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Latest changes in the molecular classification of breast cancer and triple negative breast cancer

Vassilena Tsvetkova


Breast cancer (BC) is a heterogeneous disease including multiple histological subtypes with different biological behavior and clinical outcome for the patient. Due to its heterogeneity, BC is classified into different groups, providing possibilities for target therapies and improving the outcome – histological, TNM classification, molecular classification. The molecular classification, proposed at the beginning by Perou et al in 2000, divides BC into 5 subtypes - Luminal A, Luminal B, HER 2 enriched, claudin-low and basal like.

More attention should be paid to the further classification of basal like BC. This is also a heterogeneous disease including triple negative breast cancers (TNBC). They show no expression of ER, PrR or HER2 and are considered difficult to treat. Despite the bad prognosis, some of these patients demonstrate great benefit from the traditional neoadjuvant chemotherapy. Lehman et al. identified 6 molecular subtypes of TNBC, using gene expression profiling – basal like 1 (BL1), basal like 2 (BL2), mesenchymal (M), mesenchymal stem-like (MSL), immunomodulatory (IM) and luminal androgen receptor (LAR).

However, after histopathological quantification and laser-capture microdissection they refined their classification and in 2016 the new molecular classification of TNBC excluding the IM and MSL types was published. The working group has concluded that the characteristics of the tumors in these two groups were due to tumor-infiltrating lymphocytes and tumor-associated stromal cells and not to the tumor cells. The refinement of the classification of TNBC provides a better distribution of the patients into the different groups and better response to the applied therapy.


breast cancer; triple negative; molecular classification

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Angajala A, Mothershed E, Davis MB, Tripathi S, He Q, Bedi D, Dean-Colomb W, Yates C. Quadruple Negative Breast Cancers (QNBC) Demonstrate Subtype Consistency among Primary and Recurrent or Metastatic Breast Cancer. Transl Oncol. 2019 Mar;12(3):493-501. doi: 10.1016/j.tranon.2018.11.008.

Brewster AM, Chavez-MacGregor M, Brown P. Epidemiology, biology, and treatment of triple-negative breast cancer in women of African ancestry. Lancet Oncol.2014 Dec;15(13):e625-34.

Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 2007; 25:1329-1333.

Chia K, O’Brien M, Brown M and Lim E. Targeting the androgen receptor in breast cancer. Curr Oncol Rep 2015; 17: 4.

Eroles P, Bosch A, Perez-Fidalgo JA et al. Molecular biology in breast cancer: intrinsic subtypes and signaling pathays. Canc Treat Rev 2012;38:698-707.

Foulkes, W.D., Stefansson, I.M., Chappuis, P.O., Bégin, L.R., Goffin, J.R., Wong, N. et al, Germline BRCA1 mutations and a basal epithelial phenotype in breast Cancer. J Natl Cancer Inst. 2003;95:1482–1485.

Giannos A, Filipits M, Zagouri F, Brandstetter A, Tsigginou A, Sotiropoulou M, Papaspyrou I, Sergentanis TN, Psaltopoulou T, Rodolakis A, Antsaklis A, Dimopoulos MA and Dimitrakakis C. Expression of ARs in triple negative breast cancer tumors: a potential prognostic factor? Onco Targets Ther 2015; 8: 1843-1847.

Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, Livasy C, Carey LA, Reynolds E, Dressler L, Nobel A, Parker J, Ewend MG, Sawyer LR, Wu J, Liu Y, Nanda R, Tretiakova M, Ruiz Orrico A, Dreher D, Palazzo JP, Perreard L, Nelson E, Mone M, Hansen H, Mullins M, Quackenbush JF, Ellis MJ, Olopade OI, Bernard PS, Perou CM. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics. 2006; 7():96.

Hudis CA. Transtuzumab – mechanism of action and use in clinical practice. New Engl J Med 2007;357:39-51.

Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van der Vijer MJ. World Health Organization Classification of Tumors of the Breast. Lyon: IARC Press; 2012.

Classification of Tumors of the

Breast. Lyon: IARC Press; 2012Le Du F, Eckhardt BL, Lim B, Litton JK, Moulder S, Meric-Bernstam F, Gonzalez-Angulo AM, Ueno NT. Is the future of personalized therapy in triple-negative breast cancer based on molecular subtype? Oncotarget. 2015 May 30;6(15):12890-908.

Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011 Jul; 121:2750-67.

Lehmann BD, Jovanović B, Chen X, Estrada MV, Johnson KN, Shyr Y, Moses HL, Sanders ME, Pietenpol JA. Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection. PLoS One. 2016 Jun 16;11(6): e0157368.

Loi S, Sirtaine N, Piette F et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. J Clin Oncol 2013; 31:860–867.

Mayer IA, Abramson VG, Lehmann BD, Pietenpol JA. New Strategies for Triple-Negative Breast Cancer – Deciphering the Heterogeneity. Clin Res. 2014 Feb 15; 20:782-90.

Melchor L, Benitez J. The complex genetic landscape of familial breast cancer. Hum Genet 2013; 132:845-863.

Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, Davies S, Fauron C, He X, Hu Z, Quackenbush JF, Stijleman IJ, Palazzo J, Marron JS, Nobel AB, Mardis E, Nielsen TO, Ellis MJ, Perou CM, Bernard PS J. Supervised risk predictor of breast cancer based on intrinsic subtypes. Clin Oncol. 2009 Mar 10; 27(8):1160-7.

Prat A, Parker J S, Karginova O, Fan C, Livasy C, Herschkowitz JI, He X, Perou CM. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Research 2010 12:R68.

Prat, A., Cruz, C., Hoadley, K., Díez, O., Perou, C., Balmaña, J. Molecular features of the basal-like breast cancer subtype based on BRCA1 mutation status. Breast Cancer Res Treat. 2014;147:185–191.

Prat A, Pineda E, Adamo B, Galván P, Fernández A, Gaba L, Díez M, Viladot M, Arance A, Muñoz M. Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast. 2015 Nov;24 Suppl 2:S26-35. doi: 10.1016/j.breast.2015.07.008. Epub 2015 Aug 5.

Proverbs-Singh T, Feldman JL, Morris MJ, Autio KA and Traina TA. Targeting the androgen receptor in prostate and breast cancer: several new agents in development. Endocr Relat Cancer 2015; 22: R87-R106.

Safarpour D, Pakneshan S and Tavassoli FA. Androgen receptor (AR) expression in 400 breast carcinomas: is routine AR assessment justified? Am J Cancer Res 2014; 4: 353-368.

Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lønning PE, Brown PO, Børresen-Dale AL, Botstein D. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A. 2003 Jul 8; 100(14):8418-23.)

Tate CR, Rhhodes LV, Segar HC, Driver JL, Pounder FN, Burow ME, Collins-Burow BM. Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat. Breast Cancer Res. 2012; 14:R79

Tsaneva M., Kuzmanova-Valcheva S. Endocrinology of breast cancer. 1 st ed. Sofia: Paradigma; 2017.


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