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Multifocal/Multicentric Breast Cancer
Wendie A. Berg, MD, PhD, FACR, FSBI
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KEY FACTS

  • Terminology

    • Imaging

      • Pathology

        • Clinical Issues

          TERMINOLOGY

          • Definitions

            • Breast cancer (BC): Invasive ductal (IDC) or invasive lobular (ILC) carcinoma, DCIS, or combination of these entities
            • Multifocal BC: Multiple (≥ 2) separate foci of BC in same quadrant, separated by at least 0.5 cm and ≤ 4 cm, in same duct system
            • Multicentric BC: Multiple (≥ 2) separate foci of BC, usually in different quadrants, where greatest distance between 2 foci is variably > 4-5 cm
              • Usually in different duct systems
            • Diffuse BC: Foci scattered over > 4 cm without discrete tumor mass; DCIS involving large ducts
            • Breast conservation therapy (BCT): Breast-conserving surgery (BCS) followed by radiation therapy (XRT)

          IMAGING

          • General Features

            • Mammographic Findings

              • Ultrasonographic Findings

                • MR Findings

                  • Nuclear Medicine Findings

                    • Imaging Recommendations

                      • Image-Guided Biopsy

                        DIFFERENTIAL DIAGNOSIS

                          PATHOLOGY

                          • General Features

                            • Staging, Grading, & Classification

                              • Gross Pathologic & Surgical Features

                                • Microscopic Features

                                  CLINICAL ISSUES

                                  • Demographics

                                    • Natural History & Prognosis

                                      • Treatment

                                        DIAGNOSTIC CHECKLIST

                                        • Consider

                                          • Image Interpretation Pearls

                                            • Reporting Tips

                                              Selected References

                                              1. Navale P et al: Evaluation of biomarkers in multiple ipsilateral synchronous invasive breast carcinomas. Arch Pathol Lab Med. 143(2):190-6, 2019
                                              2. Helal MH et al: The impact of contrast-enhanced spectral mammogram (CESM) and three-dimensional breast ultrasound (3DUS) on the characterization of the disease extent in cancer patients. Br J Radiol. 91(1087):20170977, 2018
                                              3. Karakas Y et al: The effect of total size of lesions in multifocal/multicentric breast cancer on survival. Clin Breast Cancer. 18(4):320-327, 2018
                                              4. Lewin J: Comparison of contrast-enhanced mammography and contrast-enhanced breast MR imaging. Magn Reson Imaging Clin N Am. 26(2):259-263, 2018
                                              5. Nutter EL et al: Personal history of proliferative breast disease with atypia and risk of multifocal breast cancer. Cancer. 124(7):1350-1357, 2018
                                              6. Lang Z et al: Multifocal and multicentric breast carcinoma: a significantly more aggressive tumor than unifocal breast cancer. Anticancer Res. 37(8):4593-8, 2017
                                              7. Monticciolo DL: Practical Considerations for the use of breast MRI for breast cancer evaluation in the preoperative setting. Acad Radiol. 24(11):1447-1450, 2017
                                              8. Iacconi C et al: Multicentric cancer detected at breast MR imaging and not at mammography: Important or not? Radiology. 279(2):378-84, 2016
                                              9. Coates AS et al: -Tailoring therapies-improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol. 26(8):1533-46, 2015
                                              10. East EG et al: Utility of estrogen receptor, progesterone receptor, and HER-2/neu analysis of multiple foci in multifocal ipsilateral invasive breast carcinoma. Am J Clin Pathol. 144(6):952-9, 2015
                                              11. Kanumuri P et al: Characteristics of multifocal and multicentric breast cancers. Ann Surg Oncol. 22(8):2475-82, 2015
                                              12. Pekar G et al: Multifocal breast cancer documented in large-format histology sections: long-term follow-up results by molecular phenotypes. Cancer. 119(6):1132-9, 2013
                                              13. Wolters R et al: Comparing the outcome between multicentric and multifocal breast cancer: what is the impact on survival, and is there a role for guideline-adherent adjuvant therapy? A retrospective multicenter cohort study of 8,935 patients. Breast Cancer Res Treat. 142(3):579-90, 2013
                                              14. Pediconi F et al: Effect of preoperative breast magnetic resonance imaging on surgical decision making and cancer recurrence rates. Invest Radiol. 47(2):128-35, 2012
                                              15. Tot T: Axillary lymph node status in unifocal, multifocal, and diffuse breast carcinomas: differences are related to macrometastatic disease. Ann Surg Oncol. 19(11):3395-401, 2012
                                              16. Berg WA et al: Breast cancer: comparative effectiveness of positron emission mammography and MR imaging in presurgical planning for the ipsilateral breast. Radiology. 258(1):59-72, 2011
                                              17. Girardi V et al: Multifocal, multicentric and contralateral breast cancers: breast MR imaging in the preoperative evaluation of patients with newly diagnosed breast cancer. Radiol Med. 116(8):1226-38, 2011
                                              18. Morrow M et al: MRI for breast cancer screening, diagnosis, and treatment. Lancet. 378(9805):1804-11, 2011
                                              19. Peters NH et al: Preoperative MRI and surgical management in patients with nonpalpable breast cancer: the MONET - randomised controlled trial. Eur J Cancer. 47(6):879-86, 2011
                                              20. Tot T et al: Breast cancer multifocality, disease extent, and survival. Hum Pathol. 42(11):1761-9, 2011
                                              21. Brem RF et al: Detection of occult foci of breast cancer using breast-specific gamma imaging in women with one mammographic or clinically suspicious breast lesion. Acad Radiol. 17(6):735-43, 2010
                                              22. Turnbull L et al: Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial. Lancet. 375(9714):563-71, 2010
                                              23. Bleicher RJ et al: Association of routine pretreatment magnetic resonance imaging with time to surgery, mastectomy rate, and margin status. J Am Coll Surg. 2009 Aug;209(2):180-7; quiz 294-5. Epub 2009 Jun 18. Erratum in: J Am Coll Surg. 209(5):679, 2009
                                              24. Houssami N et al: Accuracy and surgical impact of magnetic resonance imaging in breast cancer staging: systematic review and meta-analysis in detection of multifocal and multicentric cancer. J Clin Oncol. 26(19):3248-58, 2008
                                              25. Gentilini O et al: Sentinel lymph node biopsy in multicentric breast cancer. The experience of the European Institute of Oncology. Eur J Surg Oncol. 32(5):507-10, 2006
                                              26. Andea AA et al: Correlation of tumor volume and surface area with lymph node status in patients with multifocal/multicentric breast carcinoma. Cancer. 100(1):20-7, 2004
                                              27. Berg WA et al: Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. Radiology. 233(3):830-49, 2004
                                              28. Fischer U et al: The influence of preoperative MRI of the breasts on recurrence rate in patients with breast cancer. Eur Radiol. 14(10):1725-31, 2004
                                              29. Sardanelli F et al: Sensitivity of MRI versus mammography for detecting foci of multifocal, multicentric breast cancer in Fatty and dense breasts using the whole-breast pathologic examination as a gold standard. AJR Am J Roentgenol. 183(4):1149-57, 2004
                                              30. Bedrosian I et al: Changes in the surgical management of patients with breast carcinoma based on preoperative magnetic resonance imaging. Cancer. 98(3):468-73, 2003
                                              31. Liberman L et al: MR imaging of the ipsilateral breast in women with percutaneously proven breast cancer. AJR Am J Roentgenol. 180(4):901-10, 2003
                                              32. Tousimis E et al: The accuracy of sentinel lymph node biopsy in multicentric and multifocal invasive breast cancers. J Am Coll Surg. 197(4):529-35, 2003
                                              33. Hlawatsch A et al: Preoperative assessment of breast cancer: sonography versus MR imaging. AJR Am J Roentgenol. 179(6):1493-501, 2002
                                              34. Moon WK et al: Multifocal, multicentric, and contralateral breast cancers: bilateral whole-breast US in the preoperative evaluation of patients. Radiology. 224(2):569-76, 2002
                                              35. Elling D et al: Intraductal component in invasive breast cancer: analysis of 250 resected surgical specimens. Breast. 10(5):405-10, 2001
                                              36. Fukutomi T et al: Multicentricity and histopathological background features of familial breast cancers stratified by menopausal status. Int J Clin Oncol. 6(2):80-3, 2001
                                              37. Berg WA et al: Multicentric and multifocal cancer: whole-breast US in preoperative evaluation. Radiology. 214(1):59-66, 2000
                                              38. Fischer U et al: Breast carcinoma: effect of preoperative contrast-enhanced MR imaging on the therapeutic approach. Radiology. 213(3):881-8, 1999
                                              39. Lagios MD et al: Ductal carcinoma in situ. The success of breast conservation therapy: a shared experience of two single institutional nonrandomized prospective studies. Surg Oncol Clin N Am. 6(2):385-92, 1997
                                              40. Hartsell WF et al: Should multicentric disease be an absolute contraindication to the use of breast-conserving therapy? Int J Radiat Oncol Biol Phys. 30(1):49-53, 1994
                                              41. Harms SE et al: MR imaging of the breast with rotating delivery of excitation off resonance: clinical experience with pathologic correlation. Radiology. 187(2):493-501, 1993
                                              42. Holland R et al: Histologic multifocality of Tis, T1-2 breast carcinomas. Implications for clinical trials of breast-conserving surgery. Cancer. 56(5):979-90, 1985
                                              43. Lesser ML et al: Multicentricity and bilaterality in invasive breast carcinoma. Surgery. 91(2):234-40, 1982
                                              Related Anatomy
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                                              Related Differential Diagnoses
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                                              References
                                              Tables

                                              Tables

                                              KEY FACTS

                                              • Terminology

                                                • Imaging

                                                  • Pathology

                                                    • Clinical Issues

                                                      TERMINOLOGY

                                                      • Definitions

                                                        • Breast cancer (BC): Invasive ductal (IDC) or invasive lobular (ILC) carcinoma, DCIS, or combination of these entities
                                                        • Multifocal BC: Multiple (≥ 2) separate foci of BC in same quadrant, separated by at least 0.5 cm and ≤ 4 cm, in same duct system
                                                        • Multicentric BC: Multiple (≥ 2) separate foci of BC, usually in different quadrants, where greatest distance between 2 foci is variably > 4-5 cm
                                                          • Usually in different duct systems
                                                        • Diffuse BC: Foci scattered over > 4 cm without discrete tumor mass; DCIS involving large ducts
                                                        • Breast conservation therapy (BCT): Breast-conserving surgery (BCS) followed by radiation therapy (XRT)

                                                      IMAGING

                                                      • General Features

                                                        • Mammographic Findings

                                                          • Ultrasonographic Findings

                                                            • MR Findings

                                                              • Nuclear Medicine Findings

                                                                • Imaging Recommendations

                                                                  • Image-Guided Biopsy

                                                                    DIFFERENTIAL DIAGNOSIS

                                                                      PATHOLOGY

                                                                      • General Features

                                                                        • Staging, Grading, & Classification

                                                                          • Gross Pathologic & Surgical Features

                                                                            • Microscopic Features

                                                                              CLINICAL ISSUES

                                                                              • Demographics

                                                                                • Natural History & Prognosis

                                                                                  • Treatment

                                                                                    DIAGNOSTIC CHECKLIST

                                                                                    • Consider

                                                                                      • Image Interpretation Pearls

                                                                                        • Reporting Tips

                                                                                          Selected References

                                                                                          1. Navale P et al: Evaluation of biomarkers in multiple ipsilateral synchronous invasive breast carcinomas. Arch Pathol Lab Med. 143(2):190-6, 2019
                                                                                          2. Helal MH et al: The impact of contrast-enhanced spectral mammogram (CESM) and three-dimensional breast ultrasound (3DUS) on the characterization of the disease extent in cancer patients. Br J Radiol. 91(1087):20170977, 2018
                                                                                          3. Karakas Y et al: The effect of total size of lesions in multifocal/multicentric breast cancer on survival. Clin Breast Cancer. 18(4):320-327, 2018
                                                                                          4. Lewin J: Comparison of contrast-enhanced mammography and contrast-enhanced breast MR imaging. Magn Reson Imaging Clin N Am. 26(2):259-263, 2018
                                                                                          5. Nutter EL et al: Personal history of proliferative breast disease with atypia and risk of multifocal breast cancer. Cancer. 124(7):1350-1357, 2018
                                                                                          6. Lang Z et al: Multifocal and multicentric breast carcinoma: a significantly more aggressive tumor than unifocal breast cancer. Anticancer Res. 37(8):4593-8, 2017
                                                                                          7. Monticciolo DL: Practical Considerations for the use of breast MRI for breast cancer evaluation in the preoperative setting. Acad Radiol. 24(11):1447-1450, 2017
                                                                                          8. Iacconi C et al: Multicentric cancer detected at breast MR imaging and not at mammography: Important or not? Radiology. 279(2):378-84, 2016
                                                                                          9. Coates AS et al: -Tailoring therapies-improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol. 26(8):1533-46, 2015
                                                                                          10. East EG et al: Utility of estrogen receptor, progesterone receptor, and HER-2/neu analysis of multiple foci in multifocal ipsilateral invasive breast carcinoma. Am J Clin Pathol. 144(6):952-9, 2015
                                                                                          11. Kanumuri P et al: Characteristics of multifocal and multicentric breast cancers. Ann Surg Oncol. 22(8):2475-82, 2015
                                                                                          12. Pekar G et al: Multifocal breast cancer documented in large-format histology sections: long-term follow-up results by molecular phenotypes. Cancer. 119(6):1132-9, 2013
                                                                                          13. Wolters R et al: Comparing the outcome between multicentric and multifocal breast cancer: what is the impact on survival, and is there a role for guideline-adherent adjuvant therapy? A retrospective multicenter cohort study of 8,935 patients. Breast Cancer Res Treat. 142(3):579-90, 2013
                                                                                          14. Pediconi F et al: Effect of preoperative breast magnetic resonance imaging on surgical decision making and cancer recurrence rates. Invest Radiol. 47(2):128-35, 2012
                                                                                          15. Tot T: Axillary lymph node status in unifocal, multifocal, and diffuse breast carcinomas: differences are related to macrometastatic disease. Ann Surg Oncol. 19(11):3395-401, 2012
                                                                                          16. Berg WA et al: Breast cancer: comparative effectiveness of positron emission mammography and MR imaging in presurgical planning for the ipsilateral breast. Radiology. 258(1):59-72, 2011
                                                                                          17. Girardi V et al: Multifocal, multicentric and contralateral breast cancers: breast MR imaging in the preoperative evaluation of patients with newly diagnosed breast cancer. Radiol Med. 116(8):1226-38, 2011
                                                                                          18. Morrow M et al: MRI for breast cancer screening, diagnosis, and treatment. Lancet. 378(9805):1804-11, 2011
                                                                                          19. Peters NH et al: Preoperative MRI and surgical management in patients with nonpalpable breast cancer: the MONET - randomised controlled trial. Eur J Cancer. 47(6):879-86, 2011
                                                                                          20. Tot T et al: Breast cancer multifocality, disease extent, and survival. Hum Pathol. 42(11):1761-9, 2011
                                                                                          21. Brem RF et al: Detection of occult foci of breast cancer using breast-specific gamma imaging in women with one mammographic or clinically suspicious breast lesion. Acad Radiol. 17(6):735-43, 2010
                                                                                          22. Turnbull L et al: Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial. Lancet. 375(9714):563-71, 2010
                                                                                          23. Bleicher RJ et al: Association of routine pretreatment magnetic resonance imaging with time to surgery, mastectomy rate, and margin status. J Am Coll Surg. 2009 Aug;209(2):180-7; quiz 294-5. Epub 2009 Jun 18. Erratum in: J Am Coll Surg. 209(5):679, 2009
                                                                                          24. Houssami N et al: Accuracy and surgical impact of magnetic resonance imaging in breast cancer staging: systematic review and meta-analysis in detection of multifocal and multicentric cancer. J Clin Oncol. 26(19):3248-58, 2008
                                                                                          25. Gentilini O et al: Sentinel lymph node biopsy in multicentric breast cancer. The experience of the European Institute of Oncology. Eur J Surg Oncol. 32(5):507-10, 2006
                                                                                          26. Andea AA et al: Correlation of tumor volume and surface area with lymph node status in patients with multifocal/multicentric breast carcinoma. Cancer. 100(1):20-7, 2004
                                                                                          27. Berg WA et al: Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. Radiology. 233(3):830-49, 2004
                                                                                          28. Fischer U et al: The influence of preoperative MRI of the breasts on recurrence rate in patients with breast cancer. Eur Radiol. 14(10):1725-31, 2004
                                                                                          29. Sardanelli F et al: Sensitivity of MRI versus mammography for detecting foci of multifocal, multicentric breast cancer in Fatty and dense breasts using the whole-breast pathologic examination as a gold standard. AJR Am J Roentgenol. 183(4):1149-57, 2004
                                                                                          30. Bedrosian I et al: Changes in the surgical management of patients with breast carcinoma based on preoperative magnetic resonance imaging. Cancer. 98(3):468-73, 2003
                                                                                          31. Liberman L et al: MR imaging of the ipsilateral breast in women with percutaneously proven breast cancer. AJR Am J Roentgenol. 180(4):901-10, 2003
                                                                                          32. Tousimis E et al: The accuracy of sentinel lymph node biopsy in multicentric and multifocal invasive breast cancers. J Am Coll Surg. 197(4):529-35, 2003
                                                                                          33. Hlawatsch A et al: Preoperative assessment of breast cancer: sonography versus MR imaging. AJR Am J Roentgenol. 179(6):1493-501, 2002
                                                                                          34. Moon WK et al: Multifocal, multicentric, and contralateral breast cancers: bilateral whole-breast US in the preoperative evaluation of patients. Radiology. 224(2):569-76, 2002
                                                                                          35. Elling D et al: Intraductal component in invasive breast cancer: analysis of 250 resected surgical specimens. Breast. 10(5):405-10, 2001
                                                                                          36. Fukutomi T et al: Multicentricity and histopathological background features of familial breast cancers stratified by menopausal status. Int J Clin Oncol. 6(2):80-3, 2001
                                                                                          37. Berg WA et al: Multicentric and multifocal cancer: whole-breast US in preoperative evaluation. Radiology. 214(1):59-66, 2000
                                                                                          38. Fischer U et al: Breast carcinoma: effect of preoperative contrast-enhanced MR imaging on the therapeutic approach. Radiology. 213(3):881-8, 1999
                                                                                          39. Lagios MD et al: Ductal carcinoma in situ. The success of breast conservation therapy: a shared experience of two single institutional nonrandomized prospective studies. Surg Oncol Clin N Am. 6(2):385-92, 1997
                                                                                          40. Hartsell WF et al: Should multicentric disease be an absolute contraindication to the use of breast-conserving therapy? Int J Radiat Oncol Biol Phys. 30(1):49-53, 1994
                                                                                          41. Harms SE et al: MR imaging of the breast with rotating delivery of excitation off resonance: clinical experience with pathologic correlation. Radiology. 187(2):493-501, 1993
                                                                                          42. Holland R et al: Histologic multifocality of Tis, T1-2 breast carcinomas. Implications for clinical trials of breast-conserving surgery. Cancer. 56(5):979-90, 1985
                                                                                          43. Lesser ML et al: Multicentricity and bilaterality in invasive breast carcinoma. Surgery. 91(2):234-40, 1982