Tumor microenvironment response to neoadjuvant therapy in breast cancer: insights from single-cell and spatial omics

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660.

Article  PubMed  CAS  Google Scholar 

Gradishar WJ, Moran MS, Abraham J, Abramson V, Aft R, Agnese D, et al. NCCN guidelines® insights: breast cancer, version 4.2023. J Natl Compr Canc Netw. 2023;21(6):594–608. https://doi.org/10.6004/jnccn.2023.0031.

Article  PubMed  Google Scholar 

Soysal SD, Tzankov A, Muenst SE. Role of the tumor microenvironment in breast cancer. Pathobiology. 2015;82(3–4):142–52. https://doi.org/10.1159/000430499.

Article  PubMed  CAS  Google Scholar 

Jiang E, Yan T, Xu Z, Shang Z. Tumor microenvironment and cell fusion. Biomed Res Int. 2019;2019:5013592. https://doi.org/10.1155/2019/5013592.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Shah DD, Chorawala MR, Raghani NR, Patel R, Fareed M, Kashid VA, et al. Tumor microenvironment: recent advances in understanding and its role in modulating cancer therapies. Med Oncol. 2025;42(4):117. https://doi.org/10.1007/s12032-025-02641-4.

Article  PubMed  Google Scholar 

von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30(15):1796–804. https://doi.org/10.1200/jco.2011.38.8595.

Article  Google Scholar 

Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–72. https://doi.org/10.1016/s0140-6736(13)62422-8.

Article  PubMed  Google Scholar 

Fisher B. Biological and clinical considerations regarding the use of surgery and chemotherapy in the treatment of primary breast cancer. Cancer. 1977;40(1 Suppl):574–87.

Article  PubMed  CAS  Google Scholar 

Rastogi P, Wickerham DL, Geyer CE Jr, Mamounas EP, Julian TB, Wolmark N. Milestone clinical trials of the National Surgical Adjuvant Breast and Bowel Project (NSABP). Chin Clin Oncol. 2017;6(1):7. https://doi.org/10.21037/cco.2017.02.02.

Article  PubMed  PubMed Central  Google Scholar 

Hensing W, Santa-Maria CA, Peterson LL, Sheng JY. Landmark trials in the medical oncology management of early stage breast cancer. Semin Oncol. 2020;47(5):278–92. https://doi.org/10.1053/j.seminoncol.2020.08.001.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Early Breast Cancer Trialists’ Collaborative Group. Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: a patient-level meta-analysis of 100 000 women from 86 randomised trials. Lancet. 2023;401(10384):1277–92. https://doi.org/10.1016/s0140-6736(23)00285-4.

Article  CAS  Google Scholar 

Barchiesi G, Mazzotta M, Krasniqi E, Pizzuti L, Marinelli D, Capomolla E, et al. Neoadjuvant endocrine therapy in breast cancer: current knowledge and future perspectives. Int J Mol Sci. 2020. https://doi.org/10.3390/ijms21103528.

Article  PubMed  PubMed Central  Google Scholar 

Loibl S, Weber KE, Timms KM, Elkin EP, Hahnen E, Fasching PA, et al. Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto. Ann Oncol. 2018;29(12):2341–7. https://doi.org/10.1093/annonc/mdy460.

Article  PubMed  CAS  Google Scholar 

Zhang L, Wu ZY, Li J, Lin Y, Liu Z, Cao Y, et al. Neoadjuvant docetaxel plus carboplatin vs epirubicin plus cyclophosphamide followed by docetaxel in triple-negative, early-stage breast cancer (NeoCART): results from a multicenter, randomized controlled, open-label phase II trial. Int J Cancer. 2022;150(4):654–62. https://doi.org/10.1002/ijc.33830.

Article  PubMed  CAS  Google Scholar 

Bae SJ, Kim JH, Kim MJ, Kook Y, Baek SH, Kim JH, et al. Stromal tumor-infiltrating lymphocytes and pathologic response to neoadjuvant chemotherapy with the addition of platinum and pembrolizumab in TNBC: a single-center real-world study. Breast Cancer Res. 2024;26(1):182. https://doi.org/10.1186/s13058-024-01944-0.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Kim J, Munster PN. Estrogens and breast cancer. Ann Oncol. 2025;36(2):134–48. https://doi.org/10.1016/j.annonc.2024.10.824.

Article  PubMed  CAS  Google Scholar 

Kim HJ, Noh WC, Lee ES, Jung YS, Kim LS, Han W, et al. Efficacy of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy in pre-menopausal patients with oestrogen receptor-positive and HER2-negative, lymph node-positive breast cancer. Breast Cancer Res. 2020;22(1):54. https://doi.org/10.1186/s13058-020-01288-5.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Early Breast Cancer Trialists’ Collaborative Group. Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials. Lancet Oncol. 2022;23(3):382–92. https://doi.org/10.1016/s1470-2045(21)00758-0.

Article  CAS  Google Scholar 

Ellis MJ, Suman VJ, Hoog J, Lin L, Snider J, Prat A, et al. Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype–ACOSOG Z1031. J Clin Oncol. 2011;29(17):2342–9. https://doi.org/10.1200/jco.2010.31.6950.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Goel S, Bergholz JS, Zhao JJ. Targeting CDK4 and CDK6 in cancer. Nat Rev Cancer. 2022;22(6):356–72. https://doi.org/10.1038/s41568-022-00456-3.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Shi Q, Yang W, Ouyang Y, Liu Y, Cai Z. CXCR4 promotes tumor stemness maintenance and CDK4/6 inhibitors resistance in ER-positive breast cancer. Breast Cancer Res. 2025;27(1):15. https://doi.org/10.1186/s13058-025-01965-3.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Johnston SRD, Toi M, O’Shaughnessy J, Rastogi P, Campone M, Neven P, et al. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24(1):77–90. https://doi.org/10.1016/s1470-2045(22)00694-5.

Article  PubMed  CAS  Google Scholar 

Sharkey RM, Goldenberg DM. Targeted therapy of cancer: new prospects for antibodies and immunoconjugates. CA Cancer J Clin. 2006;56(4):226–43. https://doi.org/10.3322/canjclin.56.4.226.

Article  PubMed  Google Scholar 

Hurvitz SA, Martin M, Jung KH, Huang CS, Harbeck N, Valero V, et al. Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2-positive breast cancer: three-year outcomes from the phase III kristine study. J Clin Oncol. 2019;37(25):2206–16. https://doi.org/10.1200/jco.19.00882.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(4):519–30. https://doi.org/10.1016/s1470-2045(19)30863-0.

Article  PubMed  CAS  Google Scholar 

Doroshow DB, Bhalla S, Beasley MB, Sholl LM, Kerr KM, Gnjatic S, et al. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat Rev Clin Oncol. 2021;18(6):345–62. https://doi.org/10.1038/s41571-021-00473-5.

Article  PubMed  CAS  Google Scholar 

Denkert C, Liedtke C, Tutt A, von Minckwitz G. Molecular alterations in triple-negative breast cancer-the road to new treatment strategies. Lancet. 2017;389(10087):2430–42. https://doi.org/10.1016/s0140-6736(16)32454-0.

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