly better overall and relapse-free survival [118], they carry a long-term risk of recurrence, especially to bone, where basal and HER2 subtypes have a higher rate of recurrence in the first 4 years [121], which can be considered when planning frequency and type of surveillance imaging. Bone Scan Whole Body Bone is the most common site for breast cancer metastasis; up to 70% of women with stage IV disease have bone metastasis, with the predilection for bone metastases not applying to basal-like tumors [117]. Up to 13.6% of women diagnosed with early stage breast cancer will develop bone metastasis within 15 years of diagnosis [122], even if the parent tumor is low grade [123]. Tc-99m bone scans detect early bone metastasis because of the new bone formation occurring at these sites [124] and have a 98% sensitivity for detecting early bone metastasis in symptomatic patients.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. The sensitivity of whole body bone scans for detecting bone metastases in patients with late-stage breast cancer ranges from 62% to 100%, regardless of tumor subtype [143]. Studies using bone scans to stage women with late- stage disease have shown the prevalence of osseous metastases ranging from 4.7% to 45% [144]. A study by Chu et al [145] on 256 women with N2/N3 disease showed a metastatic workup for asymptomatic patients was only indicated with T3 or T4 primary lesions. For patients with T0, T1, and T2 diseases, the incidence of stage IV disease was 0%, 0%, and 6%, respectively. The incidence increased with higher T stage; 22% for T3 and 36% for T4 tumors. Several studies comparing bone scan performance with CT and PET have been performed in women presenting with late-stage disease [144]. Some studies have shown up to 17.1% of women with extraosseous metastasis on CT had negative or inconclusive bone scans [144]. One of the benefits of whole body bone scans is the detection of metastasis in the peripheral skeleton, areas not included by CT chest, abdomen, and pelvis with IV contrast. Imaging of Invasive Breast Cancer However, the presence of peripheral metastasis almost always (>99%) occurs in the context of extraosseous or central osseous metastasis, and detection of additional peripheral metastases does not typically result in a change in management [144,146]. CT Chest, Abdomen, and Pelvis With IV Contrast Correctly identifying the stage of breast cancer prior to surgery has important prognostic implications, because survival decreases as stage increases [145]. In a study of 1,329 patents with breast cancer, metastatic disease of any type was identified by imaging between 15% to 16% and 22% to 36% based on N2/3 and T3/4 status, respectively [145].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. NCCN guidelines recommend chest, abdomen, and pelvic CT as an additional test prior to preoperative systemic therapy to evaluate for distant disease if the tumor size is >2 cm (T2) or there are positive lymph nodes, or >1 cm (T1c) and HER2+, or triple-negative disease [126]. In asymptomatic women with late-stage breast cancer, metastatic disease to the thorax is identified in 5% to 9% of patients [17,132,147]. The false-positive rate requiring additional imaging studies for further evaluation or follow-up ranged from 10% to 33% [17,132,148]. CT Chest, Abdomen, and Pelvis Without and With IV Contrast The majority of clinical questions for abdominal and/or pelvic CT can be appropriately answered with a single- phase study as detailed in the ACR-SABI-SPR practice parameter for the performance of CT of the abdomen and CT of the pelvis [21]. CT Chest, Abdomen, and Pelvis Without IV Contrast There is no evidence to support the use of CT chest, abdomen, and pelvis without IV contrast. Chest CT without IV contrast is often used to evaluate for metastatic disease to the lung. In asymptomatic women with late-stage breast cancer, metastatic disease to the thorax is identified in 5% to 9% of patients [17,132,147]. The false-positive rate requiring additional imaging studies for further evaluation or follow-up ranged from 10% to 33% [17,132,148]. Digital Breast Tomosynthesis Diagnostic There is no evidence to support the use of DBT to evaluate for distant disease. FDG-PET/CT Skull Base to Mid-Thigh NCCN guidelines recommend PET/CT as an optional additional test prior to preoperative systemic therapy if the tumor size is greater than T2, or there are positive lymph nodes, any HER2+, or triple-negative disease [126]. There is a large body of evidence that FDG-PET/CT is useful to detect metastatic disease in stage IIB to III breast cancer [136-139,149-158].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. This is important because patients with locoregional breast malignancy have 5-year survival rates of 76% to 99%, but for patients with distant metastases, 5-year survival rates decreases to 20% to 28% [159]. The sensitivity, specificity, PPV, NPV, and accuracy of PET/CT in identifying metastatic disease in this population are 100%, 96%, 80%, 100%, and 97%, respectively [41]. The false-positive rate of PET/CT was 19%. In comparison with CT and other modalities, 80% of patients with distant disease had the metastases exclusively identified on PET/CT [41]. Groheux et al [136] investigated 254 patients and found previously unknown metastases in 1 of 44 (2%) women with stage IIA breast cancer, 6 of 56 (11%) women with stage IIB cancer, 11 of 63 (18%) women with stage IIIA cancer, 27 of 74 (37%) women with stage IIIB cancer, and 8 of 17 (47%) women with stage IIIC cancer. PET/CT has especially high yields in the case of patients newly diagnosed at <40 years of age, revealing distant metastases in 17% of asymptomatic patients with stage IIB breast cancer <40 years of age [155]. PET/CT modified staging between 14% and 28% of patients with late-stage disease, regardless of tumor receptor status [138,139]. In a study of 163 women, PET/CT and whole body bone scan demonstrated concordance in identifying osseous metastases in 81% of cases. Also, PET/CT had the added benefit of detecting extraosseous metastasis in 62% of patients with osseous metastasis. Of those patients with extraosseous metastases, 6% had equivocal and 42% had negative bone scans [160]. The sensitivity and specificity for PET/CT in the detection of distant metastases is higher than conventional imaging, with a 97% sensitivity and 91% specificity versus an 86% sensitivity and 67% specificity, respectively (P = . 009 and P < . 001, respectively) [161]. However, PET/CT has limited sensitivity for ILC [162].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. NCCN guidelines recommend PET/CT as an optional additional test prior to preoperative systemic therapy to evaluate for distant disease if the tumor size is >2 cm (T2) or there are positive lymph nodes, or tumor size is >1 cm (T1c) and HER2+, or there is triple-negative disease [126], because these subtypes tend to be more aggressive with earlier spread to extraosseous locations compared with other molecular subtypes as described above. Mammography Diagnostic There is no evidence to support the use of diagnostic mammography to evaluate for distant disease. Imaging of Invasive Breast Cancer Mammography With IV Contrast There is no evidence to support the use of mammography with IV contrast to evaluate for distant disease. MRI Breast Without and With IV Contrast There is no evidence to support the use of MRI breast without and with IV contrast to evaluate for distant disease. MRI Breast Without IV Contrast There is no evidence to support the use of noncontrast breast MRI in evaluating the extent of disease. MRI Head Without IV Contrast There is no evidence to support the use of MRI head without IV contrast to evaluate for distant disease. US Axilla There is no evidence to support the use of US axilla to evaluate for distant disease. US Breast There is no evidence to support the use of US breast to evaluate for distant disease. Variant 6: Surveillance. Regardless of clinical stage of breast cancer at time of original presentation. Evaluation for local recurrence in patient with history of BCT. Breast-conserving treatment (BCT) of lumpectomy followed by whole-breast radiation is the most common treatment following a diagnosis of stage I and II breast cancer. Long-term studies show no significant difference in survival rates of patients treated with BCT versus mastectomy. Locoregional recurrence typically occurs 3 to 6 years post-treatment, at an average annual rate of 1% to 2.5% per year [167,168].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. More recent studies indicate the risk of developing locoregional recurrence in patients with early stage disease treated with breast-conserving surgery, whole-breast radiation, and appropriate systemic treatments is approximately 0.5% per year [169]. In 1 meta-analysis, the 10-year local recurrence rate in patients after neoadjuvant chemotherapy and breast conservation was 6.5% and locoregional disease recurrence was 10.3%. Factors found to be associated with a higher risk of local recurrence were ER-negative disease, axillary spread, especially in >3 nodes or clinically palpable disease, and a lack of pathologic complete response [170]. Studies have shown that early detection of recurrence (prior to clinical detection) improves long-term survival by approximately 17% to 28% [171]. Therefore, imaging surveillance remains important in this patient population. Digital Breast Tomosynthesis Diagnostic The most widely accepted guidelines regarding the surveillance of asymptomatic women with a history of breast cancer come from 2 national organizations: ASCO and NCCN [172,173]. Both organizations state that routine surveillance with an annual mammogram can detect an in-breast recurrence or a new primary breast cancer in women with an average risk for recurrence. However, there is institutional variation on the frequency (every 6 months versus annual) and time period (1-5 years post-BCT) for surveillance after BCT. There is also variation on whether to include women in the screening versus diagnostic patient populations, in which women in the diagnostic population wait for possible additional imaging needed to reach a final assessment prior to leaving the imaging facility. The sensitivity of mammography is decreased due to post-treatment changes from surgery and radiation therapy, and some institutions prefer closer follow-up after BCT to assess changes due to radiation and surgery and potentially detect local recurrences earlier than on annual follow-up imaging.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. A single-institution study of 2,329 women following BCT showed that a 6- month interval for surveillance detected a higher proportion of local recurrences at an earlier stage compared with annual surveillance [174]. In a single-institution study of 789 asymptomatic women after BCT, 1.2% had cancer diagnosed at the 6-month timepoint following treatment (n = 169), and 0.6% had cancer detected in women who Imaging of Invasive Breast Cancer underwent routine mammographic screening a year after treatment (n = 620) [175]. However, earlier diagnosis did not result in a difference in local and distant disease-free survival. In summary, there is insufficient evidence demonstrating superior outcomes with diagnostic versus screening mammography for breast cancer surveillance. Expert consensus is to perform an annual diagnostic examination for the first 3 years, followed by routine annual screening, due to the increased complexity of interpretation from postsurgical and postradiation changes [176] and the increased risk of recurrence in the first 3 years following treatment [177-180]. There have been multiple studies evaluating the performance of DM versus DBT for surveillance. Chikarmane et al [181] compared tomosynthesis with 2-D mammography in women with a personal history of breast cancer treated with lumpectomy and mastectomy. They reported a significant decrease in recall rate (7.9% versus 10.1%, respectively) and increased sensitivity (92.3% versus 90.0%, respectively) with tomosynthesis with no significant difference in the cancer detection rate (6.1 versus 6.0 per 1,000 women screened, respectively) or PPV (12.0% versus 6.4%, respectively). These changes in interpretive performance were similar regardless of whether the women underwent breast-conserving surgery or mastectomy. There is evidence that mammography alone may not be sufficient for surveillance in this population.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. In a large study involving 32,331 women with a history of breast cancer undergoing 117,971 surveillance mammographic examinations (112,269 digital mammographic examinations and 5,702 DBT examinations), surveillance mammography performance in the detection of interval cancers was inferior to established screening mammography benchmarks [182]. The main limitation of this study was the relative low proportion of DBT examinations, because DBT does detect more cancer than DM alone [183]. Women <50 years of age at primary breast cancer diagnosis appear to be at highest risk of a missed interval cancer using surveillance mammography [184]. These data suggest a need for evolving evidence-based surveillance recommendations on supplemental screening. Digital Breast Tomosynthesis Screening The most widely accepted guidelines regarding the surveillance of asymptomatic women with a history of breast cancer come from 2 national organizations: ASCO and NCCN [172,173]. Both organizations state that routine surveillance with an annual mammogram can detect an in-breast recurrence or a new primary breast cancer in women with an average risk for recurrence. However, there is institutional variation on the frequency (every 6 months versus annual) and time period (1-5 years post-BCT) for surveillance after BCT. There is also variation on whether to include women in the screening versus diagnostic patient populations, in which women in the diagnostic population wait for possible additional imaging needed to reach a final assessment prior to leaving the imaging facility, whereas women in the screening population could leave after their standard views are performed. The sensitivity of mammography is decreased due to post- treatment changes from surgery and radiation therapy, and some institutions prefer closer follow-up after BCT to assess changes due to radiation and surgery and potentially detect local recurrences earlier than on annual follow- up imaging.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. A single-institution study of 2,329 women following BCT showed that a 6-month interval for surveillance detected a higher proportion of local recurrences at an earlier stage, compared with annual surveillance [174]. In a single-institution study of 789 asymptomatic women after BCT, 1.2% had cancer diagnosed at the 6- month timepoint following treatment (n = 169) and 0.6% had cancer detected in women who underwent routine mammographic screening a year after treatment (n = 620) [175]. However, earlier diagnosis did not result in a difference in local and distant disease-free survival. In summary, there is insufficient evidence demonstrating superior outcomes with diagnostic versus screening mammography for breast cancer surveillance. Expert consensus is to perform an annual diagnostic examination for the first 3 years, followed by routine annual screening, due to the increased complexity of interpretation from postsurgical and post radiation changes [176] and the increased risk of recurrence in the first 3 years following treatment [177-180]. FDG-PET/CT Skull Base to Mid-Thigh There is no literature to support the use of FDG-PET/CT to evaluate local recurrence of breast cancer. Mammography Diagnostic The most widely accepted guidelines regarding the surveillance of asymptomatic women with a history of breast cancer come from 2 national organizations: ASCO and NCCN [172,173]. Both organizations state that routine surveillance with an annual mammogram can detect an in-breast recurrence or a new primary breast cancer in women with an average risk for recurrence. However, there is institutional variation on the frequency (every 6 months versus annual) and time period (1-5 years post-BCT) for surveillance after BCT. There is also variation on whether to include women in the screening versus


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Imaging of Invasive Breast Cancer diagnostic patient populations, in which women in the diagnostic population wait for possible additional imaging needed to reach a final assessment prior to leaving the imaging facility. The sensitivity of mammography is decreased due to post-treatment changes from surgery and radiation therapy, and some institutions prefer closer follow-up after BCT to assess changes due to radiation and surgery and potentially detect local recurrences earlier than annual follow-up. A single-institution study of 2,329 women following BCT showed that a 6-month interval for surveillance detected a higher proportion of local recurrences at an earlier stage compared with annual surveillance [174]. In a single-institution study of 789 asymptomatic women after BCT, 1.2% had cancer diagnosed at the 6-month timepoint following treatment (n = 169), and 0.6% had cancer detected in women who underwent routine mammographic screening a year after treatment (n = 620) [175]. However, earlier diagnosis did not result in a difference in local and distant disease-free survival. In summary, there is insufficient evidence demonstrating superior outcomes with diagnostic versus screening mammography for breast cancer surveillance. Expert consensus is to perform an annual diagnostic examination for the first 3 years, followed by routine annual screening, due to the increased complexity of interpretation from postsurgical and postradiation changes [176] and the increased risk of recurrence in the first 3 years following treatment [177-180]. There is evidence that mammography alone may not be sufficient for surveillance in this population.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. In a large study involving 32,331 women with a history of breast cancer undergoing 117,971 surveillance mammographic examinations (112,269 digital mammographic examinations and 5,702 DBT examinations), surveillance mammography performance in the detection of interval cancers was inferior to established screening mammography benchmarks [182], with the main limitation of this study being the relative low proportion of DBT examinations because DBT does detect more cancer than DM alone [183]. Women <50 years of age at primary breast cancer diagnosis appear to be at highest risk of a missed interval cancer using surveillance mammography [184]. These data suggest a need for evolving evidence-based surveillance recommendations on supplemental screening. Mammography Screening The most widely accepted guidelines regarding the surveillance of asymptomatic women with a history of breast cancer come from 2 national organizations: ASCO and NCCN [172,173]. Both organizations state that routine surveillance with an annual mammogram can detect an in-breast recurrence or a new primary breast cancer in women with an average risk for recurrence. However, there is institutional variation on the frequency (every 6 months versus annual) and time period (1-5 years post-BCT) for surveillance after BCT. There is also variation on whether to include women in the screening versus diagnostic patient populations, in which women in the diagnostic population wait for possible additional imaging needed to reach a final assessment prior to leaving the imaging facility, whereas women in the screening population could leave after their standard views are performed. The sensitivity of mammography is decreased due to post- treatment changes from surgery and radiation therapy, and some institutions prefer closer follow-up after BCT to assess changes due to radiation and surgery and potentially detect local recurrences earlier than on annual follow- up imaging.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. A single-institution study of 2,329 women following BCT showed that a 6-month interval for surveillance detected a higher proportion of local recurrences at an earlier stage compared with annual surveillance [174]. In a single-institution study of 789 asymptomatic women after BCT, 1.2% had cancer diagnosed at the 6- month timepoint following treatment (n = 169), and 0.6% had cancer detected in women who underwent routine mammographic screening a year after treatment (n = 620) [175]. However, earlier diagnosis did not result in a difference in local and distant disease-free survival. In summary, there is insufficient evidence demonstrating superior outcomes with diagnostic versus screening mammography for breast cancer surveillance. Expert consensus is to perform an annual diagnostic examination for the first 3 years, followed by routine annual screening, due to the increased complexity of interpretation from postsurgical and postradiation changes [176] and the increased risk of recurrence in the first 3 years following treatment [177-180]. Mammography With IV Contrast A large study (n = 858) comparing the use of mammography with IV contrast to 2-D mammography showed an increase in the sensitivity of cancer detection from 50% to 87.5% with minimal changes to the specificity (97.1% versus 93.7%, respectively) and PPV (25.0% versus 20.9%, respectively) [185]. This study cohort included a large portion of women with a personal history of breast cancer (40.2%) and women with dense breasts (77.5%), although no information is given about the time since breast cancer diagnosis or stage at presentation in the surveillance population. Imaging of Invasive Breast Cancer MRI Breast Without and With IV Contrast For most breast cancer survivors, there is insufficient evidence for or against the use of breast MRI to detect disease recurrence in women of average risk.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. However, the ACR recommends annual surveillance with breast MRI in women with a personal history of breast cancer and dense breast tissue, or those diagnosed before age 50 [186]. This ACR recommendation is partially due to data showing that women with a personal history of premenopausal breast cancer benefited from MRI screening [187]. Data from the Breast Cancer Surveillance Consortium (BCSC) showed that, compared with mammography, MRI identified more cancers (10.8 versus 8.2 per 1,000 women screened) at the expense of a higher biopsy rate (10.1% versus 4.0%). However, multivariate models showed no difference in interval cancer detection rate or sensitivity (61.4% versus 70.3%, respectively) [188]. Wernli et al [188] also found that surveillance breast MRI leads to higher biopsy rate (OR, 2.2; 95% CI, 1.9-2.7; P < . 001) and cancer detection rate (OR, 1.7; 95% CI, 1.1-2.7; P = . 03) than mammography alone. However, there were no differences in sensitivity (OR, 1.1; 95% CI, 0.4-2.9; P = . 84) or interval cancer rate (OR, 1.1; 95% CI, 0.6-2.2; P = . 70) compared with mammography. Single-institutional studies at academic centers evaluating MRI for surveillance report sensitivities between 75% to 100% [189-193]. The cancer detection rate ranges from 1% to 2.9% for women whose only risk factor is a personal history of breast cancer [190-192]. However, this increases to 5.4% in patients with a personal history of breast cancer and dense breasts [194]. Another study from the BCSC group showed that women with a personal history of breast cancer undergoing MRI had a 2-fold increase in biopsy rate per 1,000 screening episodes (57.1% versus 23.6%) and lower cancer yield (267.6 versus 404.6 per 1,000 episodes with biopsy) than following mammography [195].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Most recently, a meta-analysis from 2000-2019 evaluating MRI as a screening modality in 8,338 women with a history of breast cancer (12,335 MRI examinations) found insufficient data to recommend for or against MRI as a surveillance examination in addition to mammographic screening [196]. Cancer detection rates of a second breast cancer by MRI were 8 to 20 per 1,000 examinations, but the sensitivity range was from 61% to 100%, with BI- RADS benchmark for MRI screening of at least 80%. Thus, clinical performance benchmarks have not been met in this population. Still, with the exception of the study on the BCSC cohort, other studies did not account for patient characteristics that could increase risk, such as premenopausal status, breast density, mutation status, or family history, through adjustment, stratification, or descriptive analysis. MRI Breast Without IV Contrast There is no evidence to support the use of noncontrast breast MRI in evaluating extent of disease. US Breast There is limited evidence to support the use of US breast for surveillance in women with history of BCT. A single study in Asian patients with a personal history of breast cancer treated with breast-conserving surgery or mastectomy showed diagnostic performances for the sensitivity, specificity, PPV, and accuracy of US of 95.8%, 97.8%, 27.1%, and 97.9% after BCS and 42.9%, 97.5%, 9.4%, and 97.2% after mastectomy [197]. There is additional evidence that whole breast US, as an adjunct to screening mammography in all women with dense breasts, detects additional 0.3 to 7.7 cancers per 1,000 at the expense of 11.7 to 106.6 biopsies per 1,000 women [198]. Although useful as a general supplemental screening tool, these limited data do not support US breast as supplemental screening after breast cancer conservation, with more data needed to determine how postoperative changes and fat necrosis specific to this population might impact specificity and sensitivity. Variant 7: Surveillance.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Regardless of clinical stage of breast cancer at time of original presentation. Evaluation for local recurrence in patient with history of mastectomy. Minimal residual breast tissue remains after all forms of mastectomy [199]. Although locoregional recurrence is typically detected clinically, some are incidentally detected by imaging, during the screening examination of the native contralateral breast. For these reasons, ASCO recommends frequent clinical surveillance with physical examination and history every 3 to 12 months for the first 5 years after mastectomy, followed by annual clinical breast examination in subsequent years [173]. Digital Breast Tomosynthesis Diagnostic There is no evidence to support the use of DBT to evaluate for recurrence after mastectomy in an asymptomatic patient. Digital Breast Tomosynthesis Screening There is no evidence to support the use of screening DBT to evaluate for recurrence after mastectomy. Imaging of Invasive Breast Cancer FDG-PET/CT Skull Base to Mid-Thigh In asymptomatic patients with a history of breast cancer who received treatment for curative intent, there is no role for imaging to screen for locoregional recurrences with FDG-PET/CT skull base to mid-thigh. ASCO, NCCN, and ESMO all recommend against the routine use of imaging to screen for distant disease recurrence [172,173,200]. Mammography Diagnostic There is no evidence to support the use of diagnostic mammography to evaluate for recurrence after mastectomy in asymptomatic women. Mammography Screening There is no evidence to support the use of screening mammography to evaluate for recurrence after mastectomy. Mammography With IV Contrast There is no evidence to support the use of CEM to evaluate for recurrence after mastectomy in asymptomatic women. MRI Breast Without and With IV Contrast High-risk women with mastectomies may benefit from MRI surveillance of their remaining breast.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. In a small study evaluating MRI in women with a unilateral mastectomy, the cancer detection rate was 10 per 1,000 in the asymptomatic mastectomy side, and these cancers would have otherwise been undetected until symptomatic because screening mammography is not performed after mastectomy. In this population, surveillance MR had a sensitivity of 66.7%, a specificity of 99.2%, a PPV of 57.1%, and an NPV of 99.5%. Larger studies are needed to assess the utility of surveillance MR in the setting of mastectomy [201]. MRI Breast Without IV Contrast There is no evidence to support the use of noncontrast breast MRI in surveillance. US Breast There is limited evidence to support the use of US breast for surveillance in the women with history of mastectomy. Variant 8: Suspected local recurrence of breast cancer based on symptoms, physical examination, or laboratory value in patient with history of BCT. Regardless of clinical stage at time of original presentation. Digital Breast Tomosynthesis Diagnostic Mammography can assist in monitoring women with a history of breast cancer and evaluating for suspicion of local recurrence. Diagnostic DBT improves lesion characterization in noncalcified lesions when compared with conventional mammographic workup [202]. The performance of DM versus DBT has not been determined for symptomatic imaging specifically in the post-BCT population. FDG-PET/CT Skull Base to Mid-Thigh There is no evidence to support the use of FDG-PET/CT to evaluate for locoregional recurrence after BCT. Mammography Diagnostic Mammography can assist in monitoring women with a history of breast cancer and evaluating for suspicion of local recurrence. Diagnostic DBT improves lesion characterization in noncalcified lesions when compared with conventional mammographic workup [202]. The performance of DM versus DBT has not been determined for symptomatic imaging specifically in the post-BCT population.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Mammography With IV Contrast There are limited data on the use of CEM in breast cancer surveillance. Sorin et al [203] did show a high incremental cancer detection rate (13.1 cancers per 1,000 women) when mammography with IV contrast replaced DM in patients with a personal history of breast cancer or with an intermediate lifetime risk. US (targeted and whole breast) increased the number of women needing biopsy from 80 to 134 without detecting additional malignancy. MRI Breast Without and With IV Contrast Although MRI does have greater sensitivity for malignancy than diagnostic mammogram alone, this use serves to detect asymptomatic disease. If there is a finding on the mammogram or US, then workup may be performed based on the most suspicious finding identified during the standard diagnostic workup. A mammographic finding can be sampled using tomosynthesis or stereotactic biopsy, and a sonographic finding can be sampled using US-guided biopsy. If mammogram and US are unrevealing, MRI is not useful as a problem-solving test, and, therefore, further management should be based upon the clinical symptoms. For example, evidence does not support the use of MRI Imaging of Invasive Breast Cancer in cases of a palpable breast mass without corresponding suspicious finding on mammography or US. In a study, 2 of 82 patients were subsequently diagnosed with malignancy with PPV of 25% [204], and in another, 3 of 167 women with PPV of 13% [205]. Finally, a third study starting with 22,004 women with palpable abnormalities demonstrated 9,334 with negative mammogram and/or US. Thirty-one of these patients underwent subsequent MRI, with 8 subsequent biopsies and no malignancies found [206]. MRI Breast Without IV Contrast There is no role for noncontrast MRI in the setting of suspected local recurrence based on signs and symptoms.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. US breast may be helpful to further evaluate women with suspected recurrence unless the findings on mammography corresponding to the physical examination finding are classic for a benign etiology (eg, fat necrosis). Variant 9: Suspected local recurrence of breast cancer based on symptoms, physical examination, or laboratory value in patient with history of mastectomy. Regardless of clinical stage at time of original presentation. Digital Breast Tomosynthesis Diagnostic There is no evidence to support the use of DBT to evaluate suspected local recurrence in the setting of mastectomy unless the local recurrence suspected is in the axillary region or the patient has a history of breast reconstruction. FDG-PET/CT Skull Base to Mid-Thigh There is no evidence to support the use of FDG-PET/CT to evaluate suspected local recurrence in the setting of mastectomy. Mammography Diagnostic There is no evidence to support the use of mammography to evaluate suspected local recurrence in the setting of mastectomy unless the local recurrence suspected is in the axillary region or the patient has a history of breast reconstruction. Mammography With IV Contrast There is no evidence to support the use of mammography with IV contrast to evaluate suspected local recurrence in the setting of mastectomy unless the local recurrence suspected is in the axillary region or the patient has a history of breast reconstruction. MRI Breast Without and With IV Contrast Although breast MR has been evaluated in the setting of asymptomatic screening after mastectomy, there is insufficient evidence to support the use of MR as a problem-solving tool after a negative mammogram (axillary finding/reconstructed breast) and/or US. Therefore, management should be based on clinical suspicion rather than additional imaging. MRI Breast Without IV Contrast There is no evidence to support the use of noncontrast breast MRI in evaluating disease suspected recurrence. Variant 10: Surveillance.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Regardless of clinical stage of breast cancer at time of original presentation. Evaluation for distant metastatic disease. Bone Scan Whole Body In asymptomatic patients with a history of breast cancer who received treatment for curative intent, there is no evidence to support the use of bone scan whole body for surveillance of distant metastatic disease. The ASCO, NCCN, ESMO, and ESO all recommend against the routine use of imaging to screen for distant disease recurrence [126,128,209,210]. Imaging of Invasive Breast Cancer CT Chest, Abdomen, and Pelvis With IV Contrast In asymptomatic patients with a history of breast cancer who received treatment for curative intent, there is no evidence to support the use of CT chest, abdomen, and pelvis for surveillance of distant metastatic disease. The ASCO, NCCN, ESMO, and ESO all recommend against the routine use of imaging to screen for distant disease recurrence [126,128,209,210]. CT Chest, Abdomen, and Pelvis Without and With IV Contrast In asymptomatic patients with a history of breast cancer who received treatment for curative intent, there is no evidence to support the use of CT chest, abdomen, and pelvis for surveillance of distant metastatic disease. The ASCO, NCCN, ESMO, and ESO all recommend against the routine use of imaging to screen for distant disease recurrence [126,128,209,210]. CT Chest, Abdomen, and Pelvis Without IV Contrast In asymptomatic patients with a history of breast cancer who received treatment for curative intent, there is no evidence to support the use of CT chest, abdomen, and pelvis for surveillance of distant metastatic disease. The ASCO, NCCN, ESMO, and ESO all recommend against the routine use of imaging to screen for distant disease recurrence [126,128,209,210]. Digital Breast Tomosynthesis Diagnostic There is no evidence to support the use of DBT in asymptomatic women for surveillance of distant metastatic disease.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. FDG-PET/CT Skull Base to Mid-Thigh In asymptomatic patients with a history of breast cancer who received treatment for curative intent, there is no evidence to support the use of FDG-PET/CT for surveillance of distant metastatic disease. The ASCO, NCCN, ESMO, and ESO all recommend against the routine use of imaging to screen for distant disease recurrence [126,128,209,210]. Mammography Diagnostic There is no evidence to support the use of mammography to evaluate suspected distant metastatic disease unless the recurrence suspected is in the axillary region. MRI Head Without and With IV Contrast There is no evidence supporting the use of MRI head without and with IV contrast in asymptomatic women for surveillance. In asymptomatic patients with a history of breast cancer who received treatment for curative intent, there is no role for imaging to screen for distant recurrences. The ASCO, NCCN, ESMO, and ESO all recommend against the routine use of imaging to screen for distant disease recurrence [126,128,209,210]. MRI Head Without IV Contrast There is no evidence supporting the use of MRI head without IV contrast in asymptomatic women for surveillance. US Axilla There is no evidence supporting the use of US axilla in asymptomatic women for surveillance of distant metastatic disease. Variant 11: Suspected distant recurrence of breast cancer based on symptoms, physical examination, or laboratory value. Regardless of clinical stage at time of original presentation. Bone Scan Whole Body In the setting of suspected distant recurrence, bone scan along with chest, abdomen, and pelvis CT is recommended by the NCCN [126]. CT Chest, Abdomen, and Pelvis With IV Contrast In the setting of suspected distant recurrence, bone scan plus chest, abdomen, and pelvis CT is recommended by the NCCN [172].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. CT Chest, Abdomen, and Pelvis Without and With IV Contrast The majority of clinical questions for abdominal and/or pelvic CT can be appropriately answered with a single- phase study as detailed in the ACR-SABI-SPR practice parameter for the performance of CT of the abdomen and CT of the pelvis [21]. Imaging of Invasive Breast Cancer CT Chest, Abdomen, and Pelvis Without IV Contrast There is no evidence to support the use of CT chest, abdomen, and pelvis without IV contrast to evaluate for distant recurrence. FDG-PET/CT Skull Base to Mid-Thigh In symptomatic patients with a history of breast cancer who received treatment for curative intent, PET/CT can be used to evaluate for recurrence according to NCCN guidelines [126]. Imaging of Invasive Breast Cancer Supporting Documents The evidence table, literature search, and appendix for this topic are available at https://acsearch. acr.org/list. The appendix includes the strength of evidence assessment and the final rating round tabulations for each recommendation. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www. acr.org/ac. Appropriateness Category Names and Definitions Relative Radiation Level Information Potential adverse health effects associated with radiation exposure are an important factor to consider when selecting the appropriate imaging procedure. Because there is a wide range of radiation exposures associated with different diagnostic procedures, a relative radiation level (RRL) indication has been included for each imaging examination. The RRLs are based on effective dose, which is a radiation dose quantity that is used to estimate population total radiation risk associated with an imaging procedure. Patients in the pediatric age group are at inherently higher risk from exposure, because of both organ sensitivity and longer life expectancy (relevant to the long latency that appears to accompany radiation exposure).


Clinically Suspected Adnexal Mass No Acute Symptoms.  Introduction/Background Ovarian cancer is the fifth leading cause of cancer mortality among women in the United States, showing little improvement in survival over the last several decades [1,2]. In 2023, it is estimated that 19,710 women will be diagnosed with ovarian cancer in the United States, and 13,270 will die from their disease [3]. Prognostic factors associated with survival include both stage at diagnosis and treatment at a high-volume center with management by a gynecologist oncologist [4,5]. High-grade serous carcinoma, now thought to arise typically from fallopian tube epithelium, is most often diagnosed at late stage and accounts for nearly 80% of ovarian cancer deaths [1,6]. Identification of early-stage cancers is paramount for cancer-specific survival in ovarian cancer, but only 16% of patients are diagnosed at early stages. Although the 5-year relative survival for ovarian cancer is 49.1%, it increases to nearly 93% for stage I disease (confined to the ovaries/adnexa) [3]. Special Imaging Considerations Contrast-enhanced ultrasound: Contrast-enhanced ultrasound (CEUS) can be a useful real-time technique to demonstrate the presence of internal vascular soft tissue component in an indeterminate ovarian lesion that increases the risk of malignancy. Soft tissue enhancing earlier than or concurrent to the myometrium was found in 93.8% of malignant lesions in 1 study compared with 12.5% of benign lesions [11]. The International Ovarian Tumor Analysis (IOTA) simple rules performed well when applied to CEUS in 1 study, with reduction in indeterminate masses from 36.7% to 11.7% when using CEUS after conventional pelvic ultrasound (US) in a surgical cohort of suspected malignant masses [12]. Three-dimensional CEUS and 3-D contrast-enhanced power Doppler may be useful as adjunct to conventional US and 2-D CEUS [13,14].


Clinically Suspected Adnexal Mass No Acute Symptoms. In a meta-analysis, CEUS had higher accuracy for differentiating benign and malignant lesions than conventional US (94% versus 83%); however, further evaluation of the clinical use of CEUS is needed [15]. aVanderbilt University Medical Center, Nashville, Tennessee. bPanel Chair, University of Michigan, Ann Arbor, Michigan. cThe George Washington University Medical Center, Washington, District of Columbia; Commission on Nuclear Medicine and Molecular Imaging. dVanderbilt University Medical Center, Nashville, Tennessee; O-RADS Committee. eMedstar Georgetown University Hospital, Washington, District of Columbia. fBeth Israel Deaconess Medical Center, Boston, Massachusetts. gUniversity of California San Diego, San Diego, California; American College of Obstetricians and Gynecologists. hCleveland Clinic, Cleveland, Ohio. iHospital of the University of Pennsylvania, Philadelphia, Pennsylvania. jAscension St. Vincent's, Jacksonville, Florida and University of South Florida, Tampa, Florida; Gynecologic oncologist. kMayo Clinic Arizona, Phoenix, Arizona; IF Committee. lDepartment of Medical Imaging, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. mYale University School of Medicine, New Haven, Connecticut; Committee on Emergency Radiology-GSER. nMayo Clinic, Rochester, Minnesota. oUniversity of California San Diego, San Diego, California; Commission on Radiation Oncology. pSpecialty Chair, New York University Medical Center, New York, New York. Reprint requests to: publications@acr.org OR Discussion of Procedures by Variant Variant 1: Adult patient assigned female at birth. Clinically suspected adnexal mass, no acute symptoms. Premenopausal or postmenopausal. Initial imaging. CT Pelvis With IV Contrast CT pelvis with intravenous (IV) contrast is typically not useful for the initial workup and characterization of adnexal masses due to suboptimal delineation of soft tissue in the adnexal region.


Clinically Suspected Adnexal Mass No Acute Symptoms. The presence of macroscopic fat, with or without the presence of calcification and/or Rokitansky nodule, is diagnostic of a dermoid if seen on CT. CT Pelvis Without and With IV Contrast CT pelvis without and with IV contrast is typically not useful for the initial workup and characterization of adnexal masses due to suboptimal delineation of soft tissue in the adnexal region. The presence of macroscopic fat, with or without the presence of calcification and/or Rokitansky nodule, is diagnostic of a dermoid if seen on CT. CT Pelvis Without IV Contrast CT pelvis without IV contrast is typically not useful for the initial workup and characterization of adnexal masses due to suboptimal delineation of soft tissue in the adnexal region. The presence of macroscopic fat, with or without the presence of calcification and/or Rokitansky nodule, is diagnostic of a dermoid if seen on CT. FDG-PET/CT Skull Base to Mid-Thigh Fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT is not useful for the initial workup and characterization of adnexal masses due to suboptimal delineation of soft tissue in the adnexal region. MRI Pelvis Without and With IV Contrast MRI can accurately diagnose the presence of adnexal lesions and identify enhancing soft tissue as well as other distinguishing characteristics such as the type of fluid content, presence of fat, or presence of septations in a cystic lesion. It performs superior to US; however, it is not the first-line modality for initial evaluation [16,17]. If a patient with a suspected adnexal lesion is unable to be evaluated via US (due to large size of lesion >10 cm, poor acoustic window from adjacent viscera or body habitus, or unclear organ of origin), MRI would be the best alternative imaging modality for evaluation. MRI Pelvis Without IV Contrast If MRI is being used for evaluation of a suspected adnexal lesion, IV contrast is recommended to evaluate for any internal enhancing component.


Clinically Suspected Adnexal Mass No Acute Symptoms. Contrast-enhanced MRI performs superiorly to both US and noncontrast MRI due to its ability to confirm the presence of internal enhancing soft tissue components [18]. A recent study evaluating the usefulness of noncontrast MRI in 350 lesions in a population with 15% malignancies demonstrated a sensitivity of 85%, specificity of 96%, and accuracy of 94.2% to detect cancer [19]. Noncontrast MRI may be used in adnexal mass characterization when the use of IV contrast is precluded. US Duplex Doppler Pelvis Although considered a separate examination in the ACR documentation, color and power Doppler evaluation is considered an integral part of the complete transabdominal and transvaginal sonographic assessment of an adnexal lesion. Doppler can help identify internal soft tissue with vascular flow within a suspected adnexal lesion that can help differentiate a malignancy from a solid-appearing component such as a clot or debris [20-22]. Optimal sonographic evaluation is achieved by using a combination of grayscale morphologic assessment and color or power Doppler imaging to detect flow within any solid areas. Color Doppler characteristics, namely a color score of 1 to US Pelvis Transabdominal Transabdominal US may be performed without transvaginal imaging when the transvaginal examination cannot be tolerated. A full bladder provides a better acoustic window for the evaluation of pelvis/adnexa. US Pelvis Transabdominal and US Pelvis Transvaginal Transvaginal US is the most useful initial imaging modality in the assessment of adnexal pathology with a sensitivity >90%, and diagnostic performance is likely improved when undertaken by experienced operators [27,28]. It is widely accepted clinically as the initial imaging modality of choice [29-31].


Clinically Suspected Adnexal Mass No Acute Symptoms. Initial evaluation by transabdominal and transvaginal US can often definitively characterize ovarian lesions, specifically those that demonstrate classically benign US features (eg, follicles, functional cysts, hemorrhagic cysts, dermoids, and endometriomas). Lesions that demonstrate solid components such as irregular thick septations, papillary projections, or mural nodules have variable risk of malignancy. Various US and combined US/clinical based criteria have been proposed for standardized interpretation and characterization of adnexal masses to improve risk-stratified management of these lesions [23,24,32-37]. These includes the IOTA simple rules, O-RADS, Society of Radiologists in Ultrasound (SRU) consensus statement for incidental adnexal masses, and Assessment of Different NEoplasias in the adneXa (ADNEX) model. These are beyond the scope of discussion for this document, and the readers are directed to the respective literature for details [23,24,34,37-41]. These systems use some combination of classically benign imaging features, lesion size, locularity, size and number of solid components, and degree of vascularity for categorization and determining overall risk of malignancy. The SRU consensus statement [42] has been shown to decrease unnecessary follow-up care of benign adnexal lesions, correlate with the risk of malignancy in symptomatic women, and demonstrate high sensitivity and specificity for detecting ovarian malignancy [43-45]. O-RADS [23,38] has demonstrated significantly higher sensitivity for malignancy than the IOTA simple rules (96.8% versus 92.1%) and no significant difference in specificity (92.8% versus 93.2%) [46]. Combined transvaginal and transabdominal technique allows for the identification of pertinent features relevant for characterization and categorization of these lesions.