Does Metastasized Cancer to Lynnph Node Continue Getting Larger

References

1. Ferlay, J., Ervik, M., Lam, F., Colombet, M., Mery, L., Piñeros, M. et al. Global Cancer Observatory: Cancer Tomorrow. https://gco.iarc.fr/tomorrow (International Agency for Research on Cancer, Lyon, France, 2018).

2. Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin. 70, 7–30 (2020).

   PubMed  Google Scholar

3. Pantel, K. & Brakenhoff, R. H. Dissecting the metastatic cascade. Nat. Rev. Cancer 4, 448–456 (2004).

   CAS  PubMed  Google Scholar

4. Valastyan, S. & Weinberg, R. A. Tumor metastasis: molecular insights and evolving paradigms. Cell 147, 275–292 (2011).

   CAS  PubMed  PubMed Central  Google Scholar

5. Chaffer, C. L. & Weinberg, R. A. A perspective on cancer cell metastasis. Science 331, 1559–1564 (2011).

   CAS  PubMed  Google Scholar

6. Gupta, G. P. & Massague, J. Cancer metastasis: building a framework. Cell 127, 679–695 (2006).

   CAS  PubMed  Google Scholar

7. Seltzer, S., Corrigan, M. & O'Reilly, S. The clinicomolecular landscape of de novo versus relapsed stage IV metastatic breast cancer. Exp. Mol. Pathol. 114, 104404 (2020).

   CAS  PubMed  Google Scholar

8. Caswell-Jin, J. L., Plevritis, S. K., Tian, L., Cadham, C. J., Xu, C., Stout, N. K. et al. Change in survival in metastatic breast cancer with treatment advances: meta-analysis and systematic review. JNCI Cancer Spectr. 2, pky062 (2018).

   PubMed  PubMed Central  Google Scholar

9. Early Breast Cancer Trialists' Collaborative Group. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365, 1687–1717 (2005).

10. Harris, J. R., Lippman, M. E., Morrow, M. et al. (eds). Diseases of the Brest, 2nd edn. (J.B. Lippincott, Williams & Wilkins, Philadelphia, 2000).

11. Chiang, A. C. & Massagué, J. Molecular basis of metastasis. N. Engl. J. Med. 359, 2814–2823 (2008).

    CAS  PubMed  PubMed Central  Google Scholar

12. Fidler, I. J. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat. Rev. Cancer 3, 453–458 (2003).

    CAS  PubMed  Google Scholar

13. Jin, X. & Mu, P. Targeting breast cancer metastasis. Breast Cancer 9, 23–34 (2015).

    PubMed  PubMed Central  Google Scholar

14. Gerratana, L., Fanotto, V., Bonotto, M., Bolzonello, S., Minisini, A. M., Fasola, G. et al. Pattern of metastasis and outcome in patients with breast cancer. Clin. Exp. Metastasis 32, 125–133 (2015).

    CAS  PubMed  Google Scholar

15. Wang, R., Zhu, Y., Liu, X., Liao, X., He, J. & Niu, L. The clinicopathological features and survival outcomes of patients with different metastatic sites in stage IV breast cancer. BMC Cancer 19, 1091 (2019).

    PubMed  PubMed Central  Google Scholar

16. Uhr, J. W. & Pantel, K. Controversies in clinical cancer dormancy. Proc. Natl Acad. Sci. USA 108, 12396–12400 (2011).

    CAS  PubMed  PubMed Central  Google Scholar

17. Sosa, M. S., Bragado, P. & Aguirre-Ghiso, J. A. Mechanisms of disseminated cancer cell dormancy: an awakening field. Nat. Rev. Cancer 14, 611–622 (2014).

    CAS  PubMed  PubMed Central  Google Scholar

18. Fares, J., Fares, M. Y., Khachfe, H. H., Salhab, H. A. & Fares, Y. Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduct. Target Ther. 5, 28 (2020).

    PubMed  PubMed Central  Google Scholar

19. Harris, L., Fritsche, H., Mennel, R., Norton, L., Ravdin, P., Taube, S. et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J. Clin. Oncol. 25, 5287–5312 (2007).

    CAS  PubMed  Google Scholar

20. American Society of Clinical Oncology. 2007 Update of recommendations for the use of tumor markers in breast cancer. J. Oncol. Pract. 3, 336–339 (2007).

21. Perou, C. M., Sørlie, T., Eisen, M. B., van de Rijn, M., Jeffrey, S. S., Rees, C. A. et al. Molecular portraits of human breast tumours. Nature 406, 747–752 (2000).

    CAS  PubMed  Google Scholar

22. Goldhirsch, A., Wood, W. C., Coates, A. S., Gelber, R. D., Thürlimann, B. & Senn, H. J. Strategies for subtypes-dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann. Oncol. 22, 1736–1747 (2011).

    CAS  PubMed  PubMed Central  Google Scholar

23. Gomis, R. R. & Gawrzak, S. Tumor cell dormancy. Mol. Oncol. 11, 62–78 (2017).

    PubMed  PubMed Central  Google Scholar

24. Karrison, T. G., Ferguson, D. J. & Meier, P. Dormancy of mammary carcinoma after mastectomy. J. Natl Cancer Inst. 91, 80–85 (1999).

    CAS  PubMed  Google Scholar

25. Colleoni, M., Sun, Z., Price, K. N., Karlsson, P., Forbes, J. F., Thurlimann, B. et al. Annual hazard rates of recurrence for breast cancer during 24 years of follow-up: results from the international breast cancer study group trials I to V. J. Clin. Oncol. 34, 927–935 (2016).

    CAS  PubMed  PubMed Central  Google Scholar

26. Demicheli, R., Biganzoli, E., Ardoino, I., Boracchi, P., Coradini, D., Greco, M. et al. Recurrence and mortality dynamics for breast cancer patients undergoing mastectomy according to estrogen receptor status: different mortality but similar recurrence. Cancer Sci. 101, 826–830 (2010).

    CAS  PubMed  Google Scholar

27. Park, S., Koo, J. S., Kim, M. S., Park, H. S., Lee, J. S., Lee, J. S. et al. Characteristics and outcomes according to molecular subtypes of breast cancer as classified by a panel of four biomarkers using immunohistochemistry. Breast 21, 50–57 (2012).

    PubMed  Google Scholar

28. Kennecke, H., Yerushalmi, R., Woods, R., Cheang, M. C., Voduc, D., Speers, C. H. et al. Metastatic behavior of breast cancer subtypes. J. Clin. Oncol. 28, 3271–3277 (2010).

    PubMed  Google Scholar

29. Denoix, P. F. Nomenclature and classification of cancers based on an atlas. Acta Unio Int. Contra Cancrum 9, 769–771 (1953).

    CAS  PubMed  Google Scholar

30. Greene, F. L. & Sobin, L. H. The staging of cancer: a retrospective and prospective appraisal. CA Cancer J. Clin. 58, 180–190 (2008).

    PubMed  Google Scholar

31. Vieira, A. F. & Schmitt, F. An update on breast cancer multigene prognostic tests-emergent clinical biomarkers. Front. Med. 5, 248 (2018).

    Google Scholar

32. Harbeck, N. & Gnant, M. Breast cancer. Lancet 389, 1134–1150 (2017).

    PubMed  Google Scholar

33. Klein, C. A. Parallel progression of primary tumours and metastases. Nat. Rev. Cancer 9, 302–312 (2009).

    CAS  PubMed  Google Scholar

34. Talmadge, J. E. & Fidler, I. J. AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res. 70, 5649–5669 (2010).

    CAS  PubMed  PubMed Central  Google Scholar

35. Turajlic, S. & Swanton, C. Metastasis as an evolutionary process. Science 352, 169–175 (2016).

    CAS  PubMed  Google Scholar

36. Norton, L. & Massagué, J. Is cancer a disease of self-seeding? Nat. Med. 12, 875–878 (2006).

    CAS  PubMed  Google Scholar

37. Savas, P., Teo, Z. L., Lefevre, C., Flensburg, C., Caramia, F., Alsop, K. et al. The subclonal architecture of metastatic breast cancer: results from a prospective community-based rapid autopsy program "CASCADE". PLoS Med. 13, e1002204 (2016).

    PubMed  PubMed Central  Google Scholar

38. Stanley, G. A., Balani, J. P., Miller, D. S., Mansour, J. C. & Schwarz, R. E. Clinical evidence: metastases can metastasize. World J. Oncol. 3, 138–141 (2012).

    PubMed  PubMed Central  Google Scholar

39. Venet, D., Fimereli, D., Rothe, F., Boeckx, B., Maetens, M., Majjaj, S. et al. Phylogenetic reconstruction of breast cancer reveals two routes of metastatic dissemination associated with distinct clinical outcome. eBioMedicine 56, 102793 (2020).

    PubMed  PubMed Central  Google Scholar

40. Fearon, E. R. & Vogelstein, B. A genetic model for colorectal tumorigenesis. Cell 61, 759–767 (1990).

    CAS  PubMed  Google Scholar

41. Cairns, J. Mutation selection and the natural history of cancer. Nature 255, 197–200 (1975).

    CAS  PubMed  Google Scholar

42. Collins, V. P., Loeffler, R. K. & Tivey, H. Observations on growth rates of human tumors. Am. J. Roentgenol. Radium Ther. Nucl. Med. 76, 988–1000 (1956).

    CAS  PubMed  Google Scholar

43. Friberg, S. & Mattson, S. On the growth rates of human malignant tumors: implications for medical decision making. J. Surg. Oncol. 65, 284–297 (1997).

    CAS  PubMed  Google Scholar

44. Eyles, J., Puaux, A. L., Wang, X., Toh, B., Prakash, C., Hong, M. et al. Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma. J. Clin. Investig. 120, 2030–2039 (2010).

    CAS  PubMed  PubMed Central  Google Scholar

45. Harper, K. L., Sosa, M. S., Entenberg, D., Hosseini, H., Cheung, J. F., Nobre, R. et al. Mechanism of early dissemination and metastasis in Her2(+) mammary cancer. Nature 540, 588–592 (2016).

    CAS  PubMed  PubMed Central  Google Scholar

46. Hosseini, H., Obradović, M. M. S., Hoffmann, M., Harper, K. L., Sosa, M. S., Werner-Klein, M. et al. Early dissemination seeds metastasis in breast cancer. Nature 540, 552–558 (2016).

    CAS  PubMed  PubMed Central  Google Scholar

47. Hüsemann, Y., Geigl, J. B., Schubert, F., Musiani, P., Meyer, M., Burghart, E. et al. Systemic spread is an early step in breast cancer. Cancer Cell 13, 58–68 (2008).

    PubMed  Google Scholar

48. Rhim, A. D., Mirek, E. T., Aiello, N. M., Maitra, A., Bailey, J. M., McAllister, F. et al. EMT and dissemination precede pancreatic tumor formation. Cell 148, 349–361 (2012).

    CAS  PubMed  PubMed Central  Google Scholar

49. Sänger, N., Effenberger, K. E., Riethdorf, S., Van Haasteren, V., Gauwerky, J., Wiegratz, I. et al. Disseminated tumor cells in the bone marrow of patients with ductal carcinoma in situ. Int. J. Cancer 129, 2522–2526 (2011).

50. Krishnamurthy, S., Cristofanilli, M., Singh, B., Reuben, J., Gao, H., Cohen, E. N. et al. Detection of minimal residual disease in blood and bone marrow in early stage breast cancer. Cancer 116, 3330–3337 (2010).

    PubMed  Google Scholar

51. Friberg, S. & Nyström, A. Cancer metastases: early dissemination and late recurrences. Cancer Growth Metastasis 8, 43–49 (2015).

    PubMed  PubMed Central  Google Scholar

52. Ghajar, C. M. & Bissell, M. J. Metastasis: pathways of parallel progression. Nature 540, 528–529 (2016).

    CAS  PubMed  Google Scholar

53. Mouw, J. K., Ou, G. & Weaver, V. M. Extracellular matrix assembly: a multiscale deconstruction. Nat. Rev. Mol. Cell Biol. 15, 771–785 (2014).

    CAS  PubMed  PubMed Central  Google Scholar

54. Cheung, K. J. & Ewald, A. J. A collective route to metastasis: seeding by tumor cell clusters. Science 352, 167–169 (2016).

    CAS  PubMed  PubMed Central  Google Scholar

55. Friedl, P. & Wolf, K. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat. Rev. Cancer 3, 362–374 (2003).

    CAS  PubMed  Google Scholar

56. Pastushenko, I., Brisebarre, A., Sifrim, A., Fioramonti, M., Revenco, T., Boumahdi, S. et al. Identification of the tumour transition states occurring during EMT. Nature 556, 463–468 (2018).

    CAS  PubMed  Google Scholar

57. Wong, A. D. & Searson, P. C. Mitosis-mediated intravasation in a tissue-engineered tumor-microvessel platform. Cancer Res. 77, 6453–6461 (2017).

    CAS  PubMed  PubMed Central  Google Scholar

58. Dasgupta, A., Lim, A. R. & Ghajar, C. M. Circulating and disseminated tumor cells: harbingers or initiators of metastasis? Mol. Oncol. 11, 40–61 (2017).

    PubMed  PubMed Central  Google Scholar

59. Duda, D. G., Duyverman, A. M., Kohno, M., Snuderl, M., Steller, E. J., Fukumura, D. et al. Malignant cells facilitate lung metastasis by bringing their own soil. Proc. Natl Acad. Sci. USA 107, 21677–21682 (2010).

    CAS  PubMed  PubMed Central  Google Scholar

60. Szczerba, B. M., Castro-Giner, F., Vetter, M., Krol, I., Gkountela, S., Landin, J. et al. Neutrophils escort circulating tumour cells to enable cell cycle progression. Nature 566, 553–557 (2019).

    CAS  PubMed  Google Scholar

61. Aceto, N., Bardia, A., Miyamoto, D. T., Donaldson, M. C., Wittner, B. S., Spencer, J. A. et al. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 158, 1110–1122 (2014).

    CAS  PubMed  PubMed Central  Google Scholar

62. Rudzka, D. A., Spennati, G., McGarry, D. J., Chim, Y. H., Neilson, M., Ptak, A. et al. Migration through physical constraints is enabled by MAPK-induced cell softening via actin cytoskeleton re-organization. J. Cell Sci. 132, jcs224071 (2019).

63. Luzzi, K. J., MacDonald, I. C., Schmidt, E. E., Kerkvliet, N., Morris, V. L., Chambers, A. F. et al. Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am. J. Pathol. 153, 865–873 (1998).

    CAS  PubMed  PubMed Central  Google Scholar

64. Paget, S. The distribution of secondary growths in cancer of the breast. Cancer Metastasis Rev. 8, 98–101 (1989).

    CAS  PubMed  Google Scholar

65. Langley, R. R. & Fidler, I. J. The seed and soil hypothesis revisited-the role of tumor-stroma interactions in metastasis to different organs. Int. J. Cancer 128, 2527–2535 (2011).

    CAS  PubMed  PubMed Central  Google Scholar

66. Cameron, M. D., Schmidt, E. E., Kerkvliet, N., Nadkarni, K. V., Morris, V. L., Groom, A. C. et al. Temporal progression of metastasis in lung: cell survival, dormancy, and location dependence of metastatic inefficiency. Cancer Res. 60, 2541–2546 (2000).

    CAS  PubMed  Google Scholar

67. Peinado, H., Zhang, H., Matei, I. R., Costa-Silva, B., Hoshino, A., Rodrigues, G. et al. Pre-metastatic niches: organ-specific homes for metastases. Nat. Rev. Cancer 17, 302–317 (2017).

    CAS  PubMed  Google Scholar

68. Psaila, B. & Lyden, D. The metastatic niche: adapting the foreign soil. Nat. Rev. Cancer 9, 285–293 (2009).

    CAS  PubMed  PubMed Central  Google Scholar

69. Zomer, A., Maynard, C., Verweij, F. J., Kamermans, A., Schäfer, R., Beerling, E. et al. In Vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior. Cell 161, 1046–1057 (2015).

    CAS  PubMed  PubMed Central  Google Scholar

70. Shiao, S. L., Ganesan, A. P., Rugo, H. S. & Coussens, L. M. Immune microenvironments in solid tumors: new targets for therapy. Genes Dev. 25, 2559–2572 (2011).

    CAS  PubMed  PubMed Central  Google Scholar

71. Mlecnik, B., Bindea, G., Kirilovsky, A., Angell, H. K., Obenauf, A. C., Tosolini, M. et al. The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis. Sci. Transl. Med. 8, 327ra26 (2016).

    PubMed  Google Scholar

72. Blomberg, O. S., Spagnuolo, L. & de Visser, K. E. Immune regulation of metastasis: mechanistic insights and therapeutic opportunities. Dis. Model Mech. 11, dmm036236 (2018).

73. Thiery, J. P., Acloque, H., Huang, R. Y. & Nieto, M. A. Epithelial-mesenchymal transitions in development and disease. Cell 139, 871–890 (2009).

    CAS  PubMed  Google Scholar

74. Poltavets, V., Kochetkova, M., Pitson, S. M. & Samuel, M. S. The role of the extracellular matrix and its molecular and cellular regulators in cancer cell plasticity. Front. Oncol. 8, 431 (2018).

    PubMed  PubMed Central  Google Scholar

75. Jahanban-Esfahlan, R., Seidi, K., Manjili, M. H., Jahanban-Esfahlan, A., Javaheri, T. & Zare, P. Tumor cell dormancy: threat or opportunity in the fight against cancer. Cancers 11, 1207 (2019).

76. Weiss, L. Metastatic inefficiency. Adv. Cancer Res. 54, 159–211 (1990).

    CAS  PubMed  Google Scholar

77. Azevedo, A. S., Follain, G., Patthabhiraman, S., Harlepp, S. & Goetz, J. G. Metastasis of circulating tumor cells: favorable soil or suitable biomechanics, or both? Cell Adh Migr. 9, 345–356 (2015).

    CAS  PubMed  PubMed Central  Google Scholar

78. Koop, S., MacDonald, I. C., Luzzi, K., Schmidt, E. E., Morris, V. L., Grattan, M. et al. Fate of melanoma cells entering the microcirculation: over 80% survive and extravasate. Cancer Res. 55, 2520–2523 (1995).

    CAS  PubMed  Google Scholar

79. McGranahan, N. & Swanton, C. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell 168, 613–628 (2017).

    CAS  PubMed  Google Scholar

80. Somasundaram, R., Villanueva, J. & Herlyn, M. Intratumoral heterogeneity as a therapy resistance mechanism: role of melanoma subpopulations. Adv. Pharm. 65, 335–359 (2012).

    CAS  Google Scholar

81. Celià-Terrassa, T. & Kang, Y. Distinctive properties of metastasis-initiating cells. Genes Dev. 30, 892–908 (2016).

    PubMed  PubMed Central  Google Scholar

82. Marx, V. How to pull the blanket off dormant cancer cells. Nat. Methods 15, 249–252 (2018).

    CAS  PubMed  Google Scholar

83. Klein, C. A. Framework models of tumor dormancy from patient-derived observations. Curr. Opin. Genet. Dev. 21, 42–49 (2011).

    CAS  PubMed  Google Scholar

84. Coller, H. A., Sang, L. & Roberts, J. M. A new description of cellular quiescence. PLoS Biol. 4, e83 (2006).

    PubMed  PubMed Central  Google Scholar

85. Sharma, S., Xing, F., Liu, Y., Wu, K., Said, N., Pochampally, R. et al. Secreted protein acidic and rich in cysteine (SPARC) mediates metastatic dormancy of prostate cancer in bone. J. Biol. Chem. 291, 19351–19363 (2016).

    CAS  PubMed  PubMed Central  Google Scholar

86. Aguirre Ghiso, J. A., Kovalski, K. & Ossowski, L. Tumor dormancy induced by downregulation of urokinase receptor in human carcinoma involves integrin and MAPK signaling. J. Cell Biol. 147, 89–104 (1999).

    CAS  PubMed  Google Scholar

87. Barkan, D., Green, J. E. & Chambers, A. F. Extracellular matrix: a gatekeeper in the transition from dormancy to metastatic growth. Eur. J. Cancer 46, 1181–1188 (2010).

    CAS  PubMed  PubMed Central  Google Scholar

88. Humtsoe, J. O. & Kramer, R. H. Differential epidermal growth factor receptor signaling regulates anchorage-independent growth by modulation of the PI3K/AKT pathway. Oncogene 29, 1214–1226 (2010).

    CAS  PubMed  Google Scholar

89. Aguirre-Ghiso, J. A., Estrada, Y., Liu, D. & Ossowski, L. ERK(MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38(SAPK). Cancer Res. 63, 1684–1695 (2003).

    CAS  PubMed  Google Scholar

90. Aguirre-Ghiso, J. A., Liu, D., Mignatti, A., Kovalski, K. & Ossowski, L. Urokinase receptor and fibronectin regulate the ERK(MAPK) to p38(MAPK) activity ratios that determine carcinoma cell proliferation or dormancy in vivo. Mol. Biol. Cell 12, 863–879 (2001).

    CAS  PubMed  PubMed Central  Google Scholar

91. Schrader, J., Gordon-Walker, T. T., Aucott, R. L., van Deemter, M., Quaas, A., Walsh, S. et al. Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells. Hepatology 53, 1192–1205 (2011).

    CAS  PubMed  Google Scholar

92. Albrengues, J., Shields, M. A., Ng, D., Park, C. G., Ambrico, A., Poindexter, M. E. et al. Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science 361, 6409 (2018).

93. Lu, X., Mu, E., Wei, Y., Riethdorf, S., Yang, Q., Yuan, M. et al. VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging α4β1-positive osteoclast progenitors. Cancer Cell 20, 701–714 (2011).

    CAS  PubMed  PubMed Central  Google Scholar

94. Aguirre-Ghiso, J. A. Models, mechanisms and clinical evidence for cancer dormancy. Nat. Rev. Cancer 7, 834–846 (2007).

    CAS  PubMed  PubMed Central  Google Scholar

95. Folkman, J. & Kalluri, R. Cancer without disease. Nature 427, 787 (2004).

    CAS  PubMed  Google Scholar

96. Holmgren, L., O'Reilly, M. S. & Folkman, J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat. Med. 1, 149–153 (1995).

    CAS  PubMed  Google Scholar

97. Almog, N., Ma, L., Raychowdhury, R., Schwager, C., Erber, R., Short, S. et al. Transcriptional switch of dormant tumors to fast-growing angiogenic phenotype. Cancer Res. 69, 836–844 (2009).

    CAS  PubMed  Google Scholar

98. Mittal, D., Gubin, M. M., Schreiber, R. D. & Smyth, M. J. New insights into cancer immunoediting and its three component phases-elimination, equilibrium and escape. Curr. Opin. Immunol. 27, 16–25 (2014).

    CAS  PubMed  PubMed Central  Google Scholar

99. Wang, H. F., Wang, S. S., Huang, M. C., Liang, X. H., Tang, Y. J. & Tang, Y. L. Targeting immune-mediated dormancy: a promising treatment of cancer. Front. Oncol. 9, 498 (2019).

    CAS  PubMed  PubMed Central  Google Scholar

100. Risson, E., Nobre, A. R., Maguer-Satta, V. & Aguirre-Ghiso, J. A. The current paradigm and challenges ahead for the dormancy of disseminated tumor cells. Nat. Cancer https://doi.org/10.1038/s43018-020-0088-5 (2020).

101. Ghajar, C. M., Peinado, H., Mori, H., Matei, I. R., Evason, K. J., Brazier, H. et al. The perivascular niche regulates breast tumour dormancy. Nat. Cell Biol. 15, 807–817 (2013).

     CAS  PubMed  PubMed Central  Google Scholar

102. Weinstat-Saslow, D. L., Zabrenetzky, V. S., VanHoutte, K., Frazier, W. A., Roberts, D. D. & Steeg, P. S. Transfection of thrombospondin 1 complementary DNA into a human breast carcinoma cell line reduces primary tumor growth, metastatic potential, and angiogenesis. Cancer Res. 54, 6504–6511 (1994).

     CAS  PubMed  Google Scholar

103. Fehm, T., Krawczyk, N., Solomayer, E. F., Becker-Pergola, G., Dürr-Störzer, S., Neubauer, H. et al. ERalpha-status of disseminated tumour cells in bone marrow of primary breast cancer patients. Breast Cancer Res. 10, R76 (2008).

     PubMed  PubMed Central  Google Scholar

104. Schlimok, G., Funke, I., Holzmann, B., Gottlinger, G., Schmidt, G., Hauser, H. et al. Micrometastatic cancer cells in bone marrow: in vitro detection with anti-cytokeratin and in vivo labeling with anti-17-1A monoclonal antibodies. Proc. Natl Acad. Sci. USA 84, 8672–8676 (1987).

     CAS  PubMed  PubMed Central  Google Scholar

105. Weckermann, D., Polzer, B., Ragg, T., Blana, A., Schlimok, G., Arnholdt, H. et al. Perioperative activation of disseminated tumor cells in bone marrow of patients with prostate cancer. J. Clin. Oncol. 27, 1549–1556 (2009).

     PubMed  Google Scholar

106. Pantel, K., Schlimok, G., Braun, S., Kutter, D., Lindemann, F., Schaller, G. et al. Differential expression of proliferation-associated molecules in individual micrometastatic carcinoma cells. J. Natl Cancer Inst. 85, 1419–1424 (1993).

     CAS  PubMed  Google Scholar

107. Meng, S., Tripathy, D., Frenkel, E. P., Shete, S., Naftalis, E. Z., Huth, J. F. et al. Circulating tumor cells in patients with breast cancer dormancy. Clin. Cancer Res. 10, 8152–8162 (2004).

     PubMed  Google Scholar

108. Müller, V., Stahmann, N., Riethdorf, S., Rau, T., Zabel, T., Goetz, A. et al. Circulating tumor cells in breast cancer: correlation to bone marrow micrometastases, heterogeneous response to systemic therapy and low proliferative activity. Clin. Cancer Res. 11, 3678–3685 (2005).

     PubMed  Google Scholar

109. Malanchi, I., Santamaria-Martínez, A., Susanto, E., Peng, H., Lehr, H. A., Delaloye, J. F. et al. Interactions between cancer stem cells and their niche govern metastatic colonization. Nature 481, 85–89 (2011).

     PubMed  Google Scholar

110. Braun, S., Vogl, F. D., Naume, B., Janni, W., Osborne, M. P., Coombes, R. C. et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N. Engl. J. Med. 353, 793–802 (2005).

     CAS  PubMed  Google Scholar

111. Cristofanilli, M., Budd, G. T., Ellis, M. J., Stopeck, A., Matera, J., Miller, M. C. et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N. Engl. J. Med. 351, 781–791 (2004).

     CAS  PubMed  Google Scholar

112. Dawood, S., Broglio, K., Valero, V., Reuben, J., Handy, B., Islam, R. et al. Circulating tumor cells in metastatic breast cancer: from prognostic stratification to modification of the staging system? Cancer 113, 2422–2430 (2008).

     PubMed  Google Scholar

113. Weedon-Fekjaer, H., Lindqvist, B. H., Vatten, L. J., Aalen, O. O. & Tretli, S. Breast cancer tumor growth estimated through mammography screening data. Breast Cancer Res. 10, R41 (2008).

     PubMed  PubMed Central  Google Scholar

114. Lee, S. H., Kim, Y. S., Han, W., Ryu, H. S., Chang, J. M., Cho, N. et al. Tumor growth rate of invasive breast cancers during wait times for surgery assessed by ultrasonography. Medicine 95, e4874 (2016).

     PubMed  PubMed Central  Google Scholar

115. Ryu, E. B., Chang, J. M., Seo, M., Kim, S. A., Lim, J. H. & Moon, W. K. Tumour volume doubling time of molecular breast cancer subtypes assessed by serial breast ultrasound. Eur. Radiol. 24, 2227–2235 (2014).

     PubMed  Google Scholar

116. Bartmann, C., Wischnewsky, M., Stüber, T., Stein, R., Krockenberger, M., Häusler, S. et al. Pattern of metastatic spread and subcategories of breast cancer. Arch. Gynecol. Obstet. 295, 211–223 (2017).

     PubMed  Google Scholar

117. Harbeck, N., Penault-Llorca, F., Cortes, J., Gnant, M., Houssami, N., Poortmans, P. et al. Breast cancer. Nat. Rev. Dis. Prim. 5, 66 (2019).

     PubMed  Google Scholar

118. Aggelis, V. & Johnston, S. R. D. Advances in endocrine-based therapies for estrogen receptor-positive metastatic breast cancer. Drugs 79, 1849–1866 (2019).

     CAS  PubMed  Google Scholar

119. Lin, N. U. & Winer, E. P. Advances in adjuvant endocrine therapy for postmenopausal women. J. Clin. Oncol. 26, 798–805 (2008).

     CAS  PubMed  Google Scholar

120. Hanker, A. B., Sudhan, D. R. & Arteaga, C. L. Overcoming endocrine resistance in breast cancer. Cancer Cell 37, 496–513 (2020).

     CAS  PubMed  PubMed Central  Google Scholar

121. Hong, S. P., Chan, T. E., Lombardo, Y., Corleone, G., Rotmensz, N., Bravaccini, S. et al. Single-cell transcriptomics reveals multi-step adaptations to endocrine therapy. Nat. Commun. 10, 3840 (2019).

     PubMed  PubMed Central  Google Scholar

122. Ogba, N., Manning, N. G., Bliesner, B. S., Ambler, S. K., Haughian, J. M., Pinto, M. P. et al. Luminal breast cancer metastases and tumor arousal from dormancy are promoted by direct actions of estradiol and progesterone on the malignant cells. Breast Cancer Res. 16, 489 (2014).

     PubMed  PubMed Central  Google Scholar

123. Patel, H. K. & Bihani, T. Selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) in cancer treatment. Pharm. Ther. 186, 1–24 (2018).

     CAS  Google Scholar

124. Pritchard, K. I. Combining endocrine agents with chemotherapy: which patients and what sequence? Cancer 112, 718–722 (2008).

     CAS  PubMed  Google Scholar

125. Haque, M. M. & Desai, K. V. Pathways to endocrine therapy resistance in breast cancer. Front. Endocrinol. 10, 573 (2019).

     Google Scholar

126. Awada, A., Gligorov, J., Jerusalem, G., Preusser, M., Singer, C. & Zielinski, C. CDK4/6 inhibition in low burden and extensive metastatic breast cancer: summary of an ESMO Open—Cancer Horizons pro and con discussion. ESMO Open 4, e000565 (2019).

     PubMed  PubMed Central  Google Scholar

127. Murphy, C. G. & Dickler, M. N. The Role of CDK4/6 Inhibition in Breast Cancer. Oncologist 20, 483–490 (2015).

     CAS  PubMed  PubMed Central  Google Scholar

128. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 490, 61–70 (2012).

129. Miller, T. W., Balko, J. M., Fox, E. M., Ghazoui, Z., Dunbier, A., Anderson, H. et al. ERα-dependent E2F transcription can mediate resistance to estrogen deprivation in human breast cancer. Cancer Discov. 1, 338–351 (2011).

     CAS  PubMed  PubMed Central  Google Scholar

130. Lynce, F., Shajahan-Haq, A. N. & Swain, S. M. CDK4/6 inhibitors in breast cancer therapy: current practice and future opportunities. Pharm. Ther. 191, 65–73 (2018).

     CAS  Google Scholar

131. Asghar, U. S., Barr, A. R., Cutts, R., Beaney, M., Babina, I., Sampath, D. et al. Single-cell dynamics determines response to CDK4/6 inhibition in triple-negative breast cancer. Clin. Cancer Res. 23, 5561–5572 (2017).

     CAS  PubMed  PubMed Central  Google Scholar

132. Sever, R. & Brugge, J. S. Signal transduction in cancer. Cold Spring Harb. Perspect. Med. 5, a006098 (2015).

133. Rothenberger, N. J., Somasundaram, A. & Stabile, L. P. The role of the estrogen pathway in the tumor microenvironment. Int. J. Mol. Sci. 19, 611 (2018).

134. Dieci, M. V., Barbieri, E., Piacentini, F., Ficarra, G., Bettelli, S., Dominici, M. et al. Discordance in receptor status between primary and recurrent breast cancer has a prognostic impact: a single-institution analysis. Ann. Oncol. 24, 101–108 (2013).

     CAS  PubMed  Google Scholar

135. Georgescu, R., Boros, M., Moncea, D., Bauer, O., Coros, M. F., Oprea, A. et al. Discordance rate in estrogen receptor, progesterone receptor, HER2 Status, and Ki67 index between primary unifocal and multiple homogenous breast carcinomas and synchronous axillary lymph node metastases have an impact on therapeutic decision. Appl. Immunohistochem. Mol. Morphol. 26, 533–538 (2018).

     CAS  PubMed  Google Scholar

136. Jung, J., Lee, S. H., Park, M., Youn, J. H., Shin, S. H., Gwak, H. S. et al. Discordances in ER, PR, and HER2 between primary breast cancer and brain metastasis. J. Neurooncol. 137, 295–302 (2018).

     CAS  PubMed  Google Scholar

137. Matsumoto, A., Jinno, H., Murata, T., Seki, T., Takahashi, M., Hayashida, T. et al. Prognostic implications of receptor discordance between primary and recurrent breast cancer. Int. J. Clin. Oncol. 20, 701–708 (2015).

     CAS  PubMed  Google Scholar

138. Timmer, M., Werner, J. M., Röhn, G., Ortmann, M., Blau, T., Cramer, C. et al. Discordance and conversion rates of progesterone-, estrogen-, and HER2/neu-receptor status in primary breast cancer and brain metastasis mainly triggered by hormone therapy. Anticancer Res. 37, 4859–4865 (2017).

     CAS  PubMed  Google Scholar

139. Yang, Z., Li, N., Li, X., Lei, L. & Wang, X. The prognostic impact of hormonal receptor and HER-2 expression discordance in metastatic breast cancer patients. OncoTargets Ther. 13, 853–863 (2020).

     CAS  Google Scholar

140. Yuda, S., Shimizu, C., Yoshida, M., Shiino, S., Kinoshita, T., Maeshima, A. M. et al. Biomarker discordance between primary breast cancer and bone or bone marrow metastases. Jpn. J. Clin. Oncol. 49, 426–430 (2019).

     PubMed  Google Scholar

141. Hammond, M. E., Hayes, D. F., Dowsett, M., Allred, D. C., Hagerty, K. L., Badve, S. et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch. Pathol. Lab. Med. 134, e48–e72 (2010).

     CAS  PubMed  Google Scholar

142. Shiino, S., Kinoshita, T., Yoshida, M., Jimbo, K., Asaga, S., Takayama, S. et al. Prognostic impact of discordance in hormone receptor status between primary and recurrent sites in patients with recurrent breast cancer. Clin. Breast Cancer 16, e133–e140 (2016).

     CAS  PubMed  Google Scholar

143. Thompson, E. W., Paik, S., Brünner, N., Sommers, C. L., Zugmaier, G., Clarke, R. et al. Association of increased basement membrane invasiveness with absence of estrogen receptor and expression of vimentin in human breast cancer cell lines. J. Cell Physiol. 150, 534–544 (1992).

     CAS  PubMed  Google Scholar

144. Iacobuzio-Donahue, C. A., Michael, C., Baez, P., Kappagantula, R., Hooper, J. E. & Hollman, T. J. Cancer biology as revealed by the research autopsy. Nat. Rev. Cancer 19, 686–697 (2019).

     CAS  PubMed  Google Scholar

145. Steeg, P. S. Heterogeneity of drug target expression among metastatic lesions: lessons from a breast cancer autopsy program. Clin. Cancer Res. 14, 3643–3645 (2008).

     PubMed  PubMed Central  Google Scholar

146. Wu, J. M., Fackler, M. J., Halushka, M. K., Molavi, D. W., Taylor, M. E., Teo, W. W. et al. Heterogeneity of breast cancer metastases: comparison of therapeutic target expression and promoter methylation between primary tumors and their multifocal metastases. Clin. Cancer Res. 14, 1938–1946 (2008).

     CAS  PubMed  PubMed Central  Google Scholar

147. Sottoriva, A., Kang, H., Ma, Z., Graham, T. A., Salomon, M. P., Zhao, J. et al. A Big Bang model of human colorectal tumor growth. Nat. Genet. 47, 209–216 (2015).

     CAS  PubMed  PubMed Central  Google Scholar

148. American Cancer Society. Cancer Facts & Figures 2019 (American Cancer Society, Atlanta, 2019).

149. Gradishar, W. J., Anderson, B. O., Abraham, J., Aft, R., Agnese, D., Allison, K. H. et al. Breast cancer, version 3.2020, NCCN clinical practice guidelines in oncology. J. Natl Compr. Canc Netw. 18, 452–478 (2020).

     CAS  PubMed  Google Scholar

150. Khatcheressian, J. L., Hurley, P., Bantug, E., Esserman, L. J., Grunfeld, E., Halberg, F. et al. Breast cancer follow-up and management after primary treatment: American Society of Clinical Oncology clinical practice guideline update. J. Clin. Oncol. 31, 961–965 (2013).

     CAS  PubMed  Google Scholar

151. De Placido, S., De Angelis, C., Giuliano, M., Pizzi, C., Ruocco, R., Perrone, V. et al. Imaging tests in staging and surveillance of non-metastatic breast cancer: changes in routine clinical practice and cost implications. Br. J. Cancer 116, 821–827 (2017).

     PubMed  PubMed Central  Google Scholar

152. Franc, B. L., Copeland, T. P., Thombley, R., Park, M., Marafino, B., Dean, M. L. et al. Geographic variation in postoperative imaging for low-risk breast cancer. J. Natl Compr. Canc Netw. 16, 829–837 (2018).

     PubMed  Google Scholar

153. Miles, R. C., Lee, C. I., Sun, Q., Bansal, A., Lyman, G. H., Specht, J. M. et al. Patterns of surveillance advanced imaging and serum tumor biomarker testing following launch of the choosing wisely initiative. J. Natl Compr. Canc Netw. 17, 813–820 (2019).

     CAS  PubMed  Google Scholar

154. Parmar, A. D., Sheffield, K. M., Vargas, G. M., Han, Y., Chao, C. & Riall, T. S. Quality of post-treatment surveillance of early stage breast cancer in Texas. Surgery 154, 214–225 (2013).

     PubMed  Google Scholar

155. Kokko, R., Hakama, M. & Holli, K. Follow-up cost of breast cancer patients with localized disease after primary treatment: a randomized trial. Breast Cancer Res. Treat. 93, 255–260 (2005).

     CAS  PubMed  Google Scholar

156. Oltra, A., Santaballa, A., Munárriz, B., Pastor, M. & Montalar, J. Cost-benefit analysis of a follow-up program in patients with breast cancer: a randomized prospective study. Breast J. 13, 571–574 (2007).

     PubMed  Google Scholar

157. Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multicenter randomized controlled trial. The GIVIO Investigators. J. Am. Med. Assoc. 271, 1587–1592 (1994).

158. Lu, W. L., Jansen, L., Post, W. J., Bonnema, J., Van de Velde, J. C. & De Bock, G. H. Impact on survival of early detection of isolated breast recurrences after the primary treatment for breast cancer: a meta-analysis. Breast Cancer Res. Treat. 114, 403–412 (2009).

     CAS  PubMed  Google Scholar

159. Pesapane, F., Downey, K., Rotili, A., Cassano, E. & Koh, D. M. Imaging diagnosis of metastatic breast cancer. Insights Imaging 11, 79 (2020).

     PubMed  PubMed Central  Google Scholar

160. Rinnerthaler, G., Gampenrieder, S. P. & Greil, R. ASCO 2018 highlights: metastatic breast cancer. Memo 11, 276–279 (2018).

     PubMed  PubMed Central  Google Scholar

161. Bardelli, A. & Pantel, K. Liquid biopsies, what we do not know (yet). Cancer Cell 31, 172–179 (2017).

     CAS  PubMed  Google Scholar

162. Best, M. G., Wesseling, P. & Wurdinger, T. Tumor-educated platelets as a noninvasive biomarker source for cancer detection and progression monitoring. Cancer Res. 78, 3407–3412 (2018).

     CAS  PubMed  Google Scholar

163. Heitzer, E., Haque, I. S., Roberts, C. E. S. & Speicher, M. R. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat. Rev. Genet. 20, 71–88 (2019).

     CAS  PubMed  Google Scholar

164. Coombes, R. C., Page, K., Salari, R., Hastings, R. K., Armstrong, A., Ahmed, S. et al. Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence. Clin. Cancer Res. 25, 4255–4263 (2019).

     CAS  PubMed  Google Scholar

165. Garcia-Murillas, I., Chopra, N., Comino-Méndez, I., Beaney, M., Tovey, H., Cutts, R. J. et al. Assessment of molecular relapse detection in early-stage breast cancer. JAMA Oncol. 5, 1473–1478 (2019).

     PubMed  PubMed Central  Google Scholar

166. Hirsch-Ginsberg, C. Detection of minimal residual disease: relevance for diagnosis and treatment of human malignancies. Annu. Rev. Med. 49, 111–122 (1998).

     CAS  PubMed  Google Scholar

167. O'Leary, B., Cutts, R. J., Liu, Y., Hrebien, S., Huang, X., Fenwick, K. et al. The genetic landscape and clonal evolution of breast cancer resistance to palbociclib plus fulvestrant in the PALOMA-3 trial. Cancer Discov. 8, 1390–1403 (2018).

     PubMed  PubMed Central  Google Scholar

168. O'Leary, B., Hrebien, S., Morden, J. P., Beaney, M., Fribbens, C., Huang, X. et al. Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer. Nat. Commun. 9, 896 (2018).

     PubMed  PubMed Central  Google Scholar

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Acknowledgements

We thank members of the Welm labs for thoughtful discussions and input.

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1. Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

   Alessandra I. Riggio, Katherine E. Varley & Alana L. Welm

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A.I.R., K.E.V. and A.L.W. wrote and edited the paper.

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Correspondence to Alana L. Welm.

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We would like to acknowledge DOD BCRP Breakthrough Award W81XWH1810616 (to A.L.W.) and R01 CA204253 (to K.E.V.).

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Riggio, A.I., Varley, K.E. & Welm, A.L. The lingering mysteries of metastatic recurrence in breast cancer. Br J Cancer 124, 13–26 (2021). https://doi.org/10.1038/s41416-020-01161-4

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• Received: 14 July 2020

• Revised: 28 October 2020

• Accepted: 29 October 2020

• Published: 26 November 2020

• Issue Date: 05 January 2021

• DOI : https://doi.org/10.1038/s41416-020-01161-4

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