REFERENCES

1. Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025;75:10-45.

2. Swain SM, Shastry M, Hamilton E. Targeting HER2-positive breast cancer: advances and future directions. Nat Rev Drug Discov. 2023;22:101-26.

3. Choong GM, Cullen GD, O’Sullivan CC. Evolving standards of care and new challenges in the management of HER2-positive breast cancer. CA Cancer J Clin. 2020;70:355-74.

4. Tarantino P, Curigliano G, Parsons HA, et al. Aiming at a tailored cure for ERBB2-positive metastatic breast cancer: a review. JAMA Oncol. 2022;8:629-35.

5. Dong C, Wu J, Chen Y, Nie J, Chen C. Activation of PI3K/AKT/mTOR pathway causes drug resistance in breast cancer. Front Pharmacol. 2021;12:628690.

6. Triulzi T, Regondi V, De Cecco L, et al. Early immune modulation by single-agent trastuzumab as a marker of trastuzumab benefit. Br J Cancer. 2018;119:1487-94.

7. Kumagai S, Koyama S, Nishikawa H. Antitumour immunity regulated by aberrant ERBB family signalling. Nat Rev Cancer. 2021;21:181-97.

8. Low SK, Zembutsu H, Nakamura Y. Breast cancer: the translation of big genomic data to cancer precision medicine. Cancer Sci. 2018;109:497-506.

9. Zakaria NH, Hashad D, Saied MH, Hegazy N, Elkayal A, Tayae E. Genetic mutations in HER2-positive breast cancer: possible association with response to trastuzumab therapy. Hum Genomics. 2023;17:43.

10. Pohlmann PR, Mayer IA, Mernaugh R. Resistance to trastuzumab in breast cancer. Clin Cancer Res. 2009;15:7479-91.

11. Li Q, Qian W, Zhang Y, Hu L, Chen S, Xia Y. A new wave of innovations within the DNA damage response. Signal Transduct Target Ther. 2023;8:338.

12. Loibl S, Majewski I, Guarneri V, et al. PIK3CA mutations are associated with reduced pathological complete response rates in primary HER2-positive breast cancer: pooled analysis of 967 patients from five prospective trials investigating lapatinib and trastuzumab. Ann Oncol. 2016;27:1519-25.

13. Pietrantonio F, Manca P, Bellomo SE, et al. HER2 copy number and resistance mechanisms in patients with HER2-positive advanced gastric cancer receiving initial trastuzumab-based therapy in JACOB trial. Clin Cancer Res. 2023;29:571-80.

14. Baselga J. Treatment of HER2-overexpressing breast cancer. Ann Oncol. 2010;21 Suppl 7:vii36-40.

15. Salgado R, Denkert C, Campbell 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;1:448-54.

16. Collins GS, Moons KGM, Dhiman P, et al. TRIPOD+AI statement: updated guidance for reporting clinical prediction models that use regression or machine learning methods. BMJ. 2024;385:e078378.

17. Shu L, Tong Y, Li Z, Chen X, Shen K. Can HER2 1+ breast cancer be considered as HER2-low tumor? A comparison of clinicopathological features, quantitative HER2 mRNA levels, and prognosis among HER2-negative breast cancer. Cancers. 2022;14:4250.

18. Allison KH, Hammond MEH, Dowsett M, et al. Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol. 2020;38:1346-66.

19. Wolff AC, Hammond MEH, Allison KH, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018;36:2105-22.

20. Salgado R, Denkert C, Demaria S, et al; International TILs Working Group 2014. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26:259-71.

21. Tolaney SM, Garrett-Mayer E, White J, et al. Updated standardized definitions for efficacy end points (STEEP) in adjuvant breast cancer clinical trials: STEEP version 2.0. J Clin Oncol. 2021;39:2720-31.

22. Wong H, Leung R, Kwong A, et al. Integrating molecular mechanisms and clinical evidence in the management of trastuzumab resistant or refractory HER-2⁺ metastatic breast cancer. Oncologist. 2011;16:1535-46.

23. Sanchez-Vega F, Mina M, Armenia J, et al; Cancer Genome Atlas Research Network. Oncogenic signaling pathways in The Cancer Genome Atlas. Cell. 2018;173:321-37.e10.

24. Färkkilä A, Rodríguez A, Oikkonen J, et al. Heterogeneity and clonal evolution of acquired PARP inhibitor resistance in TP53- and BRCA1-deficient cells. Cancer Res. 2021;81:2774-87.

25. Viansone A, Pellegrino B, Omarini C, et al. Prognostic significance of germline BRCA mutations in patients with HER2-POSITIVE breast cancer. Breast. 2022;65:145-50.

26. Huang X, Qin F, Meng Q, Dong M. Protein tyrosine phosphatase receptor type D (PTPRD)-mediated signaling pathways for the potential treatment of hepatocellular carcinoma: a narrative review. Ann Transl Med. 2020;8:1192.

27. Shah D, Osipo C. Cancer stem cells and HER2 positive breast cancer: the story so far. Genes Dis. 2016;3:114-23.

28. Chakrabarty A, Bhola NE, Sutton C, et al. Trastuzumab-resistant cells rely on a HER2-PI3K-FoxO-survivin axis and are sensitive to PI3K inhibitors. Cancer Res. 2013;73:1190-200.

29. Dong Y, Zhao L, Duan J, et al. PAPPA2 mutation as a novel indicator stratifying beneficiaries of immune checkpoint inhibitors in skin cutaneous melanoma and non-small cell lung cancer. Cell Prolif. 2022;55:e13283.

30. Poddar A, Ahmady F, Rao SR, et al. The role of pregnancy associated plasma protein-A in triple negative breast cancer: a promising target for achieving clinical benefits. J Biomed Sci. 2024;31:23.

31. Lu Y, Zi X, Zhao Y, Mascarenhas D, Pollak M. Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin). J Natl Cancer Inst. 2001;93:1852-7.

32. Ticha P, Northey JJ, Kersten K, et al. NCOR2 represses MHC class I molecule expression to drive metastatic progression of breast cancer. bioRxiv. 2025.

33. Jiang BH, Liu LZ. Role of mTOR in anticancer drug resistance: perspectives for improved drug treatment. Drug Resist Updat. 2008;11:63-76.

34. Chen S, Lin J, Zhao J, et al. FBXW7 attenuates tumor drug resistance and enhances the efficacy of immunotherapy. Front Oncol. 2023;13:1147239.

35. Balamurugan K, Mendoza-Villanueva D, Sharan S, et al. C/EBPδ links IL-6 and HIF-1 signaling to promote breast cancer stem cell-associated phenotypes. Oncogene. 2019;38:3765-80.

36. Yicheng F, Xin L, Tian Y, Huilin L. Association of FLG mutation with tumor mutation load and clinical outcomes in patients with gastric cancer. Front Genet. 2022;13:808542.

37. Mitsui Y, Shiina H, Kato T, et al. Versican promotes tumor progression, metastasis and predicts poor prognosis in renal carcinoma. Mol Cancer Res. 2017;15:884-95.

38. Arichi N, Mitsui Y, Hiraki M, et al. Versican is a potential therapeutic target in docetaxel-resistant prostate cancer. Oncoscience. 2015;2:193-204.

39. Osipo C, Patel P, Rizzo P, et al. ErbB-2 inhibition activates Notch-1 and sensitizes breast cancer cells to a gamma-secretase inhibitor. Oncogene. 2008;27:5019-32.

40. Pandya K, Meeke K, Clementz AG, et al. Targeting both Notch and ErbB-2 signalling pathways is required for prevention of ErbB-2-positive breast tumour recurrence. Br J Cancer. 2011;105:796-806.

41. Nik-Zainal S, Davies H, Staaf J, et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature. 2016;534:47-54.

42. Zwimpfer TA, Heidinger M, Coelho R, et al. TP53 mutations and phosphatidylinositol 3-kinase/AKT pathway alterations are key determinants of breast cancer outcome independent of subtype and stage. JCO Precis Oncol. 2025;9:e2400767.

43. Dieci MV, Conte P, Bisagni G, et al. Association of tumor-infiltrating lymphocytes with distant disease-free survival in the ShortHER randomized adjuvant trial for patients with early HER2+ breast cancer. Ann Oncol. 2019;30:418-23.

44. Kim RS, Song N, Gavin PG, et al. Stromal tumor-infiltrating lymphocytes in NRG oncology/NSABP B-31 adjuvant trial for early-stage HER2-positive breast cancer. J Natl Cancer Inst. 2019;111:867-71.

45. Musolino A, Naldi N, Bortesi B, et al. Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol. 2008;26:1789-96.

46. Seo AN, Lee HJ, Kim EJ, et al. Tumour-infiltrating CD8+ lymphocytes as an independent predictive factor for pathological complete response to primary systemic therapy in breast cancer. Br J Cancer. 2013;109:2705-13.

47. Mahmoud SM, Paish EC, Powe DG, et al. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol. 2011;29:1949-55.

48. Bates GJ, Fox SB, Han C, et al. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol. 2006;24:5373-80.

49. West NR, Kost SE, Martin SD, et al. Tumour-infiltrating FOXP3⁺ lymphocytes are associated with cytotoxic immune responses and good clinical outcome in oestrogen receptor-negative breast cancer. Br J Cancer. 2013;108:155-62.

50. Gu-Trantien C, Loi S, Garaud S, et al. CD4⁺ follicular helper T cell infiltration predicts breast cancer survival. J Clin Invest. 2013;123:2873-92.

51. Teschendorff AE, Gomez S, Arenas A, et al. Improved prognostic classification of breast cancer defined by antagonistic activation patterns of immune response pathway modules. BMC Cancer. 2010;10:604.

52. Vanni S, Caputo TM, Cusano AM, et al. Engineered anti-HER2 drug delivery nanosystems for the treatment of breast cancer. Nanoscale. 2025;17:9436-57.