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Published in: Annals of Surgical Oncology 4/2017

01-04-2017 | Breast Oncology

Anti-HER2 CD4+ T-Helper Type 1 Immune Response is Superior to Breast MRI for Assessing Response to Neoadjuvant Therapy in Patients with HER2-Positive Breast Cancer

Authors: Lucy M. De La Cruz, MD, Elizabeth S. McDonald, MD, PhD, R. Mick, MS, Jashodeep Datta, MD, Nadia F. Nocera, MD, Shuwen Xu, MD, Carla S. Fisher, MD, Brian J. Czerniecki, MD, PhD

Published in: Annals of Surgical Oncology | Issue 4/2017

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Abstract

Background

In human epidermal growth factor 2-positive breast cancer (HER2+BC), neoadjuvant chemotherapy and anti-HER2-targeted therapy (nCT) achieves a complete pathologic response (pCR) in 40–67% of patients. Posttreatment magnetic resonance imaging (pMRI) is considered the gold standard, with high specificity but lower sensitivity for assessing response. The authors previously determined that anti-HER2Th1 immune response is associated with pathologic response after nCT in HER2+BC patients. This study contrasted pMRI with anti-HER2Th1 response for assessing pCR in HER2+BC.

Methods

A retrospective review of HER2+BC patients at the authors’ institution was performed. Original pMRI reports were collected, and images were reviewed by a breast radiologist blinded to pCR and immune response. The post-nCT imaging-based tumor response was assessed by Response Evaluation Criteria in Solid Tumors. The anti-HER2Th1 response was determined by ex vivo stimulation of peripheral blood mononuclear cells with six major histocompatibility complex (MHC) class 2-derived HER2 peptides via enzyme-linked immunospot (ELISPOT). Posttreatment MRI and anti-HER2Th1 responses were cross-tabulated with pCR. Standard diagnostic metrics were computed.

Results

For 30 patients, pMRI and anti-HER2Th1 immune response were measured, with 13 patients (43.3%) achieving pCR. The mean anti-HER2Th1 response in pCR was 167 (range 53–418), and <pCR was 24 (range 0.4–53). The distributions were nearly non-overlapping. The anti-HER2Th1 response was superior to the original pMRI and had higher accuracy than the blinded pMRI review (area under the curve 0.97 vs 0.55; sensitivity 100 vs 46.2%; specificity 94.1 vs 64.7%; overall accuracy 96.7 vs 56.7%).

Conclusion

The presence of a high anti-HER2Th1 response is superior to pMRI for the assessment of pCR in HER2+BC. This assay has considerable promise, and validation in a large-scale study is warranted.
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Literature
1.
go back to reference Kaufmann M, von Minckwitz G, Rody A. Preoperative (neoadjuvant) systemic treatment of breast cancer. Breast. 2005;14(6):576–81.CrossRefPubMed Kaufmann M, von Minckwitz G, Rody A. Preoperative (neoadjuvant) systemic treatment of breast cancer. Breast. 2005;14(6):576–81.CrossRefPubMed
2.
go back to reference Rastogi P, Anderson SL, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, et al., Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008;26:778–85.CrossRefPubMed Rastogi P, Anderson SL, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, et al., Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008;26:778–85.CrossRefPubMed
3.
go back to reference Gralow JR, Burstein H, Wood W, et al, Preoperative therapy in invasive breast cancer: pathologic assessment and systemic therapy issues in operable disease. J Clin Oncol. 2008;26:814–9.CrossRefPubMed Gralow JR, Burstein H, Wood W, et al, Preoperative therapy in invasive breast cancer: pathologic assessment and systemic therapy issues in operable disease. J Clin Oncol. 2008;26:814–9.CrossRefPubMed
4.
go back to reference Mieog S, van der Hage J, van de Velde CJ. Preoperative chemotherapy for women with operable breast cancer. Cochrane Database Syst Rev. 2007;18(2):CD005002. Mieog S, van der Hage J, van de Velde CJ. Preoperative chemotherapy for women with operable breast cancer. Cochrane Database Syst Rev. 2007;18(2):CD005002.
5.
go back to reference Wolff AC, Davidson NE. Preoperative therapy in breast cancer: lessons from the treatment of locally advanced disease. Oncologist. 2002;7:239–45.CrossRefPubMed Wolff AC, Davidson NE. Preoperative therapy in breast cancer: lessons from the treatment of locally advanced disease. Oncologist. 2002;7:239–45.CrossRefPubMed
6.
go back to reference Untch M, et al. Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol. 2011;29:3351–7.CrossRefPubMed Untch M, et al. Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol. 2011;29:3351–7.CrossRefPubMed
7.
go back to reference Broglio KR, Quintana M, Foster M, Olinger M, McGlothlin A, Berry SM, et al. Association of pathologic complete response to neoadjuvant therapy in HER2-positive breast cancer with long-term outcomes: a meta-analysis. JAMA Oncol. 2016. doi:10.1001/jamaoncol.2015.6113.PubMed Broglio KR, Quintana M, Foster M, Olinger M, McGlothlin A, Berry SM, et al. Association of pathologic complete response to neoadjuvant therapy in HER2-positive breast cancer with long-term outcomes: a meta-analysis. JAMA Oncol. 2016. doi:10.​1001/​jamaoncol.​2015.​6113.PubMed
8.
go back to reference Buzdar AU, Ibrahim N, Francis D, Booser DJ, Thomas ES, Theriault RL, et al. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005;23:3676–85.CrossRefPubMed Buzdar AU, Ibrahim N, Francis D, Booser DJ, Thomas ES, Theriault RL, et al. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005;23:3676–85.CrossRefPubMed
9.
go back to reference Rahbar H, L.C. Rethinking preoperative breast magnetic resonance imaging. JAMA Oncol. 2015;1:1226–7. Rahbar H, L.C. Rethinking preoperative breast magnetic resonance imaging. JAMA Oncol. 2015;1:1226–7.
10.
go back to reference Marinovich ML, Houssami N, Macaskill P, Sardanelli F, Irwig L, Mamounas EP, et al. Meta-analysis of magnetic resonance imaging in detecting residual breast cancer after neoadjuvant therapy. J Natl Cancer Inst. 2013;105:321–33.CrossRefPubMed Marinovich ML, Houssami N, Macaskill P, Sardanelli F, Irwig L, Mamounas EP, et al. Meta-analysis of magnetic resonance imaging in detecting residual breast cancer after neoadjuvant therapy. J Natl Cancer Inst. 2013;105:321–33.CrossRefPubMed
11.
go back to reference DeMartini W, Lehman C, Partridge S. Breast MRI for cancer detection and characterization: a review of evidence-based clinical applications. Acad Radiol. 2008;15:408–16.CrossRefPubMed DeMartini W, Lehman C, Partridge S. Breast MRI for cancer detection and characterization: a review of evidence-based clinical applications. Acad Radiol. 2008;15:408–16.CrossRefPubMed
12.
go back to reference Schaefgen B, Mati M, Sinn HP, Golatta M, Stieber A, Rauch G, et al., Can routine imaging after neoadjuvant chemotherapy in breast cancer predict pathologic complete response? Ann Surg Oncol. 2016;23:789–95.CrossRefPubMed Schaefgen B, Mati M, Sinn HP, Golatta M, Stieber A, Rauch G, et al., Can routine imaging after neoadjuvant chemotherapy in breast cancer predict pathologic complete response? Ann Surg Oncol. 2016;23:789–95.CrossRefPubMed
13.
go back to reference Datta J, et al. Anti-HER2 CD4(+) T-helper type 1 response is a novel immune correlate to pathologic response following neoadjuvant therapy in HER2-positive breast cancer. Breast Cancer Res. 2015;17:71.CrossRefPubMedPubMedCentral Datta J, et al. Anti-HER2 CD4(+) T-helper type 1 response is a novel immune correlate to pathologic response following neoadjuvant therapy in HER2-positive breast cancer. Breast Cancer Res. 2015;17:71.CrossRefPubMedPubMedCentral
14.
go back to reference Datta J, et al. Progressive loss of anti-HER2 CD4+T-helper type 1 response in breast tumorigenesis and the potential for immune restoration. Oncoimmunology. 2015;4:e1022301.CrossRefPubMedPubMedCentral Datta J, et al. Progressive loss of anti-HER2 CD4+T-helper type 1 response in breast tumorigenesis and the potential for immune restoration. Oncoimmunology. 2015;4:e1022301.CrossRefPubMedPubMedCentral
15.
go back to reference Datta J, et al. Association of depressed anti-HER2 T-helper type 1 response with recurrence in patients with completely treated HER2-positive breast cancer: role for immune monitoring. JAMA Oncol. 2016;2:242–6.CrossRefPubMed Datta J, et al. Association of depressed anti-HER2 T-helper type 1 response with recurrence in patients with completely treated HER2-positive breast cancer: role for immune monitoring. JAMA Oncol. 2016;2:242–6.CrossRefPubMed
16.
go back to reference Eisenhauer EA, Therasseb P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumors: revised REGIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed Eisenhauer EA, Therasseb P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumors: revised REGIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed
17.
go back to reference Koski GK, et al. A novel dendritic cell-based immunization approach for the induction of durable Th1-polarized anti-HER-2/neu responses in women with early breast cancer. J Immunother. 2012;35:54–65.CrossRefPubMedPubMedCentral Koski GK, et al. A novel dendritic cell-based immunization approach for the induction of durable Th1-polarized anti-HER-2/neu responses in women with early breast cancer. J Immunother. 2012;35:54–65.CrossRefPubMedPubMedCentral
18.
go back to reference Hylton NM, Blume J, Bernreuter WK, Pisano ED, Rosen MA, Morris EA, et al. Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy: results from ACRIN 6657/I-SPY TRIAL. Radiology. 2012;263:663–72.CrossRefPubMedPubMedCentral Hylton NM, Blume J, Bernreuter WK, Pisano ED, Rosen MA, Morris EA, et al. Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy: results from ACRIN 6657/I-SPY TRIAL. Radiology. 2012;263:663–72.CrossRefPubMedPubMedCentral
19.
go back to reference Abraham DC, Jones R, Jones SE, Cheek JH, Peters GN, Knox SM, et al. Evaluation of neoadjuvant chemotherapeutic response of locally advanced breast cancer by magnetic resonance imaging. Cancer. 1996;78:91–100.CrossRefPubMed Abraham DC, Jones R, Jones SE, Cheek JH, Peters GN, Knox SM, et al. Evaluation of neoadjuvant chemotherapeutic response of locally advanced breast cancer by magnetic resonance imaging. Cancer. 1996;78:91–100.CrossRefPubMed
20.
go back to reference Yeh E, Slanetz P, Kopans DB, Rafferty E, Georgian-Smith D, Moy L, et al. Prospective comparison of mammography, sonography, and MRI in patients undergoing neoadjuvant chemotherapy for palpable breast cancer. AJR Am J Roentgenol. 2005;184:868–77.CrossRefPubMed Yeh E, Slanetz P, Kopans DB, Rafferty E, Georgian-Smith D, Moy L, et al. Prospective comparison of mammography, sonography, and MRI in patients undergoing neoadjuvant chemotherapy for palpable breast cancer. AJR Am J Roentgenol. 2005;184:868–77.CrossRefPubMed
21.
go back to reference Schott AF, Roubidoux M, Helvie MA, et al., Clinical and radiological assessments to predict breast cancer pathologic complete response to neoadjuvant chemotherapy. Breast Cancer Res. 2005;92:231–8.CrossRef Schott AF, Roubidoux M, Helvie MA, et al., Clinical and radiological assessments to predict breast cancer pathologic complete response to neoadjuvant chemotherapy. Breast Cancer Res. 2005;92:231–8.CrossRef
22.
go back to reference Chagpar AB, Middleton L, Sahin AA, Dempsey P, Buzdar AU, Mirza AN, et al. Accuracy of physical examination, ultrasonography, and mammography in predicting residual pathologic tumor size in patients treated with neoadjuvant chemotherapy. Ann Surg. 2006;243:257–64.CrossRefPubMedPubMedCentral Chagpar AB, Middleton L, Sahin AA, Dempsey P, Buzdar AU, Mirza AN, et al. Accuracy of physical examination, ultrasonography, and mammography in predicting residual pathologic tumor size in patients treated with neoadjuvant chemotherapy. Ann Surg. 2006;243:257–64.CrossRefPubMedPubMedCentral
23.
go back to reference Chen JH, Feig B, Agrawal G, Yu H, Carpenter PM, Mehta RS, et al. MRI evaluation of pathologically complete response and residual tumors in breast cancer after neoadjuvant chemotherapy. Cancer. 2008;112:17–26.CrossRefPubMed Chen JH, Feig B, Agrawal G, Yu H, Carpenter PM, Mehta RS, et al. MRI evaluation of pathologically complete response and residual tumors in breast cancer after neoadjuvant chemotherapy. Cancer. 2008;112:17–26.CrossRefPubMed
Metadata
Title
Anti-HER2 CD4+ T-Helper Type 1 Immune Response is Superior to Breast MRI for Assessing Response to Neoadjuvant Therapy in Patients with HER2-Positive Breast Cancer
Authors
Lucy M. De La Cruz, MD
Elizabeth S. McDonald, MD, PhD
R. Mick, MS
Jashodeep Datta, MD
Nadia F. Nocera, MD
Shuwen Xu, MD
Carla S. Fisher, MD
Brian J. Czerniecki, MD, PhD
Publication date
01-04-2017
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 4/2017
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5651-z

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