. 2010 Nov;3(2).
doi: 10.1101/cshperspect.a003293.

Systems biology and genomics of breast cancer

Charles M Perou 1 Anne-Lise Børresen-Dale  
  • PMID: 21047916
  •     101 References
  •     69 citations


It is now accepted that breast cancer is not a single disease, but instead it is composed of a spectrum of tumor subtypes with distinct cellular origins, somatic changes, and etiologies. Gene expression profiling using DNA microarrays has contributed significantly to our understanding of the molecular heterogeneity of breast tumor formation, progression, and recurrence. For example, at least two clinical diagnostic assays exist (i.e., OncotypeDX RS and Mammaprint®) that are able to predict outcome in patients using patterns of gene expression and predetermined mathematical algorithms. In addition, a new molecular taxonomy based upon the inherent, or "intrinsic," biology of breast tumors has been developed; this taxonomy is called the "intrinsic subtypes of breast cancer," which now identifies five distinct tumor types and a normal breast-like group. Importantly, the intrinsic subtypes of breast cancer predict patient relapse, overall survival, and response to endocrine and chemotherapy regimens. Thus, most of the clinical behavior of a breast tumor is already written in its subtype profile. Here, we describe the discovery and basic biology of the intrinsic subtypes of breast cancer, and detail how this interacts with underlying genetic alternations, response to therapy, and the metastatic process.

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Combination of intermittent calorie restriction and eicosapentaenoic acid for inhibition of mammary tumors.
Nancy K Mizuno, Olga P Rogozina, +3 authors, Michael E Grossmann.
Cancer Prev Res (Phila), 2013 Apr 04; 6(6). PMID: 23550153    Free PMC article.
Metalloproteinase-disintegrin ADAM12 is associated with a breast tumor-initiating cell phenotype.
Hui Li, Sara Duhachek-Muggy, Suzanne Dubnicka, Anna Zolkiewska.
Breast Cancer Res Treat, 2013 Jun 19; 139(3). PMID: 23771733    Free PMC article.
Key genes for modulating information flow play a temporal role as breast tumor coexpression networks are dynamically rewired by letrozole.
Nadia M Penrod, Jason H Moore.
BMC Med Genomics, 2013 Jul 17; 6 Suppl 2. PMID: 23819860    Free PMC article.
14-3-3σ stabilizes a complex of soluble actin and intermediate filament to enable breast tumor invasion.
Aaron Boudreau, Kandice Tanner, +3 authors, Mina J Bissell.
Proc Natl Acad Sci U S A, 2013 Sep 27; 110(41). PMID: 24067649    Free PMC article.
Targeting Met and Notch in the Lfng-deficient, Met-amplified triple-negative breast cancer.
Shubing Zhang, Wen-cheng Chung, Lucio Miele, Keli Xu.
Cancer Biol Ther, 2014 Feb 22; 15(5). PMID: 24556651    Free PMC article.
The role of lipolysis stimulated lipoprotein receptor in breast cancer and directing breast cancer cell behavior.
Denise K Reaves, Katerina D Fagan-Solis, +3 authors, Jodie M Fleming.
PLoS One, 2014 Mar 19; 9(3). PMID: 24637461    Free PMC article.
Tissue specific DNA methylation in normal human breast epithelium and in breast cancer.
Ayelet Avraham, Sean Soonweng Cho, +9 authors, Ella Evron.
PLoS One, 2014 Mar 22; 9(3). PMID: 24651077    Free PMC article.
Magnetic resonance imaging features of breast cancer according to intrinsic subtypes: correlations with neoadjuvant chemotherapy effects.
Hiroko Kawashima, Masafumi Inokuchi, +2 authors, Seiko Kitamura.
Springerplus, 2014 Jun 04; 3. PMID: 24892001    Free PMC article.
Endoplasmic reticulum calcium pumps and cancer cell differentiation.
Béla Papp, Jean-Philippe Brouland, +6 authors, Agota Apáti.
Biomolecules, 2012 Jan 01; 2(1). PMID: 24970132    Free PMC article.
Challenging the roles of CD44 and lipolysis stimulated lipoprotein receptor in conveying Clostridium perfringens iota toxin cytotoxicity in breast cancer.
Katerina D Fagan-Solis, Denise K Reaves, +3 authors, Jodie M Fleming.
Mol Cancer, 2014 Jul 06; 13. PMID: 24990559    Free PMC article.
Benzimidazoles diminish ERE transcriptional activity and cell growth in breast cancer cells.
Florastina Payton-Stewart, Syreeta L Tilghman, LaKeisha G Williams, Leyte L Winfield.
Biochem Biophys Res Commun, 2014 Jul 06; 450(4). PMID: 24997336    Free PMC article.
Distinct luminal-type mammary carcinomas arise from orthotopic Trp53-null mammary transplantation of juvenile versus adult mice.
David H Nguyen, Haoxu Ouyang, +2 authors, Mary Helen Barcellos-Hoff.
Cancer Res, 2014 Oct 05; 74(23). PMID: 25281718    Free PMC article.
A DNA methylation-based definition of biologically distinct breast cancer subtypes.
Olafur A Stefansson, Sebastian Moran, +9 authors, Manel Esteller.
Mol Oncol, 2014 Dec 04; 9(3). PMID: 25468711    Free PMC article.
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An Introspective Update on the Influence of miRNAs in Breast Carcinoma and Neuroblastoma Chemoresistance.
Alessia Carta, Rachel Chetcuti, Duncan Ayers.
Genet Res Int, 2014 Dec 31; 2014. PMID: 25548681    Free PMC article.
Glycan-related gene expression signatures in breast cancer subtypes; relation to survival.
Ivan O Potapenko, Torben Lüders, +7 authors, Vilde D Haakensen.
Mol Oncol, 2015 Feb 07; 9(4). PMID: 25655580    Free PMC article.
Combining functional genomics strategies identifies modular heterogeneity of breast cancer intrinsic subtypes.
Nima Pouladi, Richard Cowper-Sallari, Jason H Moore.
BioData Min, 2014 Jan 01; 7. PMID: 25745517    Free PMC article.
Molecular subtyping for clinically defined breast cancer subgroups.
Xi Zhao, Einar Andreas Rødland, Robert Tibshirani, Sylvia Plevritis.
Breast Cancer Res, 2015 Apr 08; 17. PMID: 25849221    Free PMC article.
Chemotherapeutic Targeting of the Transforming Growth Factor-β Pathway in Breast Cancers.
Yong-Hun Lee, William P Schiemann.
Breast Cancer Manag, 2014 Jan 01; 3(1). PMID: 25904986    Free PMC article.
Role of IGF1R in Breast Cancer Subtypes, Stemness, and Lineage Differentiation.
Susan M Farabaugh, David N Boone, Adrian V Lee.
Front Endocrinol (Lausanne), 2015 May 13; 6. PMID: 25964777    Free PMC article.
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The impact of chemotherapy dose intensity and supportive care on the risk of febrile neutropenia in patients with early stage breast cancer: a prospective cohort study.
Eva Culakova, Marek S Poniewierski, +3 authors, Gary H Lyman.
Springerplus, 2015 Aug 08; 4. PMID: 26251780    Free PMC article.
The influence of obesity on survival in early, high-risk breast cancer: results from the randomized SUCCESS A trial.
Peter Widschwendter, Thomas Wp Friedl, +19 authors, Christoph Scholz.
Breast Cancer Res, 2015 Sep 20; 17. PMID: 26385214    Free PMC article.
CD24 Overexpression Is Associated with Poor Prognosis in Luminal A and Triple-Negative Breast Cancer.
Mi Jeong Kwon, Jinil Han, +7 authors, Young Kee Shin.
PLoS One, 2015 Oct 09; 10(10). PMID: 26444008    Free PMC article.
Cancer stem cell-driven efficacy of trastuzumab (Herceptin): towards a reclassification of clinically HER2-positive breast carcinomas.
Begoña Martin-Castillo, Eugeni Lopez-Bonet, +4 authors, Javier A Menendez.
Oncotarget, 2015 Oct 17; 6(32). PMID: 26474458    Free PMC article.
Regulators of genetic risk of breast cancer identified by integrative network analysis.
Mauro A A Castro, Ines de Santiago, +7 authors, Kerstin B Meyer.
Nat Genet, 2015 Dec 01; 48(1). PMID: 26618344    Free PMC article.
GATA3 in Breast Cancer: Tumor Suppressor or Oncogene?
Motoki Takaku, Sara A Grimm, Paul A Wade.
Gene Expr, 2015 Dec 08; 16(4). PMID: 26637396    Free PMC article.
Quantitative phosphoproteomics reveals genistein as a modulator of cell cycle and DNA damage response pathways in triple-negative breast cancer cells.
Yi Fang, Qian Zhang, +5 authors, Jing Wang.
Int J Oncol, 2016 Jan 20; 48(3). PMID: 26783066    Free PMC article.
HER2 status and disparities in luminal breast cancers.
Andreana N Holowatyj, Julie J Ruterbusch, +2 authors, Michele L Cote.
Cancer Med, 2016 Jun 03; 5(8). PMID: 27250116    Free PMC article.
Identification of Copy Number Aberrations in Breast Cancer Subtypes Using Persistence Topology.
Javier Arsuaga, Tyler Borrman, +2 authors, Catherine Park.
Microarrays (Basel), 2015 Jan 01; 4(3). PMID: 27600228    Free PMC article.
MUC1-ARF-A Novel MUC1 Protein That Resides in the Nucleus and Is Expressed by Alternate Reading Frame Translation of MUC1 mRNA.
Michael Chalick, Oded Jacobi, +10 authors, Daniel H Wreschner.
PLoS One, 2016 Oct 22; 11(10). PMID: 27768738    Free PMC article.
α3 Chains of type V collagen regulate breast tumour growth via glypican-1.
Guorui Huang, Gaoxiang Ge, Valerio Izzi, Daniel S Greenspan.
Nat Commun, 2017 Jan 20; 8. PMID: 28102194    Free PMC article.
Accuracy of MRI for prediction of response to neo-adjuvant chemotherapy in triple negative breast cancer compared to other subtypes of breast cancer.
Gaurav J Bansal, Divya Santosh.
Indian J Radiol Imaging, 2017 Jan 21; 26(4). PMID: 28104942    Free PMC article.
A New Role for ERα: Silencing via DNA Methylation of Basal, Stem Cell, and EMT Genes.
Eric A Ariazi, John C Taylor, +4 authors, Jeff Boyd.
Mol Cancer Res, 2017 Jan 22; 15(2). PMID: 28108626    Free PMC article.
Ki-67 as a prognostic marker according to breast cancer molecular subtype.
Nahed A Soliman, Shaimaa M Yussif.
Cancer Biol Med, 2017 Feb 06; 13(4). PMID: 28154782    Free PMC article.
A review of the importance of immune responses in luminal B breast cancer.
Delia J Nelson, Briony Clark, +5 authors, Arlene Chan.
Oncoimmunology, 2017 Apr 14; 6(3). PMID: 28405507    Free PMC article.
MMP11 and CD2 as novel prognostic factors in hormone receptor-negative, HER2-positive breast cancer.
Jinil Han, Yoon-La Choi, +11 authors, Young Kee Shin.
Breast Cancer Res Treat, 2017 Apr 15; 164(1). PMID: 28409241    Free PMC article.
The olive oil phenolic (-)-oleocanthal modulates estrogen receptor expression in luminal breast cancer in vitro and in vivo and synergizes with tamoxifen treatment.
Nehad M Ayoub, Abu Bakar Siddique, +2 authors, Khalid A El Sayed.
Eur J Pharmacol, 2017 Jun 20; 810. PMID: 28625568    Free PMC article.
Dietary Natural Products for Prevention and Treatment of Breast Cancer.
Ya Li, Sha Li, +3 authors, Hua-Bin Li.
Nutrients, 2017 Jul 13; 9(7). PMID: 28698459    Free PMC article.
Ganoderma spp.: A Promising Adjuvant Treatment for Breast Cancer.
Ivette J Suárez-Arroyo, Yaliz Loperena-Alvarez, Raysa Rosario-Acevedo, Michelle M Martínez-Montemayor.
Medicines (Basel), 2017 Aug 02; 4(1). PMID: 28758107    Free PMC article.
Lunatic Fringe and p53 Cooperatively Suppress Mesenchymal Stem-Like Breast Cancer.
Wen-Cheng Chung, Shubing Zhang, +2 authors, Keli Xu.
Neoplasia, 2017 Sep 25; 19(11). PMID: 28938159    Free PMC article.
Long non-coding RNA00544 serves as a potential novel predictive and prognostic marker for HR+ HER2- subtype breast cancer.
Lei Liu, Yayun Chi, +5 authors, Jiong Wu.
Sci Rep, 2017 Sep 30; 7(1). PMID: 28959047    Free PMC article.
Loss of the Nuclear Pool of Ubiquitin Ligase CHIP/STUB1 in Breast Cancer Unleashes the MZF1-Cathepsin Pro-oncogenic Program.
Haitao Luan, Bhopal Mohapatra, +16 authors, Hamid Band.
Cancer Res, 2018 Mar 08; 78(10). PMID: 29510992    Free PMC article.
Prediction of pathological complete response and prognosis in patients with neoadjuvant treatment for triple-negative breast cancer.
Paul Gass, Michael P Lux, +12 authors, Marius Wunderle.
BMC Cancer, 2018 Oct 31; 18(1). PMID: 30373556    Free PMC article.
Prognostic phenotypic classification for canine mammary tumors.
Giovanna Rossi Varallo, Gabriela Bottaro Gelaleti, +6 authors, Debora Aparecida Pires De Campos Zuccari.
Oncol Lett, 2019 Dec 07; 18(6). PMID: 31807173    Free PMC article.
RNA-binding protein NONO promotes breast cancer proliferation by post-transcriptional regulation of SKP2 and E2F8.
Kaori Iino, Yuichi Mitobe, +6 authors, Satoshi Inoue.
Cancer Sci, 2019 Nov 17; 111(1). PMID: 31733123    Free PMC article.
Novel secretome-to-transcriptome integrated or secreto-transcriptomic approach to reveal liquid biopsy biomarkers for predicting individualized prognosis of breast cancer patients.
J Astor Ankney, Ling Xie, +2 authors, Xian Chen.
BMC Med Genomics, 2019 May 31; 12(1). PMID: 31146747    Free PMC article.
Clinical and epidemiologic factors associated with breast cancer and its subtypes among Northeast Chinese women.
Dong-Man Ye, Qiang Li, +3 authors, Wen-Qing Li.
Cancer Med, 2019 Oct 24; 8(17). PMID: 31642614    Free PMC article.
Implication of environmental estrogens on breast cancer treatment and progression.
Thomas L Gonzalez, James M Rae, Justin A Colacino.
Toxicology, 2019 Apr 04; 421. PMID: 30940549    Free PMC article.
Basal-Type Breast Cancer Stem Cells Over-Express Chromosomal Passenger Complex Proteins.
Angela Schwarz-Cruz Y Celis, Gisela Ceballos-Cancino, +6 authors, Jorge Melendez-Zajgla.
Cells, 2020 Mar 19; 9(3). PMID: 32183150    Free PMC article.
The Application of Radiomics in Breast MRI: A Review.
Dong-Man Ye, Hao-Tian Wang, Tao Yu.
Technol Cancer Res Treat, 2020 Apr 30; 19. PMID: 32347167    Free PMC article.
Focus on Triple-Negative Breast Cancer: Potassium Channel Expression and Clinical Correlates.
Elena Lastraioli.
Front Pharmacol, 2020 Jun 09; 11. PMID: 32508650    Free PMC article.
IGF1R constitutive activation expands luminal progenitors and influences lineage differentiation during breast tumorigenesis.
Susan M Farabaugh, Beate C Litzenburger, +4 authors, Adrian V Lee.
Dev Biol, 2020 May 08; 463(1). PMID: 32376245    Free PMC article.
The prognostic impact of age in different molecular subtypes of breast cancer: a population-based study.
Dongjun Dai, Yiming Zhong, +3 authors, Xian Wang.
PeerJ, 2019 Jul 17; 7. PMID: 31309004    Free PMC article.
HER2-positive breast-cancer cell lines are sensitive to KDM5 inhibition: definition of a gene-expression model for the selection of sensitive cases.
Gabriela Paroni, Marco Bolis, +8 authors, Enrico Garattini.
Oncogene, 2018 Dec 13; 38(15). PMID: 30538297
Whole Grain Consumption for the Prevention and Treatment of Breast Cancer.
Mingsi Xie, Jie Liu, +3 authors, Jing Wang.
Nutrients, 2019 Aug 04; 11(8). PMID: 31374888    Free PMC article.
Topsentinol L Trisulfate, a Marine Natural Product That Targets Basal-like and Claudin-Low Breast Cancers.
Nader N El-Chaar, Thomas E Smith, +8 authors, Philip J Moos.
Mar Drugs, 2021 Jan 23; 19(1). PMID: 33477536    Free PMC article.
Targeting the purinergic pathway in breast cancer and its therapeutic applications.
Julia Beatrice de Araújo, Vanessa Vitória Kerkhoff, Sarah Franco Vieira de Oliveira Maciel, Débora Tavares de Resende E Silva.
Purinergic Signal, 2021 Feb 13;. PMID: 33576905    Free PMC article.