Basic Molecular Pathology in Breast Carcinoma

  • Maria Comanescu


Breast cancer is a multifactorial heterogeneous disease, reflected in a wide range of phenotypic subsets of tumors with varied degrees of aggressiveness and a significant global impact on women’s health. In addition to defining the profiles of breast tumors, it is necessary to identify the individual gene and protein expression aberrations and their impact on the biology of the tumor. Molecular pathology changed the way we think about the classification of breast cancer, by no longer relying on just the histological alterations, but also on their biologic pathways. However, it should be noted that although the identification of breast cancer genes contributes to the detection of precursor lesions and prevention of invasive disease, a correlation between phenotype and genotype is necessary, as the sole assessment of gene alterations is insufficient for the identification of predictive and prognostic factors allowing the application of new and individualized cancer therapies. In conclusion, this chapter focuses on the basic molecular pathology knowledge needed in everyday routine practice.


Molecular diagnosis Breast Genes Proteins 


  1. 1.
    Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.CrossRefPubMedGoogle Scholar
  2. 2.
    Russo J, Yun-Fu H, Xiaoqi Y, Russo IH. Developmental, cellular, and molecular basis of human breast cancer. J Natl Cancer Inst Monogr. 2000;27:17–37.CrossRefGoogle Scholar
  3. 3.
    Bannasch P. Cancer diagnosis: early detection. New York, NY: Springer; 1992. p. 170.CrossRefGoogle Scholar
  4. 4.
    Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, et al. Tailoring therapies—improving the management of early breast cancer: St Gallen International expert consensus on the primary therapy of early breast cancer 2015. Ann Oncol. 2015;26(8):1533–46.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Reis-Filho JS, Pusztai L. Gene expression profiling in breast cancer: classification, prognostication, and prediction. Lancet. 2011;378:1812–23.CrossRefPubMedGoogle Scholar
  6. 6.
    Gomez-Wolff R, Garcia H, Ossa C. Impact of “immunohistochemistry-based molecular subtype” on chemo-sensitivity and survival in Hispanic breast cancer patients following neoadjuvant chemotherapy (NAC) [abstract]. In: Proceedings of the 2016 San Antonio breast cancer symposium; San Antonio, TX. Philadelphia (PA): AACR. Cancer Res. 2017;77(4 Suppl):Abstract no. P5-16-20.CrossRefGoogle Scholar
  7. 7.
    Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101:736–50.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Kimberly H, Allison MD. Molecular pathology of breast cancer: what a pathologist needs to know. Am J Clin Pathol. 2012;138(6):770–80.CrossRefGoogle Scholar
  9. 9.
    Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ, et al. 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. 2011;22(8):1736–47.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, et al. Personalizing the treatment of women with early breast cancer: highlights of the St. Gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol. 2013;24(9):2206–23.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Vaz-Luis I, Ottesen RA, Hughes ME, Marcom PK, Moy B, Rugo HS, et al. Impact of hormone receptor status on patterns of recurrence and clinical outcomes among patients with human epidermal growth factor-2-positive breast cancer in the National Comprehensive Cancer Network: a prospective cohort study. Breast Cancer Res. 2012;14:R129.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10(16):5367–74.CrossRefPubMedGoogle Scholar
  13. 13.
    Lakhani SR, Reis-Filho JS, Fulford L, Penault-Llorca F, van der Vijver M, Parry S, et al. Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res. 2005;11:5175–80.CrossRefPubMedGoogle Scholar
  14. 14.
    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.CrossRefPubMedGoogle Scholar
  15. 15.
    Tian S, Roepman P, Van’t Veer LJ, Bernards R, de Snoo F, Glas AM. Biological functions of the genes in the MammaPrint breast cancer profile reflect the hallmarks of cancer. Biomark Insights. 2010;5:129–38.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Onitilo AA, Engel JM, Greenlee RT, Mukesh BN. Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res. 2009;7(1–2):4–13.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Halilovic A, Bulte J, Jacobs Y, Braam H, van Cleef P, Schlooz-Vries M, et al. Brief fixation enables same-day breast cancer diagnosis with reliable assessment of hormone receptors, E-cadherin and HER2/Neu. J Clin Pathol. 2017;70(9):781–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Lee EYHP, Muller WJ. Oncogenes and tumor suppressor genes. Cold Spring Harb Perspect Biol. 2010;2(10):a003236.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Dillon RL, White DE, Muller WJ. The phosphatidyl inositol 3-kinase signaling network: Implications for human breast cancer. Oncogene. 2007b;26:1338–45.CrossRefPubMedGoogle Scholar
  20. 20.
    Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31:3997–4013.CrossRefPubMedGoogle Scholar
  21. 21.
    Van de Vijver MJ. Molecular genetic changes in breast cancer. In: Weinberg RA, editor. Oncogenes and the molecular origins of cancer. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 1989. p. 25–60.Google Scholar
  22. 22.
    Chial H. Tumor suppressor (TS) genes and the two-hit hypothesis. Nat Educ. 2008;1(1):177.Google Scholar
  23. 23.
    Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007;25(11):1329–33.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Krawczyk N, Hartkopf A, Banys M, Meier-Stiegen F, Staebler A, Wallwiener M, et al. Prognostic relevance of induced and spontaneous apoptosis of disseminated tumor cells in primary breast cancer patients. BMC Cancer. 2014;14:394.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Aktas B, Kasimir-Bauer S, Müller V, Janni W, Fehm T, Wallwiener D, et al. Comparison of the HER2, estrogen and progesterone receptor expression profile of primary tumor, metastases and circulating tumor cells in metastatic breast cancer patients. BMC Cancer. 2016;16:522.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Wu CY, Du SL, Zhang J, Liang AL, Liu YJ. Exosomes and breast cancer: a comprehensive review of novel therapeutic strategies from diagnosis to treatment. Cancer Gene Ther. 2017;24:6–12.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Maria Comanescu
    • 1
  1. 1.Department of PathologyUniversity of Medicine and Pharmacy “Carol Davila”BucharestRomania

Personalised recommendations