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Breast
Histopathologic Diagnoses
Malignant Lesions
Triple-Negative and Basal-Like Breast Cancer
Triple-Negative and Basal-Like Breast Cancer
Kanchan Phalak, MD; Wei Tse Yang, MBBS
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KEY FACTS

  • Terminology

    • Imaging

      • Top Differential Diagnoses

        • Pathology

          • Clinical Issues

            TERMINOLOGY

            • Abbreviations

              • Triple-negative breast cancer (TNBC)
              • Basal-like breast cancer (BLBC)

            • Definitions

              • TNBC: Invasive carcinoma lacking expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)
                • Cytokeratin and EGFR(+) in 70-80% (those that are BLBC); (-) in 20-30% of TNBC
                  • Worse prognosis if CK and EGFR(+)
                • HER2 1+ on immunohistochemistry (IHC) is negative
                • HER2 2+ on IHC prompts FISH, copy number ≥ 4.0 and ratio of ≥ 2.0 copies relative to chromosome 17 centromere is positive for gene amplification as is copy number ≥ 6.0 even if ratio is < 2.0
                • HER2 3+ on IHC is positive
              • PAM50 = 50-gene assay of RNA using formalin-fixed tissue to determine intrinsic molecular tumor subtype
              • TNBC defined based on receptor expression and BLBC intrinsic subtype defined by genetic profiling
              • ~ 10-12% of TNBC are HER2(+) intrinsic subtype; 3% luminal A; and 4% luminal B by PAM50 analysis
              • ~ 70-77% of TNBC are BLBC
                • Generally lack expression of ER, PR, and HER2
                  • ~ 6% of ER(+) disease basal-like by PAM50 analysis
                • Strong expression of high-molecular-weight basal cytokeratins (e.g., CK5/6, CK14, and CK17) &/or EGFR
                • Medullary, metaplastic, secretory, adenoid cystic carcinoma are subtypes of BLBC, latter 2 with good prognosis
              • Claudin-low tumors: Poor prognosis ER/PR/HER2(-) IDC with high frequency of metaplastic and medullary differentiation

            IMAGING

            • General Features

              • Mammographic Findings

                • Ultrasonographic Findings

                  • Imaging Recommendations

                    • MR Findings

                      • Nuclear Medicine Findings

                        DIFFERENTIAL DIAGNOSIS

                          PATHOLOGY

                          • General Features

                            • Staging, Grading, & Classification

                              • Gross Pathologic & Surgical Features

                                • Microscopic Features

                                  CLINICAL ISSUES

                                  • Presentation

                                    • Demographics

                                      • Natural History & Prognosis

                                        • Treatment

                                          DIAGNOSTIC CHECKLIST

                                          • Consider

                                            • Image Interpretation Pearls

                                              Selected References

                                              1. Curigliano G: Addition of platinum salts to neoadjuvant chemotherapy in triple-negative breast cancer: a new standard of care? Lancet Oncol. 19(4):434-436, 2018
                                              2. Engel C et al: Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history. BMC Cancer. 18(1):265, 2018
                                              3. McAndrew N et al: Neoadjuvant chemotherapy considerations in triple-negative breast cancer. J Target Ther Cancer. 7(1):52-69, 2018
                                              4. Schmid P et al: Atezolizumab and Nab-Paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 379(22):2108-2121, 2018
                                              5. Tolba MF et al: Immunotherapy, an evolving approach for the management of triple negative breast cancer: Converting non-responders to responders. Crit Rev Oncol Hematol. 122:202-207, 2018
                                              6. Yoon GY et al: Sonographic features that can be used to differentiate between small triple-negative breast cancer and fibroadenoma. Ultrasonography. 37(2):149-156, 2018
                                              7. Yadav S et al: Impact of BRCA Mutation Status on Survival of Women With Triple-negative Breast Cancer. Clin Breast Cancer. ePub, 2017
                                              8. Zeng Z et al: Mammography and ultrasound effective features in differentiating basal-like and normal-like subtypes of triple negative breast cancer. Oncotarget. 8(45):79670-79679, 2017
                                              9. Doebar SC et al: Extent of ductal carcinoma in situ according to breast cancer subtypes: a population-based cohort study. Breast Cancer Res Treat. 158(1):179-87, 2016
                                              10. Plasilova ML et al: Features of triple-negative breast cancer: Analysis of 38,813 cases from the national cancer database. Medicine (Baltimore). 95(35):e4614, 2016
                                              11. Schmadeka R et al: Triple-negative breast carcinoma: current and emerging concepts. Am J Clin Pathol. 141(4):462-77, 2014
                                              12. Groheux D et al: Triple-negative breast cancer: early assessment with 18F-FDG PET/CT during neoadjuvant chemotherapy identifies patients who are unlikely to achieve a pathologic complete response and are at a high risk of early relapse. J Nucl Med. 53(2):249-54, 2012
                                              13. Iorfida M et al: Invasive lobular breast cancer: subtypes and outcome. Breast Cancer Res Treat. 133(2):713-23, 2012
                                              14. Groheux D et al: Correlation of high 18F-FDG uptake to clinical, pathological and biological prognostic factors in breast cancer. Eur J Nucl Med Mol Imaging. 38(3):426-35, 2011
                                              15. Koo JS et al: Clinicopathlogic and immunohistochemical characteristics of triple negative invasive lobular carcinoma. Yonsei Med J. 52(1):89-97, 2011
                                              16. Reis-Filho JS et al: Gene expression profiling in breast cancer: classification, prognostication, and prediction. Lancet. 378(9805):1812-23, 2011
                                              17. Whitman GJ et al: Triple-negative breast cancer: what the radiologist needs to know. Semin Roentgenol. 46(1):26-39, 2011
                                              18. Dogan BE et al: Multimodality imaging of triple receptor-negative tumors with mammography, ultrasound, and MRI. AJR Am J Roentgenol. 194(4):1160-6, 2010
                                              19. Hama Y et al: Early distant relapse in early stage triple-negative breast cancer: usefulness of FDG-PET for diagnosis of distant metastases. Breast Cancer. Epub ahead of print, 2010
                                              20. Ko ES et al: Triple-negative breast cancer: correlation between imaging and pathological findings. Eur Radiol. 20(5):1111-7, 2010
                                              21. Tchou J et al: Degree of tumor FDG uptake correlates with proliferation index in triple negative breast cancer. Mol Imaging Biol. 12(6):657-62, 2010
                                              22. Voduc KD et al: Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol. 28(10):1684-91, 2010
                                              23. Dent R et al: Pattern of metastatic spread in triple-negative breast cancer. Breast Cancer Res Treat. 115(2):423-8, 2009
                                              24. Foulkes WD et al: Tumor size is an unreliable predictor of prognosis in basal-like breast cancers and does not correlate closely with lymph node status. Breast Cancer Res Treat. 117(1):199-204, 2009
                                              25. Ma H et al: Is there a difference in the association between percent mammographic density and subtypes of breast cancer? Luminal A and triple-negative breast cancer. Cancer Epidemiol Biomarkers Prev. 18(2):479-85, 2009
                                              26. Moran MS et al: The Yale University experience of early-stage invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) treated with breast conservation treatment (BCT): analysis of clinical-pathologic features, long-term outcomes, and molecular expression of COX-2, Bcl-2, and p53 as a function of histology. Breast J. 15(6):571-8, 2009
                                              27. Uematsu T et al: Triple-negative breast cancer: correlation between MR imaging and pathologic findings. Radiology. 250(3):638-47, 2009
                                              28. Basu S et al: Comparison of triple-negative and estrogen receptor-positive/progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization. Cancer. 112(5):995-1000, 2008
                                              29. Liedtke C et al: Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 26(8):1275-81, 2008
                                              30. Smid M et al: Subtypes of breast cancer show preferential site of relapse. Cancer Res. 68(9):3108-14, 2008
                                              31. Yang WT et al: Mammographic features of triple receptor-negative primary breast cancers in young premenopausal women. Breast Cancer Res Treat. 111(3):405-10, 2008
                                              32. Chen JH et al: Magnetic resonance imaging in predicting pathological response of triple negative breast cancer following neoadjuvant chemotherapy. J Clin Oncol. 25(35):5667-9, 2007
                                              33. Chen JH et al: Triple-negative breast cancer: MRI features in 29 patients. Ann Oncol. 18(12):2042-3, 2007
                                              34. Dent R et al: Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 13(15 Pt 1):4429-34, 2007
                                              35. Carey LA et al: Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 295(21):2492-502, 2006
                                              36. Livasy CA et al: Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol. 19(2):264-71, 2006
                                              37. Brenton JD et al: Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol. 23(29):7350-60, 2005
                                              38. Collett K et al: A basal epithelial phenotype is more frequent in interval breast cancers compared with screen detected tumors. Cancer Epidemiol Biomarkers Prev. 14(5):1108-12, 2005
                                              39. Rouzier R et al: Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 11(16):5678-85, 2005
                                              40. Sørlie T: Molecular portraits of breast cancer: tumour subtypes as distinct disease entities. Eur J Cancer. 40(18):2667-75, 2004
                                              41. Perou CM et al: Molecular portraits of human breast tumours. Nature. 406(6797):747-52, 2000
                                              42. Sørlie T et al: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 98(19):10869-74, 2001
                                              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

                                                        • Abbreviations

                                                          • Triple-negative breast cancer (TNBC)
                                                          • Basal-like breast cancer (BLBC)

                                                        • Definitions

                                                          • TNBC: Invasive carcinoma lacking expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)
                                                            • Cytokeratin and EGFR(+) in 70-80% (those that are BLBC); (-) in 20-30% of TNBC
                                                              • Worse prognosis if CK and EGFR(+)
                                                            • HER2 1+ on immunohistochemistry (IHC) is negative
                                                            • HER2 2+ on IHC prompts FISH, copy number ≥ 4.0 and ratio of ≥ 2.0 copies relative to chromosome 17 centromere is positive for gene amplification as is copy number ≥ 6.0 even if ratio is < 2.0
                                                            • HER2 3+ on IHC is positive
                                                          • PAM50 = 50-gene assay of RNA using formalin-fixed tissue to determine intrinsic molecular tumor subtype
                                                          • TNBC defined based on receptor expression and BLBC intrinsic subtype defined by genetic profiling
                                                          • ~ 10-12% of TNBC are HER2(+) intrinsic subtype; 3% luminal A; and 4% luminal B by PAM50 analysis
                                                          • ~ 70-77% of TNBC are BLBC
                                                            • Generally lack expression of ER, PR, and HER2
                                                              • ~ 6% of ER(+) disease basal-like by PAM50 analysis
                                                            • Strong expression of high-molecular-weight basal cytokeratins (e.g., CK5/6, CK14, and CK17) &/or EGFR
                                                            • Medullary, metaplastic, secretory, adenoid cystic carcinoma are subtypes of BLBC, latter 2 with good prognosis
                                                          • Claudin-low tumors: Poor prognosis ER/PR/HER2(-) IDC with high frequency of metaplastic and medullary differentiation

                                                        IMAGING

                                                        • General Features

                                                          • Mammographic Findings

                                                            • Ultrasonographic Findings

                                                              • Imaging Recommendations

                                                                • MR Findings

                                                                  • Nuclear Medicine Findings

                                                                    DIFFERENTIAL DIAGNOSIS

                                                                      PATHOLOGY

                                                                      • General Features

                                                                        • Staging, Grading, & Classification

                                                                          • Gross Pathologic & Surgical Features

                                                                            • Microscopic Features

                                                                              CLINICAL ISSUES

                                                                              • Presentation

                                                                                • Demographics

                                                                                  • Natural History & Prognosis

                                                                                    • Treatment

                                                                                      DIAGNOSTIC CHECKLIST

                                                                                      • Consider

                                                                                        • Image Interpretation Pearls

                                                                                          Selected References

                                                                                          1. Curigliano G: Addition of platinum salts to neoadjuvant chemotherapy in triple-negative breast cancer: a new standard of care? Lancet Oncol. 19(4):434-436, 2018
                                                                                          2. Engel C et al: Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history. BMC Cancer. 18(1):265, 2018
                                                                                          3. McAndrew N et al: Neoadjuvant chemotherapy considerations in triple-negative breast cancer. J Target Ther Cancer. 7(1):52-69, 2018
                                                                                          4. Schmid P et al: Atezolizumab and Nab-Paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 379(22):2108-2121, 2018
                                                                                          5. Tolba MF et al: Immunotherapy, an evolving approach for the management of triple negative breast cancer: Converting non-responders to responders. Crit Rev Oncol Hematol. 122:202-207, 2018
                                                                                          6. Yoon GY et al: Sonographic features that can be used to differentiate between small triple-negative breast cancer and fibroadenoma. Ultrasonography. 37(2):149-156, 2018
                                                                                          7. Yadav S et al: Impact of BRCA Mutation Status on Survival of Women With Triple-negative Breast Cancer. Clin Breast Cancer. ePub, 2017
                                                                                          8. Zeng Z et al: Mammography and ultrasound effective features in differentiating basal-like and normal-like subtypes of triple negative breast cancer. Oncotarget. 8(45):79670-79679, 2017
                                                                                          9. Doebar SC et al: Extent of ductal carcinoma in situ according to breast cancer subtypes: a population-based cohort study. Breast Cancer Res Treat. 158(1):179-87, 2016
                                                                                          10. Plasilova ML et al: Features of triple-negative breast cancer: Analysis of 38,813 cases from the national cancer database. Medicine (Baltimore). 95(35):e4614, 2016
                                                                                          11. Schmadeka R et al: Triple-negative breast carcinoma: current and emerging concepts. Am J Clin Pathol. 141(4):462-77, 2014
                                                                                          12. Groheux D et al: Triple-negative breast cancer: early assessment with 18F-FDG PET/CT during neoadjuvant chemotherapy identifies patients who are unlikely to achieve a pathologic complete response and are at a high risk of early relapse. J Nucl Med. 53(2):249-54, 2012
                                                                                          13. Iorfida M et al: Invasive lobular breast cancer: subtypes and outcome. Breast Cancer Res Treat. 133(2):713-23, 2012
                                                                                          14. Groheux D et al: Correlation of high 18F-FDG uptake to clinical, pathological and biological prognostic factors in breast cancer. Eur J Nucl Med Mol Imaging. 38(3):426-35, 2011
                                                                                          15. Koo JS et al: Clinicopathlogic and immunohistochemical characteristics of triple negative invasive lobular carcinoma. Yonsei Med J. 52(1):89-97, 2011
                                                                                          16. Reis-Filho JS et al: Gene expression profiling in breast cancer: classification, prognostication, and prediction. Lancet. 378(9805):1812-23, 2011
                                                                                          17. Whitman GJ et al: Triple-negative breast cancer: what the radiologist needs to know. Semin Roentgenol. 46(1):26-39, 2011
                                                                                          18. Dogan BE et al: Multimodality imaging of triple receptor-negative tumors with mammography, ultrasound, and MRI. AJR Am J Roentgenol. 194(4):1160-6, 2010
                                                                                          19. Hama Y et al: Early distant relapse in early stage triple-negative breast cancer: usefulness of FDG-PET for diagnosis of distant metastases. Breast Cancer. Epub ahead of print, 2010
                                                                                          20. Ko ES et al: Triple-negative breast cancer: correlation between imaging and pathological findings. Eur Radiol. 20(5):1111-7, 2010
                                                                                          21. Tchou J et al: Degree of tumor FDG uptake correlates with proliferation index in triple negative breast cancer. Mol Imaging Biol. 12(6):657-62, 2010
                                                                                          22. Voduc KD et al: Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol. 28(10):1684-91, 2010
                                                                                          23. Dent R et al: Pattern of metastatic spread in triple-negative breast cancer. Breast Cancer Res Treat. 115(2):423-8, 2009
                                                                                          24. Foulkes WD et al: Tumor size is an unreliable predictor of prognosis in basal-like breast cancers and does not correlate closely with lymph node status. Breast Cancer Res Treat. 117(1):199-204, 2009
                                                                                          25. Ma H et al: Is there a difference in the association between percent mammographic density and subtypes of breast cancer? Luminal A and triple-negative breast cancer. Cancer Epidemiol Biomarkers Prev. 18(2):479-85, 2009
                                                                                          26. Moran MS et al: The Yale University experience of early-stage invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) treated with breast conservation treatment (BCT): analysis of clinical-pathologic features, long-term outcomes, and molecular expression of COX-2, Bcl-2, and p53 as a function of histology. Breast J. 15(6):571-8, 2009
                                                                                          27. Uematsu T et al: Triple-negative breast cancer: correlation between MR imaging and pathologic findings. Radiology. 250(3):638-47, 2009
                                                                                          28. Basu S et al: Comparison of triple-negative and estrogen receptor-positive/progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization. Cancer. 112(5):995-1000, 2008
                                                                                          29. Liedtke C et al: Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 26(8):1275-81, 2008
                                                                                          30. Smid M et al: Subtypes of breast cancer show preferential site of relapse. Cancer Res. 68(9):3108-14, 2008
                                                                                          31. Yang WT et al: Mammographic features of triple receptor-negative primary breast cancers in young premenopausal women. Breast Cancer Res Treat. 111(3):405-10, 2008
                                                                                          32. Chen JH et al: Magnetic resonance imaging in predicting pathological response of triple negative breast cancer following neoadjuvant chemotherapy. J Clin Oncol. 25(35):5667-9, 2007
                                                                                          33. Chen JH et al: Triple-negative breast cancer: MRI features in 29 patients. Ann Oncol. 18(12):2042-3, 2007
                                                                                          34. Dent R et al: Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 13(15 Pt 1):4429-34, 2007
                                                                                          35. Carey LA et al: Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 295(21):2492-502, 2006
                                                                                          36. Livasy CA et al: Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol. 19(2):264-71, 2006
                                                                                          37. Brenton JD et al: Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol. 23(29):7350-60, 2005
                                                                                          38. Collett K et al: A basal epithelial phenotype is more frequent in interval breast cancers compared with screen detected tumors. Cancer Epidemiol Biomarkers Prev. 14(5):1108-12, 2005
                                                                                          39. Rouzier R et al: Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 11(16):5678-85, 2005
                                                                                          40. Sørlie T: Molecular portraits of breast cancer: tumour subtypes as distinct disease entities. Eur J Cancer. 40(18):2667-75, 2004
                                                                                          41. Perou CM et al: Molecular portraits of human breast tumours. Nature. 406(6797):747-52, 2000
                                                                                          42. Sørlie T et al: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 98(19):10869-74, 2001