Clinical advancements in breast cancer research: A comprehensive review

Abstract

Breast cancer remains the most frequently diagnosed malignancy among women worldwide, with significant morbidity and mortality rates despite advances in early detection and treatment. This review provides a comprehensive overview of recent developments in breast cancer research, spanning genetic and molecular insights, novel diagnostic techniques, and emerging therapeutic strategies. The advent of next-generation sequencing and multi-omics approaches has deepened our understanding of tumor heterogeneity, revealing key genetic drivers, epigenetic regulators, and the role of cancer stem cells in disease progression. Early detection strategies have also evolved with digital breast tomosynthesis and molecular breast imaging, offering improved sensitivity and specificity. On the therapeutic front, breakthroughs in targeted treatments—including cyclin-dependent kinase 4/6 and phosphoinositide 3-kinase inhibitors, antibody-drug conjugates, and immune checkpoint inhibitors—have transformed patient outcomes. The integration of chimeric antigen receptor T-cell therapy and mRNA-based therapeutics holds great promise in overcoming treatment resistance and improving long-term survival. However, challenges such as treatment accessibility, drug resistance, and disparities in healthcare persist, particularly in low- and middle-income regions. Emerging technologies, including artificial intelligence-driven diagnostics and risk-adapted screening, are paving the way for more precise and personalized interventions. This review highlights the latest innovations and ongoing challenges in breast cancer research, emphasizing the need for continued efforts to translate scientific advancements into clinical practice to improve patient outcomes globally.

Keywords

Breast cancer / Antibody-drug conjugates / Therapeutics / Chimeric antigen receptor T-cell therapy / Small molecule inhibitors

References

[1] Sung H, Ferlay J, Siegel RL, 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):209-249. doi: 10.3322/caac.21660

[2] Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023; 73(1):17-48. doi: 10.3322/caac.21763

[3] Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022; 72(1):7-33. doi: 10.3322/caac.21708

[4] Ferlay J, Ervik M, Lam F, et al. Global Cancer Observatory:Cancer Today. Lyon: International Agency for Research on Cancer; 2020. Available from: https://gco.iarc.fr/today [Last accessed on 2021 Feb 01].

[5] Ferlay J, Colombet M, Soerjomataram I, et al. Cancer statistics for the year 2020: An overview. Int J Cancer. 2021; 149(4):778-789. doi: 10.1002/ijc.33588

[6] Breast Cancer Facts & Figures 2024-2025; 2024. Available from: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/2024/breast-cancer-facts-and-figures-2024.pdf [Last accessed on 2025 Jun 17].

[7] Just the Facts: Breast Cancer Disparities; 2025. Available from: https://www.fightcancer.org/sites/default/files/just_the_facts_breast_cancer_disparities_april_2025_0.pdf [Last accessed on 2025 Jun 17].

[8] Giaquinto AN, Sung H, Newman LA, et al. Breast cancer statistics 2024. CA Cancer J Clin. 2024; 74(6):477-495. doi: 10.3322/caac.21863

[9] Breast Cancer. Available from: https://www.who.int/news-room/fact-sheets/detail/breast-cancer [Last accessed on 2025 Jun 17].

[10] Kim J, Harper A, McCormack V, et al. Global patterns and trends in breast cancer incidence and mortality across 185 countries. Nat Med. 2025; 31(4):1154-1162. doi: 10.1038/s41591-025-03502-3

[11] Harbeck N, Penault-Llorca F, Cortes J, et al. Breast cancer. Nat Rev Dis Primers. 2019; 5(1):66. doi: 10.1038/s41572-019-0111-2

[12] Emens LA. Breast cancer immunotherapy: Facts and hopes. Clin Cancer Res. 2018; 24(3):511-520. doi: 10.1158/1078-0432.CCR-16-3001

[13] Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the human development index (2008-2030): A population-based study. Lancet Oncol. 2012; 13(8):790-801. doi: 10.1016/S1470-2045(12)70211-5

[14] Pashayan N, Antoniou AC, Ivanus U, et al. Personalized early detection and prevention of breast cancer: ENVISION consensus statement. Nat Rev Clin Oncol. 2020; 17(11):687-705. doi: 10.1038/s41571-020-0388-9

[15] Turnbull C, Sud A, Houlston RS. Cancer genetics, precision prevention and a call to action. Nat Genet. 2018; 50(9):1212-1218. doi: 10.1038/s41588-018-0202-0

[16] Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017; 317(23):2402-2416. doi: 10.1001/jama.2017.7112

[17] Mavaddat N, Michailidou K, Dennis J, et al. Polygenic risk scores for prediction of breast cancer and breast cancer subtypes. Am J Hum Genet. 2019; 104(1):21-34. doi: 10.1016/j.ajhg.2018.11.002

[18] Bouras A, Guidara S, Leone M, et al. Overview of the genetic causes of hereditary breast and ovarian cancer syndrome in a large french patient cohort. Cancers (Basel). 2023; 15(13):3420. doi: 10.3390/cancers15133420

[19] Su J, Deng L, Wang YD. Roles and mechanisms of long non- coding RNAs in breast cancer. Int J Mol Sci. 2022; 24(1):4538. doi: 10.3390/ijms24010089

[20] Takahashi RU, Takeshita F, Fujiwara T, Ono M, Ochiya T. Cancer stem cells in breast cancer. Cancers (Basel). 2011; 3(1):1311-1328. doi: 10.3390/cancers3011311

[21] Chung N, Jonaid GM, Quinton S, et al. Transcriptome analyses of tumor-adjacent somatic tissues reveal genes co-expressed with transposable elements. Mob DNA. 2019;10:39. doi: 10.1186/s13100-019-0180-5

[22] Ahn JS, Shin S, Yang SA, et al. Artificial intelligence in breast cancer diagnosis and personalized medicine. J Breast Cancer. 2023; 26(5):405-435. doi: 10.4048/jbc.2023.26.e45

[23] Conant EF, Zuckerman SP, McDonald ES, et al. Five consecutive years of screening with digital breast tomosynthesis: Outcomes by screening year and round. Radiology. 2020; 295(2):285-293. doi: 10.1148/radiol.2020191751

[24] Bettegowda C, Sausen M, Leary RJ, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014; 6(224):224ra24. doi: 10.1126/scitranslmed.3007094

[25] Eklund M, Broglio K, Yau C, Connor JT, Stover Fiscalini A, Esserman LJ. The WISDOM personalized breast cancer screening trial: Simulation study to assess potential bias and analytic approaches. JNCI Cancer Spectr. 2018; 2(4):pky067. doi: 10.1093/jncics/pky067

[26] Esserman L, Eklund M, Veer LV, et al. The WISDOM study: A new approach to screening can and should be tested. Breast Cancer Res Treat. 2021; 189(3):593-598. doi: 10.1007/s10549-021-06346-w

[27] Molla Desta G, Birhanu AG. Advancements in single-cell RNA sequencing and spatial transcriptomics: Transforming biomedical research. Acta Biochim Pol. 2025;72:13922. doi: 10.3389/abp.2025.13922

[28] Hakala S, Hämäläinen A, Sandelin S, Giannareas N, Närvä E. Detection of cancer stem cells from patient samples. Cells. 2025; 14(2):148. doi: 10.3390/cells14020148

[29] Hashem H, Sultan I. Revolutionizing precision oncology: The role of artificial intelligence in personalized pediatric cancer care. Front Med (Lausanne). 2025;12:1555893. doi: 10.3389/fmed.2025.1555893

[30] Paul D, Sanap G, Shenoy S, Kalyane D, Kalia K, Tekade RK. Artificial intelligence in drug discovery and development. Drug Discov Today. 2021; 26(1):80-93. doi: 10.1016/j.drudis.2020.10.010

[31] Velpula T, Buddolla V. Enhancing detection and monitoring of circulating tumor cells: Integrative approaches in liquid biopsy advances. J Liquid Biopsy. 2025;8:100297. doi: 10.1016/j.jlb.2025.100297

[32] Adhit KK, Wanjari A, Menon S, Siddhaarth K. Liquid biopsy: An evolving paradigm for non-invasive disease diagnosis and monitoring in medicine. Cureus. 2023; 15(12):e50176. doi: 10.7759/cureus.50176

[33] Reinert T, Gonçalves R, Bines J. Implications of ESR1 mutations in hormone receptor-positive breast cancer. Curr Treat Options Oncol. 2018; 19(5):24. doi: 10.1007/s11864-018-0542-0

[34] De Santo I, McCartney A, Migliaccio I, Di Leo A, Malorni L. The emerging role of ESR1 mutations in luminal breast cancer as a prognostic and predictive biomarker of response to endocrine therapy. Cancers (Basel). 2019; 11(12):1894. doi: 10.3390/cancers11121894

[35] Reinert T, Saad ED, Barrios CH, Bines J. Clinical implications of ESR1 mutations in hormone receptor-positive advanced breast cancer. Front Oncol. 2017;7:26. doi: 10.3389/fonc.2017.00026

[36] Glaviano A, Foo ASC, Lam HY, et al. PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer. Mol Cancer. 2023; 22(1):138. doi: 10.1186/s12943-023-01827-6

[37] Pegram M, Jackisch C, Johnston SRD. Estrogen/HER2 receptor crosstalk in breast cancer: Combination therapies to improve outcomes for patients with hormone receptor- positive/HER2-positive breast cancer. NPJ Breast Cancer. 2023; 9(1):45. doi: 10.1038/s41523-023-00533-2

[38] Pohlmann PR, Mayer IA, Mernaugh R. Resistance to trastuzumab in breast cancer. Clin Cancer Res. 2009; 15(24):7479-7491. doi: 10.1158/1078-0432.CCR-09-0636

[39] Luque-Cabal M, García-Teijido P, Fernández-Pérez Y, Sánchez-Lorenzo L, Palacio-Vázquez I. Mechanisms behind the resistance to trastuzumab in HER2-amplified breast cancer and strategies to overcome it. Clin Med Insights Oncol. 2016; 10(Suppl 1):21-30. doi: 10.4137/CMO.S34537

[40] Abd El-Aziz YS, Spillane AJ, Jansson PJ, Sahni S. Role of ABCB 1 in mediating chemoresistance of triple-negative breast cancers. Biosci Rep. 2021; 41(2):BSR20204092. doi: 10.1042/BSR20204092

[41] Turk AA, Wisinski KB. PARP inhibitors in breast cancer: Bringing synthetic lethality to the bedside. Cancer. 2018; 124(12):2498-2506. doi: 10.1002/cncr.31307

[42] Bhamidipati D, Haro-Silerio JI, Yap TA, Ngoi N. PARP inhibitors: Enhancing efficacy through rational combinations. Br J Cancer. 2023; 129(6):904-916. doi: 10.1038/s41416-023-02326-7

[43] Bai X, Ni J, Beretov J, Graham P, Li Y. Cancer stem cell in breast cancer therapeutic resistance. Cancer Treat Rev. 2018; 69:152-163. doi: 10.1016/j.ctrv.2018.07.004

[44] Zheng Q, Zhang M, Zhou F, Zhang L, Meng X. the breast cancer stem cells traits and drug resistance. Front Pharmacol. 2020;11:599965. doi: 10.3389/fphar.2020.599965

[45] Xie Y, Wang X, Wang W, Pu N, Liu L. Epithelial-mesenchymal transition orchestrates tumor microenvironment: current perceptions and challenges. J Transl Med. 2025; 23(1):386. doi: 10.1186/s12967-025-06422-5

[46] Roy S, Kumaravel S, Sharma A, Duran CL, Bayless KJ, Chakraborty S. Hypoxic tumor microenvironment: Implications for cancer therapy. Exp Biol Med (Maywood). 2020; 245(13):1073-1086. doi: 10.1177/1535370220934038

[47] Basheeruddin M, Qausain S. Hypoxia-inducible factor 1-alpha (HIF-1α) and cancer: Mechanisms of tumor hypoxia and therapeutic targeting. Cureus. 2024; 16(10):e70700. doi: 10.7759/cureus.70700

[48] Jing X, Yang F, Shao C, et al. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer. 2019; 18(1):157. doi: 10.1186/s12943-019-1089-9

[49] Fu YC, Liang SB, Luo M, Wang XP. Intratumoral heterogeneity and drug resistance in cancer. Cancer Cell Int. 2025; 25(1):103. doi: 10.1186/s12935-025-03734-w

[50] Chen TWW, Hsiao W, Dai MS, et al. Plasma cell-free tumor DNA, PIK3CA and TP53 mutations predicted inferior endocrine-based treatment outcome in endocrine receptor- positive metastatic breast cancer. Breast Cancer Res Treat. 2023; 201(3):377-385. doi: 10.1007/s10549-023-06967-3

[51] Bharde A, Nadagouda S, Dongare M, et al. ctDNA-based liquid biopsy reveals wider mutational profile with therapy resistance and metastasis susceptibility signatures in early- stage breast cancer patients. J Liquid Biopsy. 2025;7:100284. doi: 10.1016/j.jlb.2024.100284

[52] Niu Z, Wu J, Zhao Q, Zhang J, Zhang P, Yang Y. CAR-based immunotherapy for breast cancer: Peculiarities, ongoing investigations, and future strategies. Front Immunol. 2024;15:1385571. doi: 10.3389/fimmu.2024.1385571

[53] Buono G, Capozzi M, Caputo R, et al. CAR-T cell therapy for breast cancer: Current status and future perspective. Cancer Treat Rev. 2025;133:102868. doi: 10.1016/j.ctrv.2024.102868

[54] Yang YH, Liu JW, Lu C, Wei JF. CAR-T cell therapy for breast cancer: From basic research to clinical application. Int J Biol Sci. 2022; 18(6):2609-2626. doi: 10.7150/ijbs.70120

[55] Rojas-Quintero J, Díaz MP, Palmar J, et al. Car T cells in solid tumors: Overcoming obstacles. Int J Mol Sci. 2024; 25(8):4170. doi: 10.3390/ijms25084170

[56] Morgan MA, Schambach A. Engineering CAR-T cells for improved function against solid tumors. Front Immunol. 2018;9:2493. doi: 10.3389/fimmu.2018.02493

[57] Drago JZ, Modi S, Chandarlapaty S. Unlocking the potential of antibody-drug conjugates for cancer therapy. Nat Rev Clin Oncol. 2021; 18(6):327-344. doi: 10.1038/s41571-021-00470-8

[58] Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022; 387(1):9-20. doi: 10.1056/NEJMoa2203690

[59] Bardia A, Jhaveri K, Kalinsky K, et al. TROPION-Breast01: Datopotamab deruxtecan vs chemotherapy in pre-treated inoperable or metastatic HR+/HER2- breast cancer. Future Oncol. 2024; 20(8):423-436. doi: 10.2217/fon-2023-0188

[60] Bardia A, Jhaveri K, Im SA, et al. Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/ metastatic hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer: Primary Results from TROPION-Breast01. J Clin Oncol. 2025; 43(3):285-296. doi: 10.1200/JCO.24.00920

[61] Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020; 382(9):810-821. doi: 10.1056/NEJMoa1910549

[62] Schmid P, Cortes J, Dent R, et al. Overall survival with pembrolizumab in early-stage triple-negative breast cancer. N Engl J Med. 2024; 391(21):1981-1991. doi: 10.1056/NEJMoa2409932

[63] Kong B, Kim Y, Kim EH, Suk JS, Yang Y. mRNA: A promising platform for cancer immunotherapy. Adv Drug Deliv Rev. 2023;199:114993. doi: 10.1016/j.addr.2023.114993

[64] Miao L, Zhang Y, Huang L.mRNA vaccine for cancer immunotherapy. Mol Cancer. 2021; 20(1):41. doi: 10.1186/s12943-021-01335-5

[65] Yu Y, Jin X, Zhu X, Xu Y, Si W, Zhao J. PD-1/PD-L1 immune checkpoint inhibitors in metastatic triple-negative breast cancer: A systematic review and meta-analysis. Front Immunol. 2023;14:1206689. doi: 10.3389/fimmu.2023.1206689

[66] Tang Q, Chen Y, Li X, et al. The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers. Front Immunol. 2022;13:964442. doi: 10.3389/fimmu.2022.964442

[67] Ni L.Advances in mRNA-based cancer vaccines. Vaccines (Basel). 2023; 11(10):1599. doi: 10.3390/vaccines11101599

[68] Cox K, Alford B, Soliman H. Emerging therapeutic strategies in breast cancer. South Med J. 2017; 110(10):632-637. doi: 10.14423/SMJ.0000000000000709

[69] Tarekegn K, Keskinkilic M, Kristoff TJ, Evans ST, Kalinsky K. The role of immune checkpoint inhibition in triple negative breast cancer. Expert Rev Anticancer Ther. 2023; 23(10):1095-1106. doi: 10.1080/14737140.2023.2265059

[70] Agostinetto E, Losurdo A, Nader-Marta G, et al. Progress and pitfalls in the use of immunotherapy for patients with triple negative breast cancer. Expert Opin Investig Drugs. 2022; 31(6):567-591. doi: 10.1080/13543784.2022.2049232

[71] Pivot X. Pembrolizumab in the treatment of breast cancer. N Engl J Med. 2022; 387(3):273-274. doi: 10.1056/NEJMe2207532

[72] Cirella A, Luri-Rey C, Di Trani CA, et al. Novel strategies exploiting interleukin-12 in cancer immunotherapy. Pharmacol Ther. 2022;239:108189. doi: 10.1016/j.pharmthera.2022.108189

[73] Beck JD, Reidenbach D, Salomon N, et al. mRNA therapeutics in cancer immunotherapy. Mol Cancer. 2021; 20(1):69. doi: 10.1186/s12943-021-01348-0

[74] Liu C, Shi Q, Huang X, Koo S, Kong N, Tao W.mRNA-based cancer therapeutics. Nat Rev Cancer. 2023; 23(8):526-543. doi: 10.1038/s41568-023-00586-2

[75] Zhou XK, Tang SS, Yi G, et al. RNAi knockdown of PIK3CA preferentially inhibits invasion of mutant PIK3CA cells. World J Gastroenterol. 2011; 17(32):3700-3708. doi: 10.3748/wjg.v17.i32.3700

[76] Yu X, Ghamande S, Liu H, et al. Targeting EGFR/HER2/ HER3 with a three-in-one aptamer-siRNA chimera confers superior activity against HER2+ breast cancer. Mol Ther Nucleic Acids. 2018; 10:317-330. doi: 10.1016/j.omtn.2017.12.015

[77] Kalita T, Dezfouli SA, Pandey LM, Uludag H. siRNA functionalized lipid nanoparticles (LNPs) in management of diseases. Pharmaceutics. 2022; 14(11):250. doi: 10.3390/pharmaceutics14112520

[78] Gu S, Hu Z, Ngamcherdtrakul W, et al. Therapeutic siRNA for drug-resistant HER2-positive breast cancer. Oncotarget. 2016; 7(12):14727-14741. doi: 10.18632/oncotarget.7409

[79] Heidel JD, Liu JYC, Yen Y, et al. Potent siRNA inhibitors of ribonucleotide reductase subunit RRM2 reduce cell proliferation in vitro and in vivo. Clin Cancer Res. 2007; 13(7):2207-2215. doi: 10.1158/1078-0432.CCR-06-2218

[80] Rahman MA, Amin ARMR, Wang X, et al. Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses head and neck tumor growth. J Control Release. 2012; 159(3):384-392. doi: 10.1016/j.jconrel.2012.01.045

[81] Zuckerman JE, Gritli I, Tolcher A, et al. Correlating animal and human phase Ia/Ib clinical data with CALAA-01, a targeted, polymer-based nanoparticle containing siRNA. Proc Natl Acad Sci U S A. 2014; 111(31):11449-11454. doi: 10.1073/pnas.1411393111

[82] El Dika I, Lim HY, Yong WP, et al. An open-label, multicenter, phase I, dose escalation study with phase II expansion cohort to determine the safety, pharmacokinetics, and preliminary antitumor activity of intravenous TKM- 080301 in subjects with advanced hepatocellular carcinoma. Oncologist. 2019; 24(6):747-e218. doi: 10.1634/theoncologist.2018-0838

[83] Morry J, Ngamcherdtrakul W, Gu S, et al. Targeted treatment of metastatic breast cancer by PLK1 siRNA delivered by an antioxidant nanoparticle platform. Mol Cancer Ther. 2017; 16(4):763-772. doi: 10.1158/1535-7163.MCT-16-0644

[84] Faltus T, Yuan J, Zimmer B, et al. Silencing of the HER2/neu gene by siRNA inhibits proliferation and induces apoptosis in HER2/neu-overexpressing breast cancer cells. Neoplasia. 2004; 6(6):786-795. doi: 10.1593/neo.04313

[85] Li XJ, Ren ZJ, Tang JH. MicroRNA-34a: A potential therapeutic target in human cancer. Cell Death Dis. 2014; 5(7):e1327. doi: 10.1038/cddis.2014.270

[86] Li WJ, Wang Y, Liu R, et al. MicroRNA-34a: Potent tumor suppressor, cancer stem cell inhibitor, and potential anticancer therapeutic. Front Cell Dev Biol. 2021;9:640587. doi: 10.3389/fcell.2021.640587

[87] Kim T, Croce CM. MicroRNA: Trends in clinical trials of cancer diagnosis and therapy strategies. Exp Mol Med. 2023; 55(7):1314-1321. doi: 10.1038/s12276-023-01050-9

[88] Hong DS, Kang YK, Borad M, et al. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. Br J Cancer. 2020; 122(11):1630-1637. doi: 10.1038/s41416-020-0802-1

[89] Ma L. Role of miR-10b in breast cancer metastasis. Breast Cancer Res. 2010; 12(5):210. doi: 10.1186/bcr2720

[90] Halim A, Al-Qadi N, Kenyon E, et al. Inhibition of miR-10b treats metastatic breast cancer by targeting stem cell-like properties. Oncotarget. 2024; 15:591-606. doi: 10.18632/oncotarget.28641

[91] Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH. Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem. 2008; 283(2):1026-1033. doi: 10.1074/jbc.M707224200

[92] Buscaglia LEB, Li Y.Apoptosis and the target genes of microRNA-21. Chin J Cancer. 2011; 30(6):371-380. doi: 10.5732/cjc.011.10132

[93] Fang H, Xie J, Zhang M, Zhao Z, Wan Y, Yao Y. miRNA-21 promotes proliferation and invasion of triple-negative breast cancer cells through targeting PTEN. Am J Transl Res. 2017; 9(3):953-961.

[94] Qi L, Bart J, Tan LP, et al. Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma. BMC Cancer. 2009;9:163. doi: 10.1186/1471-2407-9-163

[95] Chawra HS, Agarwal M, Mishra A, et al. MicroRNA-21’s role in PTEN suppression and PI3K/AKT activation: Implications for cancer biology. Pathol Res Pract. 2024;254:155091. doi: 10.1016/j.prp.2024.155091

[96] Serpico L, Zhu Y, Maia RF, Sumedha S, Shahbazi MA, Santos HA. Lipid nanoparticles-based RNA therapies for breast cancer treatment. Drug Deliv Transl Res. 2024; 14(10):2823-2844. doi: 10.1007/s13346-024-01638-2

[97] Chaudhuri A, Kumar DN, Shaik RA, et al. Lipid-based nanoparticles as a pivotal delivery approach in triple negative breast cancer (TNBC) therapy. Int J Mol Sci. 2022; 23(17). doi: 10.3390/ijms231710068

[98] Joun I, Nixdorf S, Deng W. Advances in lipid-based nanocarriers for breast cancer metastasis treatment. Front Med Technol. 2022;4:893056. doi: 10.3389/fmedt.2022.893056

[99] Mo K, Kim A, Choe S, Shin M, Yoon H. Overview of solid lipid nanoparticles in breast cancer therapy. Pharmaceutics. 2023; 15(8):2065. doi: 10.3390/pharmaceutics15082065

[100] Fan R, Tao X, Zhai X, et al. Application of aptamer-drug delivery system in the therapy of breast cancer. Biomed Pharmacother. 2023;161:114444. doi: 10.1016/j.biopha.2023.114444

[101] Han J, Gao L, Wang J, Wang J. Application and development of aptamer in cancer: from clinical diagnosis to cancer therapy. J Cancer. 2020; 11(23):6902-6915. doi: 10.7150/jca.49532

[102] Varty K, O’Brien C, Ignaszak A. Breast cancer aptamers: Current sensing targets, available aptamers, and their evaluation for clinical use in diagnostics. Cancers (Basel). 2021; 13(16):3984. doi: 10.3390/cancers13163984

[103] Wang Y, Minden A. Current molecular combination therapies used for the treatment of breast cancer. Int J Mol Sci. 2022; 23(19):11046. doi: 10.3390/ijms231911046

[104] Fares J, Kanojia D, Rashidi A, Ulasov I, Lesniak MS. Landscape of combination therapy trials in breast cancer brain metastasis. Int J Cancer. 2020; 147(7):1939-1952. doi: 10.1002/ijc.32937

[105] Soliman H, Hogue D, Han H, et al. Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer: A phase 2 trial. Nat Med. 2023; 29(2):450-457. doi: 10.1038/s41591-023-02210-0

[106] Ferrucci PF, Pala L, Conforti F, Cocorocchio E. Talimogene laherparepvec (T-VEC): An intralesional cancer immunotherapy for advanced melanoma. Cancers (Basel). 2021; 13(6):1383. doi: 10.3390/cancers13061383

[107] Illingworth S, Di Y, Bauzon M, et al. Preclinical safety studies of enadenotucirev, a chimeric group B human-specific oncolytic adenovirus. Mol Ther Oncolytics. 2017; 5:62-74. doi: 10.1016/j.omto.2017.03.003

[108] Robert S, Roman Ortiz NI, LaRocca CJ, Ostrander JH, Davydova J. Oncolytic adenovirus for the targeting of paclitaxel-resistant breast cancer stem cells. Viruses. 2024; 16(4):567. doi: 10.3390/v16040567

[109] INGN 201: Ad-p53, Ad5CMV-p53, adenoviral p53, p53 gene therapy--introgen, RPR/INGN 201. Drugs R D. 2007; 8(3):176-187. doi: 10.2165/00126839-200708030-00005

[110] Gabrilovich DI. INGN 201 (Advexin): Adenoviral p53 gene therapy for cancer. Expert Opin Biol Ther. 2006; 6(8):823-832. doi: 10.1517/14712598.6.8.823

[111] Geurts V, Kok M. Immunotherapy for metastatic triple negative breast cancer: Current paradigm and future approaches. Curr Treat Options Oncol. 2023; 24(6):628-643. doi: 10.1007/s11864-023-01069-0

[112] Chowaniec H, Ślubowska A, Mroczek M, et al. New hopes for the breast cancer treatment: Perspectives on the oncolytic virus therapy. Front Immunol. 2024;15:1375433. doi: 10.3389/fimmu.2024.1375433

[113] Javanbakht M, Tahmasebzadeh S, Cegolon L, et al. Oncolytic viruses: A novel treatment strategy for breast cancer. Genes Dis. 2023; 10(2):430-446. doi: 10.1016/j.gendis.2021.11.011

[114] Guo ZS, Lu B, Guo Z, et al. Vaccinia virus-mediated cancer immunotherapy: Cancer vaccines and oncolytics. J Immunother Cancer. 2019; 7(1):6. doi: 10.1186/s40425-018-0495-7

[115] Xu D, McCarty D, Fernandes A, Fisher M, Samulski RJ, Juliano RL. Delivery of MDR1 small interfering RNA by self-complementary recombinant adeno-associated virus vector. Mol Ther. 2005; 11(4):523-530. doi: 10.1016/j.ymthe.2004.12.019

[116] Carter ME, Koch A, Lauer UM, Hartkopf AD. Clinical trials of oncolytic viruses in breast cancer. Front Oncol. 2021;11:803050. doi: 10.3389/fonc.2021.803050

[117] Hemminki O, Parviainen S, Juhila J, et al. Immunological data from cancer patients treated with Ad5/3-E2F-Δ24- GMCSF suggests utility for tumor immunotherapy. Oncotarget. 2015;6(6):4467-4481. doi: 10.18632/oncotarget.2901

[118] Limacher JM, Quoix E. TG4010: A therapeutic vaccine against MUC1 expressing tumors. Oncoimmunology. 2012;1(5):791-792. doi: 10.4161/onci.19863

[119] Bagegni NA, Davis AA, Clifton KK, Ademuyiwa FO. Targeted treatment for high-risk early-stage triple-negative breast cancer: Spotlight on pembrolizumab. Breast Cancer (Dove Med Press). 2022;14:113-123. doi: 10.2147/BCTT.S293597

[120] Haiderali A, Huang M, Pan W, Akers KG, Maciel D, Frederickson AM. Pembrolizumab plus chemotherapy for first-line treatment of advanced triple-negative breast cancer. Future Oncol. 2024;20(22):1587-1600. doi: 10.2217/fon-2023-0301

[121] Schlam I, Tarantino P, Tolaney SM. Managing adverse events of sacituzumab govitecan. Expert Opin Biol Ther. 2023;23(11):1103-1111. doi: 10.1080/14712598.2023.2267975

[122] Weiss J, Glode A, Messersmith WA, Diamond J. Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer. Expert Rev Anticancer Ther. 2019;19(8):673-679. doi: 10.1080/14737140.2019.1654378

[123] Cortesi L, Rugo HS, Jackisch C. An overview of PARP inhibitors for the treatment of breast cancer. Target Oncol. 2021;16(3):255-282. doi: 10.1007/s11523-021-00796-4

[124] Morganti S, Bychkovsky BL, Poorvu PD, et al. Adjuvant olaparib for germline BRCA carriers with HER2-negative early breast cancer: Evidence and controversies. Oncologist. 2023;28(7):565-574. doi: 10.1093/oncolo/oyad123

[125] Dowling GP, Daly GR, Keelan S, et al. Efficacy and safety of trastuzumab deruxtecan in breast cancer: A systematic review and meta-analysis. Clin Breast Cancer. 2023;23(8):847-855.e2. doi: 10.1016/j.clbc.2023.09.005

[126] Martín M, Pandiella A, Vargas-Castrillón E, et al. Trastuzumab deruxtecan in breast cancer. Crit Rev Oncol Hematol. 2024;198:104355. doi: 10.1016/j.critrevonc.2024.104355

[127] Venkatesan P. Largest trial of AI in breast cancer screening launched. Lancet Oncol. 2025;26:285. doi: 10.1016/S1470-2045(25)00080-4

[128] Kuerer HM, Smith BD, Krishnamurthy S, et al. Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: A multicentre, single-arm, phase 2 trial. Lancet Oncol. 2022;23(12):1517-1524. doi: 10.1016/S1470-2045(22)00613-1

[129] Heist RS, Sands J, Bardia A, et al. Clinical management, monitoring, and prophylaxis of adverse events of special interest associated with datopotamab deruxtecan. Cancer Treat Rev. 2024;125:102720. doi: 10.1016/j.ctrv.2024.102720

[130] Gadaleta-Caldarola G, Lanotte L, Infusino S, et al. Safety evaluation of Datopotamab deruxtecan for triple-negative breast cancer: A meta-analysis. Cancer Treat Res Commun. 2023;37:100775. doi: 10.1016/j.ctarc.2023.100775

[131] Spring LM, Nakajima E, Hutchinson J, et al. Sacituzumab govitecan for metastatic triple-negative breast cancer: Clinical overview and management of potential toxicities. Oncologist. 2021;26(10):827-834. doi: 10.1002/onco.13878

[132] Kwapisz D. Sacituzumab govitecan-hziy in breast cancer. Am J Clin Oncol. 2022;45(7):279-285. doi: 10.1097/COC.0000000000000919

[133] Eli LD, Kavuri SM. Mechanisms of neratinib resistance in HER2-mutant metastatic breast cancer. Cancer Drug Resist. 2022;5(4):873-881. doi: 10.20517/cdr.2022.48

[134] Guo L, Shao W, Zhou C, et al. Neratinib for HER2-positive breast cancer with an overlooked option. Mol Med. 2023;29(1):134. doi: 10.1186/s10020-023-00736-0

[135] O’Rourke H, Hart C, De Boer RH. Current usage of pembrolizumab in triple negative breast cancer (TNBC). Expert Rev Anticancer Ther. 2024;24(5):253-261. doi: 10.1080/14737140.2024.2341729

[136] Kwapisz D. Pembrolizumab and atezolizumab in triple- negative breast cancer. Cancer Immunol Immunother. 2021;70(3):607-617. doi: 10.1007/s00262-020-02736-z

[137] Jairath NK, Dal Pra A, Vince R, et al. A systematic review of the evidence for the decipher genomic classifier in prostate cancer. Eur Urol. 2021;79(3):374-383. doi: 10.1016/j.eururo.2020.11.021

[138] Aranaz Murillo A, Cruz Ciria S, García Barrado A, García Mur C. MRI biomarkers and their correlation with the Oncotype DX test. Radiologia. 2025;67(1):54-60. doi: 10.1016/j.rxeng.2023.11.012

[139] McVeigh TP, Kerin MJ. Clinical use of the Oncotype DX genomic test to guide treatment decisions for patients with invasive breast cancer. Breast Cancer (Dove Med Press). 2017;9:393-400. doi: 10.2147/BCTT.S109847

[140] Horgan D, Hofman P, Giacomini P, et al. Challenges and barriers for the adoption of personalized medicine in Europe: The case of Oncotype DX Breast Recurrence Score® test. Diagnosis (Berl). 2024;12:175-181. doi: 10.1515/dx-2024-0127

[141] Stueber TN, Weiss CR, Woeckel A, Haeusler S. Influences of adjuvant treatments in hormone receptor positive breast cancer on receptor conversion in recurrent breast cancer. Arch Gynecol Obstet. 2019;299(2):533-541. doi: 10.1007/s00404-018-4954-7

[142] Young JA, Tan AR. Targeted treatment of triple-negative breast cancer. Cancer J. 27(1):50-58. doi: 10.1097/PPO.0000000000000495

[143] Matutino A, Amaro C, Verma S. CDK4/6 inhibitors in breast cancer: Beyond hormone receptor-positive HER2-negative disease. Ther Adv Med Oncol. 2018;10:1758835918818346. doi: 10.1177/1758835918818346

[144] de Melo Gagliato D, C Buzaid A, Perez-Garcia JM, Llombart A, Cortes J. CDK4/6 inhibitors in hormone receptor-positive metastatic breast cancer: Current practice and knowledge. Cancers (Basel). 2020;12(9):2480. doi: 10.3390/cancers12092480

[145] Morrison L, Loibl S, Turner NC. The CDK4/6 inhibitor revolution - a game-changing era for breast cancer treatment. Nat Rev Clin Oncol. 2024;21(2):89-105. doi: 10.1038/s41571-023-00840-4

[146] Heimes AS, Schmidt M. Atezolizumab for the treatment of triple-negative breast cancer. Expert Opin Investig Drugs. 2019;28(1):1-5. doi: 10.1080/13543784.2019.1552255

[147] Reddy SM, Carroll E, Nanda R. Atezolizumab for the treatment of breast cancer. Expert Rev Anticancer Ther. 2020;20(3):151-158. doi: 10.1080/14737140.2020.1732211

[148] Turner NC, Im SA, Saura C, et al. Inavolisib-based therapy in PIK3CA-mutated advanced breast cancer. N Engl J Med. 2024;391(17):1584-1596. doi: 10.1056/NEJMoa2404625

[149] Fanucci K, Giordano A, Erick T, Tolaney SM, Sammons S. Practical treatment strategies and novel therapies in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) pathway in hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) advanced breast cancer. ESMO Open. 2024;9(12):103997. doi: 10.1016/j.esmoop.2024.103997

[150] Blair HA. Inavolisib: First approval. Drugs. 2025;85(2):271-278. doi: 10.1007/s40265-024-02136-y

[151] Nanda R, Liu MC, Yau C, 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):676-684. doi: 10.1001/jamaoncol.2019.6650

[152] Ueno NT, Cottone F, Dunton K, et al. Patient-reported outcomesfromDESTINY-Breast04:Trastuzumabderuxtecan versus physician’s choice of chemotherapy in patients with HER2-low mBC. Oncologist. 2025;30(5):oyaf048. doi: 10.1093/oncolo/oyaf048

[153] Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384(16):1529-1541. doi: 10.1056/NEJMoa2028485

[154] De Mattos-Arruda L, Blanco-Heredia J, Aguilar-Gurrieri C, Carrillo J, Blanco J. New emerging targets in cancer immunotherapy: The role of neoantigens. ESMO Open. 2020;4(Suppl 3):e000684. doi: 10.1136/esmoopen-2020-000684