Research progress of immunotherapy for metastatic breast cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YU Xin ¹ ,  SUN Shengrong ¹ ,  WANG Weixing ²

1. Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, P. R. China;
2. Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, P. R. China;

Corresponding author：

SUN Shengrong, Email: sun137@sina.com; WANG Weixing, Email: sate.llite@163.com

Keywords：

metastatic breast cancer; immunotherapy; triple-negative breast cancer; immune checkpoint inhibitor

DOI：

10.7507/1007-9424.202107040

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To summarize the research progress of immunotherapy for metastatic breast cancer. Method Literatures about immunotherapy for metastatic breast cancer were reviewed by searching the literatures in domestic and foreign database. Results In recent years, immunotherapy had been initially attempted in patients with metastatic breast cancer and showed its unique value. It provided a new way to improve the therapeutic effect and prolong the survival time of patients with metastatic breast cancer. Conclusions Immunotherapy is the most effective in triple-negative metastatic breast cancers. The immuno-oncology needs to be developed to improve the clinical benefits of immunotherapy for breast cancer.

Citation： YU Xin, SUN Shengrong, WANG Weixing. Research progress of immunotherapy for metastatic breast cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(4): 539-544. doi: 10.7507/1007-9424.202107040 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	Jazieh K, Bell R, Agarwal N, et al. Novel targeted therapies for metastatic breast cancer. Ann Transl Med, 2020, 8(14): 907. doi: 10.21037/atm.2020.03.43.
3.	Bhoo-Pathy N, Verkooijen HM, Tan EY, et al. Trends in presentation, management and survival of patients with de novo metastatic breast cancer in a Southeast Asian setting. Sci Rep, 2015, 5: 16252. doi: 10.1038/srep16252.
4.	Mendes D, Alves C, Afonso N, et al. The benefit of HER2-targeted therapies on overall survival of patients with metastatic HER2-positive breast cancer—a systematic review. Breast Cancer Res, 2015, 17: 140. doi: 10.1186/s13058-015-0648-2.
5.	Kennecke H, Yerushalmi R, Woods R, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol, 2010, 28(20): 3271-3277.
6.	Gerratana L, Fanotto V, Bonotto M, et al. Pattern of metastasis and outcome in patients with breast cancer. Clin Exp Metastasis, 2015, 32(2): 125-133.
7.	Peart O. Metastatic Breast Cancer. Radiol Technol, 2017, 88(5): 519M-539M.
8.	Al-Mahmood S, Sapiezynski J, Garbuzenko OB, et al. Metastatic and triple-negative breast cancer: challenges and treatment options. Drug Deliv Transl Res, 2018, 8(5): 1483-1507.
9.	Fragomeni SM, Sciallis A, Jeruss JS. Molecular subtypes and local-regional control of breast cancer. Surg Oncol Clin N Am, 2018, 27(1): 95-120.
10.	Feys L, Descamps B, Vanhove C, et al. Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling. Oncotarget, 2015, 6(29): 26615-26632.
11.	陈洁, 彭榆富. 乳腺癌的免疫治疗进展. 中国普外基础与临床杂志, 2019, 26(12): 1403-1408.
12.	Lipson EJ, Forde PM, Hammers HJ, et al. Antagonists of PD-1 and PD-L1 in cancer treatment. Semin Oncol, 2015, 42(4): 587-600.
13.	Emens LA, Ascierto PA, Darcy PK, et al. Cancer immunotherapy: Opportunities and challenges in the rapidly evolving clinical landscape. Eur J Cancer, 2017, 81: 116-129.
14.	Emens LA. Breast cancer immunotherapy: facts and hopes. Clin Cancer Res, 2018, 24(3): 511-520.
15.	de Miguel M, Calvo E. Clinical challenges of immune checkpoint inhibitors. Cancer Cell, 2020, 38(3): 326-333.
16.	Heeke AL, Tan AR. Checkpoint inhibitor therapy for metastatic triple-negative breast cancer. Cancer Metastasis Rev, 2021, 40(2): 537-547.
17.	Bense RD, Sotiriou C, Piccart-Gebhart MJ, et al. Relevance of tumor-infiltrating immune cell composition and functionality for disease outcome in breast cancer. J Natl Cancer Inst, 2016, 109(1): djw192. doi: 10.1093/jnci/djw192. Print 2017 Jan.
18.	Loi S, Sirtaine N, Piette 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): 860-867.
19.	Budczies J, Bockmayr M, Denkert C, et al. Classical pathology and mutational load of breast cancer—integration of two worlds. J Pathol Clin Res, 2015, 1(4): 225-238.
20.	Simmons CE, Brezden-Masley C, McCarthy J, et al. Positive progress: current and evolving role of immune checkpoint inhibitors in metastatic triple-negative breast cancer. Ther Adv Med Oncol, 2020, 12: 1758835920909091. doi: 10.1177/1758835920909091.
21.	Nanda R, Chow LQ, Dees EC, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ⅰ b KEYNOTE-012 study. J Clin Oncol, 2016, 34(21): 2460-2467.
22.	Adams S, Schmid P, Rugo H S, et al. Phase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A. J Clin Oncol, 2017, 35: 1008-1008.
23.	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.
24.	Adams S, Loi S, Toppmeyer D, et al. Phase 2 study of pembrolizumab as first-line therapy for PD-L1–positive metastatic triple-negative breast cancer (mTNBC): preliminary data from KEYNOTE-086 cohort B. J Clin Oncol, 2017, 35(15 Suppl): 1088.
25.	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) . J Clin Oncol, 2016, 34(15 Suppl) : TPS1102.
26.	Winer EP, Lipatov O, Im SA, et al. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Lancet Oncol, 2021, 22(4): 499-511.
27.	Emens LA, Cruz C, Eder JP, et al. Long-term clinical outcomes and biomarker analyses of atezolizumab therapy for patients with metastatic triple-negative breast cancer: A phase 1 study. JAMA Oncol, 2019, 5(1): 74-82.
28.	Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1. 1). Eur J Cancer, 2009, 45(2): 228-247.
29.	Wolchok JD, Hoos A, O'Day S, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res, 2009, 15(23): 7412-7420.
30.	Dirix LY, Takacs I, Jerusalem G, 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): 671-686.
31.	Emens LA, Middleton G. The interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol Res, 2015, 3(5): 436-443.
32.	Tolaney S, Savulsky C, Aktan G, et al. Phase 1b/2 study to evaluate eribulin mesylate in combination with pembrolizumab in patients with metastatic triple-negative breast cancer. Asia Pac J Clin Oncol, 2018, 14(7 Suppl): 176.
33.	Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet, 2020, 396(10265): 1817-1828.
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.	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.
36.	Miles D, Gligorov J, André F, et al. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase Ⅲ trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol, 2021, 32(8): 994-1004.
37.	Esteva FJ, Hubbard-Lucey VM, Tang J, et al. Immunotherapy and targeted therapy combinations in metastatic breast cancer. Lancet Oncol, 2019, 20(3): e175-e186. doi: 10.1016/S1470-2045(19)30026-9.
38.	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.
39.	Chia S, Bedard PL, Hilton J, et al. A phase Ⅰ b trial of durvalumab in combination with trastuzumab in HER2-positive metastatic breast cancer (CCTG IND. 229). Oncologist, 2019, 24(11): 1439-1445.
40.	Emens LA, Esteva FJ, Beresford M, et al. Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial. Lancet Oncol, 2020, 21(10): 1283-1295.
41.	Jiao S, Xia W, Yamaguchi H, et al. PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. Clin Cancer Res, 2017, 23(14): 3711-3720.
42.	Vinayak S, Tolaney S M, Schwartzberg L S, et al. TOPACIO/Keynote-162: Niraparib + pembrolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC), a phase 2 trial. J Clin Oncol, 2018, 36(15 Suppl): 1011 .
43.	Domchek SM, Postel-Vinay S, Im SA, et al. Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Lancet Oncol, 2020, 21(9): 1155-1164.
44.	Pan C, Liu H, Robins E, et al. Next-generation immuno-oncology agents: current momentum shifts in cancer immunotherapy. J Hematol Oncol, 2020, 13(1): 29. doi: 10.1186/s13045-020-00862-w.
45.	Wu Q, Yu X, Li J, et al. Metabolic regulation in the immune response to cancer. Cancer Commun (Lond), 2021, 41(8): 661-694.
46.	Moon YW, Hajjar J, Hwu P, et al. Targeting the indoleamine 2, 3-dioxygenase pathway in cancer. J Immunother Cancer, 2015, 3: 51. doi: 10.1186/s40425-015-0094-9.
47.	Hamid O, Bauer T M, Spira A I, et al. Safety of epacadostat 100 mg bid plus pembrolizumab 200 mg Q3W in advanced solid tumors: Phase 2 data from ECHO-202/KEYNOTE-037. J Clin Oncol, 2017, 35(15 Suppl): 3012.
48.	Li J, Eu JQ, Kong LR, et al. Targeting metabolism in cancer cells and the tumour microenvironment for cancer therapy. Molecules, 2020, 25(20): 4831. doi: 10.3390/molecules25204831.
49.	Szekely B, Bossuyt V, Li X, et al. Immunological differences between primary and metastatic breast cancer. Ann Oncol, 2018, 29(11): 2232-2239.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Jazieh K, Bell R, Agarwal N, et al. Novel targeted therapies for metastatic breast cancer. Ann Transl Med, 2020, 8(14): 907. doi: 10.21037/atm.2020.03.43.
3. Bhoo-Pathy N, Verkooijen HM, Tan EY, et al. Trends in presentation, management and survival of patients with de novo metastatic breast cancer in a Southeast Asian setting. Sci Rep, 2015, 5: 16252. doi: 10.1038/srep16252.
4. Mendes D, Alves C, Afonso N, et al. The benefit of HER2-targeted therapies on overall survival of patients with metastatic HER2-positive breast cancer—a systematic review. Breast Cancer Res, 2015, 17: 140. doi: 10.1186/s13058-015-0648-2.
5. Kennecke H, Yerushalmi R, Woods R, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol, 2010, 28(20): 3271-3277.
6. Gerratana L, Fanotto V, Bonotto M, et al. Pattern of metastasis and outcome in patients with breast cancer. Clin Exp Metastasis, 2015, 32(2): 125-133.
7. Peart O. Metastatic Breast Cancer. Radiol Technol, 2017, 88(5): 519M-539M.
8. Al-Mahmood S, Sapiezynski J, Garbuzenko OB, et al. Metastatic and triple-negative breast cancer: challenges and treatment options. Drug Deliv Transl Res, 2018, 8(5): 1483-1507.
9. Fragomeni SM, Sciallis A, Jeruss JS. Molecular subtypes and local-regional control of breast cancer. Surg Oncol Clin N Am, 2018, 27(1): 95-120.
10. Feys L, Descamps B, Vanhove C, et al. Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling. Oncotarget, 2015, 6(29): 26615-26632.
11. 陈洁, 彭榆富. 乳腺癌的免疫治疗进展. 中国普外基础与临床杂志, 2019, 26(12): 1403-1408.
12. Lipson EJ, Forde PM, Hammers HJ, et al. Antagonists of PD-1 and PD-L1 in cancer treatment. Semin Oncol, 2015, 42(4): 587-600.
13. Emens LA, Ascierto PA, Darcy PK, et al. Cancer immunotherapy: Opportunities and challenges in the rapidly evolving clinical landscape. Eur J Cancer, 2017, 81: 116-129.
14. Emens LA. Breast cancer immunotherapy: facts and hopes. Clin Cancer Res, 2018, 24(3): 511-520.
15. de Miguel M, Calvo E. Clinical challenges of immune checkpoint inhibitors. Cancer Cell, 2020, 38(3): 326-333.
16. Heeke AL, Tan AR. Checkpoint inhibitor therapy for metastatic triple-negative breast cancer. Cancer Metastasis Rev, 2021, 40(2): 537-547.
17. Bense RD, Sotiriou C, Piccart-Gebhart MJ, et al. Relevance of tumor-infiltrating immune cell composition and functionality for disease outcome in breast cancer. J Natl Cancer Inst, 2016, 109(1): djw192. doi: 10.1093/jnci/djw192. Print 2017 Jan.
18. Loi S, Sirtaine N, Piette 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): 860-867.
19. Budczies J, Bockmayr M, Denkert C, et al. Classical pathology and mutational load of breast cancer—integration of two worlds. J Pathol Clin Res, 2015, 1(4): 225-238.
20. Simmons CE, Brezden-Masley C, McCarthy J, et al. Positive progress: current and evolving role of immune checkpoint inhibitors in metastatic triple-negative breast cancer. Ther Adv Med Oncol, 2020, 12: 1758835920909091. doi: 10.1177/1758835920909091.
21. Nanda R, Chow LQ, Dees EC, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ⅰ b KEYNOTE-012 study. J Clin Oncol, 2016, 34(21): 2460-2467.
22. Adams S, Schmid P, Rugo H S, et al. Phase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A. J Clin Oncol, 2017, 35: 1008-1008.
23. 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.
24. Adams S, Loi S, Toppmeyer D, et al. Phase 2 study of pembrolizumab as first-line therapy for PD-L1–positive metastatic triple-negative breast cancer (mTNBC): preliminary data from KEYNOTE-086 cohort B. J Clin Oncol, 2017, 35(15 Suppl): 1088.
25. 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) . J Clin Oncol, 2016, 34(15 Suppl) : TPS1102.
26. Winer EP, Lipatov O, Im SA, et al. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Lancet Oncol, 2021, 22(4): 499-511.
27. Emens LA, Cruz C, Eder JP, et al. Long-term clinical outcomes and biomarker analyses of atezolizumab therapy for patients with metastatic triple-negative breast cancer: A phase 1 study. JAMA Oncol, 2019, 5(1): 74-82.
28. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1. 1). Eur J Cancer, 2009, 45(2): 228-247.
29. Wolchok JD, Hoos A, O'Day S, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res, 2009, 15(23): 7412-7420.
30. Dirix LY, Takacs I, Jerusalem G, 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): 671-686.
31. Emens LA, Middleton G. The interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol Res, 2015, 3(5): 436-443.
32. Tolaney S, Savulsky C, Aktan G, et al. Phase 1b/2 study to evaluate eribulin mesylate in combination with pembrolizumab in patients with metastatic triple-negative breast cancer. Asia Pac J Clin Oncol, 2018, 14(7 Suppl): 176.
33. Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet, 2020, 396(10265): 1817-1828.
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. 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.
36. Miles D, Gligorov J, André F, et al. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase Ⅲ trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol, 2021, 32(8): 994-1004.
37. Esteva FJ, Hubbard-Lucey VM, Tang J, et al. Immunotherapy and targeted therapy combinations in metastatic breast cancer. Lancet Oncol, 2019, 20(3): e175-e186. doi: 10.1016/S1470-2045(19)30026-9.
38. 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.
39. Chia S, Bedard PL, Hilton J, et al. A phase Ⅰ b trial of durvalumab in combination with trastuzumab in HER2-positive metastatic breast cancer (CCTG IND. 229). Oncologist, 2019, 24(11): 1439-1445.
40. Emens LA, Esteva FJ, Beresford M, et al. Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial. Lancet Oncol, 2020, 21(10): 1283-1295.
41. Jiao S, Xia W, Yamaguchi H, et al. PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. Clin Cancer Res, 2017, 23(14): 3711-3720.
42. Vinayak S, Tolaney S M, Schwartzberg L S, et al. TOPACIO/Keynote-162: Niraparib + pembrolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC), a phase 2 trial. J Clin Oncol, 2018, 36(15 Suppl): 1011 .
43. Domchek SM, Postel-Vinay S, Im SA, et al. Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Lancet Oncol, 2020, 21(9): 1155-1164.
44. Pan C, Liu H, Robins E, et al. Next-generation immuno-oncology agents: current momentum shifts in cancer immunotherapy. J Hematol Oncol, 2020, 13(1): 29. doi: 10.1186/s13045-020-00862-w.
45. Wu Q, Yu X, Li J, et al. Metabolic regulation in the immune response to cancer. Cancer Commun (Lond), 2021, 41(8): 661-694.
46. Moon YW, Hajjar J, Hwu P, et al. Targeting the indoleamine 2, 3-dioxygenase pathway in cancer. J Immunother Cancer, 2015, 3: 51. doi: 10.1186/s40425-015-0094-9.
47. Hamid O, Bauer T M, Spira A I, et al. Safety of epacadostat 100 mg bid plus pembrolizumab 200 mg Q3W in advanced solid tumors: Phase 2 data from ECHO-202/KEYNOTE-037. J Clin Oncol, 2017, 35(15 Suppl): 3012.
48. Li J, Eu JQ, Kong LR, et al. Targeting metabolism in cancer cells and the tumour microenvironment for cancer therapy. Molecules, 2020, 25(20): 4831. doi: 10.3390/molecules25204831.
49. Szekely B, Bossuyt V, Li X, et al. Immunological differences between primary and metastatic breast cancer. Ann Oncol, 2018, 29(11): 2232-2239.

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Research progress of immunotherapy for metastatic breast cancer

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