Supplemental Breast Cancer Screening Based on Breast Density. Although overall sensitivity of mammography is in the range of 70% to 85%, the sensitivity can vary significantly with breast density [5-7]. The mammographic sensitivity is higher in women with fatty breast parenchyma; however, the sensitivity may decrease to as low as 30% in women with dense breast tissue [5-9]. Although the overall performance of digital mammography is similar to film screen mammography, digital mammography has better performance in specific subgroups, such as in women with dense breasts [8,9]. In addition, even with regular mammographic screening, the interval cancer rate may be as high as 30% [10-13]. Given the limitations of mammography, supplemental screening has been advocated for women with dense breast tissue. In order to bring uniformity to the language, a federal law passed in February 2019, enables the FDA to develop a statement that the effect of breast density on mammographic sensitivity be included in all mammography report.


Supplemental Breast Cancer Screening Based on Breast Density. aPerelman School of Medicine of the University of Pennsylvania, Philadelphia, PennsylvaniabPanel Chair, Boston University School of Medicine, Boston, Massachusetts. cPanel Vice-Chair, New York University School of Medicine, New York, New York. dBoston University Schools of Medicine and Public Health, Boston, Massachusetts. eYale School of Medicine, New Haven, Connecticut; Society of Surgical Oncology. fThomas Jefferson University Hospital, Robbinsville, New Jersey; American College of Obstetricians and Gynecologists. gAlpert Medical School of Brown University, Providence, Rhode Island. hFeinberg School of Medicine, Northwestern University, Chicago, Illinois; American College of Physicians. iUniversity of California San Francisco, San Francisco, California. jSutter Medical Group and Sutter Cancer Center, Roseville, California. kThe University of Texas MD Anderson Cancer Center, Houston, Texas. lEmory University Hospital, Atlanta, Georgia. mSanford Health of Northern Minnesota, Bemidji, Minnesota. nUniversity of Washington, Seattle, Washington. oDonald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York. pNorthShore University HealthSystem, Evanston, Illinois; American College of Surgeons. qSpecialty Chair, NYU Clinical Cancer Center, New York, New York.


Supplemental Breast Cancer Screening Based on Breast Density. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization.


Supplemental Breast Cancer Screening Based on Breast Density. Reprint requests to: publications@acr.org


Supplemental Breast Cancer Screening Based on Breast Density. Supplemental Screening Based on Breast Density Discussion of Procedures by Variant Variant 1: Supplemental breast cancer screening. Average-risk females with nondense breasts. Mammography remains the only validated screening tool for breast cancer screening. Despite widespread mammographic screening, breast cancer represents the leading cause of cancer mortality in women. Although multiple studies have demonstrated improved survival and reduction in breast cancer mortality by up to 30% with regular mammographic screening, there continues to be approximately 40,000 breast cancer deaths annually [10- 13]. Women who have <15% lifetime risk are considered to be at average risk [15]. In women with nondense breast tissue, the sensitivity of mammography is high [5].


Supplemental Breast Cancer Screening Based on Breast Density. In addition to the increase in the CDR, another benefit of adding DBT to 2-D mammography is the reduction in the recall rate [16-19]. In a single-center screening program, Sharpe et al [18] reported a reduction in the recall rate by 18.8%. In the prospective Oslo Tomosynthesis Screening Trial, the recall rate was reduced from 6.7/1,000 to 3.6/1,000 [19]. There is also evidence that the reduction in the recall rate is maintained over consecutive screening episodes [18].


Supplemental Breast Cancer Screening Based on Breast Density. Mammography With IV Contrast CEDM combines the techniques of conventional mammography with administration of IV contrast, thus leveraging functional imaging by assessing for lesion vascularity. A dual-energy technique is utilized to acquire the images in the conventional craniocaudal and mediolateral oblique projections. The acquired data are processed and produce a low-energy image and a diagnostic recombined image. There is limited but emerging literature regarding the use of CEDM in the screening setting [26,27]. However, in the diagnostic setting, CEDM has been shown to demonstrate improved sensitivity and specificity over 2-D mammography [28-31]. The greatest improvement in the sensitivity and specificity is seen in women with dense breast tissue [29,30]. However, at this time there is no relevant literature regarding the use of mammography with IV contrast for supplemental screening in average-risk women with nondense breasts.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without IV Contrast There is no relevant literature regarding the use of MRI breast without IV contrast for supplemental screening in average-risk women with nondense breasts.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without IV Contrast Abbreviated There is no relevant literature regarding the use of AB-MRI breast without IV contrast for supplemental screening in average-risk women with nondense breasts.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without and With IV Contrast There are limited data regarding screening average-risk women with breast MRI with and without IV contrast. In a prospective observational trial, after negative mammographic screening, Kuhl et al [33] reported an additional CDR of 15.5/1,000 with MRI screening in average-risk women across all densities. However, the authors did not analyze the added CDR by breast density.


Supplemental Breast Cancer Screening Based on Breast Density. FDG-PET Breast Dedicated There is limited relevant literature regarding the use of FDG-PET breast dedicated for supplemental screening in average-risk women with nondense breasts. This is not currently widely used in clinical practice.


Supplemental Breast Cancer Screening Based on Breast Density. Sestamibi MBI There is limited relevant literature regarding the use of Tc-99m sestamibi MBI for supplemental screening in average-risk women with nondense breasts. This is not currently widely used in clinical practice.


Supplemental Breast Cancer Screening Based on Breast Density. Variant 2: Supplemental breast cancer screening. Intermediate-risk females with nondense breasts. Women at intermediate risk for breast cancer are defined as having a 15% to 20% lifetime risk [15]. Although there are clear screening guidelines for women with >20% lifetime risk, the screening guidelines have not clearly been defined for women who are at intermediate risk. Women in this category may include patients who have been diagnosed with lobular neoplasia, atypical ductal hyperplasia, previous history of breast cancer, or have a family history of breast cancer without known genetic mutations such as breast cancer gene (BRCA)1/2.


Supplemental Breast Cancer Screening Based on Breast Density. Supplemental Screening Based on Breast Density In women with a personal history of breast cancer, the supplemental CDR of screening ultrasound (US) has been reported to be 2.88/1,000 [34]. There was no difference in the CDR based on breast density or age. However, the authors reported an interval cancer rate of 1.5/1,000, which was higher in women who were <50 years of age and in those with dense breast tissue, indicating the failure of screening US in these 2 subgroups.


Supplemental Breast Cancer Screening Based on Breast Density. Cortesi et al [35] evaluated the efficacy of biennial screening US examination in women who were BRCA mutation carriers, high-risk (non-BRCA1/2), and intermediate-risk patients. Overall, MRI had sensitivity of 93.7%, followed by mammography with sensitivity of 55.0% and US with 29.4% sensitivity. In the nondense breast, the sensitivity of mammography was 82.5% versus 10% for US. In the dense breast, the sensitivity of mammography was 50% versus 42.6% for US. Sensitivity analysis by risk level was also performed. The US sensitivities for BRCA1/2, high-risk (non-BRCA1/2), and intermediate-risk patients were 22.7%, 24.5%, and 33.6%, respectively. The mammographic sensitivities for BRCA1/2, high-risk (non-BRCA1/2), and intermediate-risk patients were 25.0%, 66.4%, and 56.6%, respectively. Only the BRCA1/2 mutation carriers underwent MRI screening, which demonstrated a sensitivity of 93.7%. The authors did not analyze the efficacy of US screening based on both density and risk.


Supplemental Breast Cancer Screening Based on Breast Density. Mammography With IV Contrast CEDM combines the techniques of conventional mammography with administration of IV contrast, thus leveraging functional imaging by assessing for lesion vascularity. A dual-energy technique is used to acquire the images in the conventional craniocaudal and mediolateral oblique projections. The acquired data are processed, producing a low- energy image and a diagnostic recombined image. There is limited but emerging literature regarding the use of CEDM in the screening setting. However, in the diagnostic setting, CEDM has been shown to demonstrate improved sensitivity and specificity over 2-D mammography [28-31]. The greatest improvement in the sensitivity and specificity is seen in women with dense breast tissue [29,30]. However, at this time, there is no relevant literature regarding the use of mammography with IV contrast for supplemental screening in intermediate-risk women with nondense breasts.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without IV Contrast Abbreviated There is no relevant literature regarding the use of AB-MRI breast without IV contrast for supplemental screening in intermediate-risk women with nondense breasts.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without and With IV Contrast Abbreviated AB-MRI performed with IV contrast is an abbreviated breast MRI examination. It is similar to a full MRI examination yet does not have a standard protocol; however, at minimum, it must include a precontrast and one postcontrast sequence. A T2-weighted sequence may also be included. There are currently limited data on screening women with nondense breasts at intermediate lifetime risk with AB-MRI. In 2 retrospective reader studies, in women recently diagnosed with unifocal breast cancer, the sensitivity of AB-MRI was comparable with the full protocol [36,37]. When the performance of AB-MRI was compared with screening US and mammography, there were 12 cancers in 12 women (CDR 15/1,000), 7 of which were not detected on WBUS and mammography [38]. In a prospective observational study of 443 women with mild to moderately elevated lifetime risk for breast cancer, AB-MRI had a similar diagnostic accuracy as the full MRI protocol [39].


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without IV Contrast There is no relevant literature regarding the use of MRI breast without IV contrast for supplemental screening in intermediate-risk women with nondense breasts.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without and With IV Contrast There is some relevant literature supporting the use of MRI breast without and with IV contrast for supplemental screening in intermediate-risk women, specifically in women with a history of lobular carcinoma in situ or a personal history of breast cancer, although these studies included all breast densities [40-42]. At the time of this writing, the American Cancer Society is currently re-reviewing the literature regarding intermediate-risk women; however, its current stance, last updated in 2007, states there is insufficient evidence to formulate a recommendation in this group [15]. As of 2018, ACR recommends annual surveillance MRI in women with dense breasts and a personal history of breast cancer as well as in women who were diagnosed before age 50 [43]. The ACR suggests that MRI should be considered in the following categories: in women with personal histories of breast cancer and who do not fit the 2 previously stated categories and in women with atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ [43].


Supplemental Breast Cancer Screening Based on Breast Density. Supplemental Screening Based on Breast Density FDG-PET Breast Dedicated There is limited relevant literature regarding the use of FDG-PET breast dedicated for supplemental screening in intermediate-risk women with nondense breasts. This is not currently widely used in clinical practice.


Supplemental Breast Cancer Screening Based on Breast Density. Sestamibi MBI There is limited relevant literature regarding the use of Tc-99m sestamibi MBI for supplemental screening in intermediate-risk women with nondense breasts. This is not currently widely used in clinical practice.


Supplemental Breast Cancer Screening Based on Breast Density. In addition to the increase in the CDR, another benefit of adding DBT to 2-D mammography is the reduction in the recall rate [16-19]. In a single-center screening program, Sharpe et al [18] reported a reduction in the recall rate by 18.8%. In the prospective Oslo Tomosynthesis Screening Trial, the recall rate was reduced from 6.7/1,000 to 3.6/1,000 [19]. There is also evidence that the reduction in the recall rate is maintained over consecutive screening episodes [18].


Supplemental Breast Cancer Screening Based on Breast Density. Cortesi et al [35] evaluated the efficacy of biannual screening US examination in women who were BRCA mutation carriers, high-risk (non-BRCA1/2), and intermediate-risk patients. Overall, MRI had sensitivity of 93.7%, which was followed by mammography (55.0%), and US (29.4%). In the nondense breast, the sensitivity of mammography was 82.5% versus 10% for US. In the dense breast, the sensitivity of mammography was 50% versus 42.6% for US. Sensitivity analysis by risk level was also performed. The US sensitivitities for BRCA1/2, high-risk (non- BRCA1/2), and intermediate-risk patients were 22.7%, 24.5%, and 33.6%, respectively. The mammographic sensitivities for BRCA1/2, high-risk (non-BRCA1/2), and intermediate-risk patients were 25.0%, 66.4%, and 56.6%, respectively. Only the BRCA1/2 mutation carriers underwent MRI screening, which demonstrated a sensitivity of 93.7%. The authors did not analyze the efficacy of US screening based on both density and risk.


Supplemental Breast Cancer Screening Based on Breast Density. The addition of WBUS to mammography increases the CDR in high-risk women. In a surveillance cohort study of 529 women with elevated lifetime risk, the sensitivity of mammography, WBUS, and the 2 modalities combined was 33%, 40%, and 49%, respectively [44]. However, subgroup analysis was not performed by breast density. In the same population, MRI had a sensitivity of 91% [44]. In the ACRIN 6666 trial, after 3 rounds of screening mammography and screening WBUS in women with dense breast tissue at intermediate to elevated lifetime risk, the sensitivity, specificity, and positive predictive value (PPV3) of mammography was 0.52, 0.91, and 0.38,


Supplemental Breast Cancer Screening Based on Breast Density. Supplemental Screening Based on Breast Density respectively. The addition of US to mammography increased the sensitivity (0.76) but decreased the specificity (0.84) and the PPV3 (0.38) [45]. In a prospective cohort trial of 687 high-risk women, the cancer yield of mammography alone was 5.4/1,000 and increased to 7.7/1,000 with the addition of US [46].


Supplemental Breast Cancer Screening Based on Breast Density. Mammography With IV Contrast CEDM combines the techniques of conventional mammography with administration of IV contrast, thus leveraging functional imaging by assessing for lesion vascularity. A dual-energy technique is utilized to acquire the images in the conventional craniocaudal and mediolateral oblique projections. The acquired data are processed, producing a low-energy image and a diagnostic recombined image. There is limited literature regarding the use of CEDM in the screening setting. However, in the diagnostic setting, CEDM has been shown to demonstrate improved sensitivity and specificity over 2-D mammography [28-31]. The greatest improvement in the sensitivity and specificity is seen in women with dense breast tissue [29,30]. At this time, there is limited but emerging literature regarding the use of mammography with IV contrast for supplemental screening in high-risk women with nondense breasts. Jochelson et al [47] screened 318 high-risk women using both CEDM and MRI [47]. Both techniques detected carcinomas not visualized on mammography, 2 using CEDM and 3 using MRI.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without IV Contrast Abbreviated There is no relevant literature regarding the use of AB-MRI breast without IV contrast for supplemental screening in high-risk women with nondense breasts.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without and With IV Contrast Abbreviated AB-MRI performed with IV contrast is an abbreviated breast MRI examination. It is similar to a full MRI examination yet does not have a standard protocol; however, at minimum, it must include a precontrast and one postcontrast sequence. A T2-weighted sequence may also be included. There is limited relevant literature regarding the use of AB-MRI breast without and with IV contrast in high-risk women with nondense breasts. In 2 retrospective studies comparing the full diagnostic protocol with an abbreviated protocol in high-risk women, the authors found both protocols to have similar sensitivity [48,49]. However, neither study evaluated the CDR by breast density.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without IV Contrast There is no relevant literature regarding the use of MRI breast without IV contrast for supplemental screening in high-risk women with nondense breasts.


Supplemental Breast Cancer Screening Based on Breast Density. FDG-PET Breast Dedicated There is limited relevant literature regarding the use of FDG-PET breast dedicated for supplemental screening in high-risk women with nondense breasts. This is not currently widely used in clinical practice.


Supplemental Breast Cancer Screening Based on Breast Density. Sestamibi MBI There is limited relevant literature regarding the use of Tc-99m sestamibi MBI for supplemental screening in high- risk women with nondense breasts. This is not currently widely used in clinical practice.


Supplemental Breast Cancer Screening Based on Breast Density. Variant 4: Supplemental breast cancer screening. Average-risk females with dense breasts. Mammography remains the only validated screening tool for breast cancer screening. Despite widespread mammographic screening, breast cancer represents the leading cause of cancer mortality in women. Although multiple studies have demonstrated improved survival and reduction in breast cancer mortality by up to 30% with regular mammographic screening, there continues to be approximately 40,000 breast cancer deaths annually [10- 13]. Women who have <15% lifetime risk are considered to be at average risk [15].


Supplemental Breast Cancer Screening Based on Breast Density. The greatest improvement in the CDR with DBT is seen in women with dense breast tissue [21,22,57,58]. Although the TOMMY trial did not reach statistical significance across all breast densities, in women with >50% breast density, statistical significance was achieved with the sensitivity of 2-D mammography plus DBT reaching 93% versus 86% for 2-D mammography alone [21,22]. In a meta-analysis of 16 studies evaluating women with dense breasts, addition of DBT improved the CDR, compared with 2-D mammography alone, in both diagnostic (relative risk [RR]: 1.16) and the screening (RR: 1.33) settings [58].


Supplemental Breast Cancer Screening Based on Breast Density. At a high-volume screening center, when women with heterogeneously or extremely dense breast tissue were offered automated 3-D US screening in addition to full-field digital mammography (FFDM), the added CDR rose by 2.4/1,000 screened (6.6/1,000 automated 3-D US screening plus FFDM versus 4.2/1,000 for FFDM alone) [59]. However, the risk level of the population was not defined other than patients with a personal history of breast cancer were excluded, and 3.5% of the patients reported a family history of breast cancer.


Supplemental Breast Cancer Screening Based on Breast Density. Buchberger et al [60] compared the performance of screening mammography with and without screening US in average-risk women. In the subgroup of women with dense breasts, the CDR increased from 1.8/1,000 to 2.4/1,000, with the addition of screening US. However, the PPV2 decreased from 52.7/1,000 with mammography alone to 37.7/1,000 with mammography plus US. For the entire population, there were 28 interval cancer rates within a 12- month period after screening (0.42/1,000): 18 in women with dense breasts and 10 in women with nondense breasts.


Supplemental Breast Cancer Screening Based on Breast Density. In the Japan Strategic Anti-cancer Randomized Trial, 72,998 asymptomatic women 40 to 49 years of age were randomized to mammographic screening alone or mammographic plus US screening [61]. The sensitivity and specificity in the mammogram arm were 77.0% and 91.4%, respectively. In comparison, the mammogram plus US arm had a higher sensitivity (91.1%) but lower specificity (87.7%). The interval cancer rate was halved in the arm that received US screening, from the baseline level of 0.10% to 0.05%.


Supplemental Breast Cancer Screening Based on Breast Density. Using Breast Cancer Surveillance Consortium data, Lee et al [62] assessed the performance of the addition of screening US in women with dense breasts in the community. The CDR of mammography plus US was 5.4/1,000 versus 5.5/1,000 for mammography alone. The false-positive biopsy rate and PPV of biopsy recommendations for


Supplemental Breast Cancer Screening Based on Breast Density. Supplemental Screening Based on Breast Density


Supplemental Breast Cancer Screening Based on Breast Density. mammography plus US were 52.0/1,000 and 9.5%, respectively, compared with 22.2/1,000 and 21.4%, respectively, for mammography alone. The interval cancer rate did not differ significantly in the 2 arms: the mammography plus US arm was 1.5/1,000 versus 1.9/1,000 for mammography alone. Utilizing the registry data and data from the literature, Sprague et al [63] used simulation models to assess the outcomes of supplemental US screening after negative screening mammography in women with dense breasts. Per 1,000 women screened, the authors concluded there would be 0.36 breast cancer deaths averted, 354 additional biopsy recommendations, and 1.7 quality-adjusted life-years gained at a cost $325,000 for each quality-adjusted life-year gained [63].


Supplemental Breast Cancer Screening Based on Breast Density. Although the supplemental screening debate was initiated partly because of the limitations of screening mammography in women with dense breast tissue, there is some evidence to suggest that breast density alone may not be sufficient reason to recommend supplemental screening. One way to assess the failure of mammography is by determining the interval cancer rate in the study population. Using the Breast Cancer Surveillance Consortium data, the women most likely to present with interval cancers were women with an elevated 5-year risk for breast cancer >1.67% and with dense breast tissue, representing approximately 24% of all women with dense breasts [64].


Supplemental Breast Cancer Screening Based on Breast Density. Mammography With IV Contrast CEDM combines the techniques of conventional mammography with administration of IV contrast, thus leveraging functional imaging by assessing for lesion vascularity. A dual-energy technique is used to acquire the images in the conventional craniocaudal and mediolateral oblique projections. The acquired data are processed, producing a low- energy image and a diagnostic recombined image. There is limited but emerging literature regarding the use of CEDM in the screening setting. However, in the diagnostic setting, CEDM has been shown to demonstrate improved sensitivity and specificity over 2-D mammography [28-31]. The greatest improvement in the sensitivity and specificity is seen in women with dense breast tissue [29,30]. At this time, there is limited literature regarding the use of mammography with IV contrast for supplemental screening in average-risk women with dense breasts.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without IV Contrast Abbreviated There is no relevant literature regarding the use of AB-MRI breast without IV contrast for supplemental screening in average-risk women with dense breasts.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without IV Contrast There is no relevant literature regarding the use of MRI breast without IV contrast for supplemental screening in average-risk women with dense breasts.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without and With IV Contrast There are limited data regarding screening average-risk women with breast MRI with and without IV contrast. In a prospective observational trial, after negative mammographic screening, Kuhl et al [33] reported an additional CDR of 15.5/1,000 with MRI screening in average-risk women across all densities. However, the authors did not analyze the added CDR by breast density.


Supplemental Breast Cancer Screening Based on Breast Density. FDG-PET Breast Dedicated There is limited relevant literature regarding the use of FDG-PET breast dedicated for supplemental screening in average-risk women with dense breasts [67]. This is not currently widely used in clinical practice.


Supplemental Breast Cancer Screening Based on Breast Density. Supplemental Screening Based on Breast Density Sestamibi MBI There is limited relevant literature regarding the use of Tc-99m sestamibi MBI for supplemental screening in average-risk women with dense breasts. This is not currently widely used in clinical practice.


Supplemental Breast Cancer Screening Based on Breast Density. Variant 5: Supplemental breast cancer screening. Intermediate-risk females with dense breasts. Women at intermediate risk for breast cancer are defined as having a 15% to 20% lifetime risk [15]. Although there are clear screening guidelines for women with >20% lifetime risk, the screening guidelines have not been clearly defined for women who are at intermediate risk. Women in this category may include patients who have been diagnosed with lobular neoplasia, atypical ductal hyperplasia, previous history of breast cancer, or have a family history of breast cancer without known genetic mutations such as BRCA1/2.


Supplemental Breast Cancer Screening Based on Breast Density. The greatest improvement in the CDR with DBT is seen in women with dense breast tissue [21,22,57,58]. Although the TOMMY trial did not reach statistical significance across all breast densities, in women with >50% breast density, statistical significance was achieved with the sensitivity of 2-D mammography plus DBT reaching 93% versus 86% for 2-D mammography alone [21,22]. In a meta-analysis of 16 studies evaluating women with dense breasts, DBT improved the CDR compared with 2-D mammography alone, in both the diagnostic (RR: 1.16) and the screening (RR: 1.33) settings [58].


Supplemental Breast Cancer Screening Based on Breast Density. In addition to the increase in the CDR, another benefit of adding DBT to 2-D mammography is the reduction in the recall rate [16-19]. In a single-center screening program, Sharpe et al [18] reported a reduction in the recall rate by 18.8%. In the prospective Oslo Tomosynthesis Screening Trial, the recall rate was reduced from 6.7/1,000 to 3.6/1,000 [19]. There is also evidence that the reduction in the recall rate is maintained over consecutive screening episodes [18].


Supplemental Breast Cancer Screening Based on Breast Density. In women with a personal history of breast cancer, the supplemental CDR of screening US has been reported to be 2.88/1,000 [34]. There was no difference in the CDR based on breast density or age. However, the authors reported an interval cancer rate of 1.5/1,000, which was higher in women who were <50 years of age and in those with dense breast tissue, indicating the failure of screening US in the 2 subgroups.


Supplemental Breast Cancer Screening Based on Breast Density. Cortesi et al [35] evaluated the efficacy of biannual screening US examination in women who were BRCA mutation carriers, high-risk (non-BRCA1/2), and intermediate-risk patients. Overall, MRI had sensitivity of 93.7%, followed by mammography (55.0%) and US (29.4%). In the nondense breast, the sensitivity of mammography was 82.5% versus 10% for US. In the dense breast, the sensitivity of mammography was 50% versus 42.6% for US. Sensitivity analysis by risk level was also performed. The US sensitivities for BRCA1/2, high-risk (non-BRCA1/2), and


Supplemental Breast Cancer Screening Based on Breast Density. 12 Supplemental Screening Based on Breast Density


Supplemental Breast Cancer Screening Based on Breast Density. intermediate-risk patients were 22.7%, 24.5%, and 33.6%, respectively. The mammographic sensitivities for BRCA1/2, high-risk (non-BRCA1/2), and intermediate-risk patients were 25.0%, 66.4%, and 56.6%, respectively. Only the BRCA1/2 mutation carriers underwent MRI screening, which demonstrated a sensitivity of 93.7%. The authors did not analyze the efficacy of US screening based on both density and risk.


Supplemental Breast Cancer Screening Based on Breast Density. Although the supplemental screening debate was initiated partly because of the limitations of screening mammography in women with dense breast tissue, there is some evidence to suggest that breast density alone may not be sufficient reason to recommend supplemental screening. One way to assess the failure of mammography is by determining the interval cancer rate in the study population. Using Breast Cancer Surveillance Consortium data, the women most likely to present with interval cancers were women with an elevated 5-year risk for breast cancer >1.67% and with dense breast tissue, representing approximately 24% of all women with dense breasts [64].


Supplemental Breast Cancer Screening Based on Breast Density. Mammography With IV Contrast CEDM combines the techniques of conventional mammography with administration of IV contrast, thus leveraging functional imaging by assessing for lesion vascularity. A dual-energy technique is utilized to acquire the images in the conventional craniocaudal and mediolateral oblique projections. The acquired data are processed, producing a low-energy image and a diagnostic recombined image. There is limited literature regarding the use of CEDM in the screening setting. However, in the diagnostic setting, CEDM has been shown to demonstrate improved sensitivity and specificity over 2-D mammography [28-31]. The greatest improvement in the sensitivity and specificity is seen in women with dense breast tissue [29,30]. At this time, there is limited but emerging literature regarding the use of mammography with IV contrast for supplemental screening in intermediate-risk women with dense breasts. However, in women with dense breast tissue and given the limited sensitivity of mammography and the need for supplemental screening, CEDM may have a potential role; however, more data on CEDM in the screening setting in intermediate-risk women with dense breast tissue are needed.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without IV Contrast Abbreviated There is no relevant literature regarding the use of AB-MRI breast without IV contrast for supplemental screening in intermediate-risk women with dense breasts.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without and With IV Contrast Abbreviated AB-MRI performed with IV contrast is an abbreviated breast MRI examination. It is similar to a full MRI examination yet does not have a standard protocol; however, at minimum, it must include a precontrast and one postcontrast sequence. A T2-weighted sequence may also be included. There are currently limited data on screening women with dense breasts at intermediate lifetime risk with AB-MRI. In 2 retrospective reader studies, in women recently diagnosed with unifocal breast cancer, the sensitivity of AB-MRI was comparable with the full protocol [36,37]. When the performance of AB-MRI was compared with screening US and mammography, 12 cancers in 12 women (CDR 15/1,000) were detected, 7 of which were not detected on WBUS and mammography [38]. In a prospective observational study of 443 women with mild to moderately elevated lifetime risk for breast cancer, AB- MRI had a similar diagnostic accuracy as the full MRI protocol [39].


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without IV Contrast There is no relevant literature regarding the use of MRI breast without IV contrast for supplemental screening in intermediate-risk women with dense breasts.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without and With IV Contrast There is some relevant literature supporting the use of MRI breast without and with IV contrast for supplemental screening in intermediate-risk women, specifically in women with a history of lobular carcinoma in situ or a personal history of breast cancer, although these studies included all breast densities [40-42]. At the time of this writing, the American Cancer Society was re-reviewing the literature regarding intermediate-risk women; however, its current stance, last updated in 2007, states there is insufficient evidence to formulate a recommendation in this group [15]. As of 2018, the ACR recommends annual surveillance MRI in women with dense breasts and with a personal history of breast cancer, as well as in women who were diagnosed before age 50 [43]. The ACR suggests that MRI should be considered in the following categories: in women with personal histories of breast cancer and who do not fit the 2 previously stated categories as well as in women with atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ [43].


Supplemental Breast Cancer Screening Based on Breast Density. FDG-PET Breast Dedicated There is limited relevant literature regarding the use of FDG-PET breast dedicated for supplemental screening in intermediate-risk women with dense breasts. This is not currently widely used in clinical practice.


Supplemental Breast Cancer Screening Based on Breast Density. Supplemental Screening Based on Breast Density Sestamibi MBI There is limited relevant literature regarding the use of Tc-99m sestamibi MBI for supplemental screening in intermediate-risk women with dense breasts. This is not currently widely used in clinical practice.


Supplemental Breast Cancer Screening Based on Breast Density. The greatest improvement in the CDR with DBT is seen in women with dense breast tissue [21,22,57,58]. Although the TOMMY trial did not reach statistical significance across all breast densities, in women with >50% breast density, statistical significance was achieved, with the sensitivity of 2-D mammography plus DBT reaching 93% versus 86% for 2-D mammography alone [21,22]. In a meta-analysis of 16 studies evaluating women with dense breasts, DBT improved the CDR compared with 2-D mammography alone in both the diagnostic (RR: 1.16) and the screening (RR: 1.33) settings [58].


Supplemental Breast Cancer Screening Based on Breast Density. Cortesi et al [35] evaluated the efficacy of biannual screening US examination in women who were BRCA mutation carriers, high-risk (non-BRCA1/2), and intermediate-risk patients. Overall, MRI had sensitivity of (93.7%), followed by mammography (55.0%), then US (29.4%). In the nondense breast, the sensitivity of mammography was 82.5% versus 10% for US. In the dense breast, the sensitivity of mammography was 50% versus 42.6% for US. Sensitivity analysis by risk level was also performed. The US sensitivities for BRCA1/2, high-risk (non-BRCA1/2), and intermediate-risk patients were 22.7%, 24.5%, and 33.6%, respectively. The mammographic sensitivities for BRCA1/2, high-risk (non-BRCA1/2), and intermediate-risk patients were 25.0%, 66.4%, and 56.6%, respectively. Only the BRCA1/2 mutation carriers underwent MRI screening, which demonstrated a sensitivity of 93.7%. The authors did not analyze the efficacy of US screening based on both density and risk.


Supplemental Breast Cancer Screening Based on Breast Density. The addition of WBUS to mammography increases the CDR in high-risk women. In a surveillance cohort study of 529 women with elevated lifetime risk, the sensitivity of mammography, WBUS, and the 2 modalities combined was 33%, 40%, and 49%, respectively [44]. However, subgroup analysis was not performed by breast density. In


Supplemental Breast Cancer Screening Based on Breast Density. Supplemental Screening Based on Breast Density the same population, MRI had a sensitivity of 91% [44]. In the ACRIN 6666 trial, after 3 rounds of screening mammography and screening WBUS in women with dense breast tissue at intermediate to elevated lifetime risk, the sensitivity, specificity, and PPV3 of mammography was 0.52, 0.91, and 0.38, respectively. The addition of US to mammography increased the sensitivity (0.76) but decreased the specificity (0.84) and PPV3 (0.38) [45]. In a prospective cohort trial of 687 high-risk women, the cancer yield of mammography alone was 5.4/1,000 and increased to 7.7/1,000 with the addition of US [46].


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without IV Contrast Abbreviated There is no relevant literature regarding the use of AB-MRI breast without IV contrast for supplemental screening in high-risk women with dense breasts.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without and With IV Contrast Abbreviated AB-MRI performed with IV contrast is an abbreviated breast MRI examination. It is similar to a full MRI examination yet does not have a standard protocol; however, at minimum, it must include a precontrast and one postcontrast sequence. A T2-weighted sequence may also be included. There is limited relevant literature regarding the use of AB-MRI breast without and with IV contrast in high-risk women with dense breasts. In 2 retrospective studies comparing the full diagnostic protocol to an abbreviated protocol in high-risk women, the authors found both protocols to have similar sensitivity [48,49]. However, neither study evaluated the CDR by breast density.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without IV Contrast There is no relevant literature regarding the use of MRI breast without IV contrast for supplemental screening in high-risk women with dense breasts.


Supplemental Breast Cancer Screening Based on Breast Density. MRI Breast Without and With IV Contrast The American Cancer Society advocates MRI screening in high-risk women regardless of breast density [15]. There is ample evidence in the literature supporting this recommendation [46,50-54]. In the high-risk population, sensitivity of mammography alone is approximately 31% to 33%, compared with the sensitivity of MRI alone which is 87% to 96% [45,46,55]. The combination of mammography and MRI yields 100% sensitivity compared with the 44% to 48% sensitivity of combined mammography and US [45,46]. In addition, the types of carcinoma detected on MRI compared with mammography may differ. Cancers detected on MRI are more likely to be invasive carcinomas (71%), whereas cancers detected on mammography were are likely to be ductal carcinoma in situ (65%), or associated with calcifications (88%) [56].


Supplemental Breast Cancer Screening Based on Breast Density. FDG-PET Breast Dedicated There is limited relevant literature regarding the use of FDG-PET breast dedicated for supplemental screening in high-risk women with dense breasts. This is not currently widely used in clinical practice.


Supplemental Breast Cancer Screening Based on Breast Density. Sestamibi MBI There is limited relevant literature regarding the use of Tc-99m sestamibi MBI for supplemental screening in high- risk women with dense breasts. This is not currently widely used in clinical practice.


Supplemental Breast Cancer Screening Based on Breast Density. Supplemental Screening Based on Breast Density 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.


Supplemental Breast Cancer Screening Based on Breast Density. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www.acr.org/ac.


Supplemental Breast Cancer Screening Based on Breast Density. 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


Chronic Cough

Chronic Cough. Introduction/Background Chronic cough is defined by a duration lasting at least 8 weeks [1], often contributing to patient discomfort and altered psychosocial well-being [2]. The most common causes of chronic cough include smoking-related lung disease, upper airway cough syndrome (UACS), asthma, gastroesophageal reflux disease (GERD), and nonasthmatic eosinophilic bronchitis [1-3]. Cough can further be characterized by quality, that is productive or nonproductive. Conditions that may be associated with productive cough include bronchiectasis, chronic bronchitis, asthma, and immunodeficiencies [4-6]. There is varied opinion in the literature regarding the utility of cough productivity in the phenotypic stratification of chronic cough patients [5,7,8].


Chronic Cough

Chronic Cough. Cough is a protective reflex mediated by a complex network of afferent and efferent neuronal pathways [9]. Stimuli for cough can occur in the chest wall, airways, esophagus, larynx, and middle ear [10]. It is believed that a significant number of individuals with chronic cough may be suffering from cough hypersensitivity [11,12], in which the threshold for cough is lowered by repeated exposure to stimulus or inflammation [11-13]. There may be similarity in the neuronal hyperstimulation seen in chronic cough with that of chronic pain [14]. The etiology of chronic cough in some patients may be difficult to localize to an isolated source and is often multifactorial [15]. The complex pathophysiology, clinical presentation, and variable manifestations of chronic cough underscore the challenges faced by clinicians in the evaluation and management of these patients.


Chronic Cough

Chronic Cough. Varying guidelines and algorithms exist for the evaluation and management of chronic cough, driven by a thorough history and physical examination, empiric treatment, and often diagnosis by exclusion [1,15,16]. Standardized clinical algorithms have shown efficacy in the diagnosis and treatment of chronic cough [7,10,16,17]. Imaging plays a role in the evaluation, although there is lack of high-quality evidence guiding which modalities are useful and at what time point in the clinical evaluation they should be performed. Further research may be needed to evaluate which imaging modalities performed earlier in the clinical assessment are beneficial in long-term outcomes.


Chronic Cough

Chronic Cough. Special Imaging Considerations Our literature review has identified several studies investigating thoracic ultrasound (US) in the evaluation of the noncardiac chest pain. Noncardiac thoracic US performed better than radiography in small prospective cohorts staged in the postoperative intensive care unit [18] and primary care setting [19], confidently identifying findings such as pneumothorax, pleural effusion, consolidation, and interstitial patterns of lung disease. US was shown to correlate well with high-resolution CT (HRCT) and pulmonary function test (PFT) abnormalities [20], and it performed well in several small studies of patients with known interstitial lung disease [21-23]. US may be prone to diminished specificity. For instance, Moazedi-Fuerst et al [24] showed that up to 12% of patients with normal HRCT studies had sonographic findings of an interstitial pattern based on B-lines and artifacts. Adequate US evaluation is operator dependent and requires experience to perform and interpret examination findings. To our knowledge, there is no relevant literature to support the use of thoracic US in the evaluation of chronic cough; however, it is included in this section for awareness and to promulgate future research into this particular topic.


Chronic Cough

Chronic Cough. Reprint requests to: publications@acr.org


Chronic Cough

Chronic Cough. Chronic Cough Low-dose chest CT (LDCT) has been clinically validated in the National Lung Screening Trial Research Team for early detection of lung cancer [25]. LDCT has been investigated for early detection of pulmonary infection in elderly patients with normal or equivocal chest radiographs. Park et al [26] showed that 49 out of 166 elderly patients presenting to the emergency room who had normal chest radiographs were subsequently diagnosed with acute respiratory infection from findings on LDCT. In a prospective case comparison, Christe et al [27] showed good correlation between standard dose (150 mAs) and low-dose (40 mAs) CT protocols for evaluating the majority of pulmonary abnormalities, including bronchiectasis, air trapping, and pleural disease. Investigators did identify a drop in sensitivity in low-dose scans for ground-glass nodules, reticulation, and mucus plugging [27]. Ultra-low- dose CT demonstrated 91% sensitivity and 100% specificity in identifying asbestos-related lung abnormalities in a prospective cohort of 55 asymptomatic persons with relevant exposure history [28]. To our knowledge, there is no relevant literature to support the use of LDCT in the evaluation of chronic cough, and further research into this topic may be warranted.


Chronic Cough

Chronic Cough. OR Discussion of Procedures by Variant Variant 1: Chronic cough lasting more than 8 weeks. No known risk factors for lung cancer. Initial imaging. Radiography Chest Chest radiography is recommended by numerous pulmonary and thoracic societies for the evaluation of chronic cough [1,10,15,29], although the exact timing of imaging has varied between groups. The American College of Chest Physicians (ACCP) includes a recommendation for an initial chest radiograph in their chronic cough algorithm [1]. The evidence supporting chest radiography at initial evaluation of chronic cough is limited to case series, observational studies, and retrospective analysis. Initial evaluation with posteroanterior chest radiography has been included as part of two investigative case series using standardized clinical protocols for chronic cough [7,17]. Of the 131 patients evaluated, 49 chest radiographs were reported abnormal, with the final diagnosis of primary lung pathology other than asthma made in 29 patients, including 8 patients with bronchiectasis, 8 patients with interstitial lung disease, and 2 patients with neoplasm. The authors did not report the sensitivity or specificity of chest radiography in the setting of chronic cough; however, abnormal radiography was positively associated with underlying primary pulmonary pathology other than asthma (odds ratio 7.7) [7]. Ojoo et al [17] prospectively evaluated 112 patients with chronic cough in a similar standardized clinical investigative protocol. In this study, 7 radiographs (6.3%) were reported contributory to the final diagnosis. Of the 92 patients with diagnosis found at discharge, 12 (13%) patients had pathologies including bronchiectasis, interstitial lung disease, self-limiting cough, and 2 cases of lung cancer. Both of these studies reported clinical efficacy with standardized protocols utilizing initial chest radiography, with diagnosis achieved in 93% in the Kastelik et al study [7] and 82% in the Ojoo et al study [17]. The most commonly reported etiologies were reflux, asthma, postinfective or viral cough, and rhinitis, representing between 61% to 67% of final diagnosis, which were more common than bronchiectasis, interstitial lung disease, and neoplasm, which represents <13% to 18% of final diagnosis [7,17]. Both case series are limited by sample size, and both studies were performed out of referral centers, likely contributing to selection bias.


Chronic Cough

Chronic Cough. Retrospective analyses have been performed specific to chronic cough and normal chest radiography. Turner et al [16] retrospectively reviewed the medical records of 404 patients with chronic cough referred to specialty care who either had or subsequently were found to have a normal chest radiograph. Of the 266 patients who were given a diagnosis, 8 patients were found to have a diagnosis that could be made on imaging (4 with lower respiratory tract infection, 2 with malignancy, 1 with bronchiectasis, and 1 with pulmonary fibrosis). Although made explicit for the 2 cases with malignancy, it is only implied that the other 6 patients had normal chest radiography and that the diagnosis was made by other means (ie, chest CT). Additionally, the cases of malignancy were suspected on the


Chronic Cough

Chronic Cough

Chronic Cough. Chronic Cough


Chronic Cough

Chronic Cough. The diagnostic performance of chest radiography varies among the reviewed literature. In a systematic review of the literature, Piccazzo et al [30] reported a high negative predictive value for chest radiography in the evaluation of active and inactive tuberculosis. Abnormalities on chest radiography did have a lower specificity, and findings, which were equivalent the authors concluded, should prompt consideration for CT as this modality was shown to have better performance for both active and inactive tuberculosis. Colaci et al [31] prospectively evaluated 107 consecutive patients with systemic sclerosis with both radiography and HRCT. Their study showed strong correlation between radiographic and HRCT findings of interstitial lung disease, with strong association between cough symptoms and HRCT findings. Interstitial lung pattern and restrictive PFT was more commonly identified than airway involvement and obstructive disease. The authors, however, did not publish sensitivity or specificity for radiography [31]. The diagnostic performance of radiography for other patterns of lung disease may be worse. In a retrospective analysis of 236 patients with CT-proven bronchiectasis, Altenburg et al [32] reported that up to 34% of chest radiographs were reported unremarkable. As mentioned above, the most common CT findings in those patients with chronic cough with normal radiographs were in fact bronchiectasis (28%) and bronchial wall thickening (21%) [3]. The sensitivity of chest radiography for airway abnormalities was found to be 69% to 71% when referenced to helical CT in 70 patients with known airway abnormalities and lesions [33]. In a retrospective analysis of elderly emergency room patients who were evaluated for acute respiratory infection, Park et al [26] showed that chest radiographs were normal in 49 out of 166 confirmed cases on LDCT. Chest radiography was more often normal when LDCT identified ground-glass opacity (GGO), bronchial wall thickening, centrilobular nodules, and small and dependent consolidations. Chest radiography was also found to have poor correlation with chest CT for the presence of pulmonary opacities [34,35], with a positive predictive value of only 27% when compared with chest CT in a secondary analysis of a large retrospective cohort of 3,400 patients.


Chronic Cough

Chronic Cough. Limitations of chest radiography reflect superimposed soft-tissue structures, radiographic findings related to comorbidities, and limited contrast resolution. Unfortunately, there are no high-quality studies evaluating the clinical efficacy of chest radiography in the early evaluation of patients with chronic cough, and this may be an area of future investigation. Based on the available literature, there is a suggestion that initial evaluation of chronic cough with chest radiography is beneficial in the clinical setting. There does remain question regarding the sensitivity of chest radiography in this group [3], which is likely skewed toward early disease and airway abnormalities. This could potentially result in delayed diagnosis for a small percent of patients with chronic cough.


Chronic Cough

Chronic Cough. CT Chest There is no high-quality evidence to support the use of chest CT in the initial evaluation of patients presenting with chronic cough. No studies have directly compared the utility of contrast-enhanced versus noncontrast-enhanced CT imaging in regard to chronic cough. Contrast-enhanced studies offer improved visualization of cardiopulmonary vasculature, mediastinal structures, and soft-tissue abnormalities [35], although MRI is developing a more consistent role for the latter. For the majority of studies, however, the noncontrast technique appears to be adequate. Chest CT is more sensitive than chest radiographs for the evaluation of most pulmonary abnormalities as well as mediastinal, cardiac, and chest wall findings, combining improved soft-tissue contrast and anatomical localization. This was demonstrated in a few small studies included in our literature review [3,32,36]. Chest CT is considered the reference standard for the noninvasive diagnosis of bronchiectasis [37] as well as of interstitial lung disease.


Chronic Cough

Chronic Cough. CT abnormalities have been described in patients with chronic cough. Truba et al [3] performed a retrospective analysis of patients with chronic cough with negative initial chest radiograph findings, reporting 21 out of 59 patients with CT abnormalities believed to be relevant to chronic cough. The authors identified bronchiectasis and


Chronic Cough

Chronic Cough. Other studies showed a lack of association between cough symptoms and chest CT findings. Ooi et al [6] was unable to correlate respiratory symptom exacerbation (including cough symptoms) with HRCT findings of small airways abnormality, mosaic attenuation, and bronchial wall thickening in 60 patients with CT-proven bronchiectasis, although there was association between CT findings and sputum production and PFT abnormality. Wilsher et al [40], in a prospective analysis of 60 consecutive patients newly diagnosed with RA, demonstrated that bronchiectasis was prevalent in up to 48% of patients, despite only 30% of patients presenting with respiratory complaints. There was no association between the cough symptoms and bronchiectasis, although there was a statistically significant association for dyspnea symptoms.


Chronic Cough

Chronic Cough. The major pulmonary societies recommend noncontrast chest CT for the evaluation of chronic cough when the more common causes are excluded or empirically treated [1,10,15,29], and this is usually preceded by a chest radiograph. Of the studies evaluating the clinical management of patients with chronic cough, none utilized chest CT in the initial workup [3,7,16,17], and two studies specifically addressed a cohort of patients with normal chest radiography findings [3,16]. Kastelik et al [7] utilized a probability-based clinical algorithm in the prospective treatment of 131 patients presenting with cough lasting >8 weeks. All patients were initially evaluated with chest radiography and empirically treated based on the probability of underlying etiologies. Chest CT was performed in those patients with clinical suspicion of underlying disease (n = 29) as well as in those with indications or negative initial workup otherwise (n = 17). Of these, 26 out of 29 patients (positive predictive value of 90%) suspected of having underlying pulmonary disease were diagnosed and treated as appropriate; however, 17 patients in whom chest CT was performed without cause and as part of the algorithmic evaluation did not have findings relevant to their management. The authors concluded that chest CT should be performed only in selected patients and those with abnormal chest radiographs.


Chronic Cough

Chronic Cough. In another prospective observational study, Ojoo et al [17] evaluated 112 consecutive patients with chronic cough. All patients were evaluated with chest radiography. Chest CT was performed only based on clinical suspicion. The authors reported that 74 out of 81 patients managed clinically without the need for chest CT examination, suggesting chest CT would not have made a difference in these patients. It should be noted that both studies did identify primary pulmonary etiologies felt to be associated with chronic cough, of which bronchiectasis and interstitial lung disease were the two most common. In a retrospective cohort of patients with chronic cough referred to specialty care with normal chest radiographs, Turner et al [16] showed successful clinical management of 266 patients with minimal investigation and empiric treatment, requiring chest CT in 1 patient to diagnose bronchiectasis, 1 patient with pulmonary fibrosis, and 2 patients with malignancy. Future studies may be needed to better validate CT findings with clinical features in order to determine causation/association in the context of chronic cough. Lung patterns of disease and obvious abnormalities identified on CT will still be of clinical value, and an expected number of CT


Chronic Cough

Chronic Cough. abnormalities may be noncontributory to management. The role of chest CT in the initial evaluation of chronic cough remains indeterminate. The evidence suggests that wide application in all patients presenting with chronic cough may be of low clinical yield. Appropriate selection would likely improve the specificity of findings.


Chronic Cough

Chronic Cough. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET in the initial evaluation of chronic cough. FDG-PET/CT is not listed as an imaging option in the most recent ACCP guidelines on chronic cough [1]. FDG-PET utilizes a radiolabeled glucose analog to evaluate for upregulated metabolism in areas of infection, inflammation, and neoplasm [43].


Chronic Cough

Chronic Cough. MRI Chest There is no relevant literature to support the use of thoracic MRI in the initial evaluation of chronic cough. MRI of the chest is not included in the clinical algorithms recommended by various pulmonary and thoracic societies [1,10,15,29]. Thoracic MRI (nonbreast, noncardiac, nonmusculoskeletal) is currently utilized for the evaluation of indeterminate findings on other imaging modalities, most commonly mediastinal and thymic [44], less often utilized for vascular, airway, and pulmonary parenchymal abnormalities. MRI offers improved soft-tissue contrast, with advanced sequences able to identify soft-tissue characteristics to the cellular level (ie, diffusion-weighted imaging and spectroscopy). Advanced techniques allow for calculation of total lung water density, which has been shown to correlate with disease severity in adult patients with cystic fibrosis [45]. With the addition of intravenous (IV) contrast, the vascular nature of an abnormality is exquisitely imaged and has been shown to be as accurate as contrast-enhanced CT for the evaluation for pulmonary embolism [35]. IV contrast also offers the evaluation of pulmonary perfusion [46]. Limitations of pulmonary MRI include low signal-to-noise ratio (especially with a normally aerated lung), low spatial resolution, and need for adequate breath-hold technique or respiratory gating [46]. Parenchymal lung abnormalities naturally increase cellular proton density and/or water content while displacing low signal gas, providing contrast for visualization [35]. Despite limitations, pulmonary MRI has been shown to have noninferior diagnostic quality when compared with CT [46,47]. Ohno et al [47] analyzed 85 consecutive patients with high-resolution pulmonary MR using ultrashort time to echo and compared findings with both standard CT and LDCT. The authors found equivalent diagnostic efficacy for all observed findings, noting decreased sensitivity and image quality when evaluating for emphysema, bronchiectasis, and reticular opacity. The authors concluded that based on their assessment, ultrashort time to echo pulmonary MR is equivalent to LDCT imaging [47].


Chronic Cough

Chronic Cough. There is no relevant literature evaluating IV contrast versus noncontrast MRI in the setting of chronic cough, and decisions may need to be made on a case-by-case basis. Investigational contrast agents may prove useful in the future. Hyperpolarized gas MRI is an example, which is currently FDA approved for investigational use [44,48]. Hyperpolarized Xe-129 gas MRI allows for improved contrast of the lung parenchyma with techniques allowing for the evaluation of anatomical and functional data [48]. These techniques are still in their infancy and will likely require future studies to evaluate their role in imaging in chronic cough. In 2014, Ackman et al [44] surveyed thoracic radiologists from the Society of Thoracic Radiology regarding utilization of nonvascular thoracic MRI. Respondents offered an insight into the underutilization of thoracic MRI. Challenges in implementing MRI into clinical practice were described, including ordering health care provider awareness, lack of training, and technical, as well as administration hurdle.


Chronic Cough

Chronic Cough. Variant 2: Chronic cough lasting more than 8 weeks. Increased risk for lung cancer. Initial imaging. Radiography Chest Chest radiography is often performed early in the investigation of chronic cough and is recommended by the ACCP [1]. There was no literature that addressed this modality in the setting of chronic cough with risk factors for lung cancer. In each of the available prospective case series evaluating standardized clinical protocols for chronic cough, there was a diagnosis of malignancy in 2 of 131 [7] and 2 of 122 [17] patients assessed, all of whom had initial chest radiography. Both studies reported that clinical and radiographic findings led to increased suspicion of malignancy. In a retrospective analysis of patients with chronic cough who had normal chest radiographs, 2 out of 266 diagnosis were determined to be malignant. Both patients had suspicious clinical findings, which prompted further evaluation with chest CT [16].


Chronic Cough

Chronic Cough. Cough has been shown to be a prevalent symptom in patients with lung cancer [49,50], with 57% consecutive patients with lung cancer reporting cough as a symptom (n = 223). The exact prevalence of malignancy in a population with chronic cough is not well documented and likely <1% to 2% from the small collection of case series


Chronic Cough

Chronic Cough. reviewed. Nevertheless, in the setting of elevated risk (ie, smoking and occupational exposure), the prevalence may be more significant.


Chronic Cough

Chronic Cough. The role of chest radiography in the early evaluation of patients with chronic cough is largely founded in the exclusion of treatable and/or serious underlying pulmonary pathology. When extrapolating from the available evidence, there remains a question regarding the sensitivity of chest radiography for the detection of subclinical disease and early malignancy. In this setting, there may be a population of patients with chronic cough that may benefit from earlier use of advanced imaging. Future research into this topic may elucidate the specific features and clinical qualities that would provide risk stratification and entail appropriate imaging recommendation.


Chronic Cough

Chronic Cough. CT Chest There is no relevant literature to support the use of chest CT in patients with chronic cough who have one or more high-risk factors for lung cancer. In nonsmoking adults, risk factors vary and include environmental pollutants, genetic variations, underlying chronic pulmonary disease, immunosuppression, and occupational exposures (ie, asbestos and silica) [52]. Cough has been shown to be a prevalent symptom in patients with lung cancer [49,50], 57% of a small cohort of consecutive patients with lung cancer (n = 223). However, the true prevalence of isolated cough (without any additional clinical features) in the setting of malignancy remains unknown. Some authors suggest this combination to be rare in the clinical setting of chronic cough [16]. In a retrospective analysis of patients with chronic cough who have normal chest radiographs, 2 out of 266 diagnoses were determined to be malignancy. Both patients had suspicious clinical findings, which prompted further evaluation with chest CT. It is also worth noting that both patients had a normal chest radiograph [16]. In prospective case series evaluating standardized clinical protocols for chronic cough, the prevalence of malignancy was found to be between 1% and 2% [7,17].


Chronic Cough

Chronic Cough. CT of the chest is recommended for the evaluation of suspected pulmonary neoplasm [15,53] and has been recommended for patients with chronic cough who are smokers or when chronic lung disease is clinically suspected [16,53]. Chest CT has been shown to be more sensitive than chest radiography for the detection of lung cancer in the National Lung Cancer Screening Trial [25], with significant overall mortality benefit. There is limited data regarding the differential imaging evaluation of patients with chronic cough with occupational exposures. In a small sample of male welders (n = 74) with a normal chest radiograph, HRCT identified 27 patients with micronodular disease, 5 patients with emphysematous changes, 3 patients with GGO, and 1 patient with pleural thickening [51], questioning the sensitivity of radiography for occupational disease. Red flags and concerning features are discussed by various authors and larger pulmonary societies [1,13,29], although our literature review did not identify studies directly evaluating CT of the chest in patients with chronic cough with elevated risk. Additionally, red flags in this setting have not been validated and shown to be predictive of malignancy.


Chronic Cough

Chronic Cough. In the setting of elevated lung cancer risk, there is no high-quality evidence supporting chest CT in patients with chronic cough. It is worth noting that in the few case series evaluating patients with chronic cough, malignancy was diagnosed in 1% to 2% of studied groups. This is a not an insignificant quantity and actually rivals case detection in both lung cancer and breast cancer screening. Furthermore, at least two of these reported malignancies were in the context of a normal chest radiograph. It is likely that the prevalence of malignancy in the setting of chronic cough is far lower, and these studies are likely biased by selection. Nevertheless, there may be a cohort of patients with chronic cough who would benefit from earlier chest CT, potentially leap-frogging weeks of sequential


Chronic Cough

Chronic Cough

Chronic Cough. Chronic Cough


Chronic Cough

Chronic Cough. therapeutic trials that may in fact delay diagnosis. Future research may be needed to evaluate which patients with chronic cough would gain from earlier evaluation with CT.


Chronic Cough

Chronic Cough. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of FDG-PET/CT in the evaluation of chronic cough with increased risk factors for lung cancer. FDG-PET utilizes a radiolabeled glucose analog to evaluate for upregulated metabolism in areas of infection, inflammation, and neoplasm [43]. It is often utilized in the setting of solitary pulmonary nodules to allow for risk stratification. In the setting of known malignancy, FDG-PET is suitable for staging nodal and metastatic involvement. FDG-PET provides valuable input for further noninvasive testing and operative planning. In patients with chronic cough who have elevated risk factors for lung cancer, it is unlikely that FDG- PET would significantly add value over other imaging modalities, such as chest radiography or chest CT.


Chronic Cough

Chronic Cough. MRI Chest There is no relevant literature to support the use of thoracic MRI in the evaluation of patients with chronic cough who have increased risk of lung cancer. No studies specific to chronic cough distinguished between contrast- enhanced and noncontrast MRI. In the setting of neoplasm of the chest wall or mediastinum, the addition of extracellular contrast agent would allow for differentiation of cystic and solid features and may add value in planning appropriate invasive testing. Additionally, vasculature is imaged well with the addition of contrast, and contrast-enhanced MRI has been shown to be nearly equivalent to contrast-enhanced CT for the evaluation for pulmonary embolism [29]. MRI was not evaluated in the two prospective clinical series evaluating the utility of a standardized clinical protocol for the evaluation of chronic cough [7,17]. MRI is also not explicitly recommended in the available practice guidelines for the evaluation of chronic cough by the ACCP [1]. Limitations of pulmonary MRI include low signal-to-noise ratio (especially with normally aerated lung), low spatial resolution, and need for adequate breath-hold technique or respiratory gating [46]. Based on our literature review, there is limited evidence evaluating the diagnostic quality of MRI for the evaluation of pulmonary abnormalities. Ohno et al [47] analyzed 85 consecutive patients with a high prevalence of pulmonary abnormality with high-resolution pulmonary MR using ultrashort time to echo and compared findings with both standard and LDCT acquisition. High-resolution MRI demonstrated excellent correlation with standard dose CT for mass or nodule, GGO, and lymphadenopathy. MRI demonstrated 89% sensitivity and 99% specificity for mass or nodule identification. The authors noted diminished imaging quality; however, this did not affect overall evaluation. The role of MRI in the setting of chronic cough and increased cancer risk remains unknown at this time. Future research in this setting may be warranted for certain populations.


Chronic Cough

Chronic Cough. CT Chest The most commonly identified etiologies reported for chronic cough are asthma, GERD, and UACS [1]. Prospective case series have shown clinical efficacy in diagnosing and managing chronic cough using standard clinical algorithms with minimal investigation [7,17]. When this has failed to result in diagnosis, or when empiric sequential treatment for the most common etiologies has failed to resolve symptoms, further investigative modalities and additional specialty referrals have been recommended. The ACCP and German Respiratory Society both recommend HRCT after an appropriate clinical evaluation and empiric trial has been performed [1,29]. HRCT is typically performed with multidetector helical CT, and the standard for performance can be reviewed in the ACR practice parameter for HRCT [54]. Briefly, thin-slice acquisition and high spatial resolution reconstruction algorithms allow for near-isotropic voxels. This gives the reader additional tools for a thorough evaluation of the imaged field, including multiplanar reformats and both maximum and minimum intensity projection postprocessed images. In the setting of chronic cough, however, the various modalities and specific protocol designs have not been adequately investigated and compared. It is unclear how much the added resolving power of HRCT adds to the clinical evaluation of patients with chronic cough. Contrast- and noncontrast-enhanced studies have also not been compared. The addition of contrast would allow for improved visualization of the mediastinum, chest wall, and soft


Chronic Cough

Chronic Cough. HRCT is considered the reference standard for the evaluation of bronchiectasis. Bronchiectasis has been identified as an etiology for chronic cough in up to 8% of patients in case series [2,7]. Although suspicion for bronchiectasis can be aided by clinical features [5], chest radiography has shown poor sensitivity for evaluation. Altenburg et al [32] reported that radiographic findings did not detect ectatic airways in up to 34% of patients reviewed. Bronchiectasis and bronchial wall thickening were identified in 27% and 21% of patients, respectively, referred to chest CT for the evaluation of chronic cough in whom radiographs were reportedly normal [3]. There remains variable association between identification of bronchiectasis and clinical features. Bronchiectasis has been found by chest CT in asymptomatic persons enrolled in a health survey screening setting [4], as well as in asymptomatic elderly persons [37]. Wilsher et al [40] evaluated 60 consecutive patients with newly diagnosed RA and were unable to demonstrate a correlation between cough symptoms and bronchiectasis, although association reached significance for dyspnea. Furthermore, bronchiectasis and bronchial wall thickening were identified in 48% and 58% of patients, respectively, with only 30% reporting any symptoms. Ooi et al [6] were unable to correlate the frequency of acute symptom exacerbation (including cough symptoms) and the degree of bronchial wall thickening in 60 consecutive patients with CT-proven bronchiectasis. In a large single-center prospective study, Grydeland et al [39] used quantitative analysis of bronchial wall thickening and compared findings between patients with COPD (n = 463) and those without COPD (n = 488). Airway wall thickening was found to be statistically associated with chronic cough in patients with COPD but did not reach significance in the non-COPD group.


Chronic Cough

Chronic Cough. Interstitial lung disease and pulmonary fibrosis have been reported as etiologies of chronic cough, although prevalence of diagnosed cases is variable, ranging between 0.4% and 8% of the reviewed case series [2,7,16,17]. Chest CT is considered the reference standard in the evaluation of interstitial lung disease. Although at least one study reported good correlation between chest radiography and chest CT in this setting [46], chest CT has been shown to be more sensitive than both chest radiography [31] and LDCT [27]. In 97 patients with chronic cough who also had normal chest radiographs, Truba et al [3] reported interstitial abnormalities in 4 patients. Association between cough symptoms and CT findings of interstitial lung disease has been variable. In a small prospective cohort of 36 patients with RA, cough was not found to be statistically associated with restrictive findings on either PFT or HRCT analysis [31]. In 107 consecutive patients with systemic sclerosis, cough was associated with HRCT findings [31].


Chronic Cough

Chronic Cough. In the setting of chronic cough after failed initial evaluation and/or empiric treatment, the limited evidence suggests a role for chest CT to identify underlying pulmonary disease. Although it remains unclear if HRCT or LDCT play a role, clinical features may stratify patients for appropriate imaging evaluation in order to balance diagnostic yield and dose considerations.


Chronic Cough

Chronic Cough. CT Maxillofacial CT of the sinuses and maxillofacial structures offers improved visualization of the sinonasal anatomy, allowing for localization, characterization, and grading of sinonasal pathology. UACS is largely a conglomerate terminology for cough related to inflammation or irritation of the upper airways, which includes postnasal drip, allergic and nonallergic CRS, as well as laryngeal reflux. UACS is considered one of the more common causes of chronic cough [1,53]. Based on a few case series of patients with chronic cough, UACS/rhinitis prevalence ranged from 6% to 65% [2,7,17]. Guidelines for the evaluation of chronic cough by the ACCP places sinus imaging under consideration after initial clinical examination and chest radiography [1]. The clinical evaluation of UACS is not sensitive and often not specific [53], and features may go unrecognized even by endoscopy [12,55,56], creating an integral role for noninvasive imaging. Symptoms alone were found to have a sensitivity between 37% and 73% in a retrospective analysis of 126 patients who underwent CT imaging for the evaluation of CRS [57]. Furthermore, up to 35% of patients who were diagnosed with CRS had normal endoscopic findings [57]. Abrass et al [55] reviewed 100 patients with clinical findings suspicious of CRS, all with negative endoscopic evaluations. The investigators reported between 20% and 49% of studied individuals had positive findings on point-of-care CT of the sinuses, and the utilization of imaging allowed for a decrease in unnecessary antibiotic prescription. In a small retrospective case control study evaluating patients with CRS, Conley et al [56] showed increased clinical accuracy and a lower rate of unnecessary antibiotic use when cone-beam CT was used to evaluate the sinuses at initial office visit. In a


Chronic Cough

Chronic Cough. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of FDG-PET/CT in the evaluation of chronic cough. This imaging modality was not evaluated in limited case series evaluating patients with chronic cough, nor was it recommended in the available guidelines published by various societies and groups. FDG avidity has been correlated to sites of parenchymal abnormality in a small study of 36 patients with interstitial lung disease [43,60]. Yadav et al [61] showed increased FDG activity corresponding to HRCT abnormalities in 16 patients with known interstitial lung disease. Win et al [62] evaluated a small cohort of patients with idiopathic pulmonary fibrosis and demonstrated increased FDG activity in areas of the lung with and without HRCT abnormalities, suggesting increased sensitivity of PET for early inflammation. The limited literature is suggestive of an increased sensitivity of PET/CT to various inflammatory processes, so clearly there is a role in the evaluation and staging of malignancy. Future research may be needed to evaluate the role of PET/CT in cases of idiopathic chronic cough. One could speculate that a few inflammatory processes (ie, arteritis) with minimal imaging findings on more conventional modalities may demonstrate FDG uptake.


Chronic Cough

Chronic Cough. Fluoroscopy Biphasic Esophagram There is no relevant literature to support the use of biphasic esophagram in the evaluation of chronic cough.


Chronic Cough

Chronic Cough. 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.


Chronic Cough

Chronic Cough. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www.acr.org/ac.


Female Breast Cancer Screening

Female Breast Cancer Screening. Introduction/Background Breast cancer is the most common nonskin cancer diagnosis in women and is second only to lung cancer with respect to cancer deaths. Early detection of breast cancer from regular screening substantially reduces breast cancer mortality [1]. Because regular screening identifies tumors when they are smaller and with fewer nodal metastases, patients with screen-detected breast cancers are less likely to require mastectomy or chemotherapy, thereby also decreasing morbidity [2].


Female Breast Cancer Screening

Female Breast Cancer Screening. Breast cancer risk is frequently divided into 3 major categories: average, intermediate, and high risk. Numerous factors contribute to breast cancer risk, so no single method or definition is used to classify each woman into a specific risk category [3,4]. The use of validated statistical models based largely upon family history, which also incorporate additional risk factors, represents one mechanism to estimate risk. Currently, risk categories are most frequently defined by estimated lifetime risk; however, different time horizons, such as 5 or 10 year risk, may also be valuable for guideline development and informed decision-making [3]. Women at average risk are typically defined as those with <15% estimated lifetime risk for developing breast cancer, whereas intermediate-risk women are generally defined as those with a 15% to 20% estimated lifetime risk. The high-risk category typically includes women who have a >20 to 25% estimated lifetime risk: women who carry a deleterious genetic mutation that increases breast cancer risk, as well as untested first-degree relatives of patients with these mutations and women who have received radiation therapy to the thorax or upper abdomen at an early age (<30 years). Some women with a personal history of high-risk breast lesions, a personal history of breast cancer, dense breast tissue, or a family history of breast cancer may fit into the intermediate- or high-risk categories, depending upon their specific risk factors or combination of factors [3]. Elevated risk is sometimes used to refer to women in both the intermediate- and high-risk categories [3].


Female Breast Cancer Screening

Female Breast Cancer Screening. Breast cancer screening guidelines vary across medical professional organizations, although published guidelines agree that regular breast cancer screening decreases morbidity and breast cancer mortality [5-7]. Medical professional organizations may also define breast cancer risk categories using different methodologies. Although screening guidelines for high-risk patients have typically been similar, discrepant recommendations for average- and intermediate-risk women have sparked controversy and confusion. In part due to differences in screening guidelines, use of breast cancer screening modalities remains suboptimal in women of all risk categories. The ACR encourages patients to undergo breast cancer risk assessment by 25 years of age, so elevated-risk patients have the opportunity to benefit from earlier and more aggressive breast cancer screening regimens, when appropriate [3]. The ACR recommends that both the benefits and risks of breast cancer screening and supplemental screening be considered to assist patients in making informed decisions regarding their health care [8].


Female Breast Cancer Screening

Female Breast Cancer Screening. aPanel Chair, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. bMemorial Sloan Kettering Cancer Center, New York, New York. cMemorial Sloan Kettering Cancer Center, New York, New York. dPanel Vice-Chair, University of Cincinnati, Cincinnati, Ohio. eClinica Family Health, Lafayette, Colorado; American Academy of Family Physicians. fLenox Hill Hospital, Northwell Health, New York, New York; American College of Surgeons. gWashington University School of Medicine, Saint Louis, Missouri. hPenn State Health Hershey Medical Center, Hershey, Pennsylvania. iThomas Jefferson University Hospital, Philadelphia, Pennsylvania; American College of Obstetricians and Gynecologists. jUniversity of Utah, Salt Lake City, Utah. kKaiser Permanente, Atlanta, Georgia. lUniversity of Michigan, Ann Arbor, Michigan. mSt. Bernards Healthcare, Jonesboro, Arkansas. nUMass Memorial Medical Center/UMass Chan Medical School, Worcester, Massachusetts. oNYU Clinical Cancer Center, New York, New York. pProMedica Breast Care, Toledo, Ohio. qEmory University Hospital, Atlanta, Georgia; RADS Committee. rYale School of Medicine, New Haven, Connecticut; Society of General Internal Medicine. sHarvard Medical School, Boston, Massachusetts; American Geriatrics Society. tLoyola University Chicago, Stritch School of Medicine, Department of Radiation Oncology, Cardinal Bernardin Cancer Center, Maywood, Illinois; Commission on Radiation Oncology. uHoag Family Cancer Institute, Newport Beach, California and University of Southern California, Los Angeles, California; Commission on Nuclear Medicine and Molecular Imaging. vSpecialty Chair, Boston University School of Medicine, Boston, Massachusetts.


Female Breast Cancer Screening

Female Breast Cancer Screening. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization.


Female Breast Cancer Screening

Female Breast Cancer Screening. Reprint requests to: publications@acr.org


Female Breast Cancer Screening

Female Breast Cancer Screening

Female Breast Cancer Screening. Female Breast Cancer Screening


Female Breast Cancer Screening

Female Breast Cancer Screening. Discussion of Procedures by Variant Variant 1: Adult female. Breast cancer screening. Average risk. Digital Breast Tomosynthesis Screening Digital breast tomosynthesis (DBT) displays reconstructed stacked images of the breast in combination with digital mammographic views, which may be synthetic mammograms reconstructed from the acquired tomosynthesis data set or full-field digital mammograms (FFDM). Compared to FFDM or synthetic mammograms alone, most studies demonstrate that DBT increases cancer detection rate (CDR) and decreases recall rate [14-22]; although some studies have not reached statistical significance [23] or have found less compelling results in subsets of women, such as those with extremely dense breasts [24,25]. Dense breast tissue decreases the sensitivity of mammography [26] and is an independent risk factor for developing breast cancer [27]. Compared to average breast density (near the threshold between heterogeneously dense and scattered areas of fibroglandular density), the relative risks for developing breast cancer are 1.2 for heterogeneously dense and 2.1 for extremely dense breasts [28]. Some health care providers may therefore consider women with extremely dense breasts to no longer be average risk. Irrespective of risk category, meta-analyses have demonstrated an incremental increase in CDR of 1.6 to 3.2 per 1,000 screening DBT examinations and a 2.2% pooled decrease in recall rate compared to digital mammography [18,29,30].


Female Breast Cancer Screening

Female Breast Cancer Screening. Because screening mammography decreases breast cancer mortality, screening mammography or screening DBT is still performed in women undergoing supplemental screening studies [3,8,35].


Female Breast Cancer Screening

Female Breast Cancer Screening. In addition to mortality reduction, screening mammography decreases treatment morbidity, because screen-detected tumors are typically lower stage (eg, smaller and more likely to be node-negative), compared to breast cancers detected by palpation [2,8]. Despite these benefits, screening mammograms also have risks. The most common perceived risks include false-positive recalls and biopsies, overdiagnosis, and patient anxiety [5,7,32]. Approximately 10% of screening mammograms result in a recall for additional imaging, although <2% result in a


Female Breast Cancer Screening

Female Breast Cancer Screening


Female Breast Cancer Screening

Female Breast Cancer Screening. For women 40 to 49 years of age, randomized controlled trials and observational studies demonstrate that screening mammography decreases breast cancer mortality by 15% to 50% [1,8,32,33,39]. Results from the Cancer Intervention and Surveillance Modeling Network (CISNET) suggest that annual screening mammography in women 40 to 49 years of age saves 42% more lives and life-years than biennial screening due to faster growing tumors in younger women [31]. Women screened between 40 and 49 years of age are also less likely to require mastectomy or chemotherapy than women diagnosed with palpable tumors [2].


Female Breast Cancer Screening

Female Breast Cancer Screening. Non-Hispanic Black, Hispanic Black, and Hispanic White women have higher breast cancer mortality than non- Hispanic White women, and minority women often present at younger ages with more aggressive tumor subtypes [3,8]. Therefore, decreasing access to screening mammography, especially in women 40 to 49 years of age, may disproportionately impact minority women.


Female Breast Cancer Screening

Female Breast Cancer Screening. Annual screening mammography results in a greater reduction in mortality compared to biennial screening [8]. In women 40 to 84 years of age, annual screening reduces mortality by 40%, compared to a 32% reduction for biennial screening [32]. With regular screening, interval breast cancers do occur with a higher frequency in women undergoing biennial or triennial screening compared to annual screening. The sensitivity of mammography is decreased in some groups of women, including those with dense breasts [40]. Dense breast tissue decreases the sensitivity of mammography [26] and is an independent risk factor for developing breast cancer [27]. Compared to average breast density (near the threshold between heterogeneously dense and scattered areas of fibroglandular density), the relative risks for developing breast cancer are 1.2 for heterogeneously dense and 2.1 for extremely dense breasts [28]. Some health care providers may therefore consider women with extremely dense breasts to no longer be average risk. Given the limitations of mammography and to minimize interval cancers, supplemental screening modalities have been investigated in women at average risk.


Female Breast Cancer Screening

Female Breast Cancer Screening. Because screening mammography decreases breast cancer mortality, screening mammography or screening DBT is still performed in women undergoing supplemental screening studies [3,8,35]. Rather than supplementing screening mammography with additional imaging modalities, some have suggested limiting women offered screening mammography based upon individual patient risk assessed by various risk models, breast density, or genetic information such as single-nucleotide polymorphism. However, the randomized controlled trials demonstrating mortality reduction and most large-scale observational studies enrolled women based upon geographic location and age, not other individual patient risk factors. In one observational study in women <50


Female Breast Cancer Screening

Female Breast Cancer Screening. Female Breast Cancer Screening years of age, restricting screening to women with a first-degree family history, extremely dense breast tissue, or both, would cause 66% of potentially screen-detected cancers to be missed [41].


Female Breast Cancer Screening

Female Breast Cancer Screening. To maximize the benefits, the ACR recommends screening mammography in average-risk women each year beginning at 40 years of age. Women should continue screening mammography as long as they remain in overall good health and are willing to undergo the examination and subsequent testing or biopsy, if an abnormality is identified [5,8].


Female Breast Cancer Screening

Female Breast Cancer Screening. MRI Breast Without and With IV Contrast Although data are limited regarding the use of breast MRI without and with IV contrast for screening women at average risk, one study has demonstrated that breast MRI demonstrates incremental cancer detection (15-16 cancers per 1,000 breast MRI examinations) over screening mammography with or without screening ultrasound (US) in average-risk women irrespective of breast density [42]. Breast MRI also decreases interval cancers [42,43]. In the DENSE trial, breast MRI significantly reduced interval cancers within women with extremely dense breast tissue and normal mammography, so the European Society of Breast Imaging now recommends screening breast MRI every 2 to 4 years in women 50 to 70 years of age with extremely dense breasts [43,44]. Compared to average breast density (near the threshold between heterogeneously dense and scattered areas of fibroglandular density), the relative risks for developing breast cancer are 1.2 for heterogeneously dense and 2.1 for extremely dense breasts [28]. Some health care providers may therefore consider women with extremely dense breasts to no longer be average risk.


Female Breast Cancer Screening

Female Breast Cancer Screening. MRI Breast Without and With IV Contrast Abbreviated Data are limited regarding the use of abbreviated breast MRI without and with IV contrast for screening women at average risk. The ECOG-ACRIN abbreviated MRI trial demonstrated a significantly higher CDR for abbreviated breast MRI without and with IV contrast (15 cancers per 1,000) compared with DBT (6 cancers per 1,000), although the study recruited women with dense breasts [45]. In addition to dense breasts, women enrolled in the trial had variable 5 and 10 year risk profiles based upon the Breast Cancer Surveillance Consortium risk calculator and 19% reported 1 or more first degree relatives with breast cancer [45]. Compared to average breast density (near the threshold between heterogeneously dense and scattered areas of fibroglandular density), the relative risks for developing breast cancer are 1.2 for heterogeneously dense and 2.1 for extremely dense breasts [28]. Some health care providers may therefore consider women with extremely dense breasts to no longer be average risk.


Female Breast Cancer Screening

Female Breast Cancer Screening. MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI without IV contrast for screening women at average risk.


Female Breast Cancer Screening

Female Breast Cancer Screening. MRI Breast Without IV Contrast Abbreviated There is no relevant literature to support the use of abbreviated MRI without IV contrast for screening women at average risk.


Female Breast Cancer Screening

Female Breast Cancer Screening. Sestamibi MBI Data are limited regarding the use of sestamibi molecular breast imaging (MBI) for screening women at average risk. Most studies have focused upon women with dense breasts and variable risk profiles. One of the larger studies published to date of 1,696 women with recent negative or benign mammographic examinations showed that sestamibi MBI yielded an incremental CDR of 7.7 cancers per 1,000 examinations; however, all 13 cancers were detected in women with dense breasts [46]. Although 92% of the women within the study had <20% estimated lifetime risk, the estimates ranged from 6.1% to 17.2% [46]. Additional retrospective and prospective studies have demonstrated similar incremental CDR for sestamibi MBI of 6.5 to 9 per 1,000 over mammography [40,47].


Female Breast Cancer Screening

Female Breast Cancer Screening. Sestamibi MBI demonstrates similar sensitivity, better specificity, and lower recall rate compared to supplemental screening US in women with dense breasts [47,48].


Female Breast Cancer Screening

Female Breast Cancer Screening. US Breast Most studies evaluating the utility of screening with breast US have focused on women with dense breast tissue with or without other risk factors. Dense breast tissue decreases the sensitivity of mammography [26] and is an independent risk factor for developing breast cancer [27]. Screening breast US in women with mammographically dense breasts, including those with risk factors placing them at increased breast cancer risk, identifies mammographically occult, small, node-negative invasive tumors with an increased CDR of 1.8 to 4.6 cancers per 1,000 women screened [40,49]. Although supplemental screening US in women with dense breasts results in an increased CDR, US also increases recall rate, false-positive examinations, and false-positive biopsies [26,49-55].


Female Breast Cancer Screening

Female Breast Cancer Screening. Data regarding supplemental screening US in average-risk women with nondense breasts is less compelling. In a study of 1,526 average-risk women without mammographic abnormalities, screening with US demonstrated an overall incremental CDR of 3.3 per 1,000, with 5.1 per 1,000 examinations in dense breasts and 0 per 1,000 in nondense breasts compared to digital mammography [56]. In another study of 1,003 average-risk women, US yielded an overall incremental CDR of 3.2 per 1,000 examinations, with 0 per 1,000 in nondense breasts, compared to DBT with or without digital mammography [53].


Female Breast Cancer Screening

Female Breast Cancer Screening. Digital Breast Tomosynthesis Screening DBT displays reconstructed stacked images of the breast in combination with digital mammographic views, which may be synthetic mammograms reconstructed from the acquired tomosynthesis dataset or FFDM. Compared to FFDM or synthetic mammograms alone, most studies demonstrate that DBT increases CDR and decreases recall rate [14-22]; although, some studies have not reached statistical significance [23] or have found less compelling results in subsets of women, such as those with extremely dense breasts [24,25]. Dense breast tissue decreases the sensitivity of mammography [26] and is an independent risk factor for developing breast cancer [27]. Compared to average breast density (near the threshold between heterogeneously dense and scattered areas of fibroglandular density), the relative risks for developing breast cancer are 1.2 for heterogeneously dense and 2.1 for extremely dense breasts [28]. Some health care providers may therefore consider women with extremely dense breasts to no longer be average risk. Irrespective of risk category, meta-analyses have demonstrated an incremental increase in CDR of 1.6 to 3.2 per 1,000 screening DBT examinations and a 2.2% pooled decrease in recall rate compared to digital mammography [18,29,30].


Female Breast Cancer Screening

Female Breast Cancer Screening. The degree of breast cancer mortality reduction from screening mammography varies with different screening regimens. Mortality reduction is greater when screening begins at 40 years of age rather than 45 or 50 years of age