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HER2-Positive Cancer
Kanchan Phalak, MD; Wei Tse Yang, MBBS
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KEY FACTS

  • Terminology

    • Imaging

      • Top Differential Diagnoses

        • Pathology

          • Clinical Issues

            TERMINOLOGY

            • Synonyms

              • HER-2/neu, EGFR2, NGL, TKR1, c-erb, CD340
            • Definitions

              • Human epidermal growth factor receptor 2-positive [HER2(+)] breast cancer (BC)
              • ERBB2 gene encodes HER2 protein
              • HER2(+) = 3+ by immunohistochemistry (IHC)
              • HER2 2+ by IHC prompts reflex in situ hybridization (ISH) to evaluate for gene amplification: ERBB2 gene copy number and ratio of ERBB2/CEP17 centromere signals
                • Copy number ≥ 4 and ratio ≥ 2.0 is HER2(+)
                • Copy number < 4 and ratio ≥ 2.0 is HER2(-)
                • Other combinations require 2nd observer, work-up; if consistent, then
                  • Copy number ≥ 6 and ratio < 2.0 is HER2(+)
                  • Copy number ≥ 4 and < 6 and ratio < 2.0 is HER2(-)
              • HER2(-) = 1+ or 0 by IHC
              • HER2(+) BC
                • Usually invasive ductal NOS or pleomorphic invasive lobular carcinoma
                • Classic HER2(+): ER/PR(-), HER2(+)
                • Luminal B HER2(+): ER(+), usually weakly PR(+); HER2(+); usually high Ki-67 proliferation index
              • HER2 testing performed on initial CNB, may be repeated on excision if (-) and tumor is grade 3, initial specimen had only small amount of invasive cancer, resection invasive cancer morphologically different from core, core biopsy equivocal on both IHC and ISH, or suspected mishandling of tissue or testing
              • HER2 testing should also be repeated if (+) and tumor is grade 1, ER/PR(+) IDC or ILC, tubular type, mucinous, cribriform, or adenoid cystic carcinoma as these should be HER2(-)

            IMAGING

            • Mammographic Findings

              • Ultrasonographic Findings

                • MR Findings

                  • Nuclear Medicine Findings

                    • Imaging Recommendations

                      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. Denduluri N et al: Selection of optimal adjuvant chemotherapy and targeted therapy for early breast cancer: ASCO Clinical Practice Guideline Focused Update. J Clin Oncol. 36(23):2433-2443, 2018
                                            2. Di Cosimo S et al: The use of breast imaging for predicting response to neoadjuvant lapatinib, trastuzumab and their combination in HER2-positive breast cancer: results from Neo-ALTTO. Eur J Cancer. 89:42-48, 2018
                                            3. Henry KE et al: Clinical potential of human epidermal growth factor receptor 2 and human epidermal growth factor receptor 3 imaging in breast cancer. PET Clin. 13(3):423-435, 2018
                                            4. Mazari FAK et al: Human Epidermal Growth Factor 2-positive Breast Cancer with Mammographic Microcalcification: Relationship to Pathologic Complete Response after Neoadjuvant Chemotherapy. Radiology. 170960, 2018
                                            5. Nie Z et al: Microcalcification-associated breast cancer: HER2-enriched molecular subtype is associated with mammographic features. Br J Radiol. 20170942, 2018
                                            6. O'Brien KM et al: Screening status, tumour subtype, and breast cancer survival: a national population-based analysis. Breast Cancer Res Treat. ePub, 2018
                                            7. Partridge SC et al: Diffusion-weighted MRI Findings Predict Pathologic Response in Neoadjuvant Treatment of Breast Cancer: The ACRIN 6698 Multicenter Trial. Radiology. 180273, 2018
                                            8. Plevritis SK et al: Association of Screening and Treatment With Breast Cancer Mortality by Molecular Subtype in US Women, 2000-2012. JAMA. 319(2):154-164, 2018
                                            9. Scheel JR et al: MRI, Clinical Examination, and Mammography for Preoperative Assessment of Residual Disease and Pathologic Complete Response After Neoadjuvant Chemotherapy for Breast Cancer: ACRIN 6657 Trial. AJR Am J Roentgenol. 210(6):1376-1385, 2018
                                            10. Wibmer AG et al: Trends in oncologic hybrid imaging. Eur J Hybrid Imaging. 2(1):1, 2018
                                            11. Wolff AC et al: Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. Arch Pathol Lab Med. ePub, 2018
                                            12. Chu AJ et al: Imaging Surveillance for Survivors of Breast Cancer: Correlation between Cancer Characteristics and Method of Detection. J Breast Cancer. 20(2):192-197, 2017
                                            13. Costarelli L et al: Pleomorphic lobular carcinoma: is it more similar to a classic lobular cancer or to a high-grade ductal cancer? Breast Cancer (Dove Med Press). 9:581-586, 2017
                                            14. Lee SH et al: Imaging features of breast cancers on digital breast tomosynthesis according to molecular subtype: association with breast cancer detection. Br J Radiol. 90(1080):20170470, 2017
                                            15. Lower EE et al: Discordance of the estrogen receptor and HER-2/neu in breast cancer from primary lesion to first and second metastatic site. Breast Cancer (Dove Med Press). 9:515-520, 2017
                                            16. Martin M et al: Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 18(12):1688-1700, 2017
                                            17. McGuire A et al: Differential impact of hormone receptor status on survival and recurrence for HER2 receptor-positive breast cancers treated with Trastuzumab. Breast Cancer Res Treat. 164(1):221-229, 2017
                                            18. Perez EA et al: Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2-Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study. J Clin Oncol. 35(2):141-148, 2017
                                            19. Solinas C et al: Tumor-infiltrating lymphocytes in patients with HER2-positive breast cancer treated with neoadjuvant chemotherapy plus trastuzumab, lapatinib or their combination: A meta-analysis of randomized controlled trials. Cancer Treat Rev. 57:8-15, 2017
                                            20. Ulaner GA et al: 89Zr-Trastuzumab PET/CT for Detection of Human Epidermal Growth Factor Receptor 2-Positive Metastases in Patients With Human Epidermal Growth Factor Receptor 2-Negative Primary Breast Cancer. Clin Nucl Med. 42(12):912-917, 2017
                                            21. von Minckwitz G et al: Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med. 377(2):122-131, 2017
                                            22. Bouzón A et al: Diagnostic accuracy of MRI to evaluate tumour response and residual tumour size after neoadjuvant chemotherapy in breast cancer patients. Radiol Oncol. 50(1):73-9, 2016
                                            23. Cho N: Molecular subtypes and imaging phenotypes of breast cancer. Ultrasonography. 35(4):281-8, 2016
                                            24. 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
                                            25. Hou Y et al: Correlation of Expression of Breast Biomarkers in Primary and Metastatic Breast Carcinomas: A Single-Institution Experience. Acta Cytol. 60(5):481-489, 2016
                                            26. Hylton NM et al: Neoadjuvant Chemotherapy for Breast Cancer: Functional Tumor Volume by MR Imaging Predicts Recurrence-free Survival-Results from the ACRIN 6657/CALGB 150007 I-SPY 1 TRIAL. Radiology. 279(1):44-55, 2016
                                            27. Rostami R et al: Brain metastasis in breast cancer: a comprehensive literature review. J Neurooncol. 127(3):407-14, 2016
                                            28. Vasconcelos I et al: The St. Gallen surrogate classification for breast cancer subtypes successfully predicts tumor presenting features, nodal involvement, recurrence patterns and disease free survival. Breast. 29:181-5, 2016
                                            29. Grimm LJ et al: Can breast cancer molecular subtype help to select patients for preoperative MR imaging? Radiology. 274(2):352-8, 2015
                                            30. Holm-Rasmussen EV et al: Reduced risk of axillary lymphatic spread in triple-negative breast cancer. Breast Cancer Res Treat. 149(1):229-36, 2015
                                            31. Kim MY et al: Screening mammography-detected ductal carcinoma in situ: mammographic features based on breast cancer subtypes. Clin Imaging. 39(6):983-6, 2015
                                            32. Lien HC et al: Frequent alterations of HER2 through mutation, amplification, or overexpression in pleomorphic lobular carcinoma of the breast. Breast Cancer Res Treat. 150(2):447-55, 2015
                                            33. Rossi S et al: Hormone Receptor Status and HER2 Expression in Primary Breast Cancer Compared With Synchronous Axillary Metastases or Recurrent Metastatic Disease. Clin Breast Cancer. 15(5):307-12, 2015
                                            34. Salgado R et al: Tumor-Infiltrating Lymphocytes and Associations With Pathological Complete Response and Event-Free Survival in HER2-Positive Early-Stage Breast Cancer Treated With Lapatinib and Trastuzumab: A Secondary Analysis of the NeoALTTO Trial. JAMA Oncol. 1(4):448-54, 2015
                                            35. Elias SG et al: Imaging features of HER2 overexpression in breast cancer: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 23(8):1464-83, 2014
                                            36. Loibl S et al: PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer. J Clin Oncol. 32(29):3212-20, 2014
                                            37. Perez EA et al: Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 32(33):3744-52, 2014
                                            38. Sineshaw HM et al: Association of race/ethnicity, socioeconomic status, and breast cancer subtypes in the National Cancer Data Base (2010-2011). Breast Cancer Res Treat. 145(3):753-63, 2014
                                            39. Fusco N et al: HER2 in gastric cancer: a digital image analysis in pre-neoplastic, primary and metastatic lesions. Mod Pathol. 26(6):816-24, 2013
                                            40. Mukhtar RA et al: Clinically meaningful tumor reduction rates vary by prechemotherapy MRI phenotype and tumor subtype in the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657). Ann Surg Oncol. 20(12):3823-30, 2013
                                            41. Narita T et al: Status of Tissue Expression and Serum Levels of HER2 in Gastric Cancer Patients in Japan. Hepatogastroenterology. 60(125), 2013
                                            42. Wolff AC et al: Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 31(31):3997-4013, 2013
                                            43. Zurawska U et al: Outcomes of her2-positive early-stage breast cancer in the trastuzumab era: a population-based study of Canadian patients. Curr Oncol. 20(6):e539-45, 2013
                                            44. Martincich L et al: Correlations between diffusion-weighted imaging and breast cancer biomarkers. Eur Radiol. 22(7):1519-28, 2012
                                            45. Niikura N et al: Loss of human epidermal growth factor receptor 2 (HER2) expression in metastatic sites of HER2-overexpressing primary breast tumors. J Clin Oncol. 30(6):593-9, 2012
                                            46. 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
                                            47. McGuire KP et al: MRI staging after neoadjuvant chemotherapy for breast cancer: does tumor biology affect accuracy? Ann Surg Oncol. 18(11):3149-54, 2011
                                            48. Reis-Filho JS et al: Gene expression profiling in breast cancer: classification, prognostication, and prediction. Lancet. 378(9805):1812-23, 2011
                                            49. Telli ML et al: Asian ethnicity and breast cancer subtypes: a study from the California Cancer Registry. Breast Cancer Res Treat. Epub ahead of print, 2010
                                            50. Wang CL et al: Positron emission mammography: correlation of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status and 18F-FDG. AJR Am J Roentgenol. 197(2):W247-55, 2011
                                            51. 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
                                            52. Voduc KD et al: Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol. 28(10):1684-91, 2010
                                            53. Lower EE et al: HER-2/neu expression in primary and metastatic breast cancer. Breast Cancer Res Treat. 113(2):301-6, 2009
                                            54. Uematsu T et al: Triple-negative breast cancer: correlation between MR imaging and pathologic findings. Radiology. 250(3):638-47, 2009
                                            55. 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
                                            56. Smid M et al: Subtypes of breast cancer show preferential site of relapse. Cancer Res. 68(9):3108-14, 2008
                                            57. Wang Y et al: Estrogen receptor-negative invasive breast cancer: imaging features of tumors with and without human epidermal growth factor receptor type 2 overexpression. Radiology. 246(2):367-75, 2008
                                            58. 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
                                            59. 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
                                            60. Chen JH et al: Triple-negative breast cancer: MRI features in 29 patients. Ann Oncol. 18(12):2042-3, 2007
                                            61. Carey LA et al: Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 295(21):2492-502, 2006
                                            62. Perez EA et al: HER2 testing by local, central, and reference laboratories in specimens from the North Central Cancer Treatment Group N9831 intergroup adjuvant trial. J Clin Oncol. 24(19):3032-8, 2006
                                            63. Brenton JD et al: Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol. 23(29):7350-60, 2005
                                            64. Rouzier R et al: Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 11(16):5678-85, 2005
                                            65. Sørlie T: Molecular portraits of breast cancer: tumour subtypes as distinct disease entities. Eur J Cancer. 40(18):2667-75, 2004
                                            66. Gajdos C et al: Mammographic appearance of nonpalpable breast cancer reflects pathologic characteristics. Ann Surg. 235(2):246-51, 2002
                                            67. 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
                                            68. Perou CM et al: Molecular portraits of human breast tumours. Nature. 406(6797):747-52, 2000
                                            69. Slamon DJ et al: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 235(4785):177-82, 1987
                                            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

                                                      • Synonyms

                                                        • HER-2/neu, EGFR2, NGL, TKR1, c-erb, CD340
                                                      • Definitions

                                                        • Human epidermal growth factor receptor 2-positive [HER2(+)] breast cancer (BC)
                                                        • ERBB2 gene encodes HER2 protein
                                                        • HER2(+) = 3+ by immunohistochemistry (IHC)
                                                        • HER2 2+ by IHC prompts reflex in situ hybridization (ISH) to evaluate for gene amplification: ERBB2 gene copy number and ratio of ERBB2/CEP17 centromere signals
                                                          • Copy number ≥ 4 and ratio ≥ 2.0 is HER2(+)
                                                          • Copy number < 4 and ratio ≥ 2.0 is HER2(-)
                                                          • Other combinations require 2nd observer, work-up; if consistent, then
                                                            • Copy number ≥ 6 and ratio < 2.0 is HER2(+)
                                                            • Copy number ≥ 4 and < 6 and ratio < 2.0 is HER2(-)
                                                        • HER2(-) = 1+ or 0 by IHC
                                                        • HER2(+) BC
                                                          • Usually invasive ductal NOS or pleomorphic invasive lobular carcinoma
                                                          • Classic HER2(+): ER/PR(-), HER2(+)
                                                          • Luminal B HER2(+): ER(+), usually weakly PR(+); HER2(+); usually high Ki-67 proliferation index
                                                        • HER2 testing performed on initial CNB, may be repeated on excision if (-) and tumor is grade 3, initial specimen had only small amount of invasive cancer, resection invasive cancer morphologically different from core, core biopsy equivocal on both IHC and ISH, or suspected mishandling of tissue or testing
                                                        • HER2 testing should also be repeated if (+) and tumor is grade 1, ER/PR(+) IDC or ILC, tubular type, mucinous, cribriform, or adenoid cystic carcinoma as these should be HER2(-)

                                                      IMAGING

                                                      • Mammographic Findings

                                                        • Ultrasonographic Findings

                                                          • MR Findings

                                                            • Nuclear Medicine Findings

                                                              • Imaging Recommendations

                                                                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. Denduluri N et al: Selection of optimal adjuvant chemotherapy and targeted therapy for early breast cancer: ASCO Clinical Practice Guideline Focused Update. J Clin Oncol. 36(23):2433-2443, 2018
                                                                                      2. Di Cosimo S et al: The use of breast imaging for predicting response to neoadjuvant lapatinib, trastuzumab and their combination in HER2-positive breast cancer: results from Neo-ALTTO. Eur J Cancer. 89:42-48, 2018
                                                                                      3. Henry KE et al: Clinical potential of human epidermal growth factor receptor 2 and human epidermal growth factor receptor 3 imaging in breast cancer. PET Clin. 13(3):423-435, 2018
                                                                                      4. Mazari FAK et al: Human Epidermal Growth Factor 2-positive Breast Cancer with Mammographic Microcalcification: Relationship to Pathologic Complete Response after Neoadjuvant Chemotherapy. Radiology. 170960, 2018
                                                                                      5. Nie Z et al: Microcalcification-associated breast cancer: HER2-enriched molecular subtype is associated with mammographic features. Br J Radiol. 20170942, 2018
                                                                                      6. O'Brien KM et al: Screening status, tumour subtype, and breast cancer survival: a national population-based analysis. Breast Cancer Res Treat. ePub, 2018
                                                                                      7. Partridge SC et al: Diffusion-weighted MRI Findings Predict Pathologic Response in Neoadjuvant Treatment of Breast Cancer: The ACRIN 6698 Multicenter Trial. Radiology. 180273, 2018
                                                                                      8. Plevritis SK et al: Association of Screening and Treatment With Breast Cancer Mortality by Molecular Subtype in US Women, 2000-2012. JAMA. 319(2):154-164, 2018
                                                                                      9. Scheel JR et al: MRI, Clinical Examination, and Mammography for Preoperative Assessment of Residual Disease and Pathologic Complete Response After Neoadjuvant Chemotherapy for Breast Cancer: ACRIN 6657 Trial. AJR Am J Roentgenol. 210(6):1376-1385, 2018
                                                                                      10. Wibmer AG et al: Trends in oncologic hybrid imaging. Eur J Hybrid Imaging. 2(1):1, 2018
                                                                                      11. Wolff AC et al: Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. Arch Pathol Lab Med. ePub, 2018
                                                                                      12. Chu AJ et al: Imaging Surveillance for Survivors of Breast Cancer: Correlation between Cancer Characteristics and Method of Detection. J Breast Cancer. 20(2):192-197, 2017
                                                                                      13. Costarelli L et al: Pleomorphic lobular carcinoma: is it more similar to a classic lobular cancer or to a high-grade ductal cancer? Breast Cancer (Dove Med Press). 9:581-586, 2017
                                                                                      14. Lee SH et al: Imaging features of breast cancers on digital breast tomosynthesis according to molecular subtype: association with breast cancer detection. Br J Radiol. 90(1080):20170470, 2017
                                                                                      15. Lower EE et al: Discordance of the estrogen receptor and HER-2/neu in breast cancer from primary lesion to first and second metastatic site. Breast Cancer (Dove Med Press). 9:515-520, 2017
                                                                                      16. Martin M et al: Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 18(12):1688-1700, 2017
                                                                                      17. McGuire A et al: Differential impact of hormone receptor status on survival and recurrence for HER2 receptor-positive breast cancers treated with Trastuzumab. Breast Cancer Res Treat. 164(1):221-229, 2017
                                                                                      18. Perez EA et al: Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2-Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study. J Clin Oncol. 35(2):141-148, 2017
                                                                                      19. Solinas C et al: Tumor-infiltrating lymphocytes in patients with HER2-positive breast cancer treated with neoadjuvant chemotherapy plus trastuzumab, lapatinib or their combination: A meta-analysis of randomized controlled trials. Cancer Treat Rev. 57:8-15, 2017
                                                                                      20. Ulaner GA et al: 89Zr-Trastuzumab PET/CT for Detection of Human Epidermal Growth Factor Receptor 2-Positive Metastases in Patients With Human Epidermal Growth Factor Receptor 2-Negative Primary Breast Cancer. Clin Nucl Med. 42(12):912-917, 2017
                                                                                      21. von Minckwitz G et al: Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med. 377(2):122-131, 2017
                                                                                      22. Bouzón A et al: Diagnostic accuracy of MRI to evaluate tumour response and residual tumour size after neoadjuvant chemotherapy in breast cancer patients. Radiol Oncol. 50(1):73-9, 2016
                                                                                      23. Cho N: Molecular subtypes and imaging phenotypes of breast cancer. Ultrasonography. 35(4):281-8, 2016
                                                                                      24. 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
                                                                                      25. Hou Y et al: Correlation of Expression of Breast Biomarkers in Primary and Metastatic Breast Carcinomas: A Single-Institution Experience. Acta Cytol. 60(5):481-489, 2016
                                                                                      26. Hylton NM et al: Neoadjuvant Chemotherapy for Breast Cancer: Functional Tumor Volume by MR Imaging Predicts Recurrence-free Survival-Results from the ACRIN 6657/CALGB 150007 I-SPY 1 TRIAL. Radiology. 279(1):44-55, 2016
                                                                                      27. Rostami R et al: Brain metastasis in breast cancer: a comprehensive literature review. J Neurooncol. 127(3):407-14, 2016
                                                                                      28. Vasconcelos I et al: The St. Gallen surrogate classification for breast cancer subtypes successfully predicts tumor presenting features, nodal involvement, recurrence patterns and disease free survival. Breast. 29:181-5, 2016
                                                                                      29. Grimm LJ et al: Can breast cancer molecular subtype help to select patients for preoperative MR imaging? Radiology. 274(2):352-8, 2015
                                                                                      30. Holm-Rasmussen EV et al: Reduced risk of axillary lymphatic spread in triple-negative breast cancer. Breast Cancer Res Treat. 149(1):229-36, 2015
                                                                                      31. Kim MY et al: Screening mammography-detected ductal carcinoma in situ: mammographic features based on breast cancer subtypes. Clin Imaging. 39(6):983-6, 2015
                                                                                      32. Lien HC et al: Frequent alterations of HER2 through mutation, amplification, or overexpression in pleomorphic lobular carcinoma of the breast. Breast Cancer Res Treat. 150(2):447-55, 2015
                                                                                      33. Rossi S et al: Hormone Receptor Status and HER2 Expression in Primary Breast Cancer Compared With Synchronous Axillary Metastases or Recurrent Metastatic Disease. Clin Breast Cancer. 15(5):307-12, 2015
                                                                                      34. Salgado R et al: Tumor-Infiltrating Lymphocytes and Associations With Pathological Complete Response and Event-Free Survival in HER2-Positive Early-Stage Breast Cancer Treated With Lapatinib and Trastuzumab: A Secondary Analysis of the NeoALTTO Trial. JAMA Oncol. 1(4):448-54, 2015
                                                                                      35. Elias SG et al: Imaging features of HER2 overexpression in breast cancer: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 23(8):1464-83, 2014
                                                                                      36. Loibl S et al: PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer. J Clin Oncol. 32(29):3212-20, 2014
                                                                                      37. Perez EA et al: Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 32(33):3744-52, 2014
                                                                                      38. Sineshaw HM et al: Association of race/ethnicity, socioeconomic status, and breast cancer subtypes in the National Cancer Data Base (2010-2011). Breast Cancer Res Treat. 145(3):753-63, 2014
                                                                                      39. Fusco N et al: HER2 in gastric cancer: a digital image analysis in pre-neoplastic, primary and metastatic lesions. Mod Pathol. 26(6):816-24, 2013
                                                                                      40. Mukhtar RA et al: Clinically meaningful tumor reduction rates vary by prechemotherapy MRI phenotype and tumor subtype in the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657). Ann Surg Oncol. 20(12):3823-30, 2013
                                                                                      41. Narita T et al: Status of Tissue Expression and Serum Levels of HER2 in Gastric Cancer Patients in Japan. Hepatogastroenterology. 60(125), 2013
                                                                                      42. Wolff AC et al: Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 31(31):3997-4013, 2013
                                                                                      43. Zurawska U et al: Outcomes of her2-positive early-stage breast cancer in the trastuzumab era: a population-based study of Canadian patients. Curr Oncol. 20(6):e539-45, 2013
                                                                                      44. Martincich L et al: Correlations between diffusion-weighted imaging and breast cancer biomarkers. Eur Radiol. 22(7):1519-28, 2012
                                                                                      45. Niikura N et al: Loss of human epidermal growth factor receptor 2 (HER2) expression in metastatic sites of HER2-overexpressing primary breast tumors. J Clin Oncol. 30(6):593-9, 2012
                                                                                      46. 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
                                                                                      47. McGuire KP et al: MRI staging after neoadjuvant chemotherapy for breast cancer: does tumor biology affect accuracy? Ann Surg Oncol. 18(11):3149-54, 2011
                                                                                      48. Reis-Filho JS et al: Gene expression profiling in breast cancer: classification, prognostication, and prediction. Lancet. 378(9805):1812-23, 2011
                                                                                      49. Telli ML et al: Asian ethnicity and breast cancer subtypes: a study from the California Cancer Registry. Breast Cancer Res Treat. Epub ahead of print, 2010
                                                                                      50. Wang CL et al: Positron emission mammography: correlation of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status and 18F-FDG. AJR Am J Roentgenol. 197(2):W247-55, 2011
                                                                                      51. 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
                                                                                      52. Voduc KD et al: Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol. 28(10):1684-91, 2010
                                                                                      53. Lower EE et al: HER-2/neu expression in primary and metastatic breast cancer. Breast Cancer Res Treat. 113(2):301-6, 2009
                                                                                      54. Uematsu T et al: Triple-negative breast cancer: correlation between MR imaging and pathologic findings. Radiology. 250(3):638-47, 2009
                                                                                      55. 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
                                                                                      56. Smid M et al: Subtypes of breast cancer show preferential site of relapse. Cancer Res. 68(9):3108-14, 2008
                                                                                      57. Wang Y et al: Estrogen receptor-negative invasive breast cancer: imaging features of tumors with and without human epidermal growth factor receptor type 2 overexpression. Radiology. 246(2):367-75, 2008
                                                                                      58. 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
                                                                                      59. 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
                                                                                      60. Chen JH et al: Triple-negative breast cancer: MRI features in 29 patients. Ann Oncol. 18(12):2042-3, 2007
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