Top

Current Oncology Reports

Published in:

01-05-2021 | Breast Cancer | Breast Cancer (AS Zimmer, Section Editor)

Improving Breast Cancer Responses to Immunotherapy—a Search for the Achilles Heel of the Tumor Microenvironment

Authors: Sarah Jenkins, Robert Wesolowski, Margaret E. Gatti-Mays

Published in: Current Oncology Reports | Issue 5/2021

Abstract

Purpose of review

To explore the role of the tumor microenvironment (TME) in breast cancer, identify the changes that occur in the TME during breast cancer progression, and explore the possibility of modifying the TME to improve immune checkpoint inhibitor responses.

Recent findings

Emerging evidence shows the TME may be shaped by internal and external factors. Preclinical data suggests it may be possible to shift the TME to allow for better immune infiltration. In this review, we summarize emerging evidence of changes in the TME and how it can affect prognosis and responses to therapy. We also examine pre-clinical and clinical research aiming at modulating TME to increase proportion of patients who benefit from immune checkpoint inhibitors.

Summary

The composition of the TME in breast cancer is likely dynamic and may be altered. These changes may lead to more or less responses to immunotherapy.

Bonaventura P, Shekarian T, Alcazer V, Valladeau-Guilemond J, Valsesia-Wittmann S, Amigorena S, et al. Cold Tumors: A Therapeutic Challenge for Immunotherapy. Front Immunol. 2019;10:168. https://doi.org/10.3389/fimmu.2019.00168.CrossRefPubMedPubMedCentral

Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10. https://doi.org/10.1016/j.immuni.2013.07.012.CrossRefPubMed

Dirix LY, Takacs I, Jerusalem G, Nikolinakos P, Arkenau HT, Forero-Torres A, et al. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study. Breast Cancer Res Treat. 2018;167(3):671–86. https://doi.org/10.1007/s10549-017-4537-5.CrossRefPubMed

Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, et al. Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol. 2016;34(21):2460–7. https://doi.org/10.1200/JCO.2015.64.8931.CrossRefPubMedPubMedCentral

Rugo HS, Delord JP, Im SA, Ott PA, Piha-Paul SA, Bedard PL, et al. Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. Clin Cancer Res. 2018;24(12):2804–11. https://doi.org/10.1158/1078-0432.CCR-17-3452.CrossRefPubMed

Gatti-Mays ME, Balko JM, Gameiro SR, Bear HD, Prabhakaran S, Fukui J, et al. If we build it they will come: targeting the immune response to breast cancer. NPJ Breast Cancer. 2019;5:37. https://doi.org/10.1038/s41523-019-0133-7.CrossRefPubMedPubMedCentral

Karnik T, Kimler BF, Fan F, Tawfik O. PD-L1 in breast cancer: comparative analysis of 3 different antibodies. Hum Pathol. 2018;72:28–34. https://doi.org/10.1016/j.humpath.2017.08.010.CrossRefPubMed

Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409–13. https://doi.org/10.1126/science.aan6733.CrossRefPubMedPubMedCentral

Li X, Gruosso T, Zuo D, Omeroglu A, Meterissian S, Guiot MC, et al. Infiltration of CD8(+) T cells into tumor cell clusters in triple-negative breast cancer. Proc Natl Acad Sci U S A. 2019;116(9):3678–87. https://doi.org/10.1073/pnas.1817652116.CrossRefPubMedPubMedCentral

10.

Roulois D, Loo Yau H, Singhania R, Wang Y, Danesh A, Shen SY, et al. DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts. Cell. 2015;162(5):961–73. https://doi.org/10.1016/j.cell.2015.07.056.CrossRefPubMedPubMedCentral

11.

Thomas A, Routh ED, Pullikuth A, Jin G, Su J, Chou JW, et al. Tumor mutational burden is a determinant of immune-mediated survival in breast cancer. Oncoimmunology. 2018;7(10):e1490854. https://doi.org/10.1080/2162402X.2018.1490854.CrossRefPubMedPubMedCentral

12.

Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, et al. Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma. N Engl J Med. 2016;375(9):819–29. https://doi.org/10.1056/NEJMoa1604958.CrossRefPubMedPubMedCentral

13.

•• Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH, et al. The Immune Landscape of Cancer. Immunity. 2018;48(4):812–30 e14. https://doi.org/10.1016/j.immuni.2018.03.023Comprehensive immunogenomic profiling of tumors from the TCGA. This study demonstrated there are multiple unique clusters in breast cancers but no breast cancers were classified as being immunologically quiet.CrossRefPubMedPubMedCentral

14.

Di Paola M, Angelini L, Bertolotti A, Colizza S. Host resistance in relation to survival in breast cancer. Br Med J. 1974;4(5939):268–70. https://doi.org/10.1136/bmj.4.5939.268.CrossRefPubMedPubMedCentral

15.

Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26(2):259–71. https://doi.org/10.1093/annonc/mdu450.CrossRefPubMed

16.

Barroso-Sousa R, Barry WT, Guo H, Dillon D, Tan YB, Fuhrman K, et al. The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial. Ann Oncol. 2019;30(4):575–81. https://doi.org/10.1093/annonc/mdz047.CrossRefPubMedPubMedCentral

17.

Stanton SE, Adams S, Disis ML. Variation in the Incidence and Magnitude of Tumor-Infiltrating Lymphocytes in Breast Cancer Subtypes: A Systematic Review. JAMA Oncol. 2016;2(10):1354–60. https://doi.org/10.1001/jamaoncol.2016.1061.CrossRefPubMed

18.

He L, Wang Y, Wu Q, Song Y, Ma X, Zhang B, et al. Association between levels of tumor-infiltrating lymphocytes in different subtypes of primary breast tumors and prognostic outcomes: a meta-analysis. BMC Womens Health. 2020;20(1):194. https://doi.org/10.1186/s12905-020-01038-x.CrossRefPubMedPubMedCentral

19.

Loi S, Michiels S, Salgado R, Sirtaine N, Jose V, Fumagalli D, et al. 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. 2014;25(8):1544–50. https://doi.org/10.1093/annonc/mdu112.CrossRefPubMed

20.

Loi S, Sirtaine N, Piette F, Salgado R, Viale G, Van Eenoo F, et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. J Clin Oncol. 2013;31(7):860–7. https://doi.org/10.1200/JCO.2011.41.0902.CrossRefPubMed

21.

Luen SJ, Salgado R, Fox S, Savas P, Eng-Wong J, Clark E, et al. Tumour-infiltrating lymphocytes in advanced HER2-positive breast cancer treated with pertuzumab or placebo in addition to trastuzumab and docetaxel: a retrospective analysis of the CLEOPATRA study. Lancet Oncol. 2017;18(1):52–62. https://doi.org/10.1016/S1470-2045(16)30631-3.CrossRefPubMed

22.

Salgado R, Denkert C, Campbell C, Savas P, Nuciforo P, Aura C, 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. 2015;1(4):448–54. https://doi.org/10.1001/jamaoncol.2015.0830.CrossRefPubMedPubMedCentral

23.

Yuan ZY, Luo RZ, Peng RJ, Wang SS, Xue C. High infiltration of tumor-associated macrophages in triple-negative breast cancer is associated with a higher risk of distant metastasis. Onco Targets Ther. 2014;7:1475–80. https://doi.org/10.2147/OTT.S61838.CrossRefPubMedPubMedCentral

24.

Medrek C, Ponten F, Jirstrom K, Leandersson K. The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients. BMC Cancer. 2012;12:306. https://doi.org/10.1186/1471-2407-12-306.CrossRefPubMedPubMedCentral

25.

Zhou J, Wang XH, Zhao YX, Chen C, Xu XY, Sun Q, et al. Cancer-Associated Fibroblasts Correlate with Tumor-Associated Macrophages Infiltration and Lymphatic Metastasis in Triple Negative Breast Cancer Patients. J Cancer. 2018;9(24):4635–41. https://doi.org/10.7150/jca.28583.CrossRefPubMedPubMedCentral

26.

Zhao X, Qu J, Sun Y, Wang J, Liu X, Wang F, et al. Prognostic significance of tumor-associated macrophages in breast cancer: a meta-analysis of the literature. Oncotarget. 2017;8(18):30576–86. https://doi.org/10.18632/oncotarget.15736.CrossRefPubMedPubMedCentral

27.

Tao S, Zhao Z, Zhang X, Guan X, Wei J, Yuan B, et al. The role of macrophages during breast cancer development and response to chemotherapy. Clin Transl Oncol. 2020;22:1938–51. https://doi.org/10.1007/s12094-020-02348-0.CrossRefPubMed

28.

Sousa S, Brion R, Lintunen M, Kronqvist P, Sandholm J, Monkkonen J, et al. Human breast cancer cells educate macrophages toward the M2 activation status. Breast Cancer Res. 2015;17:101. https://doi.org/10.1186/s13058-015-0621-0.CrossRefPubMedPubMedCentral

29.

Basu G D G A.; Vader, R.; Reddy, S.; Anderson, K.; McCullough, A.; Pockaj, B., editor. Expression of novel immunotherapeutic targets in luminal breast cancer patients. San Antonio Breast Cancer Symposium; 2014; San Antonio, Texas.

30.

Rom-Jurek EM, Kirchhammer N, Ugocsai P, Ortmann O, Wege AK, Brockhoff G. Regulation of Programmed Death Ligand 1 (PD-L1) Expression in Breast Cancer Cell Lines In Vitro and in Immunodeficient and Humanized Tumor Mice. Int J Mol Sci. 2018;19(2). https://doi.org/10.3390/ijms19020563.

31.

Sobral-Leite M, Van de Vijver K, Michaut M, van der Linden R, Hooijer GKJ, Horlings HM, et al. Assessment of PD-L1 expression across breast cancer molecular subtypes, in relation to mutation rate, BRCA1-like status, tumor-infiltrating immune cells and survival. Oncoimmunology. 2018;7(12):e1509820. https://doi.org/10.1080/2162402X.2018.1509820.CrossRefPubMedPubMedCentral

32.

Udall M, Rizzo M, Kenny J, Doherty J, Dahm S, Robbins P, et al. PD-L1 diagnostic tests: a systematic literature review of scoring algorithms and test-validation metrics. Diagn Pathol. 2018;13(1):12. https://doi.org/10.1186/s13000-018-0689-9.CrossRefPubMedPubMedCentral

33.

Davis AA, Patel VG. The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors. J Immunother Cancer. 2019;7(1):278. https://doi.org/10.1186/s40425-019-0768-9.CrossRefPubMedPubMedCentral

34.

Rugo H, Loi S, Adam S, Schmid P, Schneeweiss A, et al. Performance of PD-L1 Immunohistochemistry Assays in Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer: Post-Hoc Analysis of IMpassion130. ESMO; 2019. Abstract LBA20.

35.

Ancevski Hunter K, Socinski MA, Villaruz LC. PD-L1 Testing in Guiding Patient Selection for PD-1/PD-L1 Inhibitor Therapy in Lung Cancer. Mol Diagn Ther. 2018;22(1):1–10. https://doi.org/10.1007/s40291-017-0308-6.CrossRefPubMed

36.

Rugo H, Loi S, Adams S, Schmid P, Schneeweiss A, et al. Exploratory analytical harmonization of PD-L1 immunohistochemistry assays in advanced triple-negative breast cancer: A retrospective substudy of IMpassion130. San Antonio Breast Cancer Symposium; 2019; San Antonio. TX. .

37.

•• Molinero L, Li Y, Chang CW, Maund S, Berg M, Harrison J, et al. Tumor immune microenvironment and genomic evolution in a patient with metastatic triple negative breast cancer and a complete response to atezolizumab. J Immunother Cancer. 2019;7(1):274. https://doi.org/10.1186/s40425-019-0740-8A unique biomarker analysis spanning nearly 30 years of therapy in an individual TNBC patient that shows the evolution of the TME in response to cancer therapy, including ICI therapy.CrossRefPubMedPubMedCentral

38.

Li K, Luo H, Huang L, Luo H, Zhu X. Microsatellite instability: a review of what the oncologist should know. Cancer Cell Int. 2020;20:16. https://doi.org/10.1186/s12935-019-1091-8.CrossRefPubMedPubMedCentral

39.

Marcus L, Lemery SJ, Keegan P, Pazdur R. FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors. Clin Cancer Res. 2019;25(13):3753–8. https://doi.org/10.1158/1078-0432.CCR-18-4070.CrossRefPubMed

40.

Administration UFD. Keytruda (pembrolizumab) [package insert]. Merk & Co., Inc. 2014. Accessed on 9/8/20 from: accessdata.fda.gov.

41.

Cortes-Ciriano I, Lee S, Park WY, Kim TM, Park PJ. A molecular portrait of microsatellite instability across multiple cancers. Nat Commun. 2017;8:15180. https://doi.org/10.1038/ncomms15180.CrossRefPubMedPubMedCentral

42.

Bonneville R, Krook MA, Kautto EA, Miya J, Wing MR, Chen HZ, et al. Landscape of Microsatellite Instability Across 39 Cancer Types. JCO Precis Oncol. 2017;2017:1–15. https://doi.org/10.1200/PO.17.00073.CrossRef

43.

Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–8. https://doi.org/10.1126/science.aaa1348.CrossRefPubMedPubMedCentral

44.

Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2020;38(1):1–10. https://doi.org/10.1200/JCO.19.02105.CrossRefPubMed

45.

• Barroso-Sousa R, Keenan TE, Pernas S, Exman P, Jain E, Garrido-Castro AC, et al. Tumor Mutational Burden and PTEN Alterations as Molecular Correlates of Response to PD-1/L1 Blockade in Metastatic Triple-Negative Breast Cancer. Clin Cancer Res. 2020;26(11):2565–72. https://doi.org/10.1158/1078-0432.CCR-19-3507This retrospective study identified high TMB and PTEN alterations as indicators of response and non-response, respectively, to checkpoints, where as PD-L1 was not correlated with response in breast cancer patients.CrossRefPubMedPubMedCentral

46.

Narang P, Chen M, Sharma AA, Anderson KS, Wilson MA. The neoepitope landscape of breast cancer: implications for immunotherapy. BMC Cancer. 2019;19(1):200. https://doi.org/10.1186/s12885-019-5402-1.CrossRefPubMedPubMedCentral

47.

Xu J, Bao H, Wu X, Wang X, Shao YW, Sun T. Elevated tumor mutation burden and immunogenic activity in patients with hormone receptor-negative or human epidermal growth factor receptor 2-positive breast cancer. Oncol Lett. 2019;18(1):449–55. https://doi.org/10.3892/ol.2019.10287.CrossRefPubMedPubMedCentral

48.

• Loibl S, Untch M, Burchardi N, Huober J, Sinn BV, Blohmer JU, et al. 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. 2019;30(8):1279–88. https://doi.org/10.1093/annonc/mdz158This GeparNeuvo study refutes the positive improvement in pathologic complete response seen in other clinical trials, suggesting that the sequence of agents may play a role in response.CrossRefPubMed

49.

Karn T, Denkert C, Weber KE, Holtrich U, Hanusch C, Sinn BV, et al. Tumor mutational burden and immune infiltration as independent predictors of response to neoadjuvant immune checkpoint inhibition in early TNBC in GeparNuevo. Ann Oncol. 2020;31(9):1216–22. https://doi.org/10.1016/j.annonc.2020.05.015.CrossRefPubMed

50.

Castro F, Cardoso AP, Goncalves RM, Serre K, Oliveira MJ. Interferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion. Front Immunol. 2018;9:847. https://doi.org/10.3389/fimmu.2018.00847.CrossRefPubMedPubMedCentral

51.

Bald T, Landsberg J, Lopez-Ramos D, Renn M, Glodde N, Jansen P, et al. Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation. Cancer Discov. 2014;4(6):674–87. https://doi.org/10.1158/2159-8290.CD-13-0458.CrossRefPubMed

52.

Ayers M, Lunceford J, Nebozhyn M, Murphy E, Loboda A, Kaufman DR, et al. IFN-gamma-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest. 2017;127(8):2930–40. https://doi.org/10.1172/JCI91190.CrossRefPubMedPubMedCentral

53.

Ott PA, Bang YJ, Piha-Paul SA, Razak ARA, Bennouna J, Soria JC, et al. T-Cell-Inflamed Gene-Expression Profile, Programmed Death Ligand 1 Expression, and Tumor Mutational Burden Predict Efficacy in Patients Treated With Pembrolizumab Across 20 Cancers: KEYNOTE-028. J Clin Oncol. 2019;37(4):318–27. https://doi.org/10.1200/JCO.2018.78.2276.CrossRefPubMed

54.

Higgs BW, Morehouse CA, Streicher K, Brohawn PZ, Pilataxi F, Gupta A, et al. Interferon Gamma Messenger RNA Signature in Tumor Biopsies Predicts Outcomes in Patients with Non-Small Cell Lung Carcinoma or Urothelial Cancer Treated with Durvalumab. Clin Cancer Res. 2018;24(16):3857–66. https://doi.org/10.1158/1078-0432.CCR-17-3451.CrossRefPubMed

55.

Szekely B, Bossuyt V, Li X, Wali VB, Patwardhan GA, Frederick C, et al. Immunological differences between primary and metastatic breast cancer. Ann Oncol. 2018;29(11):2232–9. https://doi.org/10.1093/annonc/mdy399.CrossRefPubMed

56.

Takada K, Kashiwagi S, Goto W, Asano Y, Takahashi K, Hatano T, et al. Significance of re-biopsy for recurrent breast cancer in the immune tumour microenvironment. Br J Cancer. 2018;119(5):572–9. https://doi.org/10.1038/s41416-018-0197-4.CrossRefPubMedPubMedCentral

57.

Bertucci F, Ng CKY, Patsouris A, Droin N, Piscuoglio S, Carbuccia N, et al. Genomic characterization of metastatic breast cancers. Nature. 2019;569(7757):560–4. https://doi.org/10.1038/s41586-019-1056-z.CrossRefPubMed

58.

Angus L, Smid M, Wilting SM, van Riet J, Van Hoeck A, Nguyen L, et al. The genomic landscape of metastatic breast cancer highlights changes in mutation and signature frequencies. Nat Genet. 2019;51(10):1450–8. https://doi.org/10.1038/s41588-019-0507-7.CrossRefPubMedPubMedCentral

59.

Zhu L, Narloch JL, Onkar S, Joy M, Broadwater G, Luedke C, et al. Metastatic breast cancers have reduced immune cell recruitment but harbor increased macrophages relative to their matched primary tumors. J Immunother Cancer. 2019;7(1):265. https://doi.org/10.1186/s40425-019-0755-1.CrossRefPubMedPubMedCentral

60.

Ogiya R, Niikura N, Kumaki N, Bianchini G, Kitano S, Iwamoto T, et al. Comparison of tumor-infiltrating lymphocytes between primary and metastatic tumors in breast cancer patients. Cancer Sci. 2016;107(12):1730–5. https://doi.org/10.1111/cas.13101.CrossRefPubMedPubMedCentral

61.

Sambade MJ, Prince G, Deal AM, Trembath D, McKee M, Garrett A, et al. Examination and prognostic implications of the unique microenvironment of breast cancer brain metastases. Breast Cancer Res Treat. 2019;176(2):321–8. https://doi.org/10.1007/s10549-019-05211-1.CrossRefPubMedPubMedCentral

62.

Cimino-Mathews A, Ye X, Meeker A, Argani P, Emens LA. Metastatic triple-negative breast cancers at first relapse have fewer tumor-infiltrating lymphocytes than their matched primary breast tumors: a pilot study. Hum Pathol. 2013;44(10):2055–63. https://doi.org/10.1016/j.humpath.2013.03.010.CrossRefPubMedPubMedCentral

63.

•• Schmid P, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J, et al. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020;382(9):810–21. https://doi.org/10.1056/NEJMoa1910549Pertinent clinical trial that demonstrated improved pCR in TNBC patients treated with neoadjuvant pembrolizumab. Data regarding impact on OS is pending but based on this data, in July 2020 the USA FDA accepted a supplemental Biologics license Application (sBLA) to evaluate extending FDA approval for pembrolizumab to the neoadjuvant breast cancer setting.CrossRefPubMed

64.

•• Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, et al. Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer: An Analysis of the Ongoing Phase 2 Adaptively Randomized I-SPY2 Trial. JAMA Oncol. 2020;6(5):676–84. https://doi.org/10.1001/jamaoncol.2019.6650This was one of the first studies to demonstrate improved pCR in both TNBC and HR positive, HER2 negative breast cancer with neoadjuvant pembrolizumab.CrossRefPubMed

65.

•• Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018;379(22):2108–21. https://doi.org/10.1056/NEJMoa1809615This clinical trial led to the first breast cancer-specific FDA approval of atezolizumab plus nab-paclitaxel for the treatment of metastatic, PD-L1 positive, TNBC in the first line setting.CrossRefPubMed

66.

Schmid P, Rugo HS, Adams S, Schneeweiss A, Barrios CH, Iwata H, et al. 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. 2020;21(1):44–59. https://doi.org/10.1016/S1470-2045(19)30689-8.CrossRefPubMed

67.

FDA issues alert about efficacy and potential safety concerns with atezolizumab in combination with paclitaxel for treatment of breast cancer. Accessed 9/8/20 from:https://www.fda.gov/drugs/resources-information-approved-drugs/fda-issues-alert-about-efficacy-and-potential-safety-concerns-atezolizumab-combination-paclitaxel.

68.

Barroso-Sousa R, Tolaney SM. Clinical Development of PD-1/PD-L1 Inhibitors in Breast Cancer: Still a Long Way to Go. Curr Treat Options Oncol. 2020;21(7):59. https://doi.org/10.1007/s11864-020-00756-6.CrossRefPubMed

69.

Voorwerk L, Slagter M, Horlings HM, Sikorska K, van de Vijver KK, de Maaker M, et al. Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial. Nat Med. 2019;25(6):920–8. https://doi.org/10.1038/s41591-019-0432-4.CrossRefPubMed

70.

Bianchini G S C; Mansutti, M; Luck, HJ; Zambelli, S; Olier, C; Anton, A; Bisagni, G; Merlini, L; Murillo, SM; Martinez, LC; Chacon, JL; Semiglazov, V; Thill, M; Chan, A; Tusquets, I; Licata, L; Valagussa, P; Viale, G; Gianni, L;. Modulation by treatment of tumor infiltrating lymphocytes (TILs) and PDL1 expression in triple-negative breast cancer in the ETNA trial. ASCO2020.

71.

Hamilton E K V; Falkson, C; Vidal, GA; Ward, PJ; Patre, M; Chui, SY; Rotmensch, J; Gupta, K; Molinero, M; Li, Y; Emens, LA. Atezolizumab in combination with trastuzumab emtansine or with trastuzumab and pertuzumab in patients with HER2-positive breast cancer and atezolizumab with doxorubicin and cyclophosphamide in HER2-negative breast cancer: Safety and biomarker outcomes from a multi-cohort Phase Ib study. SABCS2019.

72.

Luke J P M R; Hamilton, HP; Chmielowski, B; Ulahannan, SV; Kindler, HL; Dahadur, SW; Clingan, PR; Mallesara, G; Weickhardt, AJ; Currence, S; Zu, L; Kaul, S; Chen, F; Moore, PA; Bonvini, E; Sumrow, B; Blumenschein, G. A phase I, first-in-human, open-label, dose-escalation study of MGD013, a bispecific DART molecule binding PD-1 and LAG-3, in patients with unresectable or metastatic neoplasms. ASCO2020.

73.

McArthur HL, Diab A, Page DB, Yuan J, Solomon SB, Sacchini V, et al. A Pilot Study of Preoperative Single-Dose Ipilimumab and/or Cryoablation in Women with Early-Stage Breast Cancer with Comprehensive Immune Profiling. Clin Cancer Res. 2016;22(23):5729–37. https://doi.org/10.1158/1078-0432.CCR-16-0190.CrossRefPubMedPubMedCentral

Title: Improving Breast Cancer Responses to Immunotherapy—a Search for the Achilles Heel of the Tumor Microenvironment
Authors: Sarah Jenkins
Robert Wesolowski
Margaret E. Gatti-Mays
Publication date: 01-05-2021
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Checkpoint Inhibitors
Published in: Current Oncology Reports / Issue 5/2021
Print ISSN: 1523-3790
Electronic ISSN: 1534-6269
DOI: https://doi.org/10.1007/s11912-021-01040-y

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose of review

Recent findings

Summary

Please log in to get access to this content

Other articles of this Issue 5/2021

Childhood Acute Leukemias in Developing Nations: Successes and Challenges

Prostate-Specific Membrane Antigen (PSMA)-Targeted Radionuclide Therapies for Prostate Cancer

Emerging Therapeutics for Patients with Triple-Negative Breast Cancer

Percutaneous Management of Recurrent Head and Neck Cancer: Current Role and Evolving Principles in the Multidisciplinary Setting

Global Perspectives on Palliative Care for Cancer Patients: Not All Countries Are the Same

The Role of Patient Support Groups in Neuroendocrine Neoplasms

Keynote webinar | Spotlight on antibody–drug conjugates in cancer