Cáncer de mama triple negativo: Del análisis multiómico a la personalización terapéutica
DOI:
https://doi.org/10.24197/yvncr364Palabras clave:
Cáncer de mama triple negativo, Análisis multiómicos, Subtipos moleculares, Terapia dirigida, Medicina de precisiónResumen
El cáncer de mama es el segundo tipo de cáncer más frecuente a nivel mundial. Dentro de sus subtipos, el cáncer de mama triple negativo (TNBC) es el más agresivo y presenta el peor pronóstico. A pesar de los avances terapéuticos, hasta un 40% de las pacientes no logra superar la enfermedad. En los últimos años, el desarrollo de análisis ómicos ha permitido identificar biomarcadores genómicos, transcriptómicos, proteómicos, metabolómicos e inmunómicos con un alto valor diagnóstico, pronóstico y terapéutico. Estos estudios han facilitado la clasificación del TNBC en distintos subtipos moleculares, con características biológicas particulares, biomarcadores y estrategias terapéuticas específicas. En esta revisión, se exploran los avances en la terapia dirigida para el TNBC, así como las perspectivas futuras en el contexto de la oncología de precisión.
Descargas
Referencias
Cancer Today [Internet]. [citado 2025 Jun 28]. Disponible en: https://gco.iarc.fr/today/en
Registros de cáncer | Redecan [Internet]. [citado 2025 Jun 29]. Disponible en https://redecan.org/es/registros-de-cancer
Ayala De La Peña F, Silvia ·, Novoa A, Joaquín ·, Gregori G, Lucía ·, et al. SEOM-GEICAM-SOLTI clinical guidelines for early-stage breast cancer (2022). Clinical and Translational Oncology 2023 25:9 [Internet]. 2023 Jun 16 [cited 2025 Feb 27];25(9):2647–64. Available from: https://link.springer.com/article/10.1007/s12094-023-03215-4
Howard FM, Olopade OI. Epidemiology of Triple-Negative Breast Cancer: A Review. Cancer Journal (United States) [Internet]. 2021 Jan 1 [cited 2025 Mar 17];27(1):8–16. Available from: https://journals.lww.com/journalppo/fulltext/2021/01000/epidemiology_of_triple_negative_breast_cancer__a.3.aspx
Karim AM, Eun Kwon J, Ali T, Jang J, Ullah I, Lee YG, et al. Triple-negative breast cancer: epidemiology, molecular mechanisms, and modern vaccine-based treatment strategies. Biochem Pharmacol. 2023 Jun 1;212:115545.
Darlix A, Louvel G, Fraisse J, Jacot W, Brain E, Debled M, et al. Impact of breast cancer molecular subtypes on the incidence, kinetics and prognosis of central nervous system metastases in a large multicentre real-life cohort. Br J Cancer [Internet]. 2019 Dec 10 [cited 2025 Mar 8];121(12):991–1000. Available from: https://pubmed.ncbi.nlm.nih.gov/31719684/
Boyle P. Triple-negative breast cancer: epidemiological considerations and recommendations. Annals of Oncology. 2012 Aug 1;23(SUPPL. 6):vi7–12.
Howard FM, Olopade OI. Epidemiology of Triple-Negative Breast Cancer: A Review. Cancer J [Internet]. 2021 Jan 1 [cited 2025 Mar 9];27(1):8–16. Available from: https://pubmed.ncbi.nlm.nih.gov/33475288/
Vargo JA, Beriwal S, Ahrendt GM, Soran A, Johnson RR, McGuire K, et al. Molecular class as a predictor of locoregional and distant recurrence in the neoadjuvant setting for breast cancer. Oncology [Internet]. 2011 Aug [cited 2025 Mar 17];80(5–6):341–9. Available from: https://pubmed.ncbi.nlm.nih.gov/21791944/
James M, Dixit A, Robinson B, Frampton C, Davey V. Outcomes for Patients with Non-metastatic Triple-negative Breast Cancer in New Zealand. Clin Oncol (R Coll Radiol) [Internet]. 2019 Jan 1 [cited 2025 Mar 17];31(1):17–24. Available from: https://pubmed.ncbi.nlm.nih.gov/30274766/
Cai SL, Liu JJ, Liu YX, Yu SH, Liu X, Lin XQ, et al. Characteristics of recurrence, predictors for relapse and prognosis of rapid relapse triple-negative breast cancer. Front Oncol [Internet]. 2023 [cited 2025 Mar 17];13:1119611. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9978400/
Baranova A, Krasnoselskyi M, Starikov V, Kartashov S, Zhulkevych I, Vlasenko V, et al. Triple-negative breast cancer: current treatment strategies and factors of negative prognosis. J Med Life [Internet]. 2022 Feb 1 [cited 2025 Mar 17];15(2):153. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8999097/
Prat A, Guarneri V, Pascual T, Brasó-Maristany F, Sanfeliu E, Paré L, et al. Development and validation of the new HER2DX assay for predicting pathological response and survival outcome in early-stage HER2-positive breast cancer. EBioMedicine [Internet]. 2022 Jan 1 [cited 2025 Mar 29];75. Available from: https://www.thelancet.com/action/showFullText?pii=S2352396421005958
Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol [Internet]. 2018 Jan 1 [cited 2025 Mar 29];19(1):40–50. Available from: https://pubmed.ncbi.nlm.nih.gov/29233559/
Garcia-Saenz JA, Blancas I, Echavarria I, Hinojo C, Margeli M, Moreno F, et al. SEOM–GEICAM–SOLTI clinical guidelines in advanced breast cancer (2022). Clinical and Translational Oncology [Internet]. 2023 Sep 1 [cited 2025 Feb 27];25(9):2665–78. Available from: https://link.springer.com/article/10.1007/s12094-023-03203-8
Korde LA, Somerfield MR, Hershman DL, for the Neoadjuvant Chemotherapy ET and TT for BCGEP. Use of Immune Checkpoint Inhibitor Pembrolizumab in the Treatment of High-Risk, Early-Stage Triple-Negative Breast Cancer: ASCO Guideline Rapid Recommendation Update. Journal of Clinical Oncology [Internet]. 2022 Apr 1 [cited 2025 Feb 27];39. Available from: https://ascopubs.org/doi/10.1200/JCO.22.00503
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell [Internet]. 2000 Jan 7 [cited 2025 Mar 30];100(1):57–70. Available from: https://www.cell.com/action/showFullText?pii=S0092867400816839
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell [Internet]. 2011 Mar 4 [cited 2025 Jun 28];144(5):646–74. Available from: https://pubmed.ncbi.nlm.nih.gov/21376230/
Hanahan D. Hallmarks of Cancer: New Dimensions. Cancer Discov [Internet]. 2022 Jan 1 [cited 2025 Mar 30];12(1):31–46. Available from: https://pubmed.ncbi.nlm.nih.gov/35022204/
Alvarez-Frutos L, Barriuso D, Duran M, Infante M, Kroemer G, Palacios-Ramirez R, et al. Multiomics insights on the onset, progression, and metastatic evolution of breast cancer. Front Oncol [Internet]. 2023 [cited 2025 Feb 27];13. Available from: https://pubmed.ncbi.nlm.nih.gov/38169859/
Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF, et al. Comprehensive molecular portraits of human breast tumours. Nature 2012 490:7418 [Internet]. 2012 Sep 23 [cited 2025 Mar 3];490(7418):61–70. Available from: https://www.nature.com/articles/nature11412
Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest [Internet]. 2011 Jul 1 [cited 2025 Feb 27];121(7):2750–67. Available from: https://expo.intgen.org/geo/
Braunstein LZ, Riaz N. Microenvironmental Heterogeneity Among Triple-Negative Breast Cancer Subtypes and the Promise of Precision Medicine. [cited 2025 Mar 8]; Available from: https://academic.oup.com/jnci/article/112/7/661/5609117
Bareche Y, Buisseret L, Gruosso T, Girard E, Venet D, Dupont F, et al. Unraveling Triple-Negative Breast Cancer Tumor Microenvironment Heterogeneity: Towards an Optimized Treatment Approach. J Natl Cancer Inst [Internet]. 2020 Jul 1 [cited 2025 Mar 8];112(7):708–19. Available from: https://pubmed.ncbi.nlm.nih.gov/31665482/
Senovilla L, Vitale I, Martins I, Tailler M, Pailleret C, Michaud M, et al. An immunosurveillance mechanism controls cancer cell ploidy. Science (1979) [Internet]. 2012 Sep 28 [cited 2025 Mar 29];337(6102):1678–84. Available from: https://www.science.org/doi/10.1126/science.1224922
Miyashita M, Sasano H, Tamaki K, Chan M, Hirakawa H, Suzuki A, et al. Tumor-infiltrating CD8+ and FOXP3+ lymphocytes in triple-negative breast cancer: its correlation with pathological complete response to neoadjuvant chemotherapy. Breast Cancer Res Treat [Internet]. 2014 Nov 25 [cited 2025 Mar 29];148(3):525–34. Available from: https://pubmed.ncbi.nlm.nih.gov/25395319/
Xuan C, Shamonki JM, Chung A, DiNome ML, Chung M, Sieling PA, et al. Microbial Dysbiosis Is Associated with Human Breast Cancer. PLoS One [Internet]. 2014 Jan 8 [cited 2025 Mar 30];9(1):e83744. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083744
Banerjee S, Tian T, Wei Z, Shih N, Feldman MD, Peck KN, et al. Distinct Microbial Signatures Associated With Different Breast Cancer Types. Front Microbiol [Internet]. 2018 May 15 [cited 2025 Mar 30];9(MAY). Available from: https://pubmed.ncbi.nlm.nih.gov/29867857/
Luan B, Ge F, Lu X, Li Z, Zhang H, Wu J, et al. Changes in the fecal microbiota of breast cancer patients based on 16S rRNA gene sequencing: a systematic review and meta-analysis. Clin Transl Oncol [Internet]. 2024 Jun 1 [cited 2025 Mar 30];26(6):1480–96. Available from: https://pubmed.ncbi.nlm.nih.gov/38217684/
Zoppino FCM, Guerrero-Gimenez ME, Castro GN, Ciocca DR. Comprehensive transcriptomic analysis of heat shock proteins in the molecular subtypes of human breast cancer. BMC Cancer [Internet]. 2018 Jun 28 [cited 2025 Mar 30];18(1):1–17. Available from: https://bmccancer.biomedcentral.com/articles/10.1186/s12885-018-4621-1
He X, Liu X, Zuo F, Shi H, Jing J. Artificial intelligence-based multi-omics analysis fuels cancer precision medicine. Semin Cancer Biol. 2023 Jan 1;88:187–200.
Díaz-Beltrán L, González-Olmedo C, Luque-Caro N, Díaz C, Martín-Blázquez A, Fernández-Navarro M, et al. Human Plasma Metabolomics for Biomarker Discovery: Targeting the Molecular Subtypes in Breast Cancer. Cancers (Basel) [Internet]. 2021 Jan 1 [cited 2025 Mar 30];13(1):1–18. Available from: https://pubmed.ncbi.nlm.nih.gov/33466323/
Takayama T, Tsutsui H, Shimizu I, Toyama T, Yoshimoto N, Endo Y, et al. Diagnostic approach to breast cancer patients based on target metabolomics in saliva by liquid chromatography with tandem mass spectrometry. Clinica Chimica Acta. 2016 Jan 15;452:18–26.
Mazzeo R, Sears J, Palmero L, Bolzonello S, Davis AA, Gerratana L, et al. Liquid biopsy in triple-negative breast cancer: unlocking the potential of precision oncology. ESMO Open [Internet]. 2024 Oct 1 [cited 2025 Mar 30];9(10):103700. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11421323/
Palazón-Carrión N, Jiménez-Cortegana C, Sánchez-León ML, Henao-Carrasco F, Nogales-Fernández E, Chiesa M, et al. Circulating immune biomarkers in peripheral blood correlate with clinical outcomes in advanced breast cancer. Sci Rep [Internet]. 2021 Dec 1 [cited 2025 Mar 30];11(1). Available from: https://pubmed.ncbi.nlm.nih.gov/34257359/
Lehmann BD, Jovanović B, Chen X, Estrada M V., Johnson KN, Shyr Y, et al. Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection. PLoS One [Internet]. 2016 Jun 1 [cited 2025 Mar 8];11(6):e0157368. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157368
Lehmann BD, Colaprico A, Silva TC, Chen J, An H, Ban Y, et al. Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes. Nature Communications 2021 12:1 [Internet]. 2021 Nov 1 [cited 2025 Feb 27];12(1):1–18. Available from: https://www.nature.com/articles/s41467-021-26502-6
Bianchini G, De Angelis C, Licata L, Gianni L. Treatment landscape of triple-negative breast cancer — expanded options, evolving needs. Nature Reviews Clinical Oncology 2021 19:2 [Internet]. 2021 Nov 9 [cited 2025 Mar 8];19(2):91–113. Available from: https://www.nature.com/articles/s41571-021-00565-2
Tutt ANJ, Garber JE, Kaufman B, Viale G, Fumagalli D, Rastogi P, et al. Adjuvant Olaparib for Patients with BRCA1 - or BRCA2 -Mutated Breast Cancer . New England Journal of Medicine [Internet]. 2021 Jun 24 [cited 2025 Mar 10];384(25):2394–405. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2105215
Do K, Chen AP. Molecular Pathways: Targeting PARP in Cancer Treatment. Clin Cancer Res [Internet]. 2010;19(5). Available from: http://aacrjournals.org/clincancerres/article-pdf/19/5/977/1928888/977.pdf
Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. New England Journal of Medicine [Internet]. 2021 Apr 22 [cited 2025 Mar 10];384(16):1529–41. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2028485
Rizzo A, Cusmai A, Acquafredda S, Rinaldi L, Palmiotti G. Ladiratuzumab vedotin for metastatic triple negative cancer: preliminary results, key challenges, and clinical potential. Expert Opin Investig Drugs [Internet]. 2022 [cited 2025 Mar 10];31(6):495–8. Available from: https://pubmed.ncbi.nlm.nih.gov/35171746/
Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. New England Journal of Medicine [Internet]. 2018 Nov 29 [cited 2025 Mar 10];379(22):2108–21. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa1809615
Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. The Lancet [Internet]. 2020 Oct 10 [cited 2025 Mar 8];396(10257):1090–100. Available from: https://www.thelancet.com/action/showFullText?pii=S014067362031953X
Pak LM, Morrow M. Addressing the problem of overtreatment in breast cancer. Expert Rev Anticancer Ther [Internet]. 2022 [cited 2025 Mar 30];22(5):535. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9448354/
Delaloge S, Khan SA, Wesseling J, Whelan T. Ductal carcinoma in situ of the breast: finding the balance between overtreatment and undertreatment. The Lancet [Internet]. 2024 Jun 22 [cited 2025 Mar 30];403(10445):2734–46. Available from: https://www.thelancet.com/action/showFullText?pii=S0140673624004252
Greaves M, Maley CC. Clonal evolution in cancer. Nature 2012 481:7381 [Internet]. 2012 Jan 18 [cited 2025 Mar 30];481(7381):306–13. Available from: https://www.nature.com/articles/nature10762
Chemotherapy induces clonal selection of TP53 mutations. Nature Reviews Clinical Oncology 2014 12:2 [Internet]. 2014 Dec 23 [cited 2025 Mar 30];12(2):64–64. Available from: https://www.nature.com/articles/nrclinonc.2014.231
Zhong Y, Xu F, Wu J, Schubert J, Li MM. Application of Next Generation Sequencing in Laboratory Medicine. Ann Lab Med [Internet]. 2021 Jan 1 [cited 2025 Mar 30];41(1):25. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7443516/
Rabbani N, Kim GYE, Suarez CJ, Chen JH. Applications of Machine Learning in Routine Laboratory Medicine: Current State and Future Directions. Clin Biochem [Internet]. 2022 May 1 [cited 2025 Mar 30];103:1. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9007900/
Descargas
Publicado
Número
Sección
Licencia
Derechos de autor 2025 Pablo Miñambres Barrio, Laura Senovilla, Lucía Álvarez Frutos
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.
Todos los trabajos publicados en la revista Clínica se distribuyen bajo una Licencia Creative Commons Atribución 4.0 Internacional (CC BY 4.0).
Los autores continúan como propietarios de sus trabajos, y pueden volver a publicar sus artículos en otro medio sin tener que solicitar autorización, siempre y cuando indiquen que el trabajo fue publicado originariamente en la revista Clínica.