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Breast
Imaging
Breast Imaging Overview
Interval Cancers
Interval Cancers
Wendie A. Berg, MD, PhD
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KEY FACTS

  • Terminology

    • Imaging

      • Top Differential Diagnoses

        • Pathology

          • Clinical Issues

            TERMINOLOGY

            • Definitions

              • Breast cancers detected due to clinical findings during interval between recommended screenings
                • Screening interval varies; range: 12-36 months
                  • American College of Radiology (ACR) and American Cancer Society (ACS) recommend every year
                  • Dutch, Scandinavian, Canadian, Australian, and New Zealand screening programs recommend every 2 years
                    • Invitation to screen in Sweden every 18-24 months
                  • UK NHS National Breast Screening Programme recommends every 3 years
                • Longer interval between screenings → higher rate of interval cancers
                • USA performs 2-view (MLO and CC) mammography; variable use of CC views in other programs
                • ± suspicious finding on retrospective review of prior screening or recall study
                  • "Missed cancer" if visible in retrospect at site of cancer and considered suspicious
                  • Many such findings below threshold even in retrospect: Benign-appearing, similar to normal tissue
                  • Many cancers occult on prior screening examination(s) even in retrospect = "true interval cancer"
                • Sometimes attributable to inferior quality of prior study
                  • Suboptimal positioning, motion, other artifacts
                • Should not include cancers detected at early subsequent screening (e.g., 11 months in USA) or prophylactic mastectomy, though these are among false-negatives
              • Interval cancers can be mammographically occult, below threshold or missed on prior mammography, or new mammographic finding
              • Screening mammogram: Testing to detect cancer in women with no signs or symptoms of breast cancer
              • Diagnostic mammogram: Examination performed with monitoring by on-site radiologist
                • Typically includes US at time of examination, if indicated
              • Indications for diagnostic mammography
                • Symptomatic patient: Lump, nipple discharge or retraction, change in breast size or shape, skin thickening, focal pain, etc.
                • Recall from screening for additional imaging following perception of abnormality
                • Short-interval follow-up of findings deemed probably benign on prior work-up
              • Screen-detected cancers: Regular interval mammographic examination reveals breast cancer, and patient is asymptomatic with respect to breasts
                • Billing may be diagnostic but audited as screening
                  • Prior biopsy for other benign lesions
                  • Routine annual mammography in women with history of lumpectomy and radiation for breast cancer
                  • Women with implants

            IMAGING

            • General Features

              • Mammographic Findings

                • Ultrasonographic Findings

                  • MR Findings

                    • Imaging Recommendations

                      DIFFERENTIAL DIAGNOSIS

                        PATHOLOGY

                        • General Features

                          • Staging, Grading, & Classification

                            • Microscopic Features

                              CLINICAL ISSUES

                              • Presentation

                                • Demographics

                                  • Natural History & Prognosis

                                    DIAGNOSTIC CHECKLIST

                                    • Consider

                                      • Image Interpretation Pearls

                                        Selected References

                                        1. Kerlikowske K et al: Automated and clinical breast imaging reporting and data system density measures predict risk for screen-detected and interval cancers: a case-control study. Ann Intern Med. 168(11):757-765, 2018
                                        2. Lee JM et al: Cumulative risk distribution for interval invasive second breast cancers after negative surveillance mammography. J Clin Oncol. 36(20):2070-2077, 2018
                                        3. McCarthy AM et al: Breast cancer with a poor prognosis diagnosed after screening mammography with negative results. JAMA Oncol. 4(7):998-1001, 2018
                                        4. Vreemann S et al: The frequency of missed breast cancers in women participating in a high-risk MRI screening program. Breast Cancer Res Treat. ePub, 2018
                                        5. Destounis S et al: Using volumetric breast density to quantify the potential masking risk of mammographic density. AJR Am J Roentgenol. 208(1):222-227, 2017
                                        6. Houssami N et al: The epidemiology, radiology and biological characteristics of interval breast cancers in population mammography screening. NPJ Breast Cancer. 3:12, 2017
                                        7. Lekanidi K et al: Breast screening: what can the interval cancer review teach us? Are we perhaps being a bit too hard on ourselves? Eur J Radiol. 94:13-15, 2017
                                        8. Wanders JOP et al: The effect of volumetric breast density on the risk of screen-detected and interval breast cancers: a cohort study. Breast Cancer Res. 19(1):67, 2017
                                        9. McDonald ES et al: Effectiveness of digital breast tomosynthesis compared with digital mammography: outcomes analysis from 3 years of breast cancer screening. JAMA Oncol. 2(6):737-43, 2016
                                        10. Holm J et al: Risk factors and tumor characteristics of interval cancers by mammographic density. J Clin Oncol. 33(9):1030-7, 2015
                                        11. Song SE et al: Undiagnosed breast cancer: features at supplemental screening US. Radiology. 277(2):372-80, 2015
                                        12. Houssami N et al: Risk factors for second screen-detected or interval breast cancers in women with a personal history of breast cancer participating in mammography screening. Cancer Epidemiol Biomarkers Prev. 22(5):946-61, 2013
                                        13. Berg WA et al: Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk. JAMA. 307(13):1394-404, 2012
                                        14. Heijnsdijk EA et al: Differences in natural history between breast cancers in BRCA1 and BRCA2 mutation carriers and effects of MRI screening-MRISC, MARIBS, and Canadian studies combined. Cancer Epidemiol Biomarkers Prev. 21(9):1458-68, 2012
                                        15. Corsetti V et al: Evidence of the effect of adjunct ultrasound screening in women with mammography-negative dense breasts: interval breast cancers at 1 year follow-up. Eur J Cancer. 47(7):1021-6, 2011
                                        16. Kirsh VA et al: Tumor characteristics associated with mammographic detection of breast cancer in the Ontario breast screening program. J Natl Cancer Inst. 103(12):942-50, 2011
                                        17. Haakinson DJ et al: A significant number of women present with palpable breast cancer even with a normal mammogram within 1 year. Am J Surg. 200(6):712-7; discussion 717-8, 2010
                                        18. Boyd NF et al: Mammographic density and the risk and detection of breast cancer. N Engl J Med. 356(3):227-36, 2007
                                        19. Kerlikowske K et al: Longitudinal measurement of clinical mammographic breast density to improve estimation of breast cancer risk. J Natl Cancer Inst. 99(5):386-95, 2007
                                        20. Shen Y et al: Role of detection method in predicting breast cancer survival: analysis of randomized screening trials. J Natl Cancer Inst. 97(16):1195-203, 2005
                                        21. Buist DS et al: Factors contributing to mammography failure in women aged 40-49 years. J Natl Cancer Inst. 96(19):1432-40, 2004
                                        22. Anttinen J et al: Her-2/neu oncogene amplification and protein over-expression in interval and screen-detected breast cancers. Anticancer Res. 23(5b):4213-8, 2003
                                        23. Ikeda DM et al: Analysis of 172 subtle findings on prior normal mammograms in women with breast cancer detected at follow-up screening. Radiology. 226(2):494-503, 2003
                                        24. Wang SC: The Singapore National Breast Screening Programme: principles and implementation. Ann Acad Med Singapore. 32(4):466-76, 2003
                                        25. Warren RM et al: Radiology review of the UKCCCR Breast Screening Frequency Trial: potential improvements in sensitivity and lead time of radiological signs. Clin Radiol. 58(2):128-32, 2003
                                        26. Gilliland FD et al: Biologic characteristics of interval and screen-detected breast cancers. J Natl Cancer Inst. 92(9):743-9, 2000
                                        27. Mandelson MT et al: Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst. 92(13):1081-7, 2000
                                        28. Porter PL et al: Breast tumor characteristics as predictors of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst. 91(23):2020-8, 1999
                                        29. Burrell HC et al: Screening interval breast cancers: mammographic features and prognosis factors. Radiology. 199(3):811-7, 1996
                                        Related Anatomy
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                                        Related Differential Diagnoses
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                                        References
                                        Tables

                                        Tables

                                        KEY FACTS

                                        • Terminology

                                          • Imaging

                                            • Top Differential Diagnoses

                                              • Pathology

                                                • Clinical Issues

                                                  TERMINOLOGY

                                                  • Definitions

                                                    • Breast cancers detected due to clinical findings during interval between recommended screenings
                                                      • Screening interval varies; range: 12-36 months
                                                        • American College of Radiology (ACR) and American Cancer Society (ACS) recommend every year
                                                        • Dutch, Scandinavian, Canadian, Australian, and New Zealand screening programs recommend every 2 years
                                                          • Invitation to screen in Sweden every 18-24 months
                                                        • UK NHS National Breast Screening Programme recommends every 3 years
                                                      • Longer interval between screenings → higher rate of interval cancers
                                                      • USA performs 2-view (MLO and CC) mammography; variable use of CC views in other programs
                                                      • ± suspicious finding on retrospective review of prior screening or recall study
                                                        • "Missed cancer" if visible in retrospect at site of cancer and considered suspicious
                                                        • Many such findings below threshold even in retrospect: Benign-appearing, similar to normal tissue
                                                        • Many cancers occult on prior screening examination(s) even in retrospect = "true interval cancer"
                                                      • Sometimes attributable to inferior quality of prior study
                                                        • Suboptimal positioning, motion, other artifacts
                                                      • Should not include cancers detected at early subsequent screening (e.g., 11 months in USA) or prophylactic mastectomy, though these are among false-negatives
                                                    • Interval cancers can be mammographically occult, below threshold or missed on prior mammography, or new mammographic finding
                                                    • Screening mammogram: Testing to detect cancer in women with no signs or symptoms of breast cancer
                                                    • Diagnostic mammogram: Examination performed with monitoring by on-site radiologist
                                                      • Typically includes US at time of examination, if indicated
                                                    • Indications for diagnostic mammography
                                                      • Symptomatic patient: Lump, nipple discharge or retraction, change in breast size or shape, skin thickening, focal pain, etc.
                                                      • Recall from screening for additional imaging following perception of abnormality
                                                      • Short-interval follow-up of findings deemed probably benign on prior work-up
                                                    • Screen-detected cancers: Regular interval mammographic examination reveals breast cancer, and patient is asymptomatic with respect to breasts
                                                      • Billing may be diagnostic but audited as screening
                                                        • Prior biopsy for other benign lesions
                                                        • Routine annual mammography in women with history of lumpectomy and radiation for breast cancer
                                                        • Women with implants

                                                  IMAGING

                                                  • General Features

                                                    • Mammographic Findings

                                                      • Ultrasonographic Findings

                                                        • MR Findings

                                                          • Imaging Recommendations

                                                            DIFFERENTIAL DIAGNOSIS

                                                              PATHOLOGY

                                                              • General Features

                                                                • Staging, Grading, & Classification

                                                                  • Microscopic Features

                                                                    CLINICAL ISSUES

                                                                    • Presentation

                                                                      • Demographics

                                                                        • Natural History & Prognosis

                                                                          DIAGNOSTIC CHECKLIST

                                                                          • Consider

                                                                            • Image Interpretation Pearls

                                                                              Selected References

                                                                              1. Kerlikowske K et al: Automated and clinical breast imaging reporting and data system density measures predict risk for screen-detected and interval cancers: a case-control study. Ann Intern Med. 168(11):757-765, 2018
                                                                              2. Lee JM et al: Cumulative risk distribution for interval invasive second breast cancers after negative surveillance mammography. J Clin Oncol. 36(20):2070-2077, 2018
                                                                              3. McCarthy AM et al: Breast cancer with a poor prognosis diagnosed after screening mammography with negative results. JAMA Oncol. 4(7):998-1001, 2018
                                                                              4. Vreemann S et al: The frequency of missed breast cancers in women participating in a high-risk MRI screening program. Breast Cancer Res Treat. ePub, 2018
                                                                              5. Destounis S et al: Using volumetric breast density to quantify the potential masking risk of mammographic density. AJR Am J Roentgenol. 208(1):222-227, 2017
                                                                              6. Houssami N et al: The epidemiology, radiology and biological characteristics of interval breast cancers in population mammography screening. NPJ Breast Cancer. 3:12, 2017
                                                                              7. Lekanidi K et al: Breast screening: what can the interval cancer review teach us? Are we perhaps being a bit too hard on ourselves? Eur J Radiol. 94:13-15, 2017
                                                                              8. Wanders JOP et al: The effect of volumetric breast density on the risk of screen-detected and interval breast cancers: a cohort study. Breast Cancer Res. 19(1):67, 2017
                                                                              9. McDonald ES et al: Effectiveness of digital breast tomosynthesis compared with digital mammography: outcomes analysis from 3 years of breast cancer screening. JAMA Oncol. 2(6):737-43, 2016
                                                                              10. Holm J et al: Risk factors and tumor characteristics of interval cancers by mammographic density. J Clin Oncol. 33(9):1030-7, 2015
                                                                              11. Song SE et al: Undiagnosed breast cancer: features at supplemental screening US. Radiology. 277(2):372-80, 2015
                                                                              12. Houssami N et al: Risk factors for second screen-detected or interval breast cancers in women with a personal history of breast cancer participating in mammography screening. Cancer Epidemiol Biomarkers Prev. 22(5):946-61, 2013
                                                                              13. Berg WA et al: Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk. JAMA. 307(13):1394-404, 2012
                                                                              14. Heijnsdijk EA et al: Differences in natural history between breast cancers in BRCA1 and BRCA2 mutation carriers and effects of MRI screening-MRISC, MARIBS, and Canadian studies combined. Cancer Epidemiol Biomarkers Prev. 21(9):1458-68, 2012
                                                                              15. Corsetti V et al: Evidence of the effect of adjunct ultrasound screening in women with mammography-negative dense breasts: interval breast cancers at 1 year follow-up. Eur J Cancer. 47(7):1021-6, 2011
                                                                              16. Kirsh VA et al: Tumor characteristics associated with mammographic detection of breast cancer in the Ontario breast screening program. J Natl Cancer Inst. 103(12):942-50, 2011
                                                                              17. Haakinson DJ et al: A significant number of women present with palpable breast cancer even with a normal mammogram within 1 year. Am J Surg. 200(6):712-7; discussion 717-8, 2010
                                                                              18. Boyd NF et al: Mammographic density and the risk and detection of breast cancer. N Engl J Med. 356(3):227-36, 2007
                                                                              19. Kerlikowske K et al: Longitudinal measurement of clinical mammographic breast density to improve estimation of breast cancer risk. J Natl Cancer Inst. 99(5):386-95, 2007
                                                                              20. Shen Y et al: Role of detection method in predicting breast cancer survival: analysis of randomized screening trials. J Natl Cancer Inst. 97(16):1195-203, 2005
                                                                              21. Buist DS et al: Factors contributing to mammography failure in women aged 40-49 years. J Natl Cancer Inst. 96(19):1432-40, 2004
                                                                              22. Anttinen J et al: Her-2/neu oncogene amplification and protein over-expression in interval and screen-detected breast cancers. Anticancer Res. 23(5b):4213-8, 2003
                                                                              23. Ikeda DM et al: Analysis of 172 subtle findings on prior normal mammograms in women with breast cancer detected at follow-up screening. Radiology. 226(2):494-503, 2003
                                                                              24. Wang SC: The Singapore National Breast Screening Programme: principles and implementation. Ann Acad Med Singapore. 32(4):466-76, 2003
                                                                              25. Warren RM et al: Radiology review of the UKCCCR Breast Screening Frequency Trial: potential improvements in sensitivity and lead time of radiological signs. Clin Radiol. 58(2):128-32, 2003
                                                                              26. Gilliland FD et al: Biologic characteristics of interval and screen-detected breast cancers. J Natl Cancer Inst. 92(9):743-9, 2000
                                                                              27. Mandelson MT et al: Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst. 92(13):1081-7, 2000
                                                                              28. Porter PL et al: Breast tumor characteristics as predictors of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst. 91(23):2020-8, 1999
                                                                              29. Burrell HC et al: Screening interval breast cancers: mammographic features and prognosis factors. Radiology. 199(3):811-7, 1996
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