Breast Cancer: Molecular Pathogenesis, Targeted Therapy, Screening, and Prevention

Abstract

Breast cancer is the most common cancer and the leading cause of cancer-related death among women worldwide. Advances in molecular biology, high-throughput sequencing, and integrative-omics have deepened the understanding of its heterogeneity by clarifying mechanisms linked to genetic susceptibility, epigenetic regulation, oncogenic signaling, and immune evasion. Although those developments have driven progress in targeted therapy and screening, concerns on drug resistance, toxicity, global inequities, and suboptimal risk stratification continue to limit outcomes. This review systematically summarizes current advances across four interconnected areas of breast cancer research and management, including molecular pathogenesis, targeted therapy, screening, and prevention. It describes key biological processes that shape tumor heterogeneity and examines targeted therapies, including endocrine agents, HER2-directed drugs, CDK4/6 and PI3K/AKT/mTOR inhibitors, antibody–drug conjugates, and immunotherapies, together with mechanisms of resistance and emerging treatment targets. It also evaluates evolving approaches in risk stratification and screening, highlighting progress in digital breast tomosynthesis, magnetic resonance imaging, contrast-enhanced mammography, and artificial intelligence-assisted interpretation. By integrating cutting-edge molecular insights with clinical advances, this review further highlights the expanding opportunities for personalized therapy and precision prevention. It outlines future directions linking multiomics and artificial intelligence to more equitable and effective breast cancer management.

Keywords

breast cancer / pathogenesis / targeted therapy / screening / prevention / risk assessment

References

[1] F. Bray, M. Laversanne, H. Sung, et al., “Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries,” CA: A Cancer Journal for Clinicians 74, no. 3 (2024): 229–263.

[2] W. Cao, K. Qin, F. Li, and W. Chen, “Comparative Study of Cancer Profiles between 2020 and 2022 Using Global Cancer Statistics (GLOBOCAN),” Journal of the National Cancer Center 4, no. 2 (2024): 128–134.

[3] A. N. Wilkinson, L. F. Ellison, J. M. Billette, and J. M. Seely, “Impact of Breast Cancer Screening on 10-Year Net Survival in Canadian Women Age 40–49 Years,” Journal of Clinical Oncology 41, no. 29 (2023): 4669–4677.

[4] J. Kim, A. Harper, V. McCormack, et al., “Global Patterns and Trends in Breast Cancer Incidence and Mortality across 185 Countries,” Nature Medicine 31, no. 4 (2025): 1154–1162.

[5] A. G. Waks and E. P. Winer, “Breast Cancer Treatment: a Review,” Jama 321, no. 3 (2019): 288–300.

[6] X. Jin, Y.-F. Zhou, D. Ma, et al., “Molecular Classification of Hormone Receptor-positive HER2-negative Breast Cancer,” Nature Genetics 55, no. 10 (2023): 1696–1708.

[7] C. Liu, L. Sun, N. Niu, et al., “Molecular Classification of Hormone Receptor-positive /HER2-positive Breast Cancer Reveals Potential Neoadjuvant Therapeutic Strategies,” Signal Transduction and Targeted Therapy 10, no. 1 (2025): 97.

[8] S. Z. Wu, G. Al-Eryani, D. L. Roden, et al., “A Single-cell and Spatially Resolved Atlas of human Breast Cancers,” Nature Genetics 53, no. 9 (2021): 1334–1347.

[9] T. Fehm, F. Cottone, K. Dunton, et al., “Trastuzumab deruxtecan versus Treatment of Physician's Choice in Patients with HER2-positive Metastatic Breast Cancer (DESTINY-Breast02): Patient-reported Outcomes from a Randomised, Open-label, Multicentre, Phase 3 Trial,” The Lancet Oncology 25, no. 5 (2024): 614–625.

[10] Y. Eguchi and M. Ishikawa, “Synthesis Studies on Anti-atherosclerotic Agents,” Tokyo Ika Shika Daigaku Iyo Kizai Kenkyusho Hokoku Reports of the Institute for Medical and Dental Engineering, Tokyo Medical and Dental University 19 (1985): 39–43.

[11] A. Dilawari, J. Buturla, C. Osgood, et al., “US Food and Drug Administration Approval Summary: Capivasertib with Fulvestrant for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer with PIK3CA/AKT1/PTEN Alterations,” Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 42, no. 34 (2024): 4103–4113.

[12] M. Oliveira, H. S. Rugo, S. J. Howell, et al., “Capivasertib and fulvestrant for Patients with Hormone Receptor-positive, HER2-negative Advanced Breast Cancer (CAPItello-291): Patient-reported Outcomes from a Phase 3, Randomised, Double-blind, Placebo-controlled Trial,” The Lancet Oncology 25, no. 9 (2024): 1231–1244.

[13] S.-A. Im, J. Cortes, D. W. Cescon, et al., “Results from the Randomized KEYNOTE-355 Study of Pembrolizumab plus Chemotherapy for Asian Patients with Advanced TNBC,” Nature partner journals breast cancer 10, no. 1 (2024): 79.

[14] K. B. Kuchenbaecker, J. L. Hopper, D. R. Barnes, et al., “Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers,” Jama 317, no. 23 (2017): 2402–2416.

[15] Collaborative Group on Hormonal Factors in Breast C. “Familial Breast Cancer: Collaborative Reanalysis of Individual Data from 52 Epidemiological Studies Including 58,209 Women with Breast Cancer and 101,986 Women without the Disease,” Lancet 2001;358(9291):1389–1399.

[16] G. S. Mannu, Z. Wang, D. Dodwell, J. Broggio, J. Charman, and S. C. Darby, “Invasive Breast Cancer and Breast Cancer Death after Non-screen Detected Ductal Carcinoma in Situ from 1990 to 2018 in England: Population Based Cohort Study,” BMJ (Clinical research ed) 384 (2024): e075498.

[17] M. L. De Bruin, J. Sparidans, M. B. van't Veer, et al., “Breast Cancer Risk in Female Survivors of Hodgkin's Lymphoma: Lower Risk after Smaller Radiation Volumes,” Journal of Clinical Oncology 27, no. 26 (2009): 4239–4246.

[18] V. A. McCormack and I. dos Santos Silva, “Breast Density and Parenchymal Patterns as Markers of Breast Cancer Risk: a Meta-analysis,” Cancer Epidemiology, Biomarkers & Prevention: A Publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 15, no. 6 (2006): 1159–1169.

[19] B. Lauby-Secretan, C. Scoccianti, D. Loomis, et al., “Breast-cancer Screening–viewpoint of the IARC Working Group,” New England Journal of Medicine 372, no. 24 (2015): 2353–2358.

[20] Independent UKPoBCS. “The Benefits and Harms of Breast Cancer Screening: an Independent Review,” Lancet 2012;380(9855):1778–1786.

[21] A. Bleyer and H. G. Welch, “Effect of Three Decades of Screening Mammography on Breast-cancer Incidence,” New England Journal of Medicine 367, no. 21 (2012): 1998–2005.

[22] N. J. Massat, A. Dibden, D. Parmar, J. Cuzick, P. D. Sasieni, and S. W. Duffy, “Impact of Screening on Breast Cancer Mortality: the UK Program 20 Years On,” Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 25, no. 3 (2016): 455–462.

[23] S. K. Plevritis, D. Munoz, A. W. Kurian, et al., “Association of Screening and Treatment with Breast Cancer Mortality by Molecular Subtype in US Women, 2000–2012,” Jama 319, no. 2 (2018): 154–164.

[24] I. Soerjomataram, C. Cabasag, A. Bardot, et al., “Cancer Survival in Africa, central and South America, and Asia (SURVCAN-3): a Population-based Benchmarking Study in 32 Countries,” The Lancet Oncology 24, no. 1 (2023): 22–32.

[25] N. Mavaddat, K. Michailidou, J. Dennis, et al., “Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes,” American Journal of Human Genetics 104, no. 1 (2019): 21–34.

[26] N. K. Stout, D. L. Miglioretti, Y. R. Su, et al., “Breast Cancer Screening Using Mammography, Digital Breast Tomosynthesis, and Magnetic Resonance Imaging by Breast Density,” JAMA internal medicine 184, no. 10 (2024): 1222–1231.

[27] N. Eisemann, S. Bunk, T. Mukama, et al., “Nationwide Real-world Implementation of AI for Cancer Detection in Population-based Mammography Screening,” Nature Medicine 31, no. 3 (2025): 917–924.

[28] Y.-W. Chang, J. K. Ryu, J. K. An, et al., “Artificial Intelligence for Breast Cancer Screening in Mammography (AI-STREAM): Preliminary Analysis of a Prospective Multicenter Cohort Study,” Nature Communications 16, no. 1 (2025): 2248.

[29] M. A. Martiniussen, M. Larsen, T. Hovda, et al., “Performance of Two Deep Learning-based AI Models for Breast Cancer Detection and Localization on Screening Mammograms from BreastScreen Norway,” Radiol Artif Intell 7, no. 3 (2025): e240039.

[30] F. Derakhshan and J. S. Reis-Filho, “Pathogenesis of Triple-negative Breast Cancer,” Annual review of pathology 17, no. 1 (2022): 181–204.

[31] Y.-Z. Jiang, D. Ma, and X. Jin, “Integrated Multiomic Profiling of Breast Cancer in the Chinese Population Reveals Patient Stratification and Therapeutic Vulnerabilities,” Nature Cancer 5, no. 4 (2024): 673–690.

[32] A. Calabrese, C. von Arx, A. A. Tafuti, M. Pensabene, and M. De Laurentiis, “Prevention, Diagnosis and Clinical Management of Hereditary Breast Cancer beyond BRCA1/2 Genes,” Cancer Treatment Reviews 129 (2024): 102785.

[33] V. Barili, E. Ambrosini, B. Bortesi, et al., “Genetic Basis of Breast and Ovarian Cancer: Approaches and Lessons Learnt from Three Decades of Inherited Predisposition Testing,” Genes 15, no. 2 (2024): 219.

[34] Breast Cancer Association C, L. Dorling, S. Carvalho, et al., “Breast Cancer Risk Genes - association Analysis in More than 113,000 Women,” New England Journal of Medicine 384, no. 5 (2021): 428–439.

[35] W. Mei, S. Faraj Tabrizi, and C. Godina, “A Commonly Inherited human PCSK9 Germline Variant Drives Breast Cancer Metastasis via LRP1 Receptor,” Cell 188, no. 2 (2025): 371–389.e28.

[36] H. Qayoom, B. Ul Haq, S. Sofi, N. Jan, A. Jan, and M. A. Mir, “Targeting Mutant p53: a Key Player in Breast Cancer Pathogenesis and beyond,” Cell Commun Signaling 22, no. 1 (2024): 484.

[37] D. Miricescu, A. Totan, I.-I. Stanescu-Spinu, S. C. Badoiu, C. Stefani, and M. Greabu, “PI3K/AKT/mTOR Signaling Pathway in Breast Cancer: from Molecular Landscape to Clinical Aspects,” International Journal of Molecular Sciences 22, no. 1 (2020): 173.

[38] A. M. Brufsky and M. N. Dickler, “Estrogen Receptor-positive Breast Cancer: Exploiting Signaling Pathways Implicated in Endocrine Resistance,” The Oncologist 23, no. 5 (2018): 528–539.

[39] F. André, E. Ciruelos, G. Rubovszky, et al., “Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive Advanced Breast Cancer,” New England Journal of Medicine 380, no. 20 (2019): 1929–1940.

[40] K. Kalinsky, G. Bianchini, E. Hamilton, et al., “Abemaciclib Plus Fulvestrant in Advanced Breast Cancer after Progression on CDK4/6 Inhibition: Results from the Phase III postMONARCH Trial,” Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 43, no. 9 (2025): 1101–1112.

[41] F.-C. Bidard, A.-C. Hardy-Bessard, F. Dalenc, et al., “Switch to Fulvestrant and Palbociclib versus no Switch in Advanced Breast Cancer with Rising ESR1 Mutation during Aromatase Inhibitor and Palbociclib Therapy (PADA-1): a Randomised, Open-label, Multicentre, Phase 3 Trial,” The Lancet Oncology 23, no. 11 (2022): 1367–1377.

[42] F.-C. Bidard, E. L. Mayer, and Y. H. Park, “First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer,” The New England Journal of Medicine 393, no. 6 (2025): 569–580.

[43] C. Yi, G. Li, W. Wang, et al., “Disruption of YY1-EZH2 Interaction Using Synthetic Peptides Inhibits Breast Cancer Development,” Cancers 13, no. 10 (2021): 2402.

[44] R. S. Lee, K. Sad, D. V. Fawwal, and J. M. Spangle, “Emerging Role of Epigenetic Modifiers in Breast Cancer Pathogenesis and Therapeutic Response,” Cancers 15, no. 15 (2023): 4005.

[45] N. Wang, T. Ma, and B. Yu, “Targeting Epigenetic Regulators to Overcome Drug Resistance in Cancers,” Signal Transduction and Targeted Therapy 8, no. 1 (2023): 69.

[46] G. Mahendran, A. D. Shangaradas, R. Romero-Moreno, et al., “Unlocking the Epigenetic Code: New Insights into Triple-negative Breast Cancer,” Frontiers in Oncology 14, (2024): 1499950.

[47] R. Shukla, K. R. Upton, M. Muñoz-Lopez, et al., “Endogenous Retrotransposition Activates Oncogenic Pathways in Hepatocellular Carcinoma,” Cell 153, no. 1 (2013):101–111.

[48] The Cancer Genome Atlas Network, “Comprehensive Molecular Portraits of Human Breast Tumours,” Nature 490, no. 7418 (2012): 61–70.

[49] J. E. Barrett, C. Herzog, A. Jones, et al., “The WID-BC-index Identifies Women with Primary Poor Prognostic Breast Cancer Based on DNA Methylation in Cervical Samples,” Nature Communications 13, no. 1 (2022): 449.

[50] M. Aine, D. F. Nacer, E. Arbajian, et al., “The DNA Methylation Landscape of Primary Triple-negative Breast Cancer,” Nature Communications 16, no. 1 (2025): 3041.

[51] J. Feng and X. Meng, “Histonemodificationandhistonemodification-targetedanti-cancerdrugsinbreastcancer:Fundamentalsandbeyond,” Frontiers in pharmacology 13 (2022): 946811.

[52] P. Guo, W. Chen, H. Li, M. Li, and L. Li, “The Histone Acetylation Modifications of Breast Cancer and Their Therapeutic Implications,” Pathology Oncology Research 24, no. 3 (2018): 403–413.

[53] L. Zhou and C.-W. Yu, “Epigenetic Modulations in Triple-negative Breast Cancer: Therapeutic Implications for Tumor Microenvironment,” Pharmacological Research 204 (2024): 107205.

[54] L. Liu, B. Xiao, A. Hirukawa, et al., “Ezh2 promotes Mammary Tumor Initiation through Epigenetic Regulation of the Wnt and mTORC1 Signaling Pathways,” Proceedings of the National Academy of Sciences of the United States of America 120, no. 33 (2023): e2303010120.

[55] D. Chen, X. Chen, M. Yang, et al., “H3K36me2 methyltransferase NSD2/WHSC1 Promotes Triple-negative Breast Cancer Metastasis via Activation of ULK1-dependent Autophagy,” Autophagy 21, no. 8 (2025): 1824–1842.

[56] R. Beňačka, D. Szabóová, Z. Guľašová, and Z. Hertelyová, “Non-coding Rnas in Breast Cancer: Diagnostic and Therapeutic Implications,” International Journal of Molecular Sciences 26, no. 1 (2024): 127.

[57] E. A. Sidorova, Y. V. Zhernov, M. A. Antsupova, et al., “The Role of Different Types of microRNA in the Pathogenesis of Breast and Prostate Cancer,” International Journal of Molecular Sciences 24, no. 3 (2023): 1980.

[58] S. Imani, R.-C. Wu, and J. Fu, “MicroRNA-34 family in Breast Cancer: from Research to Therapeutic Potential,” Journal of Cancer 9, no. 20 (2018): 3765–3775.

[59] A. Maharati and M. Moghbeli, “Long Non-coding RNAs as the Critical Regulators of PI3K/AKT, TGF-β, and MAPK Signaling Pathways during Breast Tumor Progression,” Journal of translational medicine 21, no. 1 (2023): 556.

[60] H. Zhang, N. Zhang, Y. Liu, et al., “Epigenetic Regulation of NAMPT by NAMPT-asdrives Metastatic Progression in Triple-negative Breast Cancer,” Cancer Research 79, no. 13 (2019): 3347–3359.

[61] H. Schwarzenbach and P. B. Gahan, “Interplay between LncRNAs and microRNAs in Breast Cancer,” International Journal of Molecular Sciences 24, no. 9 (2023): 8095.

[62] Y. Feng, A. Xiong, O. Mulay, et al., “Integrated Profiling of Metaplastic Breast Cancer Identifies Putative Master Regulators of Intratumoral Heterogeneity,” NPJ Breast Cancer 11, no. 1 (2025): 89.

[63] W.-Y. Sheng, Y. Zhu, S.-Q. Liu, et al., “A Novel SWI/SNF Complex Promotes Triple-negative Breast Cancer Progression,” Cellular & Molecular Biology Letters 30, no. 1 (2025): 105.

[64] C. L. Alves and H. J. D. Ditzel, “Drugging the PI3K/AKT/mTOR Pathway in ER+ Breast Cancer,” International Journal of Molecular Sciences 24, no. 5 (2023): 4522.

[65] C. Le, G. Ferreira, and F. A. Pakdel, “A Basic Review on Estrogen Receptor Signaling Pathways in Breast Cancer,” International Journal of Molecular Sciences 24 (2023): 6834.

[66] A. E. Maennling, M. K. Tur, M. Niebert, et al., “Molecular Targeting Therapy against EGFR family in Breast Cancer: Progress and Future Potentials,” Cancers 11, no. 12 (2019): 1826.

[67] S. Pernas, S. M. Tolaney, E. P. Winer, and S. Goel, “CDK4/6 inhibition in Breast Cancer: Current Practice and Future Directions,” Therapeutic Advances in Medical Oncology 10 (2018): 1758835918786451.

[68] A. Shanabag, J. Armand, E. Son, and H. W. Yang, “Targeting CDK4/6 in Breast Cancer,” Experimental & molecular medicine 57, no. 2 (2025): 312–322.

[69] M. P. Goetz, M. Toi, M. Campone, et al., “MONARCH 3: Abemaciclib as Initial Therapy for Advanced Breast Cancer,” Journal of Clinical Oncology: official journal of the American Society of Clinical Oncology 35, no. 32 (2017): 3638–3646.

[70] P. Neven, P. A. Fasching, S. Chia, et al., “Updated Overall Survival from the MONALEESA-3 Trial in Postmenopausal Women with HR+/HER2- advanced Breast Cancer Receiving First-line Ribociclib plus Fulvestrant,” Breast cancer research: BCR 25, no. 1 (2023): 103.

[71] B. O'Leary, R. J. Cutts, Y. Liu, et al., “The Genetic Landscape and Clonal Evolution of Breast Cancer Resistance to Palbociclib plus Fulvestrant in the PALOMA-3 Trial,” Cancer Discovery 8, no. 11 (2018): 1390–1403.

[72] G. W. Sledge, M. Toi, P. Neven, et al., “MONARCH 2: Abemaciclib in Combination with fulvestrant in Women with HR+/HER2- advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy,” Journal of clinical oncology: official journal of the American Society of Clinical Oncology 35, no. 25 (2017): 2875–2884.

[73] Y. Yan, J. Yu, W. Wang, et al., “Palmitoylation Prevents B7-H4 Lysosomal Degradation Sustaining Tumor Immune Evasion,” Nature Communications 16, no. 1 (2025): 4254.

[74] S. Benítez, A. Cordero, P. G. Santamaría, et al., “RANK Links Senescence to Stemness in the Mammary Epithelia, Delaying Tumor Onset but Increasing Tumor Aggressiveness,” Developmental Cell 56, no. 12 (2021): 1727–1741.e7.

[75] J. Bu, Y. Zhang, S. Wu, et al., “KK-LC-1 as a Therapeutic Target to Eliminate ALDH+ Stem Cells in Triple Negative Breast Cancer,” Nature Communications 14, no. 1 (2023): 2602.

[76] S. Ji, Y. Shi, and B. Yin, “Macrophage Barrier in the Tumor Microenvironment and Potential Clinical Applications,” Cell Commun Signaling 22, no. 1 (2024): 74.

[77] N. A. Giraldo, R. Sanchez-Salas, J. D. Peske, et al., “The Clinical Role of the TME in Solid Cancer,” British Journal of Cancer 120, no. 1 (2019): 45–53.

[78] R. D. Schreiber, L. J. Old, and M. J. Smyth, “Cancer Immunoediting: Integrating Immunity's Roles in Suppression and Promotion,” Science 331, no. 6024 (2011): 1565–1570.

[79] M. Kundu, R. Butti, V. K. Panda, et al., “Modulation of the Tumor Microenvironment and Mechanism of Immunotherapy-based Drug Resistance in Breast Cancer,” Molecular Cancer 23, no. 1 (2024): 92.

[80] S. S. Onkar, N. M. Carleton, P. C. Lucas, et al., “The Great Immune Escape: Understanding the Divergent Immune Response in Breast Cancer Subtypes,” Cancer Discovery 13, no. 1 (2023): 23–40.

[81] R. Huang, T. Kang, and S. Chen, “The Role of Tumor-associated Macrophages in Tumor Immune Evasion,” Journal of Cancer Research and Clinical Oncology 150, no. 5 (2024): 238.

[82] S. Imani, R. Farghadani, G. Roozitalab, et al., “Reprogramming the Breast Tumor Immune Microenvironment: Cold-to-hot Transition for Enhanced Immunotherapy,” Journal of Experimental & Clinical Cancer Research 44, no. 1 (2025): 131.

[83] Y. Li, C. Wang, T. Huang, X. Yu, and B. Tian, “The Role of Cancer-associated Fibroblasts in Breast Cancer Metastasis,” Frontiers in Oncology 13 (2023): 1194835.

[84] H. Zhang, X. Yue, Z. Chen, et al., “Define Cancer-associated Fibroblasts (CAFs) in the Tumor Microenvironment: New Opportunities in Cancer Immunotherapy and Advances in Clinical Trials,” Molecular Cancer 22, no. 1 (2023): 159.

[85] H. Saman, S. S. Raza, S. Uddin, and K. Rasul, “Inducing Angiogenesis, a Key Step in Cancer Vascularization, and Treatment Approaches,” Cancers 12, no. 5 (2020): 1172.

[86] D. Hu, Z. Li, B. Zheng, et al., “Cancer-associated Fibroblasts in Breast Cancer: Challenges and Opportunities,” Cancer Communications 42, no. 5 (2022): 401–434.

[87] Y. Yang, J. Li, W. Lei, et al., “CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications,” International journal of biological sciences 19, no. 11 (2023): 3341–3359.

[88] H. Zhang, S. Li, D. Wang, et al., “Metabolic Reprogramming and Immune Evasion: the Interplay in the Tumor Microenvironment,” Biomarker research 12, no. 1 (2024).

[89] G.-R. Khosravi, S. Mostafavi, S. Bastan, N. Ebrahimi, R. S. Gharibvand, and N. Eskandari, “Immunologic Tumor Microenvironment Modulators for Turning Cold Tumors Hot,” Cancer Communications 44, no. 5 (2024): 521–553.

[90] P. Xu, W. Xiong, Y. Lin, L. Fan, H. Pan, and Y. Li, “Histone Deacetylase 2 Knockout Suppresses Immune Escape of Triple-negative Breast Cancer Cells via Downregulating PD-L1 Expression,” Cell death & disease 12, no. 8 (2021): 779.

[91] L. Yan, M. Wu, T. Wang, et al., “Breast Cancer Stem Cells Secrete MIF to Mediate Tumor Metabolic Reprogramming That Drives Immune Evasion,” Cancer Research 84, no. 8 (2024): 1270–1285.

[92] S. Ding, X. Chen, and K. Shen, “Single-cell RNA Sequencing in Breast Cancer: Understanding Tumor Heterogeneity and Paving Roads to Individualized Therapy,” Cancer Commun (Lond) 40, no. 8 (2020): 329–344.

[93] X. Xiong, X. Wang, C.-C. Liu, Z.-M. Shao, and K.-D. Yu, “Deciphering Breast Cancer Dynamics: Insights from Single-cell and Spatial Profiling in the Multi-omics Era,” Biomarker research 12, no. 1 (2024): 107.

[94] Y. Zhu, Z. Zhou, X. Du, et al., “Cancer Cell-derived Arginine Fuels Polyamine Biosynthesis in Tumor-associated Macrophages to Promote Immune Evasion,” Cancer Cell 43, no. 6 (2025): 1045–1060.e7.

[95] H. S. Rugo, R. B. Rumble, E. Macrae, et al., “Endocrine Therapy for Hormone Receptor–Positive Metastatic Breast Cancer: American Society of Clinical Oncology Guideline,” Journal of Clinical Oncology 34, no. 25 (2016): 3069–3103.

[96] W. J. Gradishar, B. O. Anderson, R. Balassanian, et al., “NCCN Guidelines Insights: Breast Cancer, Version 1.2017,” Journal of the National Comprehensive Cancer Network: JNCCN 15, no. 4 (2017): 433–451.

[97] F. E. van Leeuwen, J. Benraadt, J. W. Coebergh, et al., “Risk of endometrial cancer after tamoxifen treatment of breast cancer,” Lancet 343 no. 8895, (1994): 448–452.

[98] T. Saphner, D. C. Tormey, and R. Gray, “Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer,” Journal of Clinical Oncology 9 no. 2 , (1991): 286–294.

[99] M. Lazzeroni, M. Puntoni, A. Guerrieri-Gonzaga, et al., “Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Recurrence in Breast Noninvasive Neoplasia: a 10-Year Follow-Up of TAM-01 Study,” Journal of Clinical Oncology 41, no. 17 (2023): 3116–3121.

[100] S. R. Cummings, S. Eckert, K. A. Krueger, et al., “The Effect of Raloxifene on Risk of Breast Cancer in Postmenopausal Women: Results From the MORE Randomized Trial,” JAMA 281, no. 23 (1999): 2189–2197.

[101] D. F. Hayes, J. A. Van Zyl, A. Hacking, et al., “Randomized Comparison of Tamoxifen and Two Separate Doses of Toremifene in Postmenopausal Patients With Metastatic Breast Cancer,” Journal of Clinical Oncology 13 no. 10 (1995): 2556–2566.

[102] J. F. R. Robertson, I. M. Bondarenko, E. Trishkina, et al., “Fulvestrant 500 mg versus Anastrozole 1 mg for Hormone Receptor-positive Advanced Breast Cancer (FALCON): an International, Randomised, Double-blind, Phase 3 Trial,” The Lancet 388, no. 10063 (2016): 2997–3005.

[103] J. F. R. Robertson, Z. Shao, S. Noguchi, et al., “Fulvestrant versus Anastrozole in Endocrine Therapy–Naïve Women with Hormone Receptor–Positive Advanced Breast Cancer: Final Overall Survival in the Phase III FALCON Trial,” Journal of Clinical Oncology 43, no. 13 (2025): 1539–1545.

[104] H. J. Burstein and D. L. Longo, “Systemic Therapy for Estrogen Receptor–Positive, HER2-Negative Breast Cancer,” New England Journal of Medicine 383, no. 26 (2020): 2557–2570.

[105] J. Cuzick, I. Sestak, M. Baum, et al., “Effect of Anastrozole and Tamoxifen as Adjuvant Treatment for Early-stage Breast Cancer: 10-year Analysis of the ATAC Trial,” The Lancet Oncology 11, no. 12 (2010): 1135–1141.

[106] J. P. Morden, I. Alvarez, G. Bertelli, et al., “Long-Term Follow-Up of the Intergroup Exemestane Study,” Journal of Clinical Oncology 35, no. 22 (2017): 2507–2514.

[107] O. Pagani, B. A. Walley, G. F. Fleming, et al., “Adjuvant Exemestane with Ovarian Suppression in Premenopausal Breast Cancer: Long-Term Follow-Up of the Combined TEXT and SOFT Trials,” Journal of Clinical Oncology 41, no. 7 (2023): 1376–1382.

[108] P. A. Francis, G. F. Fleming, I. Láng, et al., “Adjuvant Endocrine Therapy in Premenopausal Breast Cancer: 12-Year Results from SOFT,” Journal of Clinical Oncology 41, no. 7 (2023): 1370–1375.

[109] M. Shah, H. Lingam, X. Gao, et al., “US Food and Drug Administration Approval Summary: Elacestrant for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative, ESR1-Mutated Advanced or Metastatic Breast Cancer,” Journal of Clinical Oncology 42, no. 10 (2024): 1193–1201.

[110] F.-C. Bidard, V. G. Kaklamani, P. Neven, et al., “Elacestrant (oral selective estrogen receptor degrader) versus Standard Endocrine Therapy for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Results from the Randomized Phase III EMERALD Trial,” Journal of Clinical Oncology 40, no. 28 (2022): 3246–3256.

[111] M. Martín, E. Lim, M. Chavez-MacGregor, et al., “Giredestrant for Estrogen Receptor–Positive, HER2-Negative, Previously Treated Advanced Breast Cancer: Results from the Randomized, Phase II acelERA Breast Cancer Study,” Journal of Clinical Oncology 42, no. 18 (2024): 2149–2160.

[112] K. L. Jhaveri, P. Neven, M. L. Casalnuovo, et al., “Imlunestrant with or without Abemaciclib in Advanced Breast Cancer,” New England Journal of Medicine 392, no. 12 (2025): 1189–1202.

[113] D. J. Slamon, B. Leyland-Jones, S. Shak, et al., “Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2,” New England Journal of Medicine 344 no. 11, (2001): 783–792.

[114] I. Smith, M. Procter, R. D. Gelber, et al., “2-year Follow-up of trastuzumab after Adjuvant Chemotherapy in HER2-positive Breast Cancer: a Randomised Controlled Trial,” The Lancet 369, no. 9555 (2007): 29–36.

[115] E. A. Perez, V. J. Suman, N. E. Davidson, et al., “Cardiac Safety Analysis of Doxorubicin and Cyclophosphamide Followed by Paclitaxel with or without Trastuzumab in the North Central Cancer Treatment Group N9831 Adjuvant Breast Cancer Trial,” Journal of Clinical Oncology 26, no. 8 (2008): 1231–1238.

[116] S. M. Swain, M. Shastry, and E. Hamilton, “Targeting HER2-positive Breast Cancer: Advances and Future Directions,” Nature Reviews Drug Discovery 22, no. 2 (2022): 101–126.

[117] J. Baselga, J. Cortés, and S.-B. Kim, “Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer,” New England Journal of Medicine 366, no. 2, (2012): 109–119.

[118] S. M. Swain, S.-B. Kim, J. Cortés, et al., “Pertuzumab, Trastuzumab, and Docetaxel for HER2-positive Metastatic Breast Cancer (CLEOPATRA study): Overall Survival Results from a Randomised, Double-blind, Placebo-controlled, Phase 3 Study,” The Lancet Oncology 14, no. 6 (2013): 461–471.

[119] S. Loibl, J. Jassem, A. Sonnenblick, et al., “Adjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis with Efficacy Update,” Journal of Clinical Oncology 42, no. 31 (2024): 3643–3651.

[120] H. S. Rugo, S.-A. Im, F. Cardoso, et al., “Efficacy of Margetuximab vs Trastuzumab in Patients with Pretreated ERBB2-Positive Advanced Breast Cancer,” JAMA Oncology 7, no. 4 (2021): 573–584.

[121] H. S. Rugo, S.-A. Im, F. Cardoso, et al., “Margetuximab versus Trastuzumab in Patients with Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results from a Randomized Phase 3 Trial,” Journal of Clinical Oncology 41, no. 2 (2023): 198–205.

[122] T. Bachelot, G. Romieu, M. Campone, et al., “Lapatinib plus Capecitabine in Patients with Previously Untreated Brain Metastases from HER2-positive Metastatic Breast Cancer (LANDSCAPE): a Single-group Phase 2 Study,” The Lancet Oncology 14, no. 1 (2013): 64–71.

[123] E. Cocco, F. Javier Carmona, and P. Razavi, “Neratinib Is Effective in Breast Tumors Bearing both Amplification and Mutation of ERBB2 (HER2),” Science Signaling 11, no. 551 (2018): eaat9773.

[124] C. Saura, M. Oliveira, Y.-H. Feng, et al., “Neratinib plus Capecitabine versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated with ≥ 2 HER2-Directed Regimens: Phase III NALA Trial,” Journal of Clinical Oncology 38, no. 27 (2020): 3138–3149.

[125] R. K. Murthy, S. Loi, A. Okines, et al., “Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer,” New England Journal of Medicine 382, no. 7 (2020): 597–609.

[126] S. Verma, D. Miles, L. Gianni, et al., “Trastuzumab Emtansine for HER2-positive Advanced Breast Cancer,” The New England Journal of Medicine 367, no. 19 (2012): 1783–1791.

[127] S. Modi, C. Saura, T. Yamashita, et al., “Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer,” New England Journal of Medicine 382, no. 7 (2020): 610–621.

[128] N. Harbeck, E. Ciruelos, G. Jerusalem, et al., “Trastuzumab deruxtecan in HER2-positive Advanced Breast Cancer with or without Brain Metastases: a Phase 3b/4 Trial,” Nature Medicine 30, no. 12 (2024): 3717–3727.

[129] A. Dilawari, H. Zhang, M. Shah, et al., “US Food and Drug Administration Approval Summary: Trastuzumab Deruxtecan for the Treatment of Adult Patients with Hormone Receptor–Positive, Unresectable or Metastatic Human Epidermal Growth Factor Receptor 2–Low or Human Epidermal Growth Factor Receptor 2–Ultralow Breast Cancer,” Journal of Clinical Oncology 43, no. 26 (2025): 2942–2951.

[130] J. Wang, Y. Liu, Q. Zhang, et al., “Disitamab vedotin, a HER2-directed Antibody-drug Conjugate, in Patients with HER2-overexpression and HER2-low Advanced Breast Cancer: a Phase I/Ib Study,” Cancer Communications 44, no. 7 (2024): 833–851.

[131] Y. Yang, J. Luo, X. Chen, et al., “CDK4/6 inhibitors: a Novel Strategy for Tumor Radiosensitization,” Journal of Experimental & Clinical Cancer Research 39, no. 1 (2020): 188.

[132] R. S. Finn, M. Martin, H. S. Rugo, et al., “Palbociclib and Letrozole in Advanced Breast Cancer,” New England Journal of Medicine 375, no. 20 (2016): 1925–1936.

[133] D. J. Slamon, V. Diéras, H. S. Rugo, et al., “Overall Survival with Palbociclib plus Letrozole in Advanced Breast Cancer,” Journal of Clinical Oncology 42, no. 9 (2024): 994–1000.

[134] G. N. Hortobagyi, S. M. Stemmer, H. A. Burris, et al., “Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer,” New England Journal of Medicine 375, no. 18 (2016): 1738–1748.

[135] M. P. Goetz, M. Toi, J. Huober, et al., “Abemaciclib plus a Nonsteroidal Aromatase Inhibitor as Initial Therapy for HR+, HER2- Advanced Breast Cancer: Final Overall Survival Results of MONARCH 3,” Annals of Oncology 35, no. 8 (2024): 718–727.

[136] P. Zhang, Q. Zhang, Z. Tong, et al., “Dalpiciclib plus Letrozole or Anastrozole versus Placebo plus Letrozole or Anastrozole as First-line Treatment in Patients with Hormone Receptor-positive, HER2-negative Advanced Breast Cancer (DAWNA-2): a Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 3 Trial,” The Lancet Oncology 24, no. 6 (2023): 646–657.

[137] G. S. Sonke, A. van Ommen-Nijhof, N. Wortelboer, et al., “Early versus Deferred Use of CDK4/6 Inhibitors in Advanced Breast Cancer,” Nature 636, no. 8042 (2024): 474–480.

[138] S. Morganti, A. Marra, C. De Angelis, et al., “PARP Inhibitors for Breast Cancer Treatment,” JAMA Oncology 10, no. 5 (2024).

[139] Y. Pommier, M. J. O'Connor, and J. de Bono, “Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action,” Science translational medicine 8, no. 362, (2016): 362ps17.

[140] C. J. Lord and A. Ashworth, “PARP inhibitors: Synthetic lethality in the clinic,” Science 355, no. 6330 (2017): 1152–1158.

[141] C. E. Geyer, J. E. Garber, R. D. Gelber, et al., “Overall Survival in the OlympiA Phase III Trial of Adjuvant Olaparib in Patients with Germline Pathogenic Variants in BRCA1/2 and High-risk, Early Breast Cancer,” Annals of Oncology 33, no. 12 (2022): 1250–1268.

[142] J. E. Abraham, K. Pinilla, A. Dayimu, et al., “The PARTNER Trial of Neoadjuvant Olaparib with Chemotherapy in Triple-negative Breast Cancer,” Nature 629, no. 8014 (2024): 1142–1148.

[143] E. Rodler, P. Sharma, W. E. Barlow, et al., “Cisplatin with Veliparib or Placebo in Metastatic Triple-negative Breast Cancer and BRCA Mutation-associated Breast Cancer (S1416): a Randomised, Double-blind, Placebo-controlled, Phase 2 Trial,” The Lancet Oncology 24, no. 2 (2023): 162–174.

[144] J. J. Gruber, A. Afghahi, K. Timms, et al., “A Phase II Study of talazoparib Monotherapy in Patients with Wild-type BRCA1 and BRCA2 with a Mutation in Other Homologous Recombination Genes,” Nature Cancer 3, no. 10 (2022): 1181–1191.

[145] H. S. Han, B. K. Arun, B. Kaufman, et al., “Veliparib Monotherapy Following Carboplatin/paclitaxel plus veliparib Combination Therapy in Patients with Germline BRCA-associated Advanced Breast Cancer: Results of Exploratory Analyses from the Phase III BROCADE3 Trial,” Annals of Oncology 33, no. 3 (2022): 299–309.

[146] AZD5305 More Tolerable than Earlier PARP Agents. Cancer Discovery 2022;12(7):1602–1602.

[147] G. Bianchini, C. De Angelis, L. Licata, and L. Gianni, “Treatment Landscape of Triple-negative Breast Cancer — expanded Options, Evolving Needs,” Nature Reviews Clinical Oncology 19, no. 2 (2021): 91–113.

[148] C. Hao, Y. Wei, W. Meng, J. Zhang, and X. Yang, “PI3K/AKT/mTOR Inhibitors for Hormone Receptor-positive Advanced Breast Cancer,” Cancer Treatment Reviews 132 (2025).

[149] P. Narayan, T. M. Prowell, J. J. Gao, et al., “FDA Approval Summary: Alpelisib Plus Fulvestrant for Patients with HR-positive, HER2-negative, PIK3CA-mutated, Advanced or Metastatic Breast Cancer,” Clinical Cancer Research 27, no. 7 (2021): 1842–1849.

[150] F. André, E. M. Ciruelos, D. Juric, et al., “Alpelisib plus Fulvestrant for PIK3CA-mutated, Hormone Receptor-positive, human Epidermal Growth Factor Receptor-2–negative Advanced Breast Cancer: Final Overall Survival Results from SOLAR-1,” Annals of Oncology 32, no. 2 (2021): 208–217.

[151] P. Savas, L. L. Lo, S. J. Luen, et al., “Alpelisib Monotherapy for PI3K-Altered, Pretreated Advanced Breast Cancer: A Phase II Study,” Cancer Discovery 12, no. 9 (2022): 2058–2073.

[152] N. C. Turner, S.-A. Im, C. Saura, et al., “Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer,” New England Journal of Medicine 391, no. 17 (2024): 1584–1596.

[153] K. L. Jhaveri, S.-A. Im, C. Saura, et al., “Overall Survival with Inavolisib in PIK3CA-Mutated Advanced Breast Cancer,” New England Journal of Medicine 393, no. 2 (2025): 151–161.

[154] L. Buckbinder, D. J. St Jean, and T. Tieu, “STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts,” Cancer Discovery 13, no. 11 (2023): 2432–2447.

[155] S. J. Howell, A. Casbard, M. Carucci, et al., “Fulvestrant plus capivasertib versus Placebo after Relapse or Progression on an Aromatase Inhibitor in Metastatic, Oestrogen Receptor-positive, HER2-negative Breast Cancer (FAKTION): Overall Survival, Updated Progression-free Survival, and Expanded Biomarker Analysis from a Randomised, Phase 2 Trial,” The Lancet Oncology 23, no. 7 (2022): 851–864.

[156] N. C. Turner, M. Oliveira, S. J. Howell, et al., “Capivasertib in Hormone Receptor–Positive Advanced Breast Cancer,” New England Journal of Medicine 388, no. 22 (2023): 2058–2070.

[157] X. Hu, Q. Zhang, T. Sun, et al., “Capivasertib plus Fulvestrant in Patients with HR-positive/HER2-negative Advanced Breast Cancer: Phase 3 CAPItello-291 Study Extended Chinese Cohort,” Nature Communications 16, no. 1 (2025): 4324.

[158] M. Oliveira, C. Saura, P. Nuciforo, et al., “FAIRLANE, a Double-blind Placebo-controlled Randomized Phase II Trial of Neoadjuvant ipatasertib plus paclitaxel for Early Triple-negative Breast Cancer,” Annals of Oncology 30, no. 8 (2019): 1289–1297.

[159] N. Turner, R. A. Dent, and J. O'Shaughnessy, “Ipatasertib plus paclitaxel for PIK3CA/AKT1/PTEN-altered Hormone Receptor-positive HER2-negative Advanced Breast Cancer: Primary Results from Cohort B of the IPATunity130 Randomized Phase 3 Trial,” Breast Cancer Research and Treatment 191, no. 3 (2021): 565–576.

[160] A.-M. Tsimberidou, J. V. Shaw, D. Juric, et al., “Phase 1 Study of M2698, a p70S6K/AKT Dual Inhibitor, in Patients with Advanced Cancer,” Journal of Hematology & Oncology 14, no. 1 (2021): 127.

[161] M. D. José Baselga, M. D. Martine Piccart, and M. D. Alejandra Perez, “Everolimus in Postmenopausal HormoneReceptor–Positive Advanced Breast Cancer,” The New England Journal of Medicine 366, no. 6 (2012): 520–529.

[162] M. Chavez-MacGregor, J. Miao, L. Pusztai, et al., “Phase III Randomized, Placebo-Controlled Trial of Endocrine Therapy ± 1 Year of Everolimus in Patients with High-Risk, Hormone Receptor–Positive, Early-Stage Breast Cancer,” Journal of Clinical Oncology 42, no. 25 (2024): 3012–3021.

[163] R. M. Layman, H. S. Han, H. S. Rugo, et al., “Gedatolisib in Combination with Palbociclib and Endocrine Therapy in Women with Hormone Receptor-positive, HER2-negative Advanced Breast Cancer: Results from the Dose Expansion Groups of an Open-label, Phase 1b Study,” The Lancet Oncology 25, no. 4 (2024): 474–487.

[164] B. Xu, S. Wang, M. Yan, et al., “Sacituzumab Govitecan in HR+HER2- Metastatic Breast Cancer: the Randomized Phase 3 EVER-132-002 Trial,” Nature Medicine 30, no. 12 (2024): 3709–3716.

[165] B. E. Nelson and F. Meric-Bernstam, “Leveraging TROP2 Antibody-Drug Conjugates in Solid Tumors,” Annual Review of Medicine 75, no. 1 (2024): 31–48.

[166] H. S. Rugo, A. Bardia, F. Marmé, et al., “Overall Survival with sacituzumab govitecan in Hormone Receptor-positive and human Epidermal Growth Factor Receptor 2-negative Metastatic Breast Cancer (TROPiCS-02): a Randomised, Open-label, Multicentre, Phase 3 Trial,” The Lancet 402, no. 10411 (2023): 1423–1433.

[167] H. S. Rugo, A. Bardia, F. Marmé, et al., “Sacituzumab Govitecan in Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer,” Journal of Clinical Oncology 40, no. 29 (2022): 3365–3376.

[168] A. Bardia, I. E. Krop, T. Kogawa, et al., “Datopotamab Deruxtecan in Advanced or Metastatic HR+/HER2– and Triple-Negative Breast Cancer: Results from the Phase I TROPION-PanTumor01 Study,” Journal of Clinical Oncology 42, no. 19 (2024): 2281–2294.

[169] Y. Yin, Y. Fan, Q. Ouyang, et al., “Sacituzumab Tirumotecan in Previously Treated Metastatic Triple-negative Breast Cancer: a Randomized Phase 3 Trial,” Nature Medicine 31, no. 6 (2025): 1969–1975.

[170] I. E. Krop, N. Masuda, T. Mukohara, et al., “Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3–Directed Antibody-Drug Conjugate, in Patients with Previously Treated Human Epidermal Growth Factor Receptor 3–Expressing Metastatic Breast Cancer: a Multicenter, Phase I/II Trial,” Journal of Clinical Oncology 41, no. 36 (2023): 5550–5560.

[171] L. R. Soares, M. Vilbert, V. D. L. Rosa, J. L. Oliveira, M. M. Deus, and R. Freitas-Junior, “Incidence of Interstitial Lung Disease and Cardiotoxicity with Trastuzumab Deruxtecan in Breast Cancer Patients: a Systematic Review and Single-arm Meta-analysis,” ESMO Open 8, no. 4 (2023): 101613.

[172] E. P. Winer, O. Lipatov, S.-A. Im, et al., “Pembrolizumab versus Investigator-choice Chemotherapy for Metastatic Triple-negative Breast Cancer (KEYNOTE-119): a Randomised, Open-label, Phase 3 Trial,” The Lancet Oncology 22, no. 4 (2021): 499–511.

[173] J. Cortes, D. W. Cescon, H. S. Rugo, 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,” The Lancet 396, no. 10265 (2020): 1817–1828.

[174] J. Cortes, H. S. Rugo, D. W. Cescon, et al., “Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer,” New England Journal of Medicine 387, no. 3 (2022): 217–226.

[175] P. Schmid, J. Cortes, R. Dent, et al., “Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer,” New England Journal of Medicine 386, no. 6 (2022): 556–567.

[176] P. Schmid, J. Cortes, R. Dent, et al., “Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer,” New England Journal of Medicine 391, no. 21 (2024): 1981–1991.

[177] P. Schmid, J. Cortes, L. Pusztai, et al., “Pembrolizumab for Early Triple-Negative Breast Cancer,” New England Journal of Medicine 382, no. 9 (2020): 810–821.

[178] L. Pusztai, C. Denkert, and J. O'Shaughnessy, “Event-free Survival by Residual Cancer Burden with Pembrolizumab in Early-stage TNBC: Exploratory Analysis from KEYNOTE-522,” Annals of Oncology 35, no. 5 (2024): 429–436.

[179] F. Cardoso, J. O'Shaughnessy, and Z. Liu, “Pembrolizumab and Chemotherapy in High-risk, Early-stage, ER+/HER2- Breast Cancer: a Randomized Phase 3 Trial,” Nature Medicine 31, no. 2 (2025): 442–448.

[180] S. Kuemmel, M. Graeser, P. Schmid, et al., “Chemotherapy-free Neoadjuvant Pembrolizumab Combined with Trastuzumab and Pertuzumab in HER2-enriched Early Breast Cancer (WSG-KEYRICHED-1): a Single-arm, Phase 2 Trial,” The Lancet Oncology 26, no. 5 (2025): 629–640.

[181] P. Schmid, S. Adams, H. S. Rugo, et al., “Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer,” New England Journal of Medicine 379, no. 22 (2018): 2108–2121.

[182] D. Miles, J. Gligorov, F. André, 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,” Annals of Oncology 32, no. 8 (2021): 994–1004.

[183] Q. Zhang, M. Wang, Y. Li, et al., “Efficacy, Safety and Exploratory Analysis of Neoadjuvant Tislelizumab (a PD-1 inhibitor) plus Nab-paclitaxel Followed by Epirubicin/Cyclophosphamide for Triple-negative Breast Cancer: a Phase 2 TREND Trial,” Signal Transduction and Targeted Therapy 10, no. 1 (2025): 169.

[184] Z. Jiang, Q. Ouyang, T. Sun, et al., “Toripalimab plus nab-paclitaxel in Metastatic or Recurrent Triple-negative Breast Cancer: a Randomized Phase 3 Trial,” Nature Medicine 30, no. 1 (2024): 249–256.

[185] S. Loi, R. Salgado, G. Curigliano, et al., “Neoadjuvant Nivolumab and Chemotherapy in Early Estrogen Receptor-positive Breast Cancer: a Randomized Phase 3 Trial,” Nature Medicine 31, no. 2 (2025): 433–441.

[186] S. Li, D. Shen, J. Shao, et al., “Endocrine-Therapy-Resistant ESR1 Variants Revealed by Genomic Characterization of Breast-Cancer-Derived Xenografts,” Cell Reports 4, no. 6 (2013): 1116–1130.

[187] K. Merenbakh-Lamin, N. Ben-Baruch, A. Yeheskel, et al., “D538G Mutation in Estrogen Receptor-α: a Novel Mechanism for Acquired Endocrine Resistance in Breast Cancer,” Cancer Research 73, no. 23 (2013): 6856–6864.

[188] D. R. Robinson, Y.-M. Wu, P. Vats, et al., “Activating ESR1 Mutations in Hormone-resistant Metastatic Breast Cancer,” Nature Genetics 45, no. 12 (2013): 1446–1451.

[189] W. Toy, Y. Shen, H. Won, et al., “ESR1 ligand-binding Domain Mutations in Hormone-resistant Breast Cancer,” Nature Genetics 45, no. 12 (2013): 1439–1445.

[190] R. Jeselsohn, R. Yelensky, G. Buchwalter, et al., “Emergence of Constitutively Active Estrogen Receptor-α Mutations in Pretreated Advanced Estrogen Receptor–Positive Breast Cancer,” Clinical Cancer Research 20, no. 7 (2014): 1757–1767.

[191] S. Chandarlapaty, D. Chen, W. He, et al., “Prevalence of ESR1 Mutations in Cell-Free DNA and Outcomes in Metastatic Breast Cancer,” JAMA Oncology 2, no. 10 (2016): 1310–1315.

[192] P. Razavi, M. T. Chang, G. Xu, et al., “The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers,” Cancer Cell 34, no. 3 (2018): 427–438.

[193] M. Will, J. Liang, C. Metcalfe, and S. Chandarlapaty, “Therapeutic Resistance to Anti-oestrogen Therapy in Breast Cancer,” Nature Reviews Cancer 23, no. 10 (2023): 673–685.

[194] A. Arruabarrena-Aristorena, J. L. V. Maag, S. Kittane, et al., “FOXA1 Mutations Reveal Distinct Chromatin Profiles and Influence Therapeutic Response in Breast Cancer,” Cancer Cell 38, no. 4 (2020): 534–550.e9.

[195] L. D. C. Hoefnagel, C. B. Moelans, S. L. Meijer, et al., “Prognostic Value of Estrogen Receptor α and Progesterone Receptor Conversion in Distant Breast Cancer Metastases,” Cancer 118, no. 20 (2012): 4929–4935.

[196] A. Bardia, P. Aftimos, T. Bihani, et al., “EMERALD: Phase III Trial of Elacestrant (RAD1901) vs Endocrine Therapy for Previously Treated ER+ Advanced Breast Cancer,” Future Oncology 15, no. 28 (2019): 3209–3218.

[197] E. Hamilton, M. Oliveira, N. Turner, et al., “A Phase I Dose Escalation and Expansion Trial of the next-generation Oral SERD Camizestrant in Women with ER-positive, HER2-negative Advanced Breast Cancer: SERENA-1 Monotherapy Results,” Annals of Oncology 35, no. 8 (2024): 707–717.

[198] N. C. Turner, S. Loi, H. M. Moore, et al., “Abstract PD13-07: Activity and Biomarker Analyses from a Phase Ia/b Study of Giredestrant (GDC-9545; G) with or without Palbociclib (palbo) in Patients with Estrogen Receptor-positive, HER2-negative Locally Advanced/Metastatic Breast Cancer (ER+/HER2- LA/mBC),” Cancer Research 82, no. 4_Supplement (2022). PD13–07–PD13–07.

[199] M. R. Lloyd, S. A. Wander, E. Hamilton, P. Razavi, and A. Bardia, “Next-generation Selective Estrogen Receptor Degraders and Other Novel Endocrine Therapies for Management of Metastatic Hormone Receptor-positive Breast Cancer: Current and Emerging Role,” Therapeutic Advances in Medical Oncology 14 (2022): 17588359221113694.

[200] J. L. da Silva, L. J. C. Oliveira, C. A. A. de Resende, et al., “Understanding and Overcoming CDK4/6 Inhibitor Resistance in HR+/HER2- Metastatic Breast Cancer: Clinical and Molecular Perspectives,” Therapeutic Advances in Medical Oncology 17 (2025): 17588359251353623.

[201] R. Pal, B. Chakraborty, A. Nath, et al., “Noble Metal Nanoparticle-induced Oxidative Stress Modulates Tumor Associated Macrophages (TAMs) from an M2 to M1 Phenotype: an in Vitro Approach,” International Immunopharmacology 38 (2016): 332–341.

[202] S. Soman, S. Kulkarni, A. Pandey, et al., “2D Hetero-Nanoconstructs of Black Phosphorus for Breast Cancer Theragnosis: Technological Advancements,” Biosensors 12, no. 11 (2022): 1009.

[203] S. Zanganeh, G. Hutter, R. Spitler, et al., “Iron Oxide Nanoparticles Inhibit Tumour Growth by Inducing Pro-inflammatory Macrophage Polarization in Tumour Tissues,” Nature Nanotechnology 11, no. 11 (2016): 986–994.

[204] M. Békés, D. R. Langley, and C. M. Crews, “PROTAC Targeted Protein Degraders: the Past Is Prologue,” Nature Reviews Drug Discovery 21, no. 3 (2022): 181–200.

[205] M. Campone, M. De Laurentiis, K. Jhaveri, et al., “Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer,” New England Journal of Medicine 393, no. 6 (2025): 556–568.

[206] A. D. Parisian, S. A. Barratt, and L. Hodges-Gallagher, “Palazestrant (OP-1250), a Complete Estrogen Receptor Antagonist, Inhibits Wild-type and Mutant ER-positive Breast Cancer Models as Monotherapy and in Combination,” Molecular cancer therapeutics 23, no. 3 (2024): 285–300.

[207] E. P. Hamilton, M. R. Patel, V. F. Borges, et al., “Palazestrant, a Novel Oral Complete Estrogen Receptor Antagonist (CERAN) and Selective Estrogen Receptor Degrader (SERD), in Patients with ER+/HER2- Advanced or Metastatic Breast Cancer: Phase 1/2 Study Results,” Breast Cancer Research 27, no. 1 (2025): 119.

[208] N. Sarhangi, S. Hajjari, S. F. Heydari, M. Ganjizadeh, F. Rouhollah, and M. Hasanzad, “Breast Cancer in the Era of Precision Medicine,” Molecular Biology Reports 49, no. 10 (2022): 10023–10037.

[209] M. J. M. Magbanua, L. B. Swigart, H. T. Wu, et al., “Circulating Tumor DNA in Neoadjuvant-treated Breast Cancer Reflects Response and Survival,” Annals of Oncology 32, no. 2 (2021): 229–239.

[210] N. C. Turner, B. Kingston, L. S. Kilburn, et al., “Circulating Tumour DNA Analysis to Direct Therapy in Advanced Breast Cancer (plasma-MATCH): a Multicentre, Multicohort, Phase 2a, Platform Trial,” The Lancet Oncology 21, no. 10 (2020): 1296–1308.

[211] I. Garcia-Murillas, N. Chopra, I. Comino-Méndez, et al., “Assessment of Molecular Relapse Detection in Early-Stage Breast Cancer,” JAMA Oncology 5, no. 10 (2019): 1473–1478.

[212] I. Garcia-Murillas, C. W. Abbott, R. J. Cutts, et al., “Whole Genome Sequencing-powered ctDNA Sequencing for Breast Cancer Detection,” Annals of Oncology 36, no. 6 (2025): 673–681.

[213] National Comprehensive Cancer Network. NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2026. Accessed October, 2025, https://www.nccn.org/guidelines/guidelines-detail?category=2&id=1545.

[214] “Guidelines for Diagnosis and Treatment of Advanced Breast Cancer in China (2024 edition),” Zhonghua Zhong Liu Za Zhi [Chinese Journal of Oncology] 2024;46(12):1079–1106.

[215] C. Sessa, J. Balmaña, S. L. Bober, et al., “Risk Reduction and Screening of Cancer in Hereditary Breast-ovarian Cancer Syndromes: ESMO Clinical Practice Guideline,” Annals of Oncology 34, no. 1 (2023): 33–47.

[216] K. H. Park, S. Loibl, J. Sohn, et al., “Pan-Asian Adapted ESMO Clinical Practice Guidelines for the Diagnosis, Treatment and Follow-up of Patients with Early Breast Cancer,” ESMO Open 9, no. 5 (2024): 102974.

[217] D. L. Monticciolo, M. S. Newell, L. Moy, C. S. Lee, and S. V. Destounis, “Breast Cancer Screening for Women at Higher-Than-Average Risk: Updated Recommendations from the ACR,” Journal of the American College of Radiology: JACR 20, no. 9 (2023): 902–914.

[218] L. Hadžikadić-Gušić, T. Cerić, I. Marijanović, et al., “Guidelines for Breast Cancer Management in Bosnia and Herzegovina,” Biomol Biomed 23, no. 1 (2023): 2–14.

[219] L. Urban, L. F. Chala, I. B. de Paula, et al., “Recommendations for Breast Cancer Screening in Brazil, from the Brazilian College of Radiology and Diagnostic Imaging, the Brazilian Society of Mastology, and the Brazilian Federation of Gynecology and Obstetrics Associations,” Radiologia brasileira 56, no. 4 (2023): 207–214.

[220] J. He, W. Q. Chen, N. Li, et al., “China Guideline for the Screening and Early Detection of Female Breast Cancer(2021, Beijing)],” Zhonghua Zhong Liu Za Zhi [Chinese Journal of Oncology] 43, no. 4 (2021): 357–382.

[221] M. J. Hassett, M. R. Somerfield, E. R. Baker, et al., “Management of Male Breast Cancer: ASCO Guideline,” Journal of Clinical Oncology 38, no. 16 (2020): 1849–1863.

[222] G. Bougeard, M. Renaux-Petel, J. M. Flaman, et al., “Revisiting Li-Fraumeni Syndrome from TP53 Mutation Carriers,” Journal of Clinical Oncology 33, no. 21 (2015): 2345–2352.

[223] A. C. Antoniou, S. Casadei, T. Heikkinen, et al., “Breast-cancer Risk in Families with Mutations in PALB2,” New England Journal of Medicine 371, no. 6 (2014): 497–506.

[224] J. Mersch, M. A. Jackson, M. Park, et al., “Cancers Associated with BRCA1 and BRCA2 Mutations Other than Breast and Ovarian,” Cancer 121, no. 2 (2015): 269–275.

[225] Y. Momozawa, R. Sasai, Y. Usui, et al., “Expansion of Cancer Risk Profile for BRCA1 and BRCA2 Pathogenic Variants,” JAMA oncology 8, no. 6 (2022): 871–878.

[226] Y. Cai, J. Li, Y. Gao, et al., “A Systematic Review of Recommendations on Screening Strategies for Breast Cancer due to Hereditary Predisposition: Who, When, and How?,” Cancer medicine 10, no. 10 (2021): 3437–3448.

[227] X. A. Phi, S. Saadatmand, G. H. De Bock, et al., “Contribution of Mammography to MRI Screening in BRCA Mutation Carriers by BRCA Status and Age: Individual Patient Data Meta-analysis,” British Journal of Cancer 114, no. 6 (2016): 631–637.

[228] L. C. Hartmann, D. C. Radisky, M. H. Frost, et al., “Understanding the Premalignant Potential of atypical Hyperplasia through Its Natural History: a Longitudinal Cohort Study,” Cancer prevention research (Philadelphia, Pa) 7, no. 2 (2014): 211–217.

[229] T. O. Henderson, A. Amsterdam, S. Bhatia, et al., “Systematic Review: Surveillance for Breast Cancer in Women Treated with Chest Radiation for Childhood, Adolescent, or Young Adult Cancer,” Annals of Internal Medicine 152, no. 7 (2010): 444–455. W144–54.

[230] C. S. Moskowitz, J. F. Chou, S. L. Wolden, et al., “Breast Cancer after Chest Radiation Therapy for Childhood Cancer,” Journal of Clinical Oncology 32, no. 21 (2014): 2217–2223.

[231] V. Freitas, A. Scaranelo, R. Menezes, S. Kulkarni, D. Hodgson, and P. Crystal, “Added Cancer Yield of Breast Magnetic Resonance Imaging Screening in Women with a Prior History of Chest Radiation Therapy,” Cancer 119, no. 3 (2013): 495–503.

[232] F. L. Wong, J. M. Lee, W. M. Leisenring, et al., “Health Benefits and Cost-Effectiveness of Children's Oncology Group Breast Cancer Screening Guidelines for Chest-Irradiated Hodgkin Lymphoma Survivors,” Journal of Clinical Oncology 41, no. 5 (2023): 1046–1058.

[233] E. Lynge, I. Vejborg, M. Lillholm, M. Nielsen, G. Napolitano, and M. von Euler-Chelpin, “Breast Density and Risk of Breast Cancer,” International Journal of Cancer 152, no. 6 (2023): 1150–1158.

[234] A. J. Ironside and J. L. Jones, “Stromal Characteristics May Hold the Key to Mammographic Density: the Evidence to Date,” Oncotarget 7, no. 21 (2016): 31550–31562.

[235] N. F. Boyd, H. Guo, L. J. Martin, et al., “Mammographic Density and the Risk and Detection of Breast Cancer,” New England Journal of Medicine 356, no. 3 (2007): 227–236.

[236] J. O. Wanders, K. Holland, W. B. Veldhuis, et al., “Volumetric Breast Density Affects Performance of Digital Screening Mammography,” Breast Cancer Research and Treatment 162, no. 1 (2017): 95–103.

[237] M. F. Bakker, S. V. de Lange, R. M. Pijnappel, et al., “Supplemental MRI Screening for Women with Extremely Dense Breast Tissue,” New England Journal of Medicine 381, no. 22 (2019): 2091–2102.

[238] A. Bunnell, D. Valdez, T. K. Wolfgruber, et al., “Prediction of Mammographic Breast Density Based on Clinical Breast Ultrasound Images Using Deep Learning: a Retrospective Analysis,” Lancet regional health Americas 46 (2025): 101096.

[239] J. P. Struewing, D. Abeliovich, T. Peretz, et al., “The Carrier Frequency of the BRCA1 185delAG Mutation Is Approximately 1 Percent in Ashkenazi Jewish Individuals,” Nature Genetics 11, no. 2 (1995): 198–200.

[240] T. D. Ellington, J. W. Miller, S. J. Henley, R. J. Wilson, M. Wu, and L. C. Richardson, “Trends in Breast Cancer Incidence, by Race, Ethnicity, and Age among Women Aged >/= 20 Years - United States, 1999–2018,” Mmwr Morbidity and Mortality Weekly Report 71, no. 2 (2022): 43–47.

[241] K. Kerlikowske, S. Chen, M. C. S. Bissell, et al., “Population Attributable Risk of Advanced-Stage Breast Cancer by Race and Ethnicity,” JAMA oncology 10, no. 2 (2024): 167–175.

[242] Collaborative Group on Hormonal Factors in Breast C. “Menarche, Menopause, and Breast Cancer Risk: Individual Participant Meta-analysis, Including 118 964 Women with Breast Cancer from 117 Epidemiological Studies,” The Lancet Oncology 2012;13(11):1141–1151.

[243] G. A. Colditz and B. Rosner, “Cumulative Risk of Breast Cancer to Age 70 Years According to Risk Factor Status: Data from the Nurses' Health Study,” American Journal of Epidemiology 152, no. 10 (2000): 950–964.

[244] L. A. Torres-de la Roche, A. Acevedo-Mesa, I. L. Lizarazo, et al., “Hormonal Contraception and the Risk of Breast Cancer in Women of Reproductive Age: a Meta-Analysis,” Cancers (Basel) 15, no. 23 (2023): 5624.

[245] Collaborative Group on Hormonal Factors in Breast C. “Type and Timing of Menopausal Hormone Therapy and Breast Cancer Risk: Individual Participant Meta-analysis of the Worldwide Epidemiological Evidence,” Lancet 2019;394(10204):1159–1168.

[246] B. Lauby-Secretan, C. Scoccianti, D. Loomis, et al., “Body Fatness and Cancer–Viewpoint of the IARC Working Group,” New England Journal of Medicine 375, no. 8 (2016): 794–798.

[247] D. Hauner, J. Gunther, F. Schederecker, et al., “Effect of a Comprehensive Lifestyle Intervention Program on Body Weight and Health Behavior in Women with Breast Cancer: Results from a Randomized Controlled Trial,” Clinical Nutrition 43, no. 9 (2024): 1937–1951.

[248] E. S. Schernhammer, F. Laden, F. E. Speizer, et al., “Rotating Night Shifts and Risk of Breast Cancer in Women Participating in the Nurses' health Study,” Journal of the National Cancer Institute 93, no. 20 (2001): 1563–1568.

[249] C. Hu, S. N. Hart, R. Gnanaolivu, et al., “A Population-Based Study of Genes Previously Implicated in Breast Cancer,” The New England Journal of Medicine 384, no. 5 (2021): 440–451.

[250] M. P. Akamandisa, N. J. Boddicker, S. Yadav, et al., “Association of Gene Variant Type and Location with Breast Cancer Risk in the General Population,” Annals of Oncology 36, no. 8 (2025): 954–963.

[251] K.-A. Phillips, J. Kotsopoulos, S. M. Domchek, et al., “Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Mutations in BRCA1 and BRCA2,” Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 43, no. 4 (2025): 422–431.

[252] B. Park, Y. Chang, S. Ryu, and T. X. M. Tran, “Trajectories of Breast Density Change over Time and Subsequent Breast Cancer Risk: Longitudinal Study,” BMJ (Clinical research ed) 387 (2024): e079575.

[253] G. P. Watt, S. Thakran, J. S. Sung, et al., “Association of Breast Cancer Odds with Background Parenchymal Enhancement Quantified Using a Fully Automated Method at MRI: the IMAGINE Study,” Radiology 308, no. 3 (2023): e230367.

[254] S. H. Lee, H.-S. Ryu, M.-J. Jang, et al., “Glandular Tissue Component and Breast Cancer Risk in Mammographically Dense Breasts at Screening Breast US,” Radiology 301, no. 1 (2021): 57–65.

[255] M. H. Gail, L. A. Brinton, D. P. Byar, et al., “Projecting Individualized Probabilities of Developing Breast Cancer for White Females Who Are Being Examined Annually,” JNCI: Journal of the National Cancer Institute 81, no. 24 (1989): 1879–1886.

[256] J. P. Costantino, M. H. Gail, D. Pee, et al., “Validation Studies for Models Projecting the Risk of Invasive and Total Breast Cancer Incidence,” JNCI: Journal of the National Cancer Institute 91, no. 18 (1999): 1541–1548.

[257] D. A. Berry, G. Parmigiani, J. Sanchez, J. Schildkraut, and E. Winer, “Probability of Carrying a Mutation of Breast-ovarian Cancer Gene BRCA1 Based on family History,” JNCI: Journal of the National Cancer Institute 89, no. 3 (1997): 227–238.

[258] A. C. Antoniou, P. D. Pharoah, G. McMullan, et al., “A Comprehensive Model for Familial Breast Cancer Incorporating BRCA1, BRCA2 and Other Genes,” British Journal of Cancer 86, no. 1 (2002): 76–83.

[259] J. Tyrer, S. W. Duffy, and J. Cuzick, “A Breast Cancer Prediction Model Incorporating Familial and Personal Risk Factors,” Statistics in Medicine 23, no. 7 (2004): 1111–1130.

[260] J. A. Tice, S. R. Cummings, R. Smith-Bindman, L. Ichikawa, W. E. Barlow, and K. Kerlikowske, “Using Clinical Factors and Mammographic Breast Density to Estimate Breast Cancer Risk: Development and Validation of a New Predictive Model,” Annals of Internal Medicine 148, no. 5 (2008): 337–347.

[261] E. M. van Veen, A. R. Brentnall, H. Byers, et al., “Use of Single-Nucleotide Polymorphisms and Mammographic Density plus Classic Risk Factors for Breast Cancer Risk Prediction,” JAMA oncology 4, no. 4 (2018): 476–482.

[262] A. Lee, N. Mavaddat, A. N. Wilcox, et al., “BOADICEA: a Comprehensive Breast Cancer Risk Prediction Model Incorporating Genetic and Nongenetic Risk Factors,” Genetics in Medicine: Official Journal of the American College of Medical Genetics 21, no. 8 (2019): 1708–1718.

[263] P. Pal Choudhury, M. N. Brook, and A. N. Hurson, “Comparative Validation of the BOADICEA and Tyrer-Cuzick Breast Cancer Risk Models Incorporating Classical Risk Factors and Polygenic Risk in a Population-based Prospective Cohort of Women of European Ancestry,” Breast Cancer Research 23, no. 1 (2021): 22.

[264] K. N. Maxwell and S. M. Domchek, “Toward Application of Polygenic Risk Scores to both Enhance and Deintensify Breast Cancer Screening,” Journal of Clinical Oncology 42, no. 13 (2024): 1462–1465.

[265] A. R. Martin, M. Kanai, Y. Kamatani, Y. Okada, B. M. Neale, and M. J. Daly, “Clinical Use of Current Polygenic Risk Scores May Exacerbate Health Disparities,” Nature genetics 51, no. 4 (2019).

[266] G. Jia, J. Ping, X. Guo, et al., “Genome-wide Association Analyses of Breast Cancer in Women of African Ancestry Identify New Susceptibility Loci and Improve Risk Prediction,” Nature Genetics 56, no. 5 (2024): 819–826.

[267] L. Ficorella, X. Yang, N. Mavaddat, et al., “Adapting the BOADICEA Breast and Ovarian Cancer Risk Models for the Ethnically Diverse UK Population,” British Journal of Cancer 133, no. 6 (2025): 844–855.

[268] A. Yala, P. G. Mikhael, F. Strand, et al., “Multi-Institutional Validation of a Mammography-Based Breast Cancer Risk Model,” Journal of Clinical Oncology 40, no. 16 (2022): 1732–1740.

[269] I. Heckenbach, M. Powell, S. Fuller, et al., “Deep Learning Assessment of Senescence-associated Nuclear Morphologies in Mammary Tissue from Healthy Female Donors to Predict Future Risk of Breast Cancer: a Retrospective Cohort Study,” Lancet Digit Health 6, no. 10 (2024): e681–e690.

[270] A. Yala, P. G. Mikhael, F. Strand, et al., “Toward Robust Mammography-based Models for Breast Cancer Risk,” Science translational medicine 13, no. 578 (2021): eaba4373.

[271] H. D. Nelson, R. Fu, A. Cantor, M. Pappas, M. Daeges, and L. Humphrey, “Effectiveness of Breast Cancer Screening: Systematic Review and Meta-analysis to Update the 2009 U.S. Preventive Services Task Force Recommendation,” Annals of Internal Medicine 164, no. 4 (2016): 244–255.

[272] P. E. Freer, “Mammographic Breast Density: Impact on Breast Cancer Risk and Implications for Screening,” Radiographics 35, no. 2 (2015): 302–315.

[273] S. S. Nazari and P. Mukherjee, “An Overview of Mammographic Density and Its Association with Breast Cancer,” Breast Cancer (Tokyo, Japan) 25, no. 3 (2018): 259–267.

[274] R. E. Smith, B. Sprague, L. M. Henderson, et al., “Breast Density Knowledge in a Screening Mammography Population Exposed to Density Notification,” Journal of the American College of Radiology: JACR 19, no. 5 (2022): 615–624.

[275] P. Grabler, D. Sighoko, L. Wang, K. Allgood, and D. Ansell, “Recall and Cancer Detection Rates for Screening Mammography: Finding the Sweet Spot,” AJR American journal of roentgenology 208, no. 1 (2017): 208–213.

[276] M. L. Marinovich, K. E. Hunter, P. Macaskill, and N. Houssami, “Breast Cancer Screening Using Tomosynthesis or Mammography: a Meta-analysis of Cancer Detection and Recall,” JNCI: Journal of the National Cancer Institute 110, no. 9 (2018): 942–949.

[277] M. D. Ryser, J. Lange, L. Y. T. Inoue, et al., “Estimation of Breast Cancer Overdiagnosis in a U.S. Breast Screening Cohort,” Annals of Internal Medicine 175, no. 4 (2022): 471–478.

[278] L. Ding, K. Poelhekken, M. J. W. Greuter, et al., “Overdiagnosis of Invasive Breast Cancer in Population-based Breast Cancer Screening: a Short- and Long-term Perspective,” European Journal of Cancer 173 (2022): 1–9.

[279] S. Murphy, T. Mooney, N. Phelan, et al., “Evaluation of Recall Rates in the Irish National Breast Screening Programme: Insights from Two Million Screening Mammograms,” European Journal of Radiology 189 (2025): 112179.

[280] H. Lind, G. Svane, L. Kemetli, and S. Törnberg, “Breast Cancer Screening Program in Stockholm County, Sweden - Aspects of Organization and Quality Assurance,” Breast Care (Basel) 5, no. 5 (2010): 353–357.

[281] L. Domingo, S. Hofvind, R. A. Hubbard, et al., “Cross-national Comparison of Screening Mammography Accuracy Measures in U.S., Norway, and Spain,” European Radiology 26, no. 8 (2016): 2520–2528.

[282] K. Kemp Jacobsen, L. Abraham, D. S. M. Buist, et al., “Comparison of Cumulative False-positive Risk of Screening Mammography in the United States and Denmark,” Cancer Epidemiology 39, no. 4 (2015): 656–663.

[283] H. G. Welch, P. C. Prorok, A. J. O'Malley, and B. S. Kramer, “Breast-Cancer Tumor Size, Overdiagnosis, and Mammography Screening Effectiveness,” The New England Journal of Medicine 375, no. 15 (2016): 1438–1447.

[284] E. R. Myers, P. Moorman, J. M. Gierisch, et al., “Benefits and Harms of Breast Cancer Screening: a Systematic Review,” Jama 314, no. 15 (2015): 1615–1634.

[285] E. F. Conant, M. M. Talley, C. R. Parghi, et al., “Mammographic Screening in Routine Practice: Multisite Study of Digital Breast Tomosynthesis and Digital Mammography Screenings,” Radiology 307, no. 3 (2023): e221571.

[286] M. Alabousi, A. Wadera, M. Kashif Al-Ghita, et al., “Performance of Digital Breast Tomosynthesis, Synthetic Mammography, and Digital Mammography in Breast Cancer Screening: a Systematic Review and Meta-Analysis,” JNCI: Journal of the National Cancer Institute 113, no. 6 (2021): 680–690.

[287] W. Heindel, S. Weigel, J. Gerss, et al., “Digital Breast Tomosynthesis plus Synthesised Mammography versus Digital Screening Mammography for the Detection of Invasive Breast Cancer (TOSYMA): a Multicentre, Open-label, Randomised, Controlled, Superiority Trial,” The Lancet Oncology 23, no. 5 (2022): 601–611.

[288] S. Hofvind, A. S. Holen, H. S. Aase, et al., “Two-view Digital Breast Tomosynthesis versus Digital Mammography in a Population-based Breast Cancer Screening Programme (To-Be): a Randomised, Controlled Trial,” The Lancet Oncology 20, no. 6 (2019): 795–805.

[289] G. JWP, I. Darker, J. JJ, et al., “How Long Does It Take to Read a Mammogram? Investigating the Reading Time of Digital Breast Tomosynthesis and Digital Mammography,” European Journal of Radiology 177 (2024): 111535.

[290] K. Coffey, K. Dodelzon, V. Dialani, et al., “Survey on Current Utilization and Perception of Synthesized Mammography,” Journal of Breast Imaging 6, no. 6 (2024): 636–645.

[291] M. Rebolj, V. Assi, A. Brentnall, D. Parmar, and S. W. Duffy, “Addition of Ultrasound to Mammography in the Case of Dense Breast Tissue: Systematic Review and Meta-analysis,” British Journal of Cancer 118, no. 12 (2018): 1559–1570.

[292] R. Sood, A. F. Rositch, D. Shakoor, et al., “Ultrasound for Breast Cancer Detection Globally: a Systematic Review and Meta-Analysis,” Journal of global oncology 5 (2019): 1–17.

[293] N. Ohuchi, A. Suzuki, T. Sobue, et al., “Sensitivity and Specificity of Mammography and Adjunctive Ultrasonography to Screen for Breast Cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): a Randomised Controlled Trial,” Lancet 387, no. 10016 (2016): 341–348.

[294] N. Harada-Shoji, A. Suzuki, T. Ishida, et al., “Evaluation of Adjunctive Ultrasonography for Breast Cancer Detection among Women Aged 40–49 Years with Varying Breast Density Undergoing Screening Mammography: a Secondary Analysis of a Randomized Clinical Trial,” JAMA Network Open 4, no. 8 (2021): e2121505.

[295] A. Yi, M. J. Jang, D. Yim, B. R. Kwon, S. U. Shin, and and J. M. Chang, “Addition of Screening Breast US to Digital Mammography and Digital Breast Tomosynthesis for Breast Cancer Screening in Women at Average Risk,” Radiology 298, no. 3 (2021): 568–575.

[296] I. Allajbeu, K. Morris, M. Nanaa, et al., “Introduction of Automated Breast Ultrasound as an Additional Screening Tool for Dense Breasts in the UK: a Practical Approach from the BRAID Trial,” Clinical Radiology 79, no. 5 (2024): e641–e650.

[297] F. Sardanelli, V. Magni, G. Rossini, F. Kilburn-Toppin, N. A. Healy, and F. J. Gilbert, “The Paradox of MRI for Breast Cancer Screening: High-risk and Dense Breasts-available Evidence and Current Practice,” Insights Imaging 15, no. 1 (2024): 96.

[298] L. J. Grimm, V. L. Mango, J. A. Harvey, D. M. Plecha, and E. F. Conant, “Implementation of Abbreviated Breast MRI for Screening: AJR Expert Panel Narrative Review,” AJR American Journal of Roentgenology 218, no. 2 (2022): 202–212.

[299] M. B. Lawson, S. C. Partridge, D. S. Hippe, et al., “Comparative Performance of Contrast-enhanced Mammography, Abbreviated Breast MRI, and Standard Breast MRI for Breast Cancer Screening,” Radiology 308, no. 2 (2023): e230576.

[300] C. E. Comstock, C. Gatsonis, G. M. Newstead, et al., “Comparison of Abbreviated Breast MRI vs Digital Breast Tomosynthesis for Breast Cancer Detection among Women with Dense Breasts Undergoing Screening,” Jama 323, no. 8 (2020): 746–756.

[301] R. M. Mann and W. B. Veldhuis, “Contrast-enhanced Mammography: Moving Ahead with Perfusion Imaging,” Radiology 305, no. 1 (2022): 104–106.

[302] C. H. Hunt, R. P. Hartman, and G. K. Hesley, “Frequency and Severity of Adverse Effects of Iodinated and Gadolinium Contrast Materials: Retrospective Review of 456,930 Doses,” AJR American Journal of Roentgenology 193, no. 4 (2009): 1124–1127.

[303] J. M. Chang, “Benefits and Trade-offs of Breast Cancer Screening Using Contrast-enhanced Mammography,” Radiology 308, no. 2 (2023): e231652.

[304] J. Liu, H. Chen, Y. Li, et al., “A Novel Non-invasive Exhaled Breath Biopsy for the Diagnosis and Screening of Breast Cancer,” Journal of hematology & oncology 16, no. 1 (2023): 63.

[305] C. M. S. Herzog, B. Theeuwes, A. Jones, et al., “Systems Epigenetic Approach towards Non-invasive Breast Cancer Detection,” Nature Communications 16, no. 1 (2025): 3082.

[306] E. Heitzer, I. S. Haque, C. E. S. Roberts, and M. R. Speicher, “Current and Future Perspectives of Liquid Biopsies in Genomics-driven Oncology,” Nature Reviews Genetics 20, no. 2 (2019): 71–88.

[307] D. L. Monticciolo, “The New Proposed U.S. Preventive Services Task Force Recommendation on Breast Cancer Screening for Women in Their 40s,” Annals of Internal Medicine 177, no. 9 (2024): 1291–1292.

[308] M. V. Lee, H. V. Garrett, K. Weilbaecher, A. Toriola, and D. L. Bennett, “The New Proposed U.S. Preventive Services Task Force Recommendation on Breast Cancer Screening for Women in Their 40s,” Annals of Internal Medicine 177, no. 9 (2024): 1292–1293.

[309] D. B. Kopans, “The New Proposed U.S. Preventive Services Task Force Recommendation on Breast Cancer Screening for Women in Their 40s,” Annals of Internal Medicine 177, no. 9 (2024): 1293–1294.

[310] R. P. Harris, “The New Proposed U.S. Preventive Services Task Force Recommendation on Breast Cancer Screening for Women in Their 40s: Should the Message Change?,” Annals of Internal Medicine 177, no. 3 (2024): 389–392.

[311] R. P. Harris, “The New Proposed U.S. Preventive Services Task Force Recommendation on Breast Cancer Screening for Women in Their 40s,” Annals of Internal Medicine 177, no. 9 (2024): 1294.

[312] S. Destounis and A. Arieno, “The New Proposed U.S. Preventive Services Task Force Recommendation on Breast Cancer Screening for Women in Their 40s,” Annals of Internal Medicine 177, no. 9 (2024): 1292.

[313] K. J. Bell, B. Nickel, T. Pathirana, M. Blennerhassett, and S. Carter, “Breast Cancer Screening from Age 40 in the US,” BMJ (Clinical research ed) 385 (2024): q1353.

[314] S. W. Duffy, D. Vulkan, H. Cuckle, et al., “Effect of Mammographic Screening from Age 40 Years on Breast Cancer Mortality (UK Age trial): Final Results of a Randomised, Controlled Trial,” The Lancet Oncology 21, no. 9 (2020): 1165–1172.

[315] K. M. Ray, B. N. Joe, R. I. Freimanis, E. A. Sickles, and R. E. Hendrick, “Screening Mammography in Women 40–49 Years Old: Current Evidence,” AJR American Journal of Roentgenology 210, no. 2 (2018): 264–270.

[316] E. White, D. L. Miglioretti, B. C. Yankaskas, et al., “Biennial versus Annual Mammography and the Risk of Late-stage Breast Cancer,” JNCI: Journal of the National Cancer Institute 96, no. 24 (2004): 1832–1839.

[317] C. H. Chapman, C. B. Schechter, C. J. Cadham, et al., “Identifying Equitable Screening Mammography Strategies for Black Women in the United States Using Simulation Modeling,” Annals of Internal Medicine 174, no. 12 (2021): 1637–1646.

[318] T. Chen, E. Kharazmi, and M. Fallah, “Race and Ethnicity-Adjusted Age Recommendation for Initiating Breast Cancer Screening,” JAMA Network Open 6, no. 4 (2023): e238893.

[319] A. F. Flemban, “Overdiagnosis due to Screening Mammography for Breast Cancer among Women Aged 40 Years and Over: a Systematic Review and Meta-Analysis,” Journal of personalized medicine 13, no. 3 (2023): 523.

[320] E. F. Conant, W. E. Barlow, S. D. Herschorn, et al., “Association of Digital Breast Tomosynthesis vs Digital Mammography with Cancer Detection and Recall Rates by Age and Breast Density,” JAMA oncology 5, no. 5 (2019): 635–642.

[321] J. T. Henderson, E. M. Webber, M. S. Weyrich, M. Miller, and J. Melnikow, “Screening for Breast Cancer: Evidence Report and Systematic Review for the US Preventive Services Task Force,” Jama 331, no. 22 (2024): 1931–1946.

[322] P. Autier, M. Boniol, C. La Vecchia, et al., “Disparities in Breast Cancer Mortality Trends between 30 European Countries: Retrospective Trend Analysis of WHO Mortality Database,” BMJ 341 (2010): c3620.

[323] L. Albarqouni, E. Abukmail, M. MohammedAli, et al., “Low-Value Surgical Procedures in Low- and Middle-Income Countries: a Systematic Scoping Review,” JAMA Network Open 6, no. 11 (2023): e2342215.

[324] N. L. Schoenborn, J. Massare, R. Park, C. M. Boyd, Y. Choi, and C. E. Pollack, “Assessment of Clinician Decision-making on Cancer Screening Cessation in Older Adults with Limited Life Expectancy,” JAMA Network Open 3, no. 6 (2020): e206772.

[325] I. B. Richman, J. B. Long, P. R. Soulos, S. Y. Wang, and C. P. Gross, “Estimating Breast Cancer Overdiagnosis after Screening Mammography among Older Women in the United States,” Annals of Internal Medicine 176, no. 9 (2023): 1172–1180.

[326] I. Lansdorp-Vogelaar, R. Gulati, A. B. Mariotto, et al., “Personalizing Age of Cancer Screening Cessation Based on Comorbid Conditions: Model Estimates of Harms and Benefits,” Annals of Internal Medicine 161, no. 2 (2014): 104–112.

[327] E. Mathieu, N. Noguchi, T. Li, et al., “Health Benefits and Harms of Mammography Screening in Older Women (75+ years)-a Systematic Review,” British Journal of Cancer 130, no. 2 (2024): 275–296.

[328] J. A. Malmgren, J. Parikh, M. K. Atwood, and H. G. Kaplan, “Improved Prognosis of Women Aged 75 and Older with Mammography-detected Breast Cancer,” Radiology 273, no. 3 (2014): 686–694.

[329] J. S. Mandelblatt, K. A. Cronin, S. Bailey, et al., “Effects of Mammography Screening under Different Screening Schedules: Model Estimates of Potential Benefits and Harms,” Annals of Internal Medicine 151, no. 10 (2009): 738–747.

[330] J. T. Schousboe, B. L. Sprague, L. Abraham, et al., “Cost-Effectiveness of Screening Mammography beyond Age 75 Years: a Cost-Effectiveness Analysis,” Annals of Internal Medicine 175, no. 1 (2022): 11–19.

[331] J. Demb, L. Abraham, D. L. Miglioretti, et al., “Screening Mammography Outcomes: Risk of Breast Cancer and Mortality by Comorbidity Score and Age,” JNCI: Journal of the National Cancer Institute 112, no. 6 (2020): 599–606.

[332] X. Garcia-Albeniz, M. A. Hernan, R. W. Logan, M. Price, K. Armstrong, and J. Hsu, “Continuation of Annual Screening Mammography and Breast Cancer Mortality in Women Older than 70 Years,” Annals of Internal Medicine 172, no. 6 (2020): 381–389.

[333] D. J. Carmichael, G. C. Gillard, D. A. Lowther, C. J. Handley, and V. B. Santer, “Carrageenin-induced Arthritis. IV. Rate Changes in Cartilage Matrix Proteoglycan Synthesis,” Arthritis and Rheumatism 20, no. 3 (1977): 834–840.

[334] L. M. Kregting, V. D. V. Sankatsing, E. A. M. Heijnsdijk, H. J. de Koning, and N. T. van Ravesteyn, “Finding the Optimal Mammography Screening Strategy: a Cost-effectiveness Analysis of 920 Modelled Strategies,” International Journal of Cancer 151, no. 2 (2022): 287–296.

[335] I. B. Richman and C. P. Gross, “New Breast Cancer Screening Technologies in Older Women-Is It Time to Pump the Brakes?,” JAMA Internal Medicine 179, no. 3 (2019): 289–290.

[336] N. L. Schoenborn, R. H. Nagler, M. A. Schonberg, et al., “Willingness to Stop Screening Mammograms among Older Women in the United States: Results from a National Survey,” Journal of General Internal Medicine 38, no. 4 (2023): 1091–1093.

[337] D. Braithwaite, A. Chicaiza, K. Lopez, et al., “Clinician and Patient Perspectives on Screening Mammography among Women Age 75 and Older: a Pilot Study of a Novel Decision Aid,” PEC Innovation 2 (2023): 100132.

[338] S. Schrager, V. Ovsepyan, and E. Burnside, “Breast Cancer Screening in Older Women: the Importance of Shared Decision Making,” Journal of the American Board of Family Medicine: JABFM 33, no. 3 (2020): 473–480.

[339] M. L. Zuley, A. I. Bandos, S. W. Duffy, et al., “Breast Cancer Screening Interval: Effect on Rate of Late-Stage Disease at Diagnosis and Overall Survival,” Journal of Clinical Oncology 2024:JCO2400285.

[340] C. Canelo-Aybar, M. Posso, N. Montero, et al., “Benefits and Harms of Annual, Biennial, or Triennial Breast Cancer Mammography Screening for Women at Average Risk of Breast Cancer: a Systematic Review for the European Commission Initiative on Breast Cancer (ECIBC),” British Journal of Cancer 126, no. 4 (2022): 673–688.

[341] T. W. Park-Simon, V. Müller, U. S. Albert, et al., “AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2025,” Breast Care (Basel) (2025): 1–19.

[342] W. K. Nicholson, M. Silverstein, J. B. Wong, et al., “Screening for Breast Cancer: US Preventive Services Task Force Recommendation Statement,” Jama 331, no. 22 (2024): 1918–1930.

[343] B. L. Niell, M. S. Jochelson, T. Amir, et al., “ACR Appropriateness Criteria® Female Breast Cancer Screening: 2023 Update,” Journal of the American College of Radiology: JACR 21, no. 6s (2024): S126–S143.

[344] H. J. Schünemann, D. Lerda, C. Quinn, et al., “Breast Cancer Screening and Diagnosis: a Synopsis of the European Breast Guidelines,” Annals of Internal Medicine 172, no. 1 (2020): 46–56.

[345] H. L. Wee, K. Canfell, H. M. Chiu, et al., “Cancer Screening Programs in South-east Asia and Western Pacific,” BMC health services research 24, no. 1 (2024): 102.

[346] Y. Lin, Z. Wang, P. Meng, et al., “Breast Cancer Screening Attendance in China from 2014 to 2022: Results from Nationwide Surveys,” The Lancet Regional Health - Western Pacific 55 (2025): 101426.

[347] Y. Zheng, X. Dong, J. Li, et al., “Use of Breast Cancer Risk Factors to Identify Risk-Adapted Starting Age of Screening in China,” JAMA network open 5, no. 11 (2022): e2241441.

[348] K. Kerlikowske, S. Chen, M. K. Golmakani, et al., “Cumulative Advanced Breast Cancer Risk Prediction Model Developed in a Screening Mammography Population,” JNCI: Journal of the National Cancer Institute 114, no. 5 (2022): 676–685.

[349] C. Turnbull, M. I. Achatz, J. Balmaña, et al., “Breast Cancer Germline Multigene Panel Testing in Mainstream Oncology Based on Clinical-public Health Utility: ESMO Precision Oncology Working Group Recommendations,” Annals of Oncology 36, no. 8 (2025): 853–865.

[350] L. Cortesi, F. Miglietta, L. Arecco, et al., “Predictive Brca Genetic Testing in Italian Patients with Breast Cancer: a Position Paper of Italian Scientific Societies [Italian Association of Medical Oncology(AIOM); Italian Association of Radiotherapy and Clinical Oncology (AIRO); Italian National Association of Breast Surgeons (ANISC); Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPeC-IAP); Italian Society of Surgical Oncology (SICO); Italian Society of Human Genetic (SIGU); Italian Society of General Practice (SIMG); Italian Society of Medical and Interventional Radiology (SIRM)],” Cancer Treatment Reviews 139 (2025): 102976.

[351] B. Fisher, J. P. Costantino, D. L. Wickerham, et al., “Tamoxifen for Prevention of Breast Cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study,” JNCI: Journal of the National Cancer Institute 90, no. 18 (1998): 1371–1388.

[352] T. J. Powles, S. Ashley, A. Tidy, I. E. Smith, and M. Dowsett, “Twenty-year Follow-up of the Royal Marsden Randomized, Double-blinded tamoxifen Breast Cancer Prevention Trial,” JNCI: Journal of the National Cancer Institute 99, no. 4 (2007): 283–290.

[353] J. Cuzick, I. Sestak, S. Cawthorn, et al., “Tamoxifen for Prevention of Breast Cancer: Extended Long-term Follow-up of the IBIS-I Breast Cancer Prevention Trial,” The Lancet Oncology 16, no. 1 (2015): 67–75.

[354] S. Martino, J. A. Cauley, E. Barrett-Connor, et al., “Continuing Outcomes Relevant to Evista: Breast Cancer Incidence in Postmenopausal Osteoporotic Women in a Randomized Trial of raloxifene,” JNCI: Journal of the National Cancer Institute 96, no. 23 (2004): 1751–1761.

[355] S. R. Land, D. L. Wickerham, J. P. Costantino, et al., “Patient-reported Symptoms and Quality of Life during Treatment with Tamoxifen or Raloxifene for Breast Cancer Prevention: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 Trial,” Jama 295, no. 23 (2006): 2742–2751.

[356] H. D. Nelson, R. Fu, B. Zakher, M. Pappas, and M. McDonagh, “Medication Use for the Risk Reduction of Primary Breast Cancer in Women: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force,” Jama 322, no. 9 (2019): 868–886.

[357] V. G. Vogel, J. P. Costantino, D. L. Wickerham, et al., “Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing Breast Cancer,” Cancer prevention research (Philadelphia, Pa) 3, no. 6 (2010): 696–706.

[358] E. K. Zaluzec and L. F. Sempere, “Systemic and Local Strategies for Primary Prevention of Breast Cancer,” Cancers (Basel) 16, no. 2 (2024): 248.

[359] M. E. Ropka, J. Keim, and J. T. Philbrick, “Patient Decisions about Breast Cancer Chemoprevention: a Systematic Review and Meta-analysis,” Journal of Clinical Oncology 28, no. 18 (2010): 3090–3095.

[360] R. Heisey, N. Pimlott, M. Clemons, S. Cummings, and N. Drummond, “Women's Views on Chemoprevention of Breast Cancer: Qualitative Study,” Canadian Family Physician 52, no. 5 (2006): 624–625.

[361] S. G. Smith, I. Sestak, A. Howell, J. Forbes, and J. Cuzick, “Participant-Reported Symptoms and Their Effect on Long-Term Adherence in the International Breast Cancer Intervention Study I (IBIS I),” Journal of Clinical Oncology 35, no. 23 (2017): 2666–2673.

[362] A. Bambhroliya, M. Chavez-MacGregor, and A. M. Brewster, “Barriers to the Use of Breast Cancer Risk Reduction Therapies,” Journal of the National Comprehensive Cancer Network: JNCCN 13, no. 7 (2015): 927–935.

[363] J. Cuzick, K. Chu, B. Keevil, et al., “Effect of Baseline Oestradiol Serum Concentration on the Efficacy of Anastrozole for Preventing Breast Cancer in Postmenopausal Women at High Risk: a Case-control Study of the IBIS-II Prevention Trial,” The Lancet Oncology 25, no. 1 (2024): 108–116.

[364] I. Jatoi and Z. Kemp, “Risk-Reducing Mastectomy,” Jama 325, no. 17 (2021): 1781–1782.

[365] X. Li, R. You, X. Wang, et al., “Effectiveness of Prophylactic Surgeries in BRCA1 or BRCA2 Mutation Carriers: a Meta-analysis and Systematic Review,” Clinical Cancer Research 22, no. 15 (2016): 3971–3981.

[366] N. D. Kauff, J. M. Satagopan, M. E. Robson, et al., “Risk-reducing Salpingo-oophorectomy in Women with a BRCA1 or BRCA2 Mutation,” New England Journal of Medicine 346, no. 21 (2002): 1609–1615.

[367] X. Wei, S. Oxley, M. Sideris, et al., “Quality of Life after Risk-reducing Surgery for Breast and Ovarian Cancer Prevention: a Systematic Review and Meta-analysis,” American Journal of Obstetrics and Gynecology 229, no. 4 (2023): 388–409.

[368] F. Gaba and R. Manchanda, “Systematic Review of Acceptability, Cardiovascular, Neurological, Bone Health and HRT Outcomes Following Risk Reducing Surgery in BRCA Carriers,” Best Practice & Research Clinical Obstetrics & Gynaecology 65 (2020): 46–65.

[369] C. Marchetti, F. De Felice, S. Boccia, et al., “Hormone Replacement Therapy after Prophylactic Risk-reducing Salpingo-oophorectomy and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: a Meta-analysis,” Critical Reviews in Oncology/Hematology 132 (2018): 111–115.

[370] F. Tang, C. Barbacioru, and Y. Wang, “mRNA-Seq Whole-transcriptome Analysis of a Single Cell,” Nature methods 6, no. 5 (2009): 377–382.

[371] K. Wang, T. Kumar, J. Wang, et al., “Archival Single-cell Genomics Reveals Persistent Subclones during DCIS Progression,” Cell 186, no. 18 (2023): 3968–3982.e15.

[372] L.-P. Ge, X. Jin, D. Ma, et al., “ZNF689 deficiency Promotes Intratumor Heterogeneity and Immunotherapy Resistance in Triple-negative Breast Cancer,” Cell research 34, no. 1 (2024): 58–75.

[373] Q. Shi, K. Shao, H. Jia, et al., “Genomic Alterations and Evolution of Cell Clusters in Metastatic Invasive Micropapillary Carcinoma of the Breast,” Nature Communications 13, no. 1 (2022): 111.

[374] L. Larsson, J. Frisén, and J. Lundeberg, “Spatially Resolved Transcriptomics Adds a New Dimension to Genomics,” Nature methods 18, no. 1 (2021): 15–18.

[375] C. Ma, C. Yang, A. Peng, et al., “Pan-Cancer Spatially Resolved Single-Cell Analysis Reveals the Crosstalk Between Cancer-Associated Fibroblasts and Tumor Microenvironment,” Molecular Cancer 22, no. 1 (2023): 170.

[376] Q. Zhu, A. Balasubramanian, J. R. Asirvatham, et al., “Integrative Spatial Omics Reveals Distinct Tumor-promoting Multicellular Niches and Immunosuppressive Mechanisms in Black American and White American Patients with TNBC,” Nature Communications 16, no. 1 (2025): 6584.

[377] J. Lipkova, R. J. Chen, B. Chen, et al., “Artificial Intelligence for Multimodal Data Integration in Oncology,” Cancer Cell 40, no. 10 (2022): 1095–1110.

[378] K. Zhang, X. Yang, Y. Wang, et al., “Artificial Intelligence in Drug Development,” Nature Medicine 31, no. 1 (2025): 45–59.

[379] Y. Yang, L. Han, Y. Yuan, J. Li, and N. Hei, and H. Liang, “Gene co-expression Network Analysis Reveals Common System-level Properties of Prognostic Genes across Cancer Types,” Nature Communications 5, (2014): 3231.

[380] M. Uhlen, C. Zhang, S. Lee, et al., “A Pathology Atlas of the human Cancer Transcriptome,” Science (New York, NY) 357, no. 6352 (2017): eaan2507.

[381] J. Jee, C. Fong, K. Pichotta, et al., “Automated Real-world Data Integration Improves Cancer Outcome Prediction,” Nature 636, no. 8043 (2024): 728–736.

[382] W. Lotter, M. J. Hassett, N. Schultz, K. L. Kehl, E. M. Van Allen, and E. Cerami, “Artificial Intelligence in Oncology: Current Landscape, Challenges, and Future Directions,” Cancer Discovery 14, no. 5 (2024): 711–726.

[383] S. M. Sweeney, H. K. Hamadeh, N. Abrams, et al., “Challenges to Using Big Data in Cancer,” Cancer Research 83, no. 8 (2023): 1175–1182.

[384] A. T. M. Cheung, E. L. Palapattu, I. R. Pompa, et al., “Racial and Ethnic Disparities in a Real-world Precision Oncology Data Registry,” NPJ precision oncology 7, no. 1 (2023): 7.

RIGHTS & PERMISSIONS

2026 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.