Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Mammary Gland Biology and Neoplasia
Published in: Journal of Mammary Gland Biology and Neoplasia 4/2018

Open Access 01-12-2018

Beyond DNA: the Role of Epigenetics in the Premalignant Progression of Breast Cancer

Authors: Rebecca S. DeVaux, Jason I. Herschkowitz

Published in: Journal of Mammary Gland Biology and Neoplasia | Issue 4/2018

Login to get access

Abstract

Ductal Carcinoma in Situ (DCIS) is an early breast cancer lesion that is considered a nonobligate precursor to development of invasive ductal carcinoma (IDC). Although only a small subset of DCIS lesions are predicted to progress into a breast cancer, distinguishing innocuous from minacious DCIS lesions remains a clinical challenge. Thus, patients diagnosed with DCIS will undergo surgery with the potential for radiation and hormone therapy. This has led to a current state of overdiagnosis and overtreatment. Interrogating the transcriptome alone has yet to define clear functional determinants of progression from DCIS to IDC. Epigenetic changes, critical for imprinting and tissue specific development, in the incorrect context can lead to global signaling rewiring driving pathological phenotypes. Epigenetic signaling pathways, and the molecular players that interpret and sustain their signals, are critical to understanding the underlying pathology of breast cancer progression. The types of epigenetic changes, as well as the molecular players, are expanding. In addition to DNA methylation, histone modifications, and chromatin remodeling, we must also consider enhancers as well as the growing field of noncoding RNAs. Herein we will review the epigenetic interactions that have been uncovered in early stage lesions that impact breast cancer progression, and how these players may be utilized as biomarkers to mitigate overdiagnosis and overtreatment.
Literature
1.
Esserman LJ, Thompson IM Jr, Reid B. Overdiagnosis and overtreatment in cancer: an opportunity for improvement. JAMA. 2013;310(8):797–8.PubMed
2.
Breast Cancer Facts & Figures 2015–2016. American Cancer Society.
3.
Lopez-Garcia MA, et al. Breast cancer precursors revisited: molecular features and progression pathways. Histopathology. 2010;57(2):171–92.PubMed
4.
5.
Allegra CJ, et al. NIH state-of-the-science conference statement: diagnosis and management of ductal carcinoma in situ (DCIS). NIH Consens State Sci Statements. 2009;26(2):1–27.PubMed
6.
Siu AL, U.S.P.S.T. Force. Screening for breast cancer: U.S. preventive services task force recommendation statement. Ann Intern Med. 2016;164(4):279–96.PubMed
7.
Wickerham DL, Julian TB. Ductal carcinoma in situ: a rose by any other name. J Natl Cancer Inst. 2013;105(20):1521–2.PubMedPubMedCentral
8.
Lee S, et al. Differentially expressed genes regulating the progression of ductal carcinoma in situ to invasive breast cancer. Cancer Res. 2012;72(17):4574–86.PubMedPubMedCentral
9.
Nagaraja GM, et al. Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: comprehensive profiles by representational difference analysis, microarrays and proteomics. Oncogene. 2006;25(16):2328–38.PubMed
10.
Schuetz CS, et al. Progression-specific genes identified by expression profiling of matched ductal carcinomas in situ and invasive breast tumors, combining laser capture microdissection and oligonucleotide microarray analysis. Cancer Res. 2006;66(10):5278–86.PubMed
11.
Wulfkuhle JD, et al. Proteomics of human breast ductal carcinoma in situ. Cancer Res. 2002;62(22):6740–9.PubMed
12.
13.
Buerger H, et al. Comparative genomic hybridization of ductal carcinoma in situ of the breast-evidence of multiple genetic pathways. J Pathol. 1999;187(4):396–402.PubMed
14.
Ma XJ, et al. Gene expression profiles of human breast cancer progression. Proc Natl Acad Sci U S A. 2003;100(10):5974–9.PubMedPubMedCentral
15.
O'Connell P, et al. Analysis of loss of heterozygosity in 399 premalignant breast lesions at 15 genetic loci. J Natl Cancer Inst. 1998;90(9):697–703.PubMed
16.
Polyak K. Molecular markers for the diagnosis and management of ductal carcinoma in situ. J Natl Cancer Inst Monogr. 2010;2010(41):210–3.PubMedPubMedCentral
17.
Porter D, et al. Molecular markers in ductal carcinoma in situ of the breast. Mol Cancer Res. 2003;1(5):362–75.PubMed
18.
Allis CD, Jenuwein T. The molecular hallmarks of epigenetic control. Nat Rev Genet. 2016;17(8):487–500.PubMed
19.
Waddington CH. The epigenotype. Endeavour. 1942;1:18–20.
20.
Waddington CH. Canalization of development and the inheritance of acquired characters. Nature. 1942;150:563–5.
21.
Razin A, Riggs AD. DNA methylation and gene function. Science. 1980;210(4470):604–10.PubMed
22.
23.
Pasculli B, Barbano R, Parrella P. Epigenetics of breast cancer: biology and clinical implication in the era of precision medicine. Semin Cancer Biol. 2018.
24.
Ehrlich M. DNA hypomethylation in cancer cells. Epigenomics. 2009;1(2):239–59.PubMed
25.
26.
Soares J, et al. Global DNA hypomethylation in breast carcinoma: correlation with prognostic factors and tumor progression. Cancer. 1999;85(1):112–8.PubMed
27.
Verschuur-Maes AH, de Bruin PC, van Diest PJ. Epigenetic progression of columnar cell lesions of the breast to invasive breast cancer. Breast Cancer Res Treat. 2012;136(3):705–15.PubMed
28.
Park SY, et al. Promoter CpG island hypermethylation during breast cancer progression. Virchows Arch. 2011;458(1):73–84.PubMed
29.
van Hoesel AQ, et al. Assessment of DNA methylation status in early stages of breast cancer development. Br J Cancer. 2013;108(10):2033–8.PubMedPubMedCentral
30.
Lehmann U, et al. Quantitative assessment of promoter hypermethylation during breast cancer development. Am J Pathol. 2002;160(2):605–12.PubMedPubMedCentral
31.
Fackler MJ, et al. DNA methylation of RASSF1A, HIN-1, RAR-beta, cyclin D2 and Twist in in situ and invasive lobular breast carcinoma. Int J Cancer. 2003;107(6):970–5.PubMed
32.
Hoque MO, et al. Changes in CpG islands promoter methylation patterns during ductal breast carcinoma progression. Cancer Epidemiol Biomark Prev. 2009;18(10):2694–700.
33.
Faryna M, et al. Genome-wide methylation screen in low-grade breast cancer identifies novel epigenetically altered genes as potential biomarkers for tumor diagnosis. FASEB J. 2012;26(12):4937–50.PubMed
34.
Fleischer T, et al. Genome-wide DNA methylation profiles in progression to in situ and invasive carcinoma of the breast with impact on gene transcription and prognosis. Genome Biol. 2014;15(8):435.PubMedPubMedCentral
35.
Parrella P, et al. Nonrandom distribution of aberrant promoter methylation of cancer-related genes in sporadic breast tumors. Clin Cancer Res. 2004;10(16):5349–54.PubMed
36.
Sproul D, et al. Transcriptionally repressed genes become aberrantly methylated and distinguish tumors of different lineages in breast cancer. Proc Natl Acad Sci U S A. 2011;108(11):4364–9.PubMedPubMedCentral
37.
Tommasi S, et al. Methylation of homeobox genes is a frequent and early epigenetic event in breast cancer. Breast Cancer Res. 2009;11(1):R14.PubMedPubMedCentral
38.
Johnson KC, et al. DNA methylation in ductal carcinoma in situ related with future development of invasive breast cancer. Clin Epigenetics. 2015;7:75.PubMedPubMedCentral
39.
Cai Y, et al. Epigenetic alterations to Polycomb targets precede malignant transition in a mouse model of breast cancer. Sci Rep. 2018;8(1):5535.PubMedPubMedCentral
40.
Teschendorff AE, et al. DNA methylation outliers in normal breast tissue identify field defects that are enriched in cancer. Nat Commun. 2016;7:10478.PubMedPubMedCentral
41.
Yan PS, et al. Mapping geographic zones of cancer risk with epigenetic biomarkers in normal breast tissue. Clin Cancer Res. 2006;12(22):6626–36.PubMed
42.
Tessarz P, Kouzarides T. Histone core modifications regulating nucleosome structure and dynamics. Nat Rev Mol Cell Biol. 2014;15(11):703–8.PubMed
43.
Munshi A, et al. Histone modifications dictate specific biological readouts. J Genet Genomics. 2009;36(2):75–88.PubMed
44.
Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403(6765):41–5.PubMed
45.
46.
Vire E, et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2006;439(7078):871–4.PubMed
47.
Kleer CG, et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci U S A. 2003;100(20):11606–11.PubMedPubMedCentral
48.
Ding L, et al. Identification of EZH2 as a molecular marker for a precancerous state in morphologically normal breast tissues. Cancer Res. 2006;66(8):4095–9.PubMed
49.
Forneris F, et al. New roles of flavoproteins in molecular cell biology: histone demethylase LSD1 and chromatin. FEBS J. 2009;276(16):4304–12.PubMed
50.
Lim S, et al. Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology. Carcinogenesis. 2010;31(3):512–20.PubMed
51.
Serce N, et al. Elevated expression of LSD1 (Lysine-specific demethylase 1) during tumour progression from pre-invasive to invasive ductal carcinoma of the breast. BMC Clin Pathol. 2012;12:13.PubMedPubMedCentral
52.
Kahl P, et al. Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence. Cancer Res. 2006;66(23):11341–7.PubMed
53.
Hayami S, et al. Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. Int J Cancer. 2011;128(3):574–86.PubMed
54.
Kauffman EC, et al. Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer. Mol Carcinog. 2011;50(12):931–44.PubMedPubMedCentral
55.
Filippakopoulos P, Knapp S. Targeting bromodomains: epigenetic readers of lysine acetylation. Nat Rev Drug Discov. 2014;13(5):337–56.PubMed
56.
Fujisawa T, Filippakopoulos P. Functions of bromodomain-containing proteins and their roles in homeostasis and cancer. Nat Rev Mol Cell Biol. 2017;18(4):246–62.PubMed
57.
Perez-Salvia M, Esteller M. Bromodomain inhibitors and cancer therapy: from structures to applications. Epigenetics. 2017;12(5):323–39.PubMed
58.
Seto E, Yoshida M. Erasers of histone acetylation: the histone deacetylase enzymes. Cold Spring Harb Perspect Biol. 2014;6(4):a018713.PubMedPubMedCentral
59.
Taunton J, Hassig CA, Schreiber SL. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science. 1996;272(5260):408–11.PubMed
60.
Davis T, et al. Histone deacetylase inhibitors decrease proliferation and modulate cell cycle gene expression in normal mammary epithelial cells. Clin Cancer Res. 2000;6(11):4334–42.PubMed
61.
Lagger G, et al. The tumor suppressor p53 and histone deacetylase 1 are antagonistic regulators of the cyclin-dependent kinase inhibitor p21/WAF1/CIP1 gene. Mol Cell Biol. 2003;23(8):2669–79.PubMedPubMedCentral
62.
Lagger G, et al. Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression. EMBO J. 2002;21(11):2672–81.PubMedPubMedCentral
63.
Suzuki J, et al. Protein acetylation and histone deacetylase expression associated with malignant breast cancer progression. Clin Cancer Res. 2009;15(9):3163–71.PubMedPubMedCentral
64.
Kadota M, et al. Delineating genetic alterations for tumor progression in the MCF10A series of breast cancer cell lines. PLoS One. 2010;5(2):e9201.PubMedPubMedCentral
65.
Miller FR, et al. MCF10DCIS.com xenograft model of human comedo ductal carcinoma in situ. J Natl Cancer Inst. 2000;92(14):1185–6.PubMed
66.
Miller FR, et al. Xenograft model of progressive human proliferative breast disease. J Natl Cancer Inst. 1993;85(21):1725–32.PubMed
67.
Santner SJ, et al. Malignant MCF10CA1 cell lines derived from premalignant human breast epithelial MCF10AT cells. Breast Cancer Res Treat. 2001;65(2):101–10.PubMed
68.
Soule HD, et al. Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res. 1990;50(18):6075–86.PubMed
69.
Lapierre M, et al. Histone deacetylase 9 regulates breast cancer cell proliferation and the response to histone deacetylase inhibitors. Oncotarget. 2016;7(15):19693–708.PubMedPubMedCentral
70.
Elsheikh SE, et al. Global histone modifications in breast cancer correlate with tumor phenotypes, prognostic factors, and patient outcome. Cancer Res. 2009;69(9):3802–9.PubMed
71.
Krusche CA, et al. Histone deacetylase-1 and -3 protein expression in human breast cancer: a tissue microarray analysis. Breast Cancer Res Treat. 2005;90(1):15–23.PubMed
72.
Muller BM, et al. Differential expression of histone deacetylases HDAC1, 2 and 3 in human breast cancer--overexpression of HDAC2 and HDAC3 is associated with clinicopathological indicators of disease progression. BMC Cancer. 2013;13:215.PubMedPubMedCentral
73.
Seo J, et al. Expression of histone deacetylases HDAC1, HDAC2, HDAC3, and HDAC6 in invasive ductal carcinomas of the breast. J Breast Cancer. 2014;17(4):323–31.PubMedPubMedCentral
74.
Zhang Z, et al. Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast*. Breast Cancer Res Treat. 2005;94(1):11–6.PubMed
75.
Maniatis T, Goodbourn S, Fischer JA. Regulation of inducible and tissue-specific gene expression. Science. 1987;236(4806):1237–45.PubMed
76.
Hnisz D, et al. Convergence of developmental and oncogenic signaling pathways at transcriptional super-enhancers. Mol Cell. 2015;58(2):362–70.PubMedPubMedCentral
77.
78.
Hnisz D, et al. Super-enhancers in the control of cell identity and disease. Cell. 2013;155(4):934–47.PubMed
79.
Mansour MR, et al. Oncogene regulation. An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element. Science. 2014;346(6215):1373–7.PubMedPubMedCentral
80.
Northcott PA, et al. Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature. 2014;511(7510):428–34.PubMedPubMedCentral
81.
Rhie SK, et al. Nucleosome positioning and histone modifications define relationships between regulatory elements and nearby gene expression in breast epithelial cells. BMC Genomics. 2014;15:331.PubMedPubMedCentral
82.
83.
84.
85.
Shu S, et al. Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer. Nature. 2016;529(7586):413–7.PubMedPubMedCentral
86.
Whyte WA, et al. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell. 2013;153(2):307–19.PubMedPubMedCentral
87.
Shen H, et al. Suppression of enhancer overactivation by a RACK7-histone demethylase complex. Cell. 2016;165(2):331–42.PubMedPubMedCentral
88.
Ding XC, Weiler J, Grosshans H. Regulating the regulators: mechanisms controlling the maturation of microRNAs. Trends Biotechnol. 2009;27(1):27–36.PubMed
89.
90.
Cao Q, et al. Coordinated regulation of polycomb group complexes through microRNAs in cancer. Cancer Cell. 2011;20(2):187–99.PubMedPubMedCentral
91.
de Nigris F. Epigenetic regulators: Polycomb-miRNA circuits in cancer. Biochim Biophys Acta. 2016;1859(5):697–704.PubMed
92.
Ramassone A, et al. Epigenetics and MicroRNAs in cancer. Int J Mol Sci. 2018;19(2).
93.
Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–54.PubMed
94.
Orellana EA, Kasinski AL. MicroRNAs in Cancer: a historical perspective on the path from discovery to therapy. Cancers (Basel). 2015;7(3):1388–405.
95.
Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993;75(5):855–62.PubMed
96.
Griffiths-Jones S. miRBase: the microRNA sequence database. Methods Mol Biol. 2006;342:129–38.PubMed
97.
Gregory PA, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10(5):593–601.PubMed
98.
Huse JT, et al. The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo. Genes Dev. 2009;23(11):1327–37.PubMedPubMedCentral
99.
Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449(7163):682–8.PubMed
100.
Tavazoie SF, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 2008;451(7175):147–52.PubMedPubMedCentral
101.
102.
Lambertz I, et al. Monoallelic but not biallelic loss of Dicer1 promotes tumorigenesis in vivo. Cell Death Differ. 2010;17(4):633–41.PubMed
103.
Lu J, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–8.PubMed
104.
Blenkiron C, et al. MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol. 2007;8(10):R214.PubMedPubMedCentral
105.
Hannafon BN, et al. Expression of microRNA and their gene targets are dysregulated in preinvasive breast cancer. Breast Cancer Res. 2011;13(2):R24.PubMedPubMedCentral
106.
Hannafon BN, Ding WQ. miRNAs as biomarkers for predicting the progression of ductal carcinoma in situ. Am J Pathol. 2018;188(3):542–9.PubMedPubMedCentral
107.
Farazi TA, et al. MicroRNA sequence and expression analysis in breast tumors by deep sequencing. Cancer Res. 2011;71(13):4443–53.PubMedPubMedCentral
108.
Volinia S, et al. Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA. Proc Natl Acad Sci U S A. 2012;109(8):3024–9.PubMedPubMedCentral
109.
Kopp F, Mendell JT. Functional classification and experimental dissection of long noncoding RNAs. Cell. 2018;172(3):393–407.PubMedPubMedCentral
110.
Quinn JJ, Chang HY. Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet. 2016;17(1):47–62.PubMed
111.
Betancur JG. Pervasive lncRNA binding by epigenetic modifying complexes--the challenges ahead. Biochim Biophys Acta. 2016;1859(1):93–101.PubMed
112.
Bohmdorfer G, Wierzbicki AT. Control of chromatin structure by long noncoding RNA. Trends Cell Biol. 2015;25(10):623–32.PubMedPubMedCentral
113.
Kumar M, DeVaux RS, Herschkowitz JI. Molecular and cellular changes in breast Cancer and new roles of lncRNAs in breast Cancer initiation and progression. Prog Mol Biol Transl Sci. 2016;144:563–86.PubMed
114.
Gupta RA, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6.PubMedPubMedCentral
115.
Bhan A, Mandal SS. LncRNA HOTAIR: a master regulator of chromatin dynamics and cancer. Biochim Biophys Acta. 2015;1856(1):151–64.PubMedPubMedCentral
116.
Iacoangeli A, et al. BC200 RNA in invasive and preinvasive breast cancer. Carcinogenesis. 2004;25(11):2125–33.PubMed
117.
Iacoangeli A, Tiedge H. Translational control at the synapse: role of RNA regulators. Trends Biochem Sci. 2013;38(1):47–55.PubMed
118.
Shore AN, Rosen JM. Regulation of mammary epithelial cell homeostasis by lncRNAs. Int J Biochem Cell Biol. 2014;54:318–30.PubMedPubMedCentral
119.
Eades G, et al. lincRNA-RoR and miR-145 regulate invasion in triple-negative breast cancer via targeting ARF6. Mol Cancer Res. 2015;13(2):330–8.PubMed
120.
Liu B, et al. A cytoplasmic NF-kappaB interacting long noncoding RNA blocks IkappaB phosphorylation and suppresses breast cancer metastasis. Cancer Cell. 2015;27(3):370–81.PubMed
121.
122.
Chen S, et al. Macrophage infiltration promotes invasiveness of breast cancer cells via activating long non-coding RNA UCA1. Int J Clin Exp Pathol. 2015;8(8):9052–61.PubMedPubMedCentral
123.
Xiao C, Wu CH, Hu HZ. LncRNA UCA1 promotes epithelial-mesenchymal transition (EMT) of breast cancer cells via enhancing Wnt/beta-catenin signaling pathway. Eur Rev Med Pharmacol Sci. 2016;20(13):2819–24.PubMed
124.
Devaux Y, et al. Long noncoding RNAs in cardiac development and ageing. Nat Rev Cardiol. 2015;12(7):415–25.PubMed
125.
Li W, Notani D, Rosenfeld MG. Enhancers as non-coding RNA transcription units: recent insights and future perspectives. Nat Rev Genet. 2016;17(4):207–23.PubMed
126.
Miao Y, et al. Enhancer-associated long non-coding RNA LEENE regulates endothelial nitric oxide synthase and endothelial function. Nat Commun. 2018;9(1):292.PubMedPubMedCentral
127.
128.
Klattenhoff CA, et al. Braveheart, a long noncoding RNA required for cardiovascular lineage commitment. Cell. 2013;152(3):570–83.PubMedPubMedCentral
129.
130.
Ounzain S, et al. CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis. J Mol Cell Cardiol. 2015;89(Pt A):98–112.PubMed
131.
Wang KC, et al. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature. 2011;472(7341):120–4.PubMedPubMedCentral
132.
Xiang JF, et al. Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus. Cell Res. 2014;24(5):513–31.PubMedPubMedCentral
Metadata
Title
Beyond DNA: the Role of Epigenetics in the Premalignant Progression of Breast Cancer
Authors
Rebecca S. DeVaux
Jason I. Herschkowitz
Publication date
01-12-2018
Publisher
Springer US
Published in
Journal of Mammary Gland Biology and Neoplasia / Issue 4/2018
Print ISSN: 1083-3021
Electronic ISSN: 1573-7039
DOI
https://doi.org/10.1007/s10911-018-9414-2

Other articles of this Issue 4/2018

Journal of Mammary Gland Biology and Neoplasia 4/2018 Go to the issue

Preface

Human Ductal Carcinoma In Situ: from the Eyes of a Beholder

ReviewPaper

Current Therapeutic Approaches to DCIS

ReviewPaper

Intratumoral Heterogeneity in Ductal Carcinoma In Situ: Chaos and Consequence

ReviewPaper

Breaking through to the Other Side: Microenvironment Contributions to DCIS Initiation and Progression

ReviewPaper

Clinical Trials for Ductal Carcinoma In Situ of the Breast

OriginalPaper

CXCL1 Derived from Mammary Fibroblasts Promotes Progression of Mammary Lesions to Invasive Carcinoma through CXCR2 Dependent Mechanisms
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits