Document Type : Review Article(s)

Authors

1 Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines Manila, Manila City, Philippines

2 Department of Epidemiology and Biostatistics, College of Public Health, University of the Philippines Manila, Manila City, Philippines

3 Department of Pediatrics, College of Medicine, University of the Philippines Manila, Manila City, Philippines

4 Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, Manila City, Philippines

Abstract

Background: Adenoid cystic carcinoma (ACC) of breast is a rare type of breast cancer, which belongs to the triple-negative breast cancer associated with aggressive behavior and poor prognosis. Despite being classified as triple-negative breast cancer, ACC of breast is an indolent subtype with good biological behavior, less aggressive course, good response to treatment and clinical outcomes. It has generally a good overall survival with no propensity for metastasis. Thus, a correct diagnosis could be of great importance for providing proper and adequate treatment.
Method: Published literature was reviewed to determine differentially expressed genes that could be used as biomarkers for this disease and to elucidate the biology and carcinogenesis of ACC of breast according to this genetic profile.
Results: Several genes were differentially expressed and were found to belong to a wide range of biological processes. The most prevalent genetic alteration is a gene translocation that produces the MYB-NF1B fusion gene and the overexpression of MYB, which initiates tumorigenesis. This crucial genetic aberration is the hallmark of adenoid cystic carcinoma. The rest of the genes are involved in cell proliferation, apoptosis, stable epithelial phenotype, tumor suppression, and keeping an intact basement membrane, evasion of epithelial-mesenchymal transition, and prevention of metastasis.
Conclusion: This gene expression is responsible for various biological processes that reflect the biology of ACC of breast with an indolent course and good clinical outcomes. This genetic profile impacts biomarker research and could be used to refine patient diagnosis and selection for appropriate and less aggressive treatment options.

Keywords

How to cite this article:

Hilario AL, Medina JC, Silao CT. Adenoid cystic carcinoma of breast: A review of molecular markers to elucidate its cancer biology. Middle East J Cancer. 2022;13(1):1-13. doi: 10.30476/ mejc.2021.86695.1367.

1.Fordice J, Kershaw C, El-Naggar A, Goepfert H. Adenoid cystic carcinoma of the head and neck: predictors of morbidity and mortality. Arch Otolaryngol. 1999;125:149-52. doi:10.1001/archotol. 125.2.149.
2. Marchiò C, Weigelt B, Reis-Filho JS. Adenoid cystic carcinomas of the breast and salivary glands (or 'The strange case of Dr Jekyll and Mr Hyde' of exocrine gland carcinomas). J Clin Pathol. 2010;63(3):220-8. doi:10.1136/jcp.2009.073908.
3. Terada T. Adenoid cystic carcinoma of the oral cavity: immunohistochemical study of four cases. Int J Clin Exp Patho. 2013;6(2):932-9.
4. Sandros J, Stenman G, Mark J. Cytogenetic and molecular observations in human and experimental salivary gland tumors. Cancer Genet Cytogenet. 1990;44(22):153-67. doi:10.1016/0165-4608(90) 90042-9.
5. Huang D, Chen W, He R, Yu F, Zhang Z, Ciu W. Different cDNA microarray patterns of gene expression reflecting changes during metastatic progression in adenoid cystic carcinoma. World J Surg Oncol. 2003;1(8):220-80. doi:10.1186/1477-7819-1-28.
6. Fusco N, Geyer FC, De Filippo MR, Martelotto LG, Ng CK, Piscuoglio S, et al. Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer. Mod Pathol. 2016;29(11):1292-305. doi:10.1038/modpathol. 2016.134.
7. Seethala RR, Cieply KC, Barnes EL, Dacic S. Progressive genetic alterations of adenoid cystic carcinoma with high-grade transformation. Arch Pathol Lab Med. 2011;135:123-230. doi:10.1043/2010-0048-OAR.1.
8. Moskaluk C. Adenoid cystic carcinoma: Clinical and molecular features. Head and Neck Pathol. 2013;7:17-22. doi:10.1007/s12105-013-0426-3.
9. Poorten VLV, Balm AJ, Hilgers FJ. Prognostic factors for long term results of the treatment of patients with malignant submandibular gland tumors. Cancer. 1999; 85:2255-64. doi:10.1034/j.1399-0020.2000.290519-2.x.
10. Erovic BM, Sha MD, Bruch G, Johnston M, Kim J, O’Sullivan B, et al. Outcome analysis of 215 patients with parotid gland tumors: a retrospective cohort analysis. J Otolaryngol. 2015;44(43):1-8. doi:10.1186/ s40463-015-0097-z.
11. Shigeish H, Ohla K, Okui G, Seino S, Hashikata M, Yamamoto K, et al. Clinicopathological analysis of salivary gland carcinomas and literature review. Mol Clinic Oncol. 2015; 3:202-6.
12. Liu J, Shao C, Tan ML, Mu D, Ferris RL, Ha PK. Molecular biology of adenoid cystic carcinoma. Head Neck. 2012;4(11):1665-77. doi:10.1002/hed.21849.
13. Thomas DN, Asarian A, Xiao P. Adenoid cystic carcinoma of the breast. J Surg Case Rep. 2019;1:rfy333. doi:10.1093/jscr/rjy355.
14. Kocaay AF, Celik SU, Hesimov I, Eker T, Percinel S, Demirer S. Adenoid cystic carcinoma of the breast: A clinical case report. Med Arch. 2016;70(5):392-4. doi:10.5455/medarh.2016.70.392-394.
15. Agafonoff S, Sobolewski A, Braverman TS. Adenoid cystic carcinoma of the breast – discordant size on imaging and pathology: a case report and review of literature. Ann Med Surg. 2019;43:1-4. doi:10.1016/ j.amsu.2019.04.007.
16. Ghabach B, Anderson WF, Curtis RE, Huycke MM, Lavigne JA, Dores GM. Adenoid cystic carcinoma of the breast in the United States (1977 to 2006): a population-based cohort study. Breast Can Res. 2010;2:1-9. doi:10.1186/bcr2613.
17. Yerushalmi R, Hayes MM, Gelmon KA. Breast carcinoma—rare types: review of the literature. Ann Oncol. 2009;20:1763-70. doi:10.1093/annonc/mdp245.
18. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting item of systematic reviews and meta-analyses. Ann Intern Med. 2009;15(4):264-9. doi:10.7326/0003-4819-151-4-200908180-00135.
19. Arpino G, Clark GM, Mohsin S, Bardou VJ, Elledge RM. Adenoid cystic carcinoma of the breast molecular markers, treatment and clinical outcome. Cancer. 2002; 94:2119-27. doi:10.1002/cncr.10455.
20. Mikai K, Schwartz MR, Divatia MK, Anton RC, Park YW, Ayala AG, et al. Adenoid cystic carcinoma of the breast: recent advances. World J Clin Cases. 2014;2(12):732-41. doi:10.12998/wjcc.v2.i12.732.
21. Azoulay S, Lae M, Freneoax P, Merle S, Al Ghuzlan A, Chnecker C, et al. KIT is highly expressed in adenoid cystic carcinoma of the breast, a basal-like carcinoma associated with favorable outcome. Mod Pathol. 2005;18(12):1623-31. doi:10.1038/modpathol. 3800483.
22. Reyes C, Jordan M, Gomez-Fernandez C. salivary gland-like tumors of the breast express basal-like immunohistochemical markers. Appl Immunohistochem Mol Morphol. 2013;21(4):283-6. doi:10.1097/PAI. 0b013e31826a277e.
23. Junaianh E, Baslaim M, Shegairi S, Mashhoor R, Alsalmi J, Bajaber A, et al. Adenoid cystic carcinoma of the breast, high grade with basal phenotype, literature review. Int J Surg Open. 2018;10:43-56.
24. Chin S, Kim K. Adenoid cystic carcinoma of the breast: report of two cases and immunohistochemical profile of C-kit and MYB overexpression. Indian J Pathol Micr. 2014;57(4):611-3.
25. Perou CM. Molecular stratification of triple-negative breast cancers. Oncologist. 2010;15(Suppl 5):39-48. doi:10.1634/theoncologist.2010-S5-39.
26. Burstein MD, Tsimelzon A, Poage GM, Covington KR, Contreras A, Fuqua SA, et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res. 2015;21(7):1688-98. doi:10.1158/1078-0432.CCR-14-0432.
27. McCrate F, Dicks E, Powell E, Chafe J, Roome R, Simmonds C, et al. Surgical treatment choices for breast cancer in Newfoundland and Labrador: a retrospective cohort study. Can J Surg. 2018;61(6):377-84. doi:10.1503/cjs.015217.
28. Anampa J, Makower D, Sparano JA. Progress in adjuvant chemotherapy for breast cancer: an overview. BMC Med. 2015;13:195. doi:10.1186/s12916-015-0439-8.
29. Krug D, Baumann R, Budach W, Dunst J, Feyer P, Fietkau R, et al. Current controversies in radiotherapy for breast cancer. Radiat Oncol. 2017;12(1):25. doi:10.1186/s13014-017-0766-3.
30. 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. 2011;121(7):2750-67. doi:10.1172/ JCI45014.
31. Rodriguez D, Ramkairsingh M, Lin X, Kapoor A, Major P, Tang D. The central contributions of breast cancer stem cells in developing resistance to endocrine therapy in estrogen receptor (ER)-positive breast cancer. Cancers (Basel).11(7):1028. doi: 10.3390/cancers11071028.
32. Ontario Health (Quality). Gene expression profiling tests for early-stage invasive breast cancer: A health technology assessment. Ont Health Technol Assess Ser. 2020;20(10):1-234.
33. Chiorean EG, Nandakumar G, Fadelu T, Temin S, Alarcon-Rozas AE, Bejarano S, et al. Treatment of patients with late-stage colorectal cancer: ASCO Resource-Stratified Guideline. JCO Glob Oncol. 2020;6:414-38. doi:10.1200/jgo.19.00367.
34. Tyagi NK, Dhesy-Thind S. Clinical practice guidelines in breast cancer. Curr Oncol. 2018;25(Suppl 1):S151-S160. doi:10.3747/co.25.3729.
35. Goldhirsch A, Glick JH, Gelber RD, Thürlimann B, Senn HJ. Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol. 2005;16(10):1569-83. doi:10.1093/ annonc/mdi326.
36. Senkus E, Kyriakides S, Ohno S, Penault-Llorea F, Poortmans P, Rutgers E, et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v8-v30. doi:10.1093/annonc/ mdv298.
37. Kemp Z, Turnbull A, Yost S, Seal S, Mahamdallie S, Poyastro-Pearson E, et al. Evaluation of cancer-based criteria for use in mainstream BRCA1 and BRCA2 genetic testing in patients with breast cancer. JAMA Netw Open. 2019;2(5):e194428. doi:10.1001/jamanetworkopen.2019.4428.
38. Sharma P, Klemp JR, Kimler BF, Mahnken JP, Geier LJ, Khan QJ, et al. Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: implications for hereditary breast and/or ovarian cancer syndrome testing. Breast Can Res Treat. 2014;145(3):707-14. doi:10.1007/s10549-014-2980-0.
39. Kittaneh M, Montero AJ, Glück S. Molecular profiling for breast cancer: a comprehensive review. Biomark Cancer. 2013;5:61-70. doi:10.4137/BIC.S9455.
40. Choo JR, Nielsen TO. Biomarkers for basal-like breast cancer. Cancers. 2010;2:1040–65. doi:10.3390/ cancers2021040.
41. Massé J, Truntzer C, Romain Boidot R, Khalifa E, Pérot G, Velasco V, et al. Solid-type adenoid cystic carcinoma of the breast, a distinct molecular entity enriched in NOTCH and CREBBP mutations. Mod Pathol. 2020;33:1041-55. doi.org/10.1038/s41379-019-0425-3.
42. Weigelt B, Geyer FC, Reis-Filho JS. Histologic types of breast cancer: How special are they? Mol Oncol. 2010;4:192-208. doi:10.1016/j.molonc.2010.04.004.
43. Garrido-Castro AC, Lin NU, Polyak K. Insights into molecular classifications of triple-negative breast cancer: Improving patient selection for treatment. Cancer Discov. 2019;9(2):176-98. doi:10.1158/2159-8290.CD-18-1177.
44. Pareja F, Geyer FC, Marchiò C, Burke KA, Weigelt B, Reis-Filho JS. Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants. NPJ Breast Cancer. 2016;2:16036. doi:10.1038/npjbcancer.2016. 36.
45. Santonja A, Sánchez-Muñoz A, Lluch A, Chica-Parrado M, Albanell J, Ignacio Chacón J, et al. Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy. Oncotarget. 2018;9: 26406-16. doi:10. 18632/oncotarget.25413.
46. Mikse OR, Tchaicha JH, Esra A. Akbay EA, Chen L, Bronson RT, Hammerman PS et al. The impact of the MYB-NFIB fusion proto-oncogene in vivo. Oncotarget. 2016;7(22):31681-8. doi:10.18632/ oncotarget.9426.
47. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747-52. doi:10.1038/35021093.
48. Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98(19): 10869-74. doi:10.1073/pnas.191367098.
49. Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomic. 2006;7(96). doi:10.1186/147-21647-96.
50. Weigelt B, Horlings HM, Kreike B, Hayes MM, Hauptmann M, Wessels LF, et al. Refinement of breast cancer classification by molecular characterization of histological special types. J Pathol. 2008; 216:141-50. doi:10.1002/path.2407.
51. Lambros MB, Tan DS, Jones RL, Vatcheva R, Savage K, Tamber N, et al. Genomic profile of a secretory breast cancer with an ETV6eNTRK3 duplication. J Clin Pathol. 2009;62:604e612. doi:10.1136/jcp. 2008.059675.
52. Ho AS, Ochoa A, Jayakumaran G, Zehir A, Valero Mayor C, Tepe J, et al. Genetic hallmarks of recurrent/metastatic adenoid cystic carcinoma. J Clin Invest. 2019;129(10):4276-89. doi:10.1172/JCI128227.
53. Mhamdi HA, Kourie HR, Jungels C, Aftahos P, Belbaraka R, Piccart-Gehhart M. Adenoid cystic carcinoma of the breast-an aggressive presentation with pulmonary, kidney, brain metastases: a case report. J Med Case Rep. 2012;11:303. doi:10.1186/s13256-017-1459-0.
54. Burusapat C, Buarabporn N, Wongchansom K, Chanapai P, Parinyamit P, Supaporn A. Mammary adenoid cystic carcinoma presenting with ductal carcinoma in situ and axillary lymph node metastasis. J Surg Case Rep. 2020;2:1-4. doi:10.1093/jscr/rjz362.
55. Glover TE, Butel R, Bhuller CM, Senior EL. An unusual presentation of adenoid cystic carcinoma of the breast with metastatic disease to the clavicle. BJR Case Rep. 2017;2:20160119. doi.org/10.1259/ bjrcr.20160119.
56. Sajed DP, Faquin WC, Carey C, Severson EA, H Afrogheh A, A Johnson C, et al. Diffuse staining for activated NOTCH1 correlates with NOTCH1 mutation status and is associated with worse outcome in adenoid cystic carcinoma. Am J Surg Pathol. 2017;41(11):1473-82. doi:10.1097/PAS. 0000000000000945.
57. Martelotto LG, De Filippo MR, Ng CK, Natrajan R, Fuhrmann L, Cyrta J, et al. Genomic landscape of adenoid cystic carcinoma of the breast. J Pathol. 2015;237:179-89. doi:10.1002/path.4573.
58. Herschkowitz JI, Simin K, Weigman VJ, Mikaelian I, Usary J, Hu Z, et al. Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors. Genome Biol. 2007;8(5):R76. doi:10.1186/gb-2007-8-5-r76.
59. Thierauf J, Veit JA, Hess J. Epithelial-to-mesenchymal transition in the pathogenesis and therapy of head and neck cancer. Cancers (Basel). 2017;9(7):76. doi:10. 3390/cancers9070076.
60. Liu X, Xu Y, Han L, Yi Y. Reassessing the potential of myb-targeted anti-cancer therapy. J Cancer. 2018;9: 1259-66. doi:10.7150/jca.23992.
61. Babaei MA, Kamalidehghan B, Saleem M, Huri HZ, Ahmadipour F. Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells. Drug Des Dev Ther. 2016;10:2443-59. doi:10.2147/ DDDT.S89114.
62. Flynn JF, Wong C, Wu JM. Anti-EGFR therapy: mechanism and advances in clinical efficacy in breast cancer. J Oncol. 2009;2009:526963. doi:10. 1155/2009/526963.
63. Chae YK, Ranganath K, Hammerman PS, Vaklavas C, Mohindra N, Kalyan A, et al. Inhibition of the fibroblast growth factor receptor (FGFR) pathway: the current landscape and barriers to clinical application. Oncotarget. 2017;8(9):16052-74. doi:10. 18632/oncotarget.14109.
64. Jung S, Han W, Lee JW, Ko E, Kim E, Yu J, et al. Ki-67 expression gives additional prognostic information on St. Gallen 2007 and adjuvant! online risk categories in early breast cancer. Ann Surg Oncol. 2009;16:1112-21. doi:10.1245/s10434-009-0334-7.