Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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]. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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).


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. MRI Breast Without IV Contrast There is no evidence to support the use of noncontrast breast MRI in evaluating extent of disease.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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 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

Imaging of Invasive Breast Cancer. 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].


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 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%). 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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

Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Imaging of Invasive Breast Cancer


Imaging of Invasive Breast Cancer

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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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]. 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].


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

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. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Digital Breast Tomosynthesis Diagnostic There is no evidence to support the use of DBT to evaluate for distant disease.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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]. 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

Imaging of Invasive Breast Cancer


Imaging of Invasive Breast Cancer

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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. MRI Breast Without IV Contrast There is no evidence to support the use of noncontrast breast MRI in evaluating extent of disease.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. US Axilla There is no evidence to support the use of US axilla to evaluate for distant disease.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. US Breast There is no evidence to support the use of US breast to evaluate for distant disease.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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

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 [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

Imaging of Invasive Breast Cancer. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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]. 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].


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

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. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Digital Breast Tomosynthesis Diagnostic There is no evidence to support the use of DBT to evaluate for distant disease.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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]. 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]. 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.


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

Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Imaging of Invasive Breast Cancer


Imaging of Invasive Breast Cancer

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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. MRI Breast Without IV Contrast There is no evidence to support the use of noncontrast breast MRI in evaluating the extent of disease.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. MRI Head Without IV Contrast There is no evidence to support the use of MRI head without IV contrast to evaluate for distant disease.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. US Axilla There is no evidence to support the use of US axilla to evaluate for distant disease.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. US Breast There is no evidence to support the use of US breast to evaluate for distant disease.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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]. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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. 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

Imaging of Invasive Breast Cancer


Imaging of Invasive Breast Cancer

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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. There is evidence that mammography alone may not be sufficient for surveillance in this population. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. There is evidence that mammography alone may not be sufficient for surveillance in this population. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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

Imaging of Invasive Breast Cancer. 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. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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]. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. MRI Breast Without IV Contrast There is no evidence to support the use of noncontrast breast MRI in evaluating extent of disease.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Variant 7: Surveillance. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Digital Breast Tomosynthesis Diagnostic There is no evidence to support the use of DBT to evaluate for recurrence after mastectomy in an asymptomatic patient.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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

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 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].


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 recurrence after mastectomy in asymptomatic women.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Mammography Screening There is no evidence to support the use of screening mammography to evaluate for recurrence after mastectomy.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Mammography With IV Contrast There is no evidence to support the use of CEM to evaluate for recurrence after mastectomy in asymptomatic women.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. MRI Breast Without and With IV Contrast High-risk women with mastectomies may benefit from MRI surveillance of their remaining breast. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. MRI Breast Without IV Contrast There is no evidence to support the use of noncontrast breast MRI in surveillance.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. US Breast There is limited evidence to support the use of US breast for surveillance in the women with history of mastectomy.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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

Imaging of Invasive Breast Cancer. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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).


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. MRI Breast Without IV Contrast There is no evidence to support the use of noncontrast breast MRI in evaluating disease suspected recurrence.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Variant 10: Surveillance. 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

Imaging of Invasive Breast Cancer. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. MRI Head Without IV Contrast There is no evidence supporting the use of MRI head without IV contrast in asymptomatic women for surveillance.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. US Axilla There is no evidence supporting the use of US axilla in asymptomatic women for surveillance of distant metastatic disease.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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].


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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

Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. Imaging of Invasive Breast Cancer


Imaging of Invasive Breast Cancer

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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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

Imaging of Invasive Breast Cancer. 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.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www.acr.org/ac.


Imaging of Invasive Breast Cancer

Imaging of Invasive Breast Cancer. 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). For these reasons, the RRL dose estimate ranges for


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].


Clinically Suspected Adnexal Mass No Acute Symptoms. 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].


Clinically Suspected Adnexal Mass No Acute Symptoms. 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]. 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].


Clinically Suspected Adnexal Mass No Acute Symptoms. 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.


Clinically Suspected Adnexal Mass No Acute Symptoms. Reprint requests to: publications@acr.org


Clinically Suspected Adnexal Mass No Acute Symptoms. 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. 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.


Clinically Suspected Adnexal Mass No Acute Symptoms. 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.


Clinically Suspected Adnexal Mass No Acute Symptoms. 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.


Clinically Suspected Adnexal Mass No Acute Symptoms. 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.


Clinically Suspected Adnexal Mass No Acute Symptoms. 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.


Clinically Suspected Adnexal Mass No Acute Symptoms. 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.


Clinically Suspected Adnexal Mass No Acute Symptoms. 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


Clinically Suspected Adnexal Mass No Acute Symptoms. 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.


Clinically Suspected Adnexal Mass No Acute Symptoms. 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.


Clinically Suspected Adnexal Mass No Acute Symptoms. 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].


Clinically Suspected Adnexal Mass No Acute Symptoms. 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].


Clinically Suspected Adnexal Mass No Acute Symptoms. Combined transvaginal and transabdominal technique allows for the identification of pertinent features relevant for characterization and categorization of these lesions. The transvaginal component allows for detailed evaluation with the transabdominal component helpful for larger lesions that may be suboptimally seen transvaginally.


Clinically Suspected Adnexal Mass No Acute Symptoms. US Pelvis Transvaginal The most useful modality for evaluation of adnexal masses includes transvaginal US combined with a transabdominal US approach.


Clinically Suspected Adnexal Mass No Acute Symptoms. Variant 2: Adult patient assigned female at birth. Adnexal mass, likely benign, no acute symptoms. Premenopausal. Follow-up imaging. CT Pelvis With IV Contrast CT pelvis with IV contrast is usually not useful to follow likely or known benign adnexal masses. Because the roles of US and MRI are well established, there is little reason presently to obtain a CT for benign mass follow-up.


Clinically Suspected Adnexal Mass No Acute Symptoms. CT Pelvis Without and With IV Contrast CT pelvis without and with IV contrast is usually not useful to follow likely or known benign adnexal masses. Because the roles of US and MRI are well established, there is little reason presently to obtain a CT for benign mass follow-up.


Clinically Suspected Adnexal Mass No Acute Symptoms. CT Pelvis Without IV Contrast CT pelvis without IV contrast is usually not useful to follow likely or known benign adnexal masses. Because the roles of US and MRI are well established, there is little reason presently to obtain a CT for benign mass follow-up.


Clinically Suspected Adnexal Mass No Acute Symptoms. Clinically Suspected Adnexal Mass FDG-PET/CT Skull Base to Mid-Thigh There is no role for the use of FDG-PET/CT in the follow-up of benign adnexal masses in premenopausal patients.


Clinically Suspected Adnexal Mass No Acute Symptoms. MRI Pelvis Without and With IV Contrast Although MRI can accurately characterize these benign lesions, it is not the first-line modality [16,17]. If a known lesion requiring surveillance is unable to be followed via US, MRI would be the alternative imaging modality of choice for follow-up.


Clinically Suspected Adnexal Mass No Acute Symptoms. Classically benign lesions such as simple cysts, endometriomas and dermoid, and extraovarian benign lesions have characteristic appearances on MRI and can be confidently diagnosed as almost certainly benign [17].


Clinically Suspected Adnexal Mass No Acute Symptoms. MRI Pelvis Without IV Contrast If MRI is being used for follow-up of a benign lesion, IV contrast is recommended to evaluate for any developing 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 and 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.


Clinically Suspected Adnexal Mass No Acute Symptoms. US Duplex Doppler Pelvis Color or power Doppler should be included in the US examination of the pelvis. Color Duplex is used to evaluate vascularity of any developing solid component.


Clinically Suspected Adnexal Mass No Acute Symptoms. US Pelvis Transabdominal Transabdominal US may be performed without transvaginal imaging when the transvaginal examination cannot be tolerated. The bladder should be full to provide the best acoustic window for evaluation.


Clinically Suspected Adnexal Mass No Acute Symptoms. US Pelvis Transabdominal and US Pelvis Transvaginal US can accurately diagnose benign adnexal lesions including simple cysts, hemorrhagic cysts, endometriomas, and dermoids as well as extraovarian cystic lesions such as parovarian cysts, hydrosalpinx, and peritoneal inclusion cysts. Adnexal lesions that can be adequately assessed and characterized on US may be followed-up with US.


Clinically Suspected Adnexal Mass No Acute Symptoms. The vast majority of simple cysts in premenopausal patients are functional cysts, which will wax and wane over time or resolve, with a small portion reflecting benign neoplasms. A large body of evidence including several large recent studies has shown that simple cysts, regardless of size and menopausal status, are not associated with an increased risk of cancer [35,47-49]. Invasive serous cystadenocarcinoma is now thought to primarily originate from solid precursors in the fallopian tube and serous tubal intraepithelial carcinoma, further supporting the benignity of simple ovarian cysts [50]. A recent consensus update to the SRU in 2019 regarding management of simple cysts reflects these findings with higher threshold for follow-up of simple cysts [42]. Namely, in premenopausal women, simple cysts, including paraovarian and paratubal cysts <5 cm, do not need to be followed. The rationale of follow- up for simple cysts >5 cm (and 7 cm for exceptionally well seen cysts) is based on a potential risk of mischaracterization of larger cysts and potential clinical value of size monitoring growth rates of larger cysts, which may reflect benign neoplasms and warrant clinical follow-up along with a very small predisposition for torsion or rupture [51].


Clinically Suspected Adnexal Mass No Acute Symptoms. Classic benign lesions include endometriomas, hemorrhagic cysts, and dermoids as well as benign extraovarian lesions such as paraovarian cysts, hydrosalpinx, and peritoneal inclusion cysts have characteristic appearances on US [23,34]. Hemorrhagic functional cysts will decrease or resolve on sonographic follow-up in 8 to 12 weeks versus nonfunctional cysts, which will persist. Endometriomas may change in appearance with age, losing the classic unilocular ground glass appearance with multilocular appearance and presence of nonvascular papillary or other solid components more common in older premenopausal women [52]. These changes can overlap with malignancy and endometriomas and require yearly follow-up due to a small risk of malignant transformation [53]. Sonographically diagnosed dermoids, if not excised, can be safely followed with yearly US with the risk of missing malignant degeneration quite low [54].


Clinically Suspected Adnexal Mass No Acute Symptoms. Clinically Suspected Adnexal Mass managed conservatively with 2-year follow-up was 0.3% to 0.4% for malignancy and 0.2% to 0.4% for acute complications such as torsion or cyst rupture [51].


Clinically Suspected Adnexal Mass No Acute Symptoms. Unilocular cysts, as a whole, in the premenopausal population similarly have a very low risk of malignancy. A recent meta-analysis by Parazzini et al [56] demonstrated that in 987 unilocular cysts removed surgically in premenopausal women, the risk of malignancy was 0.6%. Similar findings were found by Valentin et al [57], with a rate of malignancy of 0.5% in 981 surgically resected lesions. Surgical cohorts have a bias of increased risk of malignancy due to persistent cysts, and thus, this can be extrapolated into an even lower theoretical risk of malignancy in the general population.


Clinically Suspected Adnexal Mass No Acute Symptoms. The most common benign solid adnexal mass is the uterine fibroid. Pedunculated lesions or broad ligament fibroids can often be mistaken for solid adnexal mass. Fibroids are present in up to 20% to 30% of reproductive age women, and the presence of bridging vessels can help identify uterine origin along with careful search for the ovaries [25].


Clinically Suspected Adnexal Mass No Acute Symptoms. US Pelvis Transvaginal The most useful modality for evaluation of adnexal masses includes transvaginal US combined with transabdominal US approach.


Clinically Suspected Adnexal Mass No Acute Symptoms. Variant 3: Adult patient assigned female at birth. Adnexal mass, likely benign, no acute symptoms. Postmenopausal. Follow-up imaging. CT Pelvis With IV Contrast CT pelvis with IV contrast is usually not useful to follow likely or known benign adnexal masses. Because the roles of US and MRI are well established, there is little reason presently to obtain a CT for benign mass follow-up.


Clinically Suspected Adnexal Mass No Acute Symptoms. CT Pelvis Without and With IV Contrast CT pelvis without and with IV contrast is usually not useful to follow likely or known benign adnexal masses. Because the roles of US and MRI are well established, there is little reason presently to obtain a CT for benign mass follow-up.


Clinically Suspected Adnexal Mass No Acute Symptoms. CT Pelvis Without IV Contrast CT pelvis without IV contrast is usually not useful to follow likely or known benign adnexal masses. Because the roles of US and MRI are well established, there is little reason presently to obtain a CT for benign mass follow-up.


Clinically Suspected Adnexal Mass No Acute Symptoms. FDG-PET/CT Skull Base to Mid-Thigh There is no role for the use of FDG-PET/CT in the follow-up of benign adnexal masses in postmenopausal patients.


Clinically Suspected Adnexal Mass No Acute Symptoms. MRI Pelvis Without and With IV Contrast Although MRI can accurately characterize these benign lesions, it is not the first-line imaging modality [16,17]. If a known lesion requiring surveillance is unable to be followed via US, MRI would be the alternative imaging modality of choice for follow-up. Classical benign lesions such as simple cysts, endometriomas and dermoid, and extraovarian benign lesions have characteristic appearances on MRI and can be confidently diagnosed as almost certainly benign [17].


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.


Clinically Suspected Adnexal Mass No Acute Symptoms. Clinically Suspected Adnexal Mass US Pelvis Transabdominal and US Pelvis Transvaginal Likely benign adnexal lesions that can be adequately assessed and characterized on US may be followed sonographically.


Clinically Suspected Adnexal Mass No Acute Symptoms. A large body of evidence including several large recent screening studies has shown that unilocular simple cysts, regardless of size and menopausal status, are not associated with an increased risk of cancer [35,47-49]. In a large series, approximately 13% to 14% of women over 50 to 55 years of age, respectively, had simple ovarian cysts, with 8% demonstrating new cysts and 32% with no cyst at 1-year follow-up, with a near nonexistent risk of malignancy [47]. A second recent study of 72,093 women, those with simple cysts, demonstrated an absolute 3- year risk of ovarian cancer, 0 to 0.5 cases per 10,000 women, not dissimilar to women with normal ovaries [47,49]. Invasive serous cystadenocarcinoma is now primarily thought to originate from solid precursors in the fallopian tube, serous tubal intraepithelial carcinoma, further supporting the benignity of simple ovarian cysts [50]. A recent consensus update to the SRU in 2019 regarding management of simple cysts reflects these findings with higher threshold for follow-up of simple cysts [42]. For postmenopausal patients, the SRU endorses follow-up of simple cysts >3 cm (and 5 cm for those that are exceptionally well seen) rather than the previous 1-cm threshold [42,58]. The rationale of follow-up for simple cysts is based on a potential risk of mischaracterization of larger cysts and potential clinical value of size monitoring growth rates of larger cysts, which may reflect benign neoplasms and warrant clinical follow-up.


Clinically Suspected Adnexal Mass No Acute Symptoms. Unilocular cysts, as a whole, in the postmenopausal population similarly have a very low risk of malignancy. In a surgical cohort of 3,511 masses, 217 of which were unilocular cysts in postmenopausal women, the rate of malignancy was 3%, with hemorrhagic contents more common in malignant unilocular lesions [57]. In a second study of 15,106 women with 3,259 unilocular cystic lesions, there were 10 cancers detected over a 6.3-year period, none of which developed from the isolated cystic lesion [59]. A more recent meta-analysis demonstrated that of 372 unilocular cysts removed surgically in postmenopausal women, the risk of malignancy was 3.2% [56].


Clinically Suspected Adnexal Mass No Acute Symptoms. Variant 4: Adult patient assigned female at birth. Adnexal mass, indeterminate on initial pelvic US, no acute symptoms. Premenopausal or postmenopausal. Next imaging study for characterization. Up to 22% to 24% of adnexal masses remain indeterminate after US evaluation [61,62]. No single definition exists for these indeterminate lesions. Some examples include multilocular cysts, or lesions with avascular or low level vascular internal solid components. In a multicenter prospective study of 303 indeterminate adnexal cysts, the incidence of malignancy was 3.6% [61]. In a second multicenter prospective study of 697 women, the prevalence of malignancy in indeterminate lesions ranged from 4.8% to 10.7% using SRU guidelines and IOTA simple rules, respectively [45]. Lesions that are not classically benign appearing have a risk of malignancy ranging from 8% to 50% [55].


Clinically Suspected Adnexal Mass No Acute Symptoms. CT Pelvis With IV Contrast CT pelvis with IV contrast is usually not useful in further characterization of indeterminate adnexal masses. Because the role of MRI is well established, there is little reason presently to obtain a CT for further characterization of an indeterminate lesion.


Clinically Suspected Adnexal Mass No Acute Symptoms. CT Pelvis Without and With IV Contrast CT pelvis without and with IV contrast is usually not useful in further characterization of indeterminate adnexal masses. Because the role of MRI is well established, there is little reason presently to obtain a CT for further characterization of an indeterminate lesion.


Clinically Suspected Adnexal Mass

Clinically Suspected Adnexal Mass No Acute Symptoms. Clinically Suspected Adnexal Mass


Clinically Suspected Adnexal Mass No Acute Symptoms. CT Pelvis Without IV Contrast CT pelvis without IV contrast is usually not useful in further characterization of indeterminate adnexal masses. Because the role of MRI is well established, there is little reason presently to obtain a CT for further characterization of an indeterminate lesion.


Clinically Suspected Adnexal Mass No Acute Symptoms. FDG-PET/CT Skull Base to Mid-Thigh PET/CT cannot reliability differentiate between benign and malignant adnexal lesions [63]. In premenopausal women, normal ovaries with late follicular or early luteal cysts can have mildly increased uptake [64]. Although maximum standardized update value (SUVmax) are higher in malignant tumors and low in benign lesions, there is no clear SUVmax cutoff value to differentiate the two [65]. Additionally, PET/CT cannot reliably differentiate between borderline tumors and benign lesions and has low uptake on clear cell and mucinous invasive adenocarcinoma subtypes [66,67]. Although PET-avid lesions in postmenopausal women are concerning for malignancy, its use to detect primary cancer is not recommended [68].


Clinically Suspected Adnexal Mass No Acute Symptoms. MRI Pelvis Without and With IV Contrast MRI is the most useful modality for further evaluation of the subset of lesions that remain indeterminate after sonographic evaluation [69]. A recent study assessing the SRU guidelines ability to risk stratify lesions demonstrated potential of MRI to decrease surgical evaluation for benign cysts by 89% [44]. MRI has an excellent accuracy of >90% for the diagnosis of malignancy [69-71]. MRI can accurately identify solid tissue from nonsolid tissue such as fat, blood, or debris that may appear solid on initial US [72]. MRI can also help determine the origin of the lesion, with up to 9% of presumed adnexal lesions on US being nonadnexal origin [73]. Sonographically visualized lesions >10 cm may need contrast-enhanced MRI to ensure complete visualization and assessment of the lesion and ensure there are no associated solid components.


Clinically Suspected Adnexal Mass No Acute Symptoms. The presence or absence of enhancing solid tissue and enhancement curve characteristics as evaluated on perfusion dynamic contrast-enhanced imaging drives the risk of malignancy on MRI [17,69,71,74-80]. The absence of enhancement renders the risk of malignancy to nearly 0%, which is of particular value in the sonographically indeterminate lesions because it confirms the benignity of the lesion [71]. Solid tissue with time intensity curves (TIC) with rapid enhancement greater than the myometrium (type 3) are only found in invasive malignant tumors with a sensitivity of 67% versus slow low level enhancement (type 1) found in benign tumors with a sensitively of 70% and specificity of 89% [79].


Clinically Suspected Adnexal Mass No Acute Symptoms. Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values of benign and malignant lesions overlap, with Fujii et al [81] demonstrating teratomas, some endometriomas, and malignant tumors demonstrating abnormal DWI signal. The primary value of DWI is in the setting of a low T2 signal mass, with low signal on DWI predicting a high likelihood of benignity [69,81,82].


Clinically Suspected Adnexal Mass No Acute Symptoms. MRI Pelvis Without IV Contrast 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]. Both the ADNEX and O-RADS MRI risk stratification systems will have some decreased usefulness in the noncontrast setting given the limited ability to identify enhancing solid tissue and its enhancement pattern, both crucial for characterizing indeterminate lesions [17,71,73]. For example, the overall specificity for malignancy of the ADNEX MR system falls below 90% if used without dynamic contrast enhancement [71,87]. Sahin et al [19] proposed a noncontrast MRI score based on ADNEX and O-RADS models using morphologic assessment and DWI with an 84.9% sensitivity, 95.9% specificity, and 94% accuracy with the caveat of a population with a lower malignancy rate (15.1%) than the original ADNEX and O- RADS models population (18.8% and 18.4%). Noncontrast MRI may be used in adnexal mass characterization when the use of IV contrast is precluded.


Clinically Suspected Adnexal Mass No Acute Symptoms. Clinically Suspected Adnexal Mass Variant 5: Adult patient assigned female at birth. Adnexal mass, indeterminate on initial pelvic US, no acute symptoms. Premenopausal. Follow-up imaging. CT Pelvis With IV Contrast CT pelvis with IV contrast is usually not useful for follow-up of an indeterminate adnexal mass. Because the role of US and MRI is well established, there is little reason presently to obtain a CT for follow-up of an indeterminate lesion.


Clinically Suspected Adnexal Mass No Acute Symptoms. CT Pelvis Without and With IV Contrast CT pelvis without and with IV contrast is usually not useful for follow-up of an indeterminate adnexal mass. Because the role of US and MRI is well established, there is little reason presently to obtain a CT for follow-up of an indeterminate lesion.


Clinically Suspected Adnexal Mass No Acute Symptoms. CT Pelvis Without IV Contrast CT pelvis without IV contrast is usually not useful for follow-up of an indeterminate adnexal mass. Because the role of US and MRI is well established, there is little reason presently to obtain a CT for follow-up of an indeterminate lesion.


Clinically Suspected Adnexal Mass No Acute Symptoms. FDG-PET/CT Skull Base to Mid-Thigh There is no role for the use of FDG-PET/CT in the follow-up of indeterminate adnexal masses in premenopausal patients.


Clinically Suspected Adnexal Mass No Acute Symptoms. MRI Pelvis Without and With IV Contrast An indeterminate mass can be followed by contrast-enhanced MRI. This is helpful if the mass cannot be optimally visualized by US or if the mass shows suspicious change of appearance during US surveillance.


Clinically Suspected Adnexal Mass No Acute Symptoms. Suspected classic lesions (cysts, endometriomas, dermoid) >10 cm, which are suboptimally seen on US due to size, can be confirmed as almost certainly benign, which may alter further imaging follow-up intervals [17].


Clinically Suspected Adnexal Mass No Acute Symptoms. US Duplex Doppler Pelvis Color or power Doppler should be included in the US examination of the pelvis. Color Duplex is used to evaluate vascularity of any developing solid component.


Clinically Suspected Adnexal Mass No Acute Symptoms. US Pelvis Transabdominal Transabdominal US may be performed without transvaginal imaging when the transvaginal examination cannot be tolerated. The bladder should be full to provide the best acoustic window for evaluation.


Clinically Suspected Adnexal Mass No Acute Symptoms. US Pelvis Transabdominal and US Pelvis Transvaginal Indeterminate lesions are typically benign. In a multicenter prospective study of 303 indeterminate adnexal cysts, the incidence of malignancy was 3.6% [61]. In a second multicenter prospective study of 697 women, the prevalence of malignancy in indeterminate lesions ranged from 4.8% to 10.7% using SRU guidelines and IOTA simple rules, respectively [45].