乳腺癌的免疫治療進展_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

陳潔 ¹ ,  彭榆富 ²

1. ;
2. ;

Corresponding?author：

彭榆富, Email: pengyufu664920@163.com

Keywords：

DOI：

10.7507/1007-9424.201908046

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Citation： 陳潔, 彭榆富. 乳腺癌的免疫治療進展. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2019, 26(12): 1403-1408. doi: 10.7507/1007-9424.201908046 Copy

1.	Coley WB. Ⅱ Contribution to the knowledge of sarcoma. Ann Surg, 1891, 14(3): 199-220.
2.	Gettinger S, Horn L, Jackman D, et al. Five-year follow-up of nivolumab in previously treated advanced non-small-cell lung cancer: results from the CA209-003 Study. J Clin Oncol, 2018, 36(17): 1675-1684.
3.	Thompson CB, Allison JP. The emerging role of CTLA-4 as an immune attenuator. Immunity, 1997, 7(4): 445-450.
4.	Nishimura H, Okazaki T, Tanaka Y, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science, 2001, 291(5502): 319-322.
5.	Abril-Rodriguez G, Ribas A. SnapShot: immune checkpoint inhibitors. Cancer Cell, 2017, 31(6): 848-848.e841.
6.	Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell, 2015, 27(4): 450-461.
7.	Granier C, De Guillebon E, Blanc C, et al. Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer. ESMO Open, 2017, 2(2): e000213.
8.	Solinas C, Gombos A, Latifyan S, et al. Targeting immune checkpoints in breast cancer: an update of early results. ESMO Open, 2017, 2(5): e000255.
9.	Salmaninejad A, Valilou SF, Shabgah AG, et al. PD-1/PD-L1 pathway: basic biology and role in cancer immunotherapy. J Cell Physiol, 2019, 234(10): 16824-16837.
10.	Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med, 2012, 366(26): 2455-2465.
11.	Okazaki T, Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol, 2007, 19(7): 813-824.
12.	Schmid P, Park YH, Munoz-Couselo E, et al. Pembrolizumab (pembro) plus chemotherapy (chemo) as neoadjuvant treatment for triple negative breast cancer (TNBC): preliminary results from KEYNOTE-173. http://apps.webofknowledge.com/Search.do?product=UA&SID=7EYfiA2D11IBlUT8WYO&search_mode=GeneralSearch&prID=088a2926-80f6-409a-a8be-ed0bc8fca996.
13.	Bertucci F, Gon?alves A. Immunotherapy in breast cancer: the emerging role of PD-1 and PD-L1. Curr Oncol Rep, 2017, 19(10): 64.
14.	Vonderheide RH, LoRusso PM, Khalil M, et al. Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cells. Clin Cancer Res, 2010, 16(13): 3485-3494.
15.	Rotte A. Combination of CTLA-4 and PD-1 blockers for treatment of cancer. J Exp Clin Cancer Res, 2019, 38(1): 255.
16.	Brignone C, Gutierrez M, Mefti F, et al. First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321(LAG-3Ig) enhances immune responses and antitumor activity. J Transl Med, 2010, 8: 71.
17.	Dirix L, Triebel F. AIPAC: a phase Ⅱb study of eftilagimod alpha (IMP321 or LAG-3Ig) added to weekly paclitaxel in patients with metastatic breast cancer. Future Oncol, 2019, 15(17): 1963-1973.
18.	Senkus E, Cardoso F, Pagani O. Time for more optimism in metastatic breast cancer? Cancer Treat Rev, 2014, 40(2): 220-228.
19.	Rugo HS, Delord JP, Im SA, 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): 2804-2811.
20.	Holgado E, Perez-Garcia J, Gion M, et al. Is there a role for immunotherapy in HER2-positive breast cancer? NPJ Breast Cancer, 2018, 4: 21.
21.	Loi S. Tumor-infiltrating lymphocytes, breast cancer subtypes and therapeutic efficacy. Oncoimmunology, 2013, 2(7): e24720.
22.	Müller P, Kreuzaler M, Khan T, et al. Trastuzumab emtansine (T-DM1) renders HER2+ breast cancer highly susceptible toCTLA-4/PD-1 blockade. Sci Transl Med, 2015, 7(315): 315ra188.
23.	Emens LA, Esteva F, Beresford M, et al. Results from KATE2, a randomized phase 2 study of atezolizumab (atezo) plus trastuzumab emtansine (T-DM1) vs placebo (pbo)+T-DM1 in previously treated HER2+ advanced breast cancer (BC). http://apps.webofknowledge.com/Search.do?product=UA&SID=7EYfiA2- D11IBlUT8WYO&search_mode=GeneralSearch&prID=ecb7443a-329b-4431-8e88-19db700cb296.
24.	Loi S, Giobbie-Hurder A, Gombos A, et al. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. Lancet Oncol, 2019, 20(3): 371-382.
25.	Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med, 2010, 134(7): e48-e72.
26.	Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res, 2007, 13(15 Pt 1): 4429-4434.
27.	Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol, 2008, 26(8): 1275-1281.
28.	Denkert C. The immunogenicity of breast cancer-molecular subtypes matter. Ann Oncol, 2014, 25(8): 1453-1455.
29.	Adams S, Loi S, Toppmeyer D, et al. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase Ⅱ KEYNOTE-086 study. Ann Oncol, 2019, 30(3): 405-411.
30.	Winer EP, Dang T, Karantza V, et al. KEYNOTE-119: A randomized phase Ⅲ study of single-agent pembrolizumab (MK-3475) vs single-agent chemotherapy per physician's choice for metastatic triple-negative breast cancer (mTNBC). http://apps.webofknowledge.com/Search.do?product=UA&SID=7EYfiA2D11I- BlUT8WYO&search_mode=GeneralSearch&prID=d76a5d7f-016b-4b40-8f9a-bcbda9acec83.
31.	Schmid P, Adams S, Rugo HS, et al. Atezolizumab and Nab-Paclitaxel in advanced triple-negative breast cancer. N Engl J Med, 2018, 379(22): 2108-2121.
32.	Schmid P, Adams S, Rugo HS, et al. IMpassion130: results from a global, randomised, double-blind, phase Ⅲ study of atezolizumab (atezo) plus nab-paclitaxel (nab-P) vs placebo plus nab-P in treatment-naive, locally advanced or metastatic triple-negative breast cancer (mTNBC). Ann Oncol, 2018, 29: 707-708.
33.	von Moos R, Emens LA, Loi S, et al. IMpassion130: efficacy in immune biomarker subgroups of atezolizumab plus nab-paclitaxel in patients with triple-negative BC. Swiss Medical Weekly, 2019, 149: 13S-14S.
34.	Adams S, Diamond JR, Hamilton E, et al. Atezolizumab plus nab-Paclitaxel in the treatment of metastatic triple-negative breast cancer with 2-year survival follow-up: a phase 1b clinical trial. JAMA Oncol, 2019, 5(3): 334-342.
35.	Page DB, Kim IK, Sanchez K, et al. Safety and efficacy of pembrolizumab (pembro) plus capecitabine (cape) in metastatic triple negative breast cancer (mTNBC). http://apps.webofknowledge.com/full_record.do?product=UA&search_mode=GeneralSearch&qid=16&SID=7EYfiA2D11IBlUT8WYO&page=1&doc=2.
36.	Cortés J, André F, Gon?alves A, et al. IMpassion132 phase Ⅲ trial: atezolizumab and chemotherapy in early relapsing metastatic triple-negative breast cancer. Future Oncol, 2019, 15(17): 1951-1961.
37.	Miles D, Kim SB, McNally V, et al. COLET: A multistage, phase 2 study evaluating the safety and efficacy of a doublet regimen of cobimetinib (C) in combination with paclitaxel (P) or triplet regimens of C in combination with atezolizumab (atezo) plus either P or nab-paclitaxel (nab-P) in metastatic triple-negative breast cancer (TNBC). http://apps.webofknowledge.com/Search.do?product=UA&SID=7EYfiA2D11IBlUT8WYO&search_mode=GeneralSearch&prID=450b237f-10de-46f3-8b8a-07bdc5fe36f1.
38.	Golden EB, Pellicciotta I, Demaria S, et al. The convergence of radiation and immunogenic cell death signaling pathways. Front Oncol, 2012, 2: 88.
39.	Deng L, Liang H, Xu M, et al. STING-dependent cytosolic DNA sensing promotes radiation-induced type i interferon-dependent antitumor immunity in immunogenic tumors. Immunity, 2014, 41(5): 843-852.
40.	Germano G, Lamba S, Rospo G, et al. Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth. Nature, 2017, 552(7683): 116-120.
41.	Matsumura S, Wang B, Kawashima N, et al. Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells. J Immunol, 2008, 181(5): 3099-3107.
42.	Sato H, Niimi A, Yasuhara T, et al. DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells. Nat Commun, 2017, 8(1): 1751.
43.	Reits EA, Hodge JW, Herberts CA, et al. Radiation modulates the peptide repertoire, enhances MHC class Ⅰ expression, and induces successful antitumor immunotherapy. J Exp Med, 2006, 203(5): 1259-1271.
44.	Deng L, Liang H, Burnette B, et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest, 2014, 124(2): 687-695.
45.	Loibl S, Untch M, Burchardi N, et al. Randomized phase Ⅱ neoadjuvant study (GeparNuevo) to investigate the addition of durvalumab to a taxane-anthracycline containing chemotherapy in triple negative breast cancer (TNBC). J Clin Oncol, 2018, 36(15_suppl): 104.
46.	Loibl S, Untch M, Burchardi N, 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, [Epub ahead of print].
47.	van’t Veer LJ, Wolf D, Yau C, et al. MammaPrint High1/High2 risk class as a pre-specified biomarker of response to nine different targeted agents plus standard neoadjuvant therapy for similar to 1 000 breast cancer patients in the I-SPY 2 TRIAL. Europ J Cancer, 2018, 103: E15.

1. Coley WB. Ⅱ Contribution to the knowledge of sarcoma. Ann Surg, 1891, 14(3): 199-220.
2. Gettinger S, Horn L, Jackman D, et al. Five-year follow-up of nivolumab in previously treated advanced non-small-cell lung cancer: results from the CA209-003 Study. J Clin Oncol, 2018, 36(17): 1675-1684.
3. Thompson CB, Allison JP. The emerging role of CTLA-4 as an immune attenuator. Immunity, 1997, 7(4): 445-450.
4. Nishimura H, Okazaki T, Tanaka Y, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science, 2001, 291(5502): 319-322.
5. Abril-Rodriguez G, Ribas A. SnapShot: immune checkpoint inhibitors. Cancer Cell, 2017, 31(6): 848-848.e841.
6. Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell, 2015, 27(4): 450-461.
7. Granier C, De Guillebon E, Blanc C, et al. Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer. ESMO Open, 2017, 2(2): e000213.
8. Solinas C, Gombos A, Latifyan S, et al. Targeting immune checkpoints in breast cancer: an update of early results. ESMO Open, 2017, 2(5): e000255.
9. Salmaninejad A, Valilou SF, Shabgah AG, et al. PD-1/PD-L1 pathway: basic biology and role in cancer immunotherapy. J Cell Physiol, 2019, 234(10): 16824-16837.
10. Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med, 2012, 366(26): 2455-2465.
11. Okazaki T, Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol, 2007, 19(7): 813-824.
12. Schmid P, Park YH, Munoz-Couselo E, et al. Pembrolizumab (pembro) plus chemotherapy (chemo) as neoadjuvant treatment for triple negative breast cancer (TNBC): preliminary results from KEYNOTE-173. http://apps.webofknowledge.com/Search.do?product=UA&SID=7EYfiA2D11IBlUT8WYO&search_mode=GeneralSearch&prID=088a2926-80f6-409a-a8be-ed0bc8fca996.
13. Bertucci F, Gon?alves A. Immunotherapy in breast cancer: the emerging role of PD-1 and PD-L1. Curr Oncol Rep, 2017, 19(10): 64.
14. Vonderheide RH, LoRusso PM, Khalil M, et al. Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cells. Clin Cancer Res, 2010, 16(13): 3485-3494.
15. Rotte A. Combination of CTLA-4 and PD-1 blockers for treatment of cancer. J Exp Clin Cancer Res, 2019, 38(1): 255.
16. Brignone C, Gutierrez M, Mefti F, et al. First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321(LAG-3Ig) enhances immune responses and antitumor activity. J Transl Med, 2010, 8: 71.
17. Dirix L, Triebel F. AIPAC: a phase Ⅱb study of eftilagimod alpha (IMP321 or LAG-3Ig) added to weekly paclitaxel in patients with metastatic breast cancer. Future Oncol, 2019, 15(17): 1963-1973.
18. Senkus E, Cardoso F, Pagani O. Time for more optimism in metastatic breast cancer? Cancer Treat Rev, 2014, 40(2): 220-228.
19. Rugo HS, Delord JP, Im SA, 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): 2804-2811.
20. Holgado E, Perez-Garcia J, Gion M, et al. Is there a role for immunotherapy in HER2-positive breast cancer? NPJ Breast Cancer, 2018, 4: 21.
21. Loi S. Tumor-infiltrating lymphocytes, breast cancer subtypes and therapeutic efficacy. Oncoimmunology, 2013, 2(7): e24720.
22. Müller P, Kreuzaler M, Khan T, et al. Trastuzumab emtansine (T-DM1) renders HER2+ breast cancer highly susceptible toCTLA-4/PD-1 blockade. Sci Transl Med, 2015, 7(315): 315ra188.
23. Emens LA, Esteva F, Beresford M, et al. Results from KATE2, a randomized phase 2 study of atezolizumab (atezo) plus trastuzumab emtansine (T-DM1) vs placebo (pbo)+T-DM1 in previously treated HER2+ advanced breast cancer (BC). http://apps.webofknowledge.com/Search.do?product=UA&SID=7EYfiA2- D11IBlUT8WYO&search_mode=GeneralSearch&prID=ecb7443a-329b-4431-8e88-19db700cb296.
24. Loi S, Giobbie-Hurder A, Gombos A, et al. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. Lancet Oncol, 2019, 20(3): 371-382.
25. Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med, 2010, 134(7): e48-e72.
26. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res, 2007, 13(15 Pt 1): 4429-4434.
27. Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol, 2008, 26(8): 1275-1281.
28. Denkert C. The immunogenicity of breast cancer-molecular subtypes matter. Ann Oncol, 2014, 25(8): 1453-1455.
29. Adams S, Loi S, Toppmeyer D, et al. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase Ⅱ KEYNOTE-086 study. Ann Oncol, 2019, 30(3): 405-411.
30. Winer EP, Dang T, Karantza V, et al. KEYNOTE-119: A randomized phase Ⅲ study of single-agent pembrolizumab (MK-3475) vs single-agent chemotherapy per physician's choice for metastatic triple-negative breast cancer (mTNBC). http://apps.webofknowledge.com/Search.do?product=UA&SID=7EYfiA2D11I- BlUT8WYO&search_mode=GeneralSearch&prID=d76a5d7f-016b-4b40-8f9a-bcbda9acec83.
31. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and Nab-Paclitaxel in advanced triple-negative breast cancer. N Engl J Med, 2018, 379(22): 2108-2121.
32. Schmid P, Adams S, Rugo HS, et al. IMpassion130: results from a global, randomised, double-blind, phase Ⅲ study of atezolizumab (atezo) plus nab-paclitaxel (nab-P) vs placebo plus nab-P in treatment-naive, locally advanced or metastatic triple-negative breast cancer (mTNBC). Ann Oncol, 2018, 29: 707-708.
33. von Moos R, Emens LA, Loi S, et al. IMpassion130: efficacy in immune biomarker subgroups of atezolizumab plus nab-paclitaxel in patients with triple-negative BC. Swiss Medical Weekly, 2019, 149: 13S-14S.
34. Adams S, Diamond JR, Hamilton E, et al. Atezolizumab plus nab-Paclitaxel in the treatment of metastatic triple-negative breast cancer with 2-year survival follow-up: a phase 1b clinical trial. JAMA Oncol, 2019, 5(3): 334-342.
35. Page DB, Kim IK, Sanchez K, et al. Safety and efficacy of pembrolizumab (pembro) plus capecitabine (cape) in metastatic triple negative breast cancer (mTNBC). http://apps.webofknowledge.com/full_record.do?product=UA&search_mode=GeneralSearch&qid=16&SID=7EYfiA2D11IBlUT8WYO&page=1&doc=2.
36. Cortés J, André F, Gon?alves A, et al. IMpassion132 phase Ⅲ trial: atezolizumab and chemotherapy in early relapsing metastatic triple-negative breast cancer. Future Oncol, 2019, 15(17): 1951-1961.
37. Miles D, Kim SB, McNally V, et al. COLET: A multistage, phase 2 study evaluating the safety and efficacy of a doublet regimen of cobimetinib (C) in combination with paclitaxel (P) or triplet regimens of C in combination with atezolizumab (atezo) plus either P or nab-paclitaxel (nab-P) in metastatic triple-negative breast cancer (TNBC). http://apps.webofknowledge.com/Search.do?product=UA&SID=7EYfiA2D11IBlUT8WYO&search_mode=GeneralSearch&prID=450b237f-10de-46f3-8b8a-07bdc5fe36f1.
38. Golden EB, Pellicciotta I, Demaria S, et al. The convergence of radiation and immunogenic cell death signaling pathways. Front Oncol, 2012, 2: 88.
39. Deng L, Liang H, Xu M, et al. STING-dependent cytosolic DNA sensing promotes radiation-induced type i interferon-dependent antitumor immunity in immunogenic tumors. Immunity, 2014, 41(5): 843-852.
40. Germano G, Lamba S, Rospo G, et al. Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth. Nature, 2017, 552(7683): 116-120.
41. Matsumura S, Wang B, Kawashima N, et al. Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells. J Immunol, 2008, 181(5): 3099-3107.
42. Sato H, Niimi A, Yasuhara T, et al. DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells. Nat Commun, 2017, 8(1): 1751.
43. Reits EA, Hodge JW, Herberts CA, et al. Radiation modulates the peptide repertoire, enhances MHC class Ⅰ expression, and induces successful antitumor immunotherapy. J Exp Med, 2006, 203(5): 1259-1271.
44. Deng L, Liang H, Burnette B, et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest, 2014, 124(2): 687-695.
45. Loibl S, Untch M, Burchardi N, et al. Randomized phase Ⅱ neoadjuvant study (GeparNuevo) to investigate the addition of durvalumab to a taxane-anthracycline containing chemotherapy in triple negative breast cancer (TNBC). J Clin Oncol, 2018, 36(15_suppl): 104.
46. Loibl S, Untch M, Burchardi N, 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, [Epub ahead of print].
47. van’t Veer LJ, Wolf D, Yau C, et al. MammaPrint High1/High2 risk class as a pre-specified biomarker of response to nine different targeted agents plus standard neoadjuvant therapy for similar to 1 000 breast cancer patients in the I-SPY 2 TRIAL. Europ J Cancer, 2018, 103: E15.

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乳腺癌的免疫治療進展

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