Molecular pathways of common breast cancer metastases and the distinguishing features of triple-negative breast cancer

Yıl 2024, Cilt: 5 Sayı: 2, 50 - 55, 31.05.2024

Kemal Kürşat Bozkurt Safiye Aktaş Merih Güray Durak

https://doi.org/10.47482/acmr.1468113

Öz

Breast cancer is the most common type of female cancer in Turkey, and metastasis is the most important cause of death, as in other solid organ cancers. Triple-negative tumors constitute 15-20% of breast cancer patients. Within three years after the development of the primary tumor, the tumor spreads to other organs. Breast cancer tends to spread to distant organs, such as bone, liver, brain, lung, and adrenal gland, either through regional lymph nodes or vascular channels. This condition, defined as the tendency to metastasize to specific organs, is called organotropism. Triple-negative breast cancer is a heterogeneous breast cancer subtype showing organotropism for the brain and the lungs. Identifying the molecular changes that may cause tropism for various regions and organs in non-metastatic tumors at the time of diagnosis is vital to developing targeted therapies and achieving longer overall and disease-free survival. In this review, we aimed to summarize the pathogenesis of breast cancer metastasis, the molecular changes involved in the metastatic process, and organotropism, as well as to emphasize the distinguishing features of triple-negative breast cancer in terms of metastatic organotropism.

Anahtar Kelimeler

Breast cancer, triple-negative breast cancer, metastasis, molecular pathway, organotropism

Kaynakça

• T. C. Sağlık Bakanlığı Halk Sağlığı Genel Müdürlüğü. Türkiye Kanser İstatistikleri 2016. 2019. Available at https://hsgm.saglik.gov.tr/depo/ birimler/ kanser_db/istatistik/Trkiye_Kanser_statistikleri_2016.pdf:44 February 20, 2024
• Yin L, Duan JJ, Bian XW, Yu SC. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res. 2020;22(1):61.
• Tungsukruthai S, Petpiroon N, Chanvorachote P. Molecular mechanisms of breast cancer metastasis and potential anti-metastatic compounds. Anticancer Res. 2018;38(5):2607-18.
• Lehmann BD, Jovanović B, Chen X, Estrada MV, Johnson KN, Shyr Y, et al. Refinement of triple-negative breast cancer molecular subtypes: Implications for neoadjuvant chemotherapy selection. PLoS One. 2016;11(6):e0157368.
• Weigelt B, Peterse JL, van ‘t Veer LJ. Breast cancer metastasis: markers and models. Nat Rev Cancer. 2005;5(8):591-602.
• Anders CK, Carey LA. Biology, metastatic patterns, and treatment of patients with triple-negative breast cancer. Clin Breast Cancer. 2009;9 Suppl 2(Suppl 2):S73-81.
• Chen W, Hoffmann AD, Liu H, Liu X. Organotropism: new insights into molecular mechanisms of breast cancer metastasis. NPJ Precis Oncol. 2018;2(1):4.
• Polyak K. Heterogeneity in breast cancer. J Clin Invest. 2011;121(10):3786- 8.
• Cheng YC, Ueno NT. Improvement of survival and prospect of cure in patients with metastatic breast cancer. Breast Cancer. 2012;19(3):191-9. 9. Polyak K. Heterogeneity in breast cancer. J Clin Invest. 2011;121(10):3786- 8.
• Welch DR, Hurst DR. Defining the hallmarks of metastasis. Cancer Res. 2019;79(12):3011-27.
• Crowe DL, Shuler CF. Regulation of tumor cell invasion by extracellular matrix. Histol Histopathol. 1999;14(2):665-71. 55 Arch Curr Med Res 2024;5(2):50-55
• Zutter MM, Mazoujian G, Santoro SA. Decreased expression of integrin adhesive protein receptors in adenocarcinoma of the breast. Am J Pathol. 1990;137(4):863-70.
• Morini M, Mottolese M, Ferrari N, Ghiorzo F, Buglioni S, Mortarini R, et al. The alpha 3 beta 1 integrin is associated with mammary carcinoma cell metastasis, invasion, and gelatinase B (MMP-9) activity. Int J Cancer. 2000;87(3):336-42.
• Li DM, Feng YM. Signaling mechanism of cell adhesion molecules in breast cancer metastasis: potential therapeutic targets. Breast Cancer Res Treat. 2011;128(1):7-21.
• Berx G, Becker KF, Höfler H, van Roy F. Mutations of the human E-cadherin (CDH1) gene. Hum Mutat. 1998;12(4):226-37.
• Gotzmann J, Mikula M, Eger A, Schulte-Hermann R, Foisner R, Beug H, et al. Molecular aspects of epithelial cell plasticity: implications for local tumor invasion and metastasis. Mutat Res. 2004;566(1):9-20.
• Cano A, Pérez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, et al. The transcription factor snail controls epithelialmesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000;2(2):76-83.
• Nagaraj NS, Datta PK. Targeting the transforming growth factor-beta signaling pathway in human cancer. Expert Opin Investig Drugs. 2010;19(1):77-91.
• Heldin CH, Landström M, Moustakas A. Mechanism of TGF-beta signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition. Curr Opin Cell Biol. 2009;21(2):166-76.
• Valcourt U, Kowanetz M, Niimi H, Heldin CH, Moustakas A. TGFbeta and the Smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition. Mol Biol Cell. 2005;16(4):1987-2002.
• Gavert N, Ben-Ze’ev A. Epithelial-mesenchymal transition and the invasive potential of tumors. Trends Mol Med. 2008;14(5):199-209.
• Schneider BP, Miller KD. Angiogenesis of breast cancer. J Clin Oncol. 2005;23(8):1782-90.
• Shibuya M. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: A crucial target for anti- and proangiogenic therapies. Genes Cancer. 2011;2(12):1097-105.
• Shibuya M. Structure and function of VEGF/VEGF-receptor system involved in angiogenesis. Cell Struct Funct. 2001;26(1):25-35.
• Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011;147(2):275-92.
• Niu G, Chen X. Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy. Curr Drug Targets. 2010;11(8):1000-17.
• Lu X, Kang Y. Organotropism of breast cancer metastasis. J Mammary Gland Biol Neoplasia. 2007;12(2-3):153-62.
• El Rayes T, Gao D, Altorki NK, Cox TR, Erler JT, Mittal V. Regulation of tumor progression and metastasis by bone marrow-derived microenvironments. In: Akslen LA and Watnick RS, editors. Biomarkers of the tumor microenvironment. Switzerland: Springer; 2017. p. 314-315.
• Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell. 2016;30(5):668-681.
• Paget S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 1989;8(2):98-101.
• Savci-Heijink CD, Halfwerk H, Koster J, van de Vijver MJ. A novel gene expression signature for bone metastasis in breast carcinomas. Breast Cancer Res Treat. 2016;156(2):249-59.
• Sporikova Z, Koudelakova V, Trojanec R, Hajduch M. Genetic Markers in Triple-Negative Breast Cancer. Clin Breast Cancer. 2018;18(5):e841-e850.
• Dunn LK, Mohammad KS, Fournier PG, McKenna CR, Davis HW, Niewolna M, et al. Hypoxia and TGF-beta drive breast cancer bone metastases through parallel signaling pathways in tumor cells and the bone microenvironment. PLoS One. 2009;4(9):e6896.
• Hess KR, Varadhachary GR, Taylor SH, Wei W, Raber MN, Lenzi R, et al. Metastatic patterns in adenocarcinoma. Cancer. 2006;106(7):1624-33.
• Bleckmann A, Conradi LC, Menck K, Schmick NA, Schubert A, Rietkötter E, et al. β-catenin-independent WNT signaling and Ki67 in contrast to the estrogen receptor status are prognostic and associated with poor prognosis in breast cancer liver metastases. Clin Exp Metastasis. 2016;33(4):309-23.
• Witzel I, Oliveira-Ferrer L, Pantel K, Müller V, Wikman H. Breast cancer brain metastases: biology and new clinical perspectives. Breast Cancer Res. 2016;18(1):8.
• Kennecke H, Yerushalmi R, Woods R, Cheang MC, Voduc D, Speers CH, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28(20):3271-7.
• Smid M, Wang Y, Zhang Y, Sieuwerts AM, Yu J, Klijn JG, et al. Subtypes of breast cancer show preferential site of relapse. Cancer Res. 2008;68(9):3108-14.
• Gao D, Du J, Cong L, Liu Q. Risk factors for initial lung metastasis from breast invasive ductal carcinoma in stages I-III of operable patients. Jpn J Clin Oncol. 2009;39(2):97-104.
• Gao H, Chakraborty G, Lee-Lim AP, Mo Q, Decker M, Vonica A, et al. The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites. Cell. 2012;150(4):764-79. Erratum in: Cell. 2012;151(6):1386-8.
• He ZY, Wu SG, Yang Q, Sun JY, Li FY, Lin Q, et al. Breast cancer subtype is associated with axillary lymph node metastasis: A retrospective cohort study. Medicine (Baltimore). 2015;94(48):e2213.
• Jatoi I, Hilsenbeck SG, Clark GM, Osborne CK. Significance of axillary lymph node metastasis in primary breast cancer. J Clin Oncol. 1999;17(8):2334-40. Erratum in: J Clin Oncol 1999;17(10):3365.
• Liang F, Qu H, Lin Q, Yang Y, Ruan X, Zhang B, et al. Molecular biomarkers screened by next-generation RNA sequencing for nonsentinel lymph node status prediction in breast cancer patients with metastatic sentinel lymph nodes. World J Surg Oncol. 2015;13:258.
• Derakhshan F, Reis-Filho JS. Pathogenesis of triple-negative breast cancer. Annu Rev Pathol. 2022;17:181-204.
• Turajlic S, Swanton C. Metastasis as an evolutionary process. Science. 2016;352(6282):169-75.