Field cancerization in mammary carcinogenesis - Implications for prevention and treatment of breast cancer - PubMed

Review

Field cancerization in mammary carcinogenesis - Implications for prevention and treatment of breast cancer

Ashley G Rivenbark et al. Exp Mol Pathol. 2012 Dec.

Abstract

The natural history of breast cancer unfolds with the development of ductal carcinoma in situ (DCIS) in normal breast tissue, and evolution of this pre-invasive neoplasm into invasive cancer. The mechanisms that drive these processes are poorly understood, but evidence from the literature suggests that mammary carcinogenesis may occur through the process of field cancerization. Clinical observations are consistent with the idea that (i) DCIS may arise in a field of altered breast epithelium, (ii) narrow surgical margins do not remove the entire altered field (contributing to recurrence and/or disease progression), and (iii) whole-breast radiation therapy is effective in elimination of the residual field of altered cells adjacent to the resected DCIS. Molecular studies suggest that the field of altered breast epithelial cells may carry cancer-promoting genetic mutations (or other molecular alterations) or cancer promoting epimutations (oncogenic alterations in the epigenome). In fact, most breast cancers develop through a succession of molecular events involving both genetic mutations and epimutations. Hence, in hereditary forms of breast cancer, the altered field reflects the entire breast tissue which is composed of cells with a predisposing molecular lesion (such as a BRCA1 mutation). In the example of a BRCA1-mutant patient, it is evident that local resection of a DCIS lesion or localized but invasive cancer will not result in elimination of the altered field. In sporadic breast cancer patients, the mechanistic basis for the altered field may not be so easily recognized. Nonetheless, identification of the nature of field cancerization in a given patient may guide clinical intervention. Thus, patients with DCIS that develops in response to an epigenetic lesion (such as a hypermethylation defect affecting the expression of tumor suppressor genes) might be treated with epigenetic therapy to normalize the altered field and reduce the risk of secondary occurrence of DCIS or progression to invasive cancer.

Similar articles

• Genetic clonal mapping of in situ and invasive ductal carcinoma indicates the field cancerization phenomenon in the breast.

  Foschini MP, Morandi L, Leonardi E, Flamminio F, Ishikawa Y, Masetti R, Eusebi V. Foschini MP, et al. Hum Pathol. 2013 Jul;44(7):1310-9. doi: 10.1016/j.humpath.2012.09.022. Epub 2013 Jan 18. Hum Pathol. 2013. PMID: 23337025

• Ductal carcinoma in situ of the breast: the importance of morphologic and molecular interactions.

  Mardekian SK, Bombonati A, Palazzo JP. Mardekian SK, et al. Hum Pathol. 2016 Mar;49:114-23. doi: 10.1016/j.humpath.2015.11.003. Epub 2015 Nov 17. Hum Pathol. 2016. PMID: 26826418 Review.

• PIK3CA mutations in ductal carcinoma in situ and adjacent invasive breast cancer.

  Agahozo MC, Sieuwerts AM, Doebar SC, Verhoef EI, Beaufort CM, Ruigrok-Ritstier K, de Weerd V, Sleddens HFBM, Dinjens WNM, Martens JWM, van Deurzen CHM. Agahozo MC, et al. Endocr Relat Cancer. 2019 May;26(5):471-482. doi: 10.1530/ERC-19-0019. Endocr Relat Cancer. 2019. PMID: 30844755

• Expression profiling of in vivo ductal carcinoma in situ progression models identified B cell lymphoma-9 as a molecular driver of breast cancer invasion.

  Elsarraj HS, Hong Y, Valdez KE, Michaels W, Hook M, Smith WP, Chien J, Herschkowitz JI, Troester MA, Beck M, Inciardi M, Gatewood J, May L, Cusick T, McGinness M, Ricci L, Fan F, Tawfik O, Marks JR, Knapp JR, Yeh HW, Thomas P, Carrasco DR, Fields TA, Godwin AK, Behbod F. Elsarraj HS, et al. Breast Cancer Res. 2015 Sep 17;17:128. doi: 10.1186/s13058-015-0630-z. Breast Cancer Res. 2015. PMID: 26384318 Free PMC article.

• Local outcomes in ductal carcinoma in situ based on patient and tumor characteristics.

  Schnitt SJ. Schnitt SJ. J Natl Cancer Inst Monogr. 2010;2010(41):158-61. doi: 10.1093/jncimonographs/lgq031. J Natl Cancer Inst Monogr. 2010. PMID: 20956823 Free PMC article. Review.

Cited by

• A genomic ruler to assess oncogenic transition between breast tumor and stroma.

  Dhage S, Ernlund A, Ruggles K, Axelrod D, Berman R, Roses D, Schneider RJ. Dhage S, et al. PLoS One. 2018 Oct 16;13(10):e0205602. doi: 10.1371/journal.pone.0205602. eCollection 2018. PLoS One. 2018. PMID: 30325954 Free PMC article.

• A computational model for the cancer field effect.

  Deutscher K, Hillen T, Newby J. Deutscher K, et al. Front Artif Intell. 2023 Jul 4;6:1060879. doi: 10.3389/frai.2023.1060879. eCollection 2023. Front Artif Intell. 2023. PMID: 37469932 Free PMC article.

• Metastatic and triple-negative breast cancer: challenges and treatment options.

  Al-Mahmood S, Sapiezynski J, Garbuzenko OB, Minko T. Al-Mahmood S, et al. Drug Deliv Transl Res. 2018 Oct;8(5):1483-1507. doi: 10.1007/s13346-018-0551-3. Drug Deliv Transl Res. 2018. PMID: 29978332 Free PMC article. Review.

• Somatic mosaicism: on the road to cancer.

  Fernández LC, Torres M, Real FX. Fernández LC, et al. Nat Rev Cancer. 2016 Jan;16(1):43-55. doi: 10.1038/nrc.2015.1. Epub 2015 Dec 18. Nat Rev Cancer. 2016. PMID: 26678315 Review.

• The conserved protective cyclic AMP-phosphodiesterase function PDE4B is expressed in the adenoma and adjacent normal colonic epithelium of mammals and silenced in colorectal cancer.

  Pleiman JK, Irving AA, Wang Z, Toraason E, Clipson L, Dove WF, Deming DA, Newton MA. Pleiman JK, et al. PLoS Genet. 2018 Sep 6;14(9):e1007611. doi: 10.1371/journal.pgen.1007611. eCollection 2018 Sep. PLoS Genet. 2018. PMID: 30188895 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Miscellaneous

  • NCI CPTAC Assay Portal