Skip to main content
Top
Published in: Breast Cancer Research and Treatment 3/2020

01-10-2020 | Breast Cancer | Preclinical study

Evaluation of PD-L1, tumor-infiltrating lymphocytes, and CD8+ and FOXP3+ immune cells in HER2-positive breast cancer treated with neoadjuvant therapies

Authors: Jing Zhao, Jane Meisel, Yi Guo, Rita Nahta, Kung Lin Hsieh, Limin Peng, Zhimin Wei, Ruth O’Regan, Xiaoxian Li

Published in: Breast Cancer Research and Treatment | Issue 3/2020

Login to get access

Abstract

Background

The tumor immune microenvironment plays a critical role in the prognosis and outcome of breast cancers. This study examined the role of tumor-infiltrating lymphocytes (TILs), CD8+, FOXP3+ lymphocytes, PD-L1 expression, and other clinicopathological parameters in HER2+ breast cancer and correlate with tumor response to neoadjuvant therapy.

Methods

We included 173 HER2+ patients treated with neoadjuvant HER2-targeted chemotherapy regimens from 2010 to 2016. 67 cases had biopsy blocks to evaluate TIL, CD8, FOXP3, and PD-L1 immunohistochemistry staining. Tumors were classified as pCR vs non-pCR group. Clinicopathological parameters, TIL, CD8+ and FOXP3+ cell count, and PD-L1 expression were correlated with pCR rate.

Results

Univariate analyses showed that pCR rate was significantly correlated with low PR, low ER, high Ki-67, high FOXP3, HER2 IHC3+ , high HER2 ratio and copy number. By multivariate analysis, Ki-67 was the only variable significantly correlated with pCR. PD-L1 expression was detected in 9.2% cases. TIL hotspot has a non-significant correlation with pCR rate (p = 0.096).

Conclusions

High Ki-67 is a strong predictor for pCR in HER2+ breast cancer. TIL and FOXP3 T cells may play a role in tumor response in HER2+ cancer. PD-L1 is expressed in a subset of HER2+ breast cancer, supporting a role of immunotherapy in treating a subset of HER2+ breast cancers. The role of PD-L1, TIL, and other markers of immunogenicity as predictors of response to neoadjuvant chemotherapy in HER2+ breast cancer should be further evaluated.
Literature
1.
go back to reference Cronin KA, Lake AJ, Scott S (2018) Annual Report to the Nation on the Status of Cancer, part I: National cancer statistics. Cancer 124:2785–2800PubMedPubMedCentral Cronin KA, Lake AJ, Scott S (2018) Annual Report to the Nation on the Status of Cancer, part I: National cancer statistics. Cancer 124:2785–2800PubMedPubMedCentral
2.
go back to reference Arciero CA, Guo Y, Jiang R et al (2019) ER(+)/HER2(+) breast cancer has different metastatic patterns and better survival than ER(-)/HER2(+) breast cancer. Clin Breast Cancer 19:236–245PubMed Arciero CA, Guo Y, Jiang R et al (2019) ER(+)/HER2(+) breast cancer has different metastatic patterns and better survival than ER(-)/HER2(+) breast cancer. Clin Breast Cancer 19:236–245PubMed
3.
go back to reference Li X, Wei B, Sonmez C et al (2017) High tumor budding count is associated with adverse clinicopathologic features and poor prognosis in breast carcinoma. Hum Pathol 66:222–229PubMed Li X, Wei B, Sonmez C et al (2017) High tumor budding count is associated with adverse clinicopathologic features and poor prognosis in breast carcinoma. Hum Pathol 66:222–229PubMed
4.
go back to reference Li X, Zhang Y, Meisel J et al (2018) Validation of the newly proposed American Joint Committee on Cancer (AJCC) breast cancer prognostic staging group and proposing a new staging system using the National Cancer Database. Breast Cancer Res Treat 171:303–313PubMed Li X, Zhang Y, Meisel J et al (2018) Validation of the newly proposed American Joint Committee on Cancer (AJCC) breast cancer prognostic staging group and proposing a new staging system using the National Cancer Database. Breast Cancer Res Treat 171:303–313PubMed
5.
go back to reference Meisel J, Zhang C, Neely C et al (2018) Evaluation of prognosis in hormone receptor-positive/HER2-negative and lymph node-negative breast cancer with low oncotype DX recurrence score. Clin Breast Cancer 18:347–352PubMed Meisel J, Zhang C, Neely C et al (2018) Evaluation of prognosis in hormone receptor-positive/HER2-negative and lymph node-negative breast cancer with low oncotype DX recurrence score. Clin Breast Cancer 18:347–352PubMed
6.
go back to reference Li X, Oprea-Ilies GM, Krishnamurti U (2017) New developments in breast cancer and their impact on daily practice in pathology. Arch Pathol Lab Med 141:490–498PubMed Li X, Oprea-Ilies GM, Krishnamurti U (2017) New developments in breast cancer and their impact on daily practice in pathology. Arch Pathol Lab Med 141:490–498PubMed
7.
go back to reference Li X, Yang J, Krishnamurti U et al (2017) Hormone receptor-positive breast cancer has a worse prognosis in male than in female patients. Clin Breast Cancer 17:356–366PubMed Li X, Yang J, Krishnamurti U et al (2017) Hormone receptor-positive breast cancer has a worse prognosis in male than in female patients. Clin Breast Cancer 17:356–366PubMed
8.
go back to reference Li X, Yang J, Peng L et al (2017) Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res Treat 161:279–287PubMed Li X, Yang J, Peng L et al (2017) Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res Treat 161:279–287PubMed
9.
go back to reference Slamon D, Pegram M (2001) Rationale for trastuzumab (Herceptin) in adjuvant breast cancer trials. Semin Oncol 28:13–19PubMed Slamon D, Pegram M (2001) Rationale for trastuzumab (Herceptin) in adjuvant breast cancer trials. Semin Oncol 28:13–19PubMed
10.
go back to reference Schneeweiss A, Chia S, Hickish T et al (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 24:2278–2284PubMed Schneeweiss A, Chia S, Hickish T et al (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 24:2278–2284PubMed
11.
go back to reference Gianni L, Pienkowski T, Im YH et al (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13:25–32PubMed Gianni L, Pienkowski T, Im YH et al (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13:25–32PubMed
12.
go back to reference Symmans WF, Wei C, Gould R et al (2017) Long-term prognostic risk after neoadjuvant chemotherapy associated with residual cancer burden and breast cancer subtype. J Clin Oncol 35:1049–1060PubMedPubMedCentral Symmans WF, Wei C, Gould R et al (2017) Long-term prognostic risk after neoadjuvant chemotherapy associated with residual cancer burden and breast cancer subtype. J Clin Oncol 35:1049–1060PubMedPubMedCentral
13.
go back to reference von Minckwitz G, Huang CS, Mano MS et al (2019) Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 380:617–628 von Minckwitz G, Huang CS, Mano MS et al (2019) Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 380:617–628
14.
go back to reference Denkert C, von Minckwitz G, Brase JC et al (2015) Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol 33:983–991PubMed Denkert C, von Minckwitz G, Brase JC et al (2015) Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol 33:983–991PubMed
15.
go back to reference Salgado R, Denkert C, Campbell C et al (2015) 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 1:448–454PubMedPubMedCentral Salgado R, Denkert C, Campbell C et al (2015) 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 1:448–454PubMedPubMedCentral
16.
go back to reference Nuciforo P, Pascual T, Cortes J et al (2018) A predictive model of pathologic response based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer treated with chemo-free dual HER2 blockade. Ann Oncol 29:170–177PubMed Nuciforo P, Pascual T, Cortes J et al (2018) A predictive model of pathologic response based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer treated with chemo-free dual HER2 blockade. Ann Oncol 29:170–177PubMed
17.
go back to reference Llombart-Cussac A, Cortes J, Pare L et al (2017) HER2-enriched subtype as a predictor of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer (PAMELA): an open-label, single-group, multicentre, phase 2 trial. Lancet Oncol 18:545–554PubMed Llombart-Cussac A, Cortes J, Pare L et al (2017) HER2-enriched subtype as a predictor of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer (PAMELA): an open-label, single-group, multicentre, phase 2 trial. Lancet Oncol 18:545–554PubMed
18.
go back to reference Wolff AC, Hammond MEH, Allison KH et al (2018) 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 142:1364–1382PubMed Wolff AC, Hammond MEH, Allison KH et al (2018) 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 142:1364–1382PubMed
19.
go back to reference Meisel JL, Zhao J, Suo A et al (2020) Clinicopathologic factors associated with response to neoadjuvant anti-HER2-directed chemotherapy in HER2-positive breast cancer. Clin Breast Cancer 20(1):19–24PubMed Meisel JL, Zhao J, Suo A et al (2020) Clinicopathologic factors associated with response to neoadjuvant anti-HER2-directed chemotherapy in HER2-positive breast cancer. Clin Breast Cancer 20(1):19–24PubMed
20.
go back to reference Afghahi A, Purington N, Han SS (2018) Higher absolute lymphocyte counts predict lower mortality from early-stage triple-negative breast cancer. Clin Cancer 24:2851–2858 Afghahi A, Purington N, Han SS (2018) Higher absolute lymphocyte counts predict lower mortality from early-stage triple-negative breast cancer. Clin Cancer 24:2851–2858
21.
go back to reference Curtis CN, West RB, Horst K et al (2014) Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. Clin Cancer Res 32:2959–2966 Curtis CN, West RB, Horst K et al (2014) Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. Clin Cancer Res 32:2959–2966
22.
go back to reference Loi S, Drubay D, Adams S et al (2019) Tumor-infiltrating lymphocytes and prognosis: a pooled individual patient analysis of early-stage triple-negative breast cancers. J Clin Oncol 37:559–569PubMedPubMedCentral Loi S, Drubay D, Adams S et al (2019) Tumor-infiltrating lymphocytes and prognosis: a pooled individual patient analysis of early-stage triple-negative breast cancers. J Clin Oncol 37:559–569PubMedPubMedCentral
23.
go back to reference Krishnamurti U, Wetherilt CS, Yang J et al (2017) Tumor-infiltrating lymphocytes are significantly associated with better overall survival and disease-free survival in triple-negative but not estrogen receptor-positive breast cancers. Hum Pathol 64:7–12PubMed Krishnamurti U, Wetherilt CS, Yang J et al (2017) Tumor-infiltrating lymphocytes are significantly associated with better overall survival and disease-free survival in triple-negative but not estrogen receptor-positive breast cancers. Hum Pathol 64:7–12PubMed
24.
go back to reference Li XB, Krishnamurti U, Bhattarai S et al (2016) Biomarkers predicting pathologic complete response to neoadjuvant chemotherapy in breast cancer. Am J Clin Pathol 145:871–878PubMed Li XB, Krishnamurti U, Bhattarai S et al (2016) Biomarkers predicting pathologic complete response to neoadjuvant chemotherapy in breast cancer. Am J Clin Pathol 145:871–878PubMed
25.
go back to reference Stanton SE, Disis ML (2016) Clinical significance of tumor-infiltrating lymphocytes in breast cancer. J Immunother Cancer 4:59PubMedPubMedCentral Stanton SE, Disis ML (2016) Clinical significance of tumor-infiltrating lymphocytes in breast cancer. J Immunother Cancer 4:59PubMedPubMedCentral
26.
go back to reference Perez EA, Ballman KV, Tenner KS et al (2016) Association of stromal tumor-infiltrating lymphocytes with recurrence-free survival in the N9831 adjuvant trial in patients with early-stage HER2-positive breast cancer. JAMA Oncol 2:56–64PubMedPubMedCentral Perez EA, Ballman KV, Tenner KS et al (2016) Association of stromal tumor-infiltrating lymphocytes with recurrence-free survival in the N9831 adjuvant trial in patients with early-stage HER2-positive breast cancer. JAMA Oncol 2:56–64PubMedPubMedCentral
27.
go back to reference Loi S, Michiels S, Salgado R et al (2014) Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol 25:1544–1550PubMed Loi S, Michiels S, Salgado R et al (2014) Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol 25:1544–1550PubMed
28.
go back to reference Kurozumi S, Inoue K, Matsumoto H et al (2019) Clinicopathological values of PD-L1 expression in HER2-positive breast cancer. Sci Rep 9:16662PubMedPubMedCentral Kurozumi S, Inoue K, Matsumoto H et al (2019) Clinicopathological values of PD-L1 expression in HER2-positive breast cancer. Sci Rep 9:16662PubMedPubMedCentral
29.
go back to reference Peng GL, Li L, Guo YW et al (2019) CD8(+) cytotoxic and FoxP3(+) regulatory T lymphocytes serve as prognostic factors in breast cancer. Am J Transl Res 11:5039–5053PubMedPubMedCentral Peng GL, Li L, Guo YW et al (2019) CD8(+) cytotoxic and FoxP3(+) regulatory T lymphocytes serve as prognostic factors in breast cancer. Am J Transl Res 11:5039–5053PubMedPubMedCentral
30.
go back to reference Lee KH, Kim EY, Yun JS et al (2018) The prognostic and predictive value of tumor-infiltrating lymphocytes and hematologic parameters in patients with breast cancer. BMC Cancer 18:938PubMedPubMedCentral Lee KH, Kim EY, Yun JS et al (2018) The prognostic and predictive value of tumor-infiltrating lymphocytes and hematologic parameters in patients with breast cancer. BMC Cancer 18:938PubMedPubMedCentral
31.
go back to reference Liu S, Chen B, Burugu S et al (2017) Role of cytotoxic tumor-infiltrating lymphocytes in predicting outcomes in metastatic HER2-positive breast cancer: a secondary analysis of a randomized clinical trial. JAMA Oncol 3:e172085PubMedPubMedCentral Liu S, Chen B, Burugu S et al (2017) Role of cytotoxic tumor-infiltrating lymphocytes in predicting outcomes in metastatic HER2-positive breast cancer: a secondary analysis of a randomized clinical trial. JAMA Oncol 3:e172085PubMedPubMedCentral
32.
go back to reference Takada K, Kashiwagi S (2018) Use of the tumor-infiltrating CD8 to FOXP3 lymphocyte ratio in predicting treatment responses to combination therapy with pertuzumab, trastuzumab, and docetaxel for advanced HER2-positive breast cancer. J Transl Med 16:86PubMedPubMedCentral Takada K, Kashiwagi S (2018) Use of the tumor-infiltrating CD8 to FOXP3 lymphocyte ratio in predicting treatment responses to combination therapy with pertuzumab, trastuzumab, and docetaxel for advanced HER2-positive breast cancer. J Transl Med 16:86PubMedPubMedCentral
33.
go back to reference De Angelis C, Nagi C, Hoyt CC et al (2020) Evaluation of the predictive role of tumor immune infiltrate in patients with HER2-positive breast cancer treated with neoadjuvant anti-HER2 therapy without chemotherapy. Clin Cancer 26:738–745 De Angelis C, Nagi C, Hoyt CC et al (2020) Evaluation of the predictive role of tumor immune infiltrate in patients with HER2-positive breast cancer treated with neoadjuvant anti-HER2 therapy without chemotherapy. Clin Cancer 26:738–745
34.
go back to reference Glajcar A, Szpor J, Hodorowicz-Zaniewska D et al (2019) The composition of T cell infiltrates varies in primary invasive breast cancer of different molecular subtypes as well as according to tumor size and nodal status. Virchows Arch 475:13–23PubMedPubMedCentral Glajcar A, Szpor J, Hodorowicz-Zaniewska D et al (2019) The composition of T cell infiltrates varies in primary invasive breast cancer of different molecular subtypes as well as according to tumor size and nodal status. Virchows Arch 475:13–23PubMedPubMedCentral
35.
go back to reference Nederlof I, De Bortoli D, Bareche Y et al (2019) Comprehensive evaluation of methods to assess overall and cell-specific immune infiltrates in breast cancer. Breast Cancer 21:151 Nederlof I, De Bortoli D, Bareche Y et al (2019) Comprehensive evaluation of methods to assess overall and cell-specific immune infiltrates in breast cancer. Breast Cancer 21:151
36.
go back to reference Li X, Wetherilt CS, Krishnamurti U et al (2016) Stromal PD-L1 expression is associated with better disease-free survival in triple-negative breast cancer. Am J Clin Pathol 146:496–502PubMed Li X, Wetherilt CS, Krishnamurti U et al (2016) Stromal PD-L1 expression is associated with better disease-free survival in triple-negative breast cancer. Am J Clin Pathol 146:496–502PubMed
37.
go back to reference Zhang L, Wang XI, Ding J et al (2019) The predictive and prognostic value of Foxp3+/CD25+ regulatory T cells and PD-L1 expression in triple negative breast cancer. Ann Diagn Pathol 40:143–151PubMed Zhang L, Wang XI, Ding J et al (2019) The predictive and prognostic value of Foxp3+/CD25+ regulatory T cells and PD-L1 expression in triple negative breast cancer. Ann Diagn Pathol 40:143–151PubMed
38.
go back to reference Hou Y, Nitta H, Wei L et al (2018) PD-L1 expression and CD8-positive T cells are associated with favorable survival in HER2-positive invasive breast cancer. Breast J 24:911–919PubMedPubMedCentral Hou Y, Nitta H, Wei L et al (2018) PD-L1 expression and CD8-positive T cells are associated with favorable survival in HER2-positive invasive breast cancer. Breast J 24:911–919PubMedPubMedCentral
39.
go back to reference Schmid P, Adams S, Rugo HS et al (2018) Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 379:2108–2121PubMed Schmid P, Adams S, Rugo HS et al (2018) Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 379:2108–2121PubMed
40.
go back to reference Schmid P, Rugo HS, Adams S et al (2020) Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 21:44–59PubMed Schmid P, Rugo HS, Adams S et al (2020) Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 21:44–59PubMed
41.
go back to reference Lawson NL, Dix CI, Scorer PW et al (2020) Mapping the binding sites of antibodies utilized in programmed cell death ligand-1 predictive immunohistochemical assays for use with immuno-oncology therapies. Mod Pathol 33:518–530PubMed Lawson NL, Dix CI, Scorer PW et al (2020) Mapping the binding sites of antibodies utilized in programmed cell death ligand-1 predictive immunohistochemical assays for use with immuno-oncology therapies. Mod Pathol 33:518–530PubMed
42.
go back to reference Martinez-Morilla S, McGuire J, Gaule P et al (2020) Quantitative assessment of PD-L1 as an analyte in immunohistochemistry diagnostic assays using a standardized cell line tissue microarray. Lab Invest 100:4–15PubMed Martinez-Morilla S, McGuire J, Gaule P et al (2020) Quantitative assessment of PD-L1 as an analyte in immunohistochemistry diagnostic assays using a standardized cell line tissue microarray. Lab Invest 100:4–15PubMed
43.
go back to reference Hirsch FR, McElhinny A, Stanforth D et al (2017) PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol 12:208–222 Hirsch FR, McElhinny A, Stanforth D et al (2017) PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol 12:208–222
44.
go back to reference Tsao MS, Kerr KM, Kockx M et al (2018) PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of blueprint phase 2 project. J Thorac Oncol 13:1302–1311 Tsao MS, Kerr KM, Kockx M et al (2018) PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of blueprint phase 2 project. J Thorac Oncol 13:1302–1311
45.
go back to reference Adams S, Schmid P, Rugo HS et al (2019) Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study. Ann Oncol 30:397–404PubMed Adams S, Schmid P, Rugo HS et al (2019) Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study. Ann Oncol 30:397–404PubMed
46.
go back to reference Adams S, Loi S, Toppmeyer D et al (2019) Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study. Ann Oncol 30:405–411PubMed Adams S, Loi S, Toppmeyer D et al (2019) Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study. Ann Oncol 30:405–411PubMed
47.
go back to reference Schmid P, Cortes J, Pusztai L et al (2020) Pembrolizumab for early triple-negative breast cancer. N Engl J Med 382:810–821PubMed Schmid P, Cortes J, Pusztai L et al (2020) Pembrolizumab for early triple-negative breast cancer. N Engl J Med 382:810–821PubMed
48.
go back to reference Voorwerk L, Slagter M, Horlings HM et al (2019) Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial. Nat Med 25:920–928PubMed Voorwerk L, Slagter M, Horlings HM et al (2019) Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial. Nat Med 25:920–928PubMed
49.
go back to reference Loibl S, Untch M, Burchardi N et al (2019) A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol 30:1279–1288PubMed Loibl S, Untch M, Burchardi N et al (2019) A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol 30:1279–1288PubMed
50.
go back to reference Emens L, Esteva F, Beresford M et al (2019) Abstract PD3–01: Results from KATE2, a randomized phase 2 study of atezolizumab (atezo)+trastuzumab emtansine (T-DM1) vs placebo (pbo)+T-DM1 in previously treated HER2+ advanced breast cancer (BC). Cancer Res 79:PD3-01-PD3-01 Emens L, Esteva F, Beresford M et al (2019) Abstract PD3–01: Results from KATE2, a randomized phase 2 study of atezolizumab (atezo)+trastuzumab emtansine (T-DM1) vs placebo (pbo)+T-DM1 in previously treated HER2+ advanced breast cancer (BC). Cancer Res 79:PD3-01-PD3-01
51.
go back to reference Loi S, Giobbie-Hurder A, Gombos A et al (2019) Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b–2 trial. Lancet Oncol 20:371–382PubMed Loi S, Giobbie-Hurder A, Gombos A et al (2019) Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b–2 trial. Lancet Oncol 20:371–382PubMed
Metadata
Title
Evaluation of PD-L1, tumor-infiltrating lymphocytes, and CD8+ and FOXP3+ immune cells in HER2-positive breast cancer treated with neoadjuvant therapies
Authors
Jing Zhao
Jane Meisel
Yi Guo
Rita Nahta
Kung Lin Hsieh
Limin Peng
Zhimin Wei
Ruth O’Regan
Xiaoxian Li
Publication date
01-10-2020
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-020-05819-8

Other articles of this Issue 3/2020

Breast Cancer Research and Treatment 3/2020 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine