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 2023 EHA Congress 2023 ASCO Annual Meeting
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
Breast Cancer Research
Published in: Breast Cancer Research 1/2013

Open Access 01-02-2013 | Research article

Metabolic biomarkers for response to PI3K inhibition in basal-like breast cancer

Authors: Siver A Moestue, Cornelia G Dam, Saurabh S Gorad, Alexandr Kristian, Anna Bofin, Gunhild M Mælandsmo, Olav Engebråten, Ingrid S Gribbestad, Geir Bjørkøy

Published in: Breast Cancer Research | Issue 1/2013

Login to get access

Abstract

Introduction

The phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in cancer cells through numerous mutations and epigenetic changes. The recent development of inhibitors targeting different components of the PI3K pathway may represent a valuable treatment alternative. However, predicting efficacy of these drugs is challenging, and methods for therapy monitoring are needed. Basal-like breast cancer (BLBC) is an aggressive breast cancer subtype, frequently associated with PI3K pathway activation. The objectives of this study were to quantify the PI3K pathway activity in tissue sections from xenografts representing basal-like and luminal-like breast cancer before and immediately after treatment with PI3K inhibitors, and to identify metabolic biomarkers for treatment response.

Methods

Tumor-bearing animals (n = 8 per treatment group) received MK-2206 (120 mg/kg/day) or BEZ235 (50 mg/kg/day) for 3 days. Activity in the PI3K/Akt/mammalian target of rapamycin pathway in xenografts and human biopsies was evaluated using a novel method for semiquantitative assessment of Aktser473 phosphorylation. Metabolic changes were assessed by ex vivo high-resolution magic angle spinning magnetic resonance spectroscopy.

Results

Using a novel dual near-infrared immunofluorescent imaging method, basal-like xenografts had a 4.5-fold higher baseline level of pAktser473 than luminal-like xenografts. Following treatment, basal-like xenografts demonstrated reduced levels of pAktser473 and decreased proliferation. This correlated with metabolic changes, as both MK-2206 and BEZ235 reduced lactate concentration and increased phosphocholine concentration in the basal-like tumors. BEZ235 also caused increased glucose and glycerophosphocholine concentrations. No response to treatment or change in metabolic profile was seen in luminal-like xenografts. Analyzing tumor sections from five patients with BLBC demonstrated that two of these patients had an elevated pAktser473 level.

Conclusion

The activity of the PI3K pathway can be determined in tissue sections by quantitative imaging using an antibody towards pAktser473. Long-term treatment with MK-2206 or BEZ235 resulted in significant growth inhibition in basal-like, but not luminal-like, xenografts. This indicates that PI3K inhibitors may have selective efficacy in basal-like breast cancer with increased PI3K signaling, and identifies lactate, phosphocholine and glycerophosphocholine as potential metabolic biomarkers for early therapy monitoring. In human biopsies, variable pAktser473 levels were observed, suggesting heterogeneous PI3K signaling activity in BLBC.
Appendix
Available only for authorised users
Literature
1.
2.
Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V: Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007, 109: 1721-1728. 10.1002/cncr.22618.CrossRefPubMed
3.
Foulkes WD, Smith IE, Reis-Filho JS: Triple-negative breast cancer. N Engl J Med. 2010, 363: 1938-1948. 10.1056/NEJMra1001389.CrossRefPubMed
4.
Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A: Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989, 244: 707-712. 10.1126/science.2470152.CrossRefPubMed
5.
Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004, 350: 2129-2139. 10.1056/NEJMoa040938.CrossRefPubMed
6.
Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M: EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004, 304: 1497-1500. 10.1126/science.1099314.CrossRefPubMed
7.
Engelman JA: Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 2009, 9: 550-562. 10.1038/nrc2664.CrossRefPubMed
8.
Lopez-Knowles E, O'Toole SA, McNeil CM, Millar EK, Qiu MR, Crea P, Daly RJ, Musgrove EA, Sutherland RL: PI3K pathway activation in breast cancer is associated with the basal-like phenotype and cancer-specific mortality. Int J Cancer. 2010, 126: 1121-1131.CrossRefPubMed
9.
Miller TW, Rexer BN, Garrett JT, Arteaga CL: Mutations in the phosphatidylinositol 3-kinase pathway: role in tumor progression and therapeutic implications in breast cancer. Breast Cancer Res. 2011, 13: 224-10.1186/bcr3039.CrossRefPubMedPubMedCentral
10.
Song MS, Salmena L, Pandolfi PP: The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 2012, 13: 283-296. 10.1038/nrg3199.PubMed
11.
Beloueche-Babari M, Workman P, Leach MO: Exploiting tumor metabolism for non-invasive imaging of the therapeutic activity of molecularly targeted anticancer agents. Cell Cycle. 2011, 10: 2883-2893. 10.4161/cc.10.17.17192.CrossRefPubMed
12.
Moestue S, Engebraaten O, Gribbestad IS: Metabolic effects of signal transduction inhibition in cancer assessed by magnetic resonance spectroscopy. Mol Oncol. 2011, 5: 224-241. 10.1016/j.molonc.2011.04.001.CrossRefPubMed
13.
Tennant DA, Duran RV, Boulahbel H, Gottlieb E: Metabolic transformation in cancer. Carcinogenesis. 2009, 30: 1269-1280. 10.1093/carcin/bgp070.CrossRefPubMed
14.
Yeung SJ, Pan J, Lee MH: Roles of p53, MYC and HIF-1 in regulating glycolysis - the seventh hallmark of cancer. Cell Mol Life Sci. 2008, 65: 3981-3999. 10.1007/s00018-008-8224-x.CrossRefPubMed
15.
Hoeflich KP, O'Brien C, Boyd Z, Cavet G, Guerrero S, Jung K, Januario T, Savage H, Punnoose E, Truong T, Zhou W, Berry L, Murray L, Amler L, Belvin M, Friedman LS, Lackner MR: In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models. Clin Cancer Res. 2009, 15: 4649-4664. 10.1158/1078-0432.CCR-09-0317.CrossRefPubMed
16.
Marty B, Maire V, Gravier E, Rigaill G, Vincent-Salomon A, Kappler M, Lebigot I, Djelti F, Tourdes A, Gestraud P, Hupe P, Barillot E, Cruzalegui F, Tucker GC, Stern MH, Thiery JP, Hickman JA, Dubois T: Frequent PTEN genomic alterations and activated phosphatidylinositol 3-kinase pathway in basal-like breast cancer cells. Breast Cancer Res. 2008, 10: R101-10.1186/bcr2204.CrossRefPubMedPubMedCentral
17.
Moulder SL: Does the PI3K pathway play a role in basal breast cancer?. Clin Breast Cancer. 2010, 10: S66-CrossRefPubMed
18.
Bergamaschi A, Hjortland GO, Triulzi T, Sorlie T, Johnsen H, Ree AH, Russnes HG, Tronnes S, Maelandsmo GM, Fodstad O, Borresen-Dale AL, Engebraaten O: Molecular profiling and characterization of luminal-like and basal-like in vivo breast cancer xenograft models. Mol Oncol. 2009, 3: 469-482. 10.1016/j.molonc.2009.07.003.CrossRefPubMed
19.
Hirai H, Sootome H, Nakatsuru Y, Miyama K, Taguchi S, Tsujioka K, Ueno Y, Hatch H, Majumder PK, Pan BS, Kotani H: MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Ther. 2010, 9: 1956-1967. 10.1158/1535-7163.MCT-09-1012.CrossRefPubMed
20.
Maira SM, Stauffer F, Brueggen J, Furet P, Schnell C, Fritsch C, Brachmann S, Chene P, De PA, Schoemaker K, Fabbro D, Gabriel D, Simonen M, Murphy L, Finan P, Sellers W, Garcia-Echeverria C: Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther. 2008, 7: 1851-1863. 10.1158/1535-7163.MCT-08-0017.CrossRefPubMed
21.
Huuse EM, Moestue SA, Lindholm EM, Bathen TF, Nalwoga H, Kruger K, Bofin A, Maelandsmo GM, Akslen LA, Engebraaten O, Gribbestad IS: In vivo MRI and histopathological assessment of tumor microenvironment in luminal-like and basal-like breast cancer xenografts. J Magn Reson Imaging. 2012, 35: 1098-1107. 10.1002/jmri.23507.CrossRefPubMed
22.
Skaland I, Janssen EA, Gudlaugsson E, Klos J, Kjellevold KH, Soiland H, Baak JP: Phosphohistone H3 expression has much stronger prognostic value than classical prognosticators in invasive lymph node-negative breast cancer patients less than 55 years of age. Mod Pathol. 2007, 20: 1307-1315. 10.1038/modpathol.3800972.CrossRefPubMed
23.
Sitter B, Lundgren S, Bathen TF, Halgunset J, Fjosne HE, Gribbestad IS: Comparison of HR MAS MR spectroscopic profiles of breast cancer tissue with clinical parameters. NMR Biomed. 2006, 19: 30-40. 10.1002/nbm.992.CrossRefPubMed
24.
Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo WL, Davies M, Carey M, Hu Z, Guan Y, Sahin A, Symmans WF, Pusztai L, Nolden LK, Horlings H, Berns K, Hung MC, van de Vijver MJ, Valero V, Gray JW, Bernards R, Mills GB, Hennessy BT: An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res. 2008, 68: 6084-6091. 10.1158/0008-5472.CAN-07-6854.CrossRefPubMedPubMedCentral
25.
Grinde MT, Moestue SA, Borgan E, Risa O, Engebraaten O, Gribbestad IS: 13C high-resolution-magic angle spinning MRS reveals differences in glucose metabolism between two breast cancer xenograft models with different gene expression patterns. NMR Biomed. 2011, 24: 1243-1252. 10.1002/nbm.1683.CrossRefPubMed
26.
Moestue SA, Borgan E, Huuse EM, Lindholm EM, Sitter B, Borresen-Dale AL, Engebraaten O, Maelandsmo GM, Gribbestad IS: Distinct choline metabolic profiles are associated with differences in gene expression for basal-like and luminal-like breast cancer xenograft models. BMC Cancer. 2010, 10: 433-10.1186/1471-2407-10-433.CrossRefPubMedPubMedCentral
27.
Vargo-Gogola T, Rosen JM: Modelling breast cancer: one size does not fit all. Nat Rev Cancer. 2007, 7: 659-672.CrossRefPubMed
28.
Moestue S, Nunez P, Healey A, Bjerke R, Indrevoll B, Skotland T, Hustvedt SO: Whole-body section fluorescence imaging - a novel method for tissue distribution studies of fluorescent substances. Contrast Media Mol Imaging. 2009, 4: 73-80. 10.1002/cmmi.264.CrossRefPubMed
29.
Baker AF, Dragovich T, Ihle NT, Williams R, Fenoglio-Preiser C, Powis G: Stability of phosphoprotein as a biological marker of tumor signaling. Clin Cancer Res. 2005, 11: 4338-4340. 10.1158/1078-0432.CCR-05-0422.CrossRefPubMed
30.
31.
Weigelt B, Warne PH, Downward J: PIK3CA mutation, but not PTEN loss of function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs. Oncogene. 2011, 30: 3222-3233. 10.1038/onc.2011.42.CrossRefPubMed
32.
Schulze A, Harris AL: How cancer metabolism is tuned for proliferation and vulnerable to disruption. Nature. 2012, 491: 364-373. 10.1038/nature11706.CrossRefPubMed
33.
Warburg O: On respiratory impairment in cancer cells. Science. 1956, 124: 269-270.PubMed
34.
Vander Heiden MG, Cantley LC, Thompson CB: Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009, 324: 1029-1033. 10.1126/science.1160809.CrossRefPubMedPubMedCentral
35.
Dang CV, Semenza GL: Oncogenic alterations of metabolism. Trends Biochem Sci. 1999, 24: 68-72. 10.1016/S0968-0004(98)01344-9.CrossRefPubMed
36.
Deberardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB: The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 2008, 7: 11-20. 10.1016/j.cmet.2007.10.002.CrossRefPubMed
37.
Yeung SJ, Pan J, Lee MH: Roles of p53, MYC and HIF-1 in regulating glycolysis - the seventh hallmark of cancer. Cell Mol Life Sci. 2008, 65: 3981-3999. 10.1007/s00018-008-8224-x.CrossRefPubMed
38.
Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR, Zhuang H, Cinalli RM, Alavi A, Rudin CM, Thompson CB: Akt stimulates aerobic glycolysis in cancer cells. Cancer Res. 2004, 64: 3892-3899. 10.1158/0008-5472.CAN-03-2904.CrossRefPubMed
39.
Beckner ME, Gobbel GT, Abounader R, Burovic F, Agostino NR, Laterra J, Pollack IF: Glycolytic glioma cells with active glycogen synthase are sensitive to PTEN and inhibitors of PI3K and gluconeogenesis. Lab Invest. 2005, 85: 1457-1470.CrossRefPubMed
40.
Beloueche-Babari M, Jackson LE, Al-Saffar NM, Eccles SA, Raynaud FI, Workman P, Leach MO, Ronen SM: Identification of magnetic resonance detectable metabolic changes associated with inhibition of phosphoinositide 3-kinase signaling in human breast cancer cells. Mol Cancer Ther. 2006, 5: 187-196. 10.1158/1535-7163.MCT-03-0220.CrossRefPubMed
41.
Serganova I, Rizwan A, Ni X, Thakur SB, Vider J, Russell J, Blasberg R, Koutcher JA: Metabolic imaging: a link between lactate dehydrogenase a, lactate, and tumor phenotype. Clin Cancer Res. 2011, 17: 6250-6261. 10.1158/1078-0432.CCR-11-0397.CrossRefPubMedPubMedCentral
42.
Kurhanewicz J, Vigneron DB, Brindle K, Chekmenev EY, Comment A, Cunningham CH, Deberardinis RJ, Green GG, Leach MO, Rajan SS, Rizi RR, Ross BD, Warren WS, Malloy CR: Analysis of cancer metabolism by imaging hyperpolarized nuclei: prospects for translation to clinical research. Neoplasia. 2011, 13: 81-97.CrossRefPubMedPubMedCentral
43.
Glunde K, Jiang L, Moestue SA, Gribbestad IS: MRS and MRSI guidance in molecular medicine: targeting and monitoring of choline and glucose metabolism in cancer. NMR Biomed. 2011, 24: 673-690.CrossRefPubMedPubMedCentral
44.
45.
Aboagye EO, Bhujwalla ZM: Malignant transformation alters membrane choline phospholipid metabolism of human mammary epithelial cells. Cancer Res. 1999, 59: 80-84.PubMed
46.
Jimenez B, del PL, Montaner S, Esteve P, Lacal JC: Generation of phosphorylcholine as an essential event in the activation of Raf-1 and MAP-kinases in growth factors-induced mitogenic stimulation. J Cell Biochem. 1995, 57: 141-149. 10.1002/jcb.240570114.CrossRefPubMed
47.
Panupinthu N, Lee HY, Mills GB: Lysophosphatidic acid production and action: critical new players in breast cancer initiation and progression. Br J Cancer. 2010, 102: 941-946. 10.1038/sj.bjc.6605588.CrossRefPubMedPubMedCentral
48.
Wen ZH, Su YC, Lai PL, Zhang Y, Xu YF, Zhao A, Yao GY, Jia CH, Lin J, Xu S, Wang L, Wang XK, Liu AL, Jiang Y, Dai YF, Bai XC: Critical role of arachidonic acid-activated mTOR signaling in breast carcinogenesis and angiogenesis. Oncogene. 2013, 32: 160-170. 10.1038/onc.2012.47.CrossRefPubMed
49.
Yalcin A, Clem B, Makoni S, Clem A, Nelson K, Thornburg J, Siow D, Lane AN, Brock SE, Goswami U, Eaton JW, Telang S, Chesney J: Selective inhibition of choline kinase simultaneously attenuates MAPK and PI3K/AKT signaling. Oncogene. 2010, 29: 139-149. 10.1038/onc.2009.317.CrossRefPubMed
50.
Park JB, Lee CS, Jang JH, Ghim J, Kim YJ, You S, Hwang D, Suh PG, Ryu SH: Phospholipase signalling networks in cancer. Nat Rev Cancer. 2012, 12: 782-792. 10.1038/nrc3379.CrossRefPubMed
51.
Ramirez de MA, Banez-Coronel M, Gutierrez R, Rodriguez-Gonzalez A, Olmeda D, Megias D, Lacal JC: Choline kinase activation is a critical requirement for the proliferation of primary human mammary epithelial cells and breast tumor progression. Cancer Res. 2004, 64: 6732-6739. 10.1158/0008-5472.CAN-04-0489.CrossRef
52.
Rodriguez-Gonzalez A, Ramirez de MA, Fernandez F, Ramos MA, del Carmen NM, Campos J, Lacal JC: Inhibition of choline kinase as a specific cytotoxic strategy in oncogene-transformed cells. Oncogene. 2003, 22: 8803-8812. 10.1038/sj.onc.1207062.CrossRefPubMed
53.
Podo F, Canevari S, Canese R, Pisanu ME, Ricci A, Iorio E: MR evaluation of response to targeted treatment in cancer cells. NMR Biomed. 2011, 24: 648-672.PubMed
54.
Aboagye EO, Bhujwalla ZM: Malignant transformation alters membrane choline phospholipid metabolism of human mammary epithelial cells. Cancer Res. 1999, 59: 80-84.PubMed
55.
Glunde K, Artemov D, Penet MF, Jacobs MA, Bhujwalla ZM: Magnetic resonance spectroscopy in metabolic and molecular imaging and diagnosis of cancer. Chem Rev. 2010, 110: 3043-3059. 10.1021/cr9004007.CrossRefPubMedPubMedCentral
56.
Keshari KR, Tsachres H, Iman R, Delos SL, Tabatabai ZL, Shinohara K, Vigneron DB, Kurhanewicz J: Correlation of phospholipid metabolites with prostate cancer pathologic grade, proliferative status and surgical stage - impact of tissue environment. NMR Biomed. 2011, 24: 691-699. 10.1002/nbm.1738.CrossRefPubMed
57.
Moestue SA, Giskeodegard GF, Cao MD, Bathen TF, Gribbestad IS: Glycerophosphocholine (GPC) is a poorly understood biomarker in breast cancer. Proc Natl Acad Sci USA. 2012, 109: E2506-10.1073/pnas.1208226109.CrossRefPubMedPubMedCentral
58.
Beloueche-Babari M, Arunan V, Jackson LE, Perusinghe N, Sharp SY, Workman P, Leach MO: Modulation of melanoma cell phospholipid metabolism in response to heat shock protein 90 inhibition. Oncotarget. 2010, 1: 185-197.CrossRefPubMedPubMedCentral
59.
Klawitter J, Kominsky DJ, Brown JL, Klawitter J, Christians U, Leibfritz D, Melo JV, Eckhardt SG, Serkova NJ: Metabolic characteristics of imatinib resistance in chronic myeloid leukaemia cells. Br J Pharmacol. 2009, 158: 588-600. 10.1111/j.1476-5381.2009.00345.x.CrossRefPubMedPubMedCentral
60.
Chung YL, Troy H, Kristeleit R, Aherne W, Jackson LE, Atadja P, Griffiths JR, Judson IR, Workman P, Leach MO, Beloueche-Babari M: Noninvasive magnetic resonance spectroscopic pharmacodynamic markers of a novel histone deacetylase inhibitor, LAQ824, in human colon carcinoma cells and xenografts. Neoplasia. 2008, 10: 303-313.CrossRefPubMedPubMedCentral
61.
Sankaranarayanapillai M, Tong WP, Maxwell DS, Pal A, Pang J, Bornmann WG, Gelovani JG, Ronen SM: Detection of histone deacetylase inhibition by noninvasive magnetic resonance spectroscopy. Mol Cancer Ther. 2006, 5: 1325-1334. 10.1158/1535-7163.MCT-05-0494.CrossRefPubMed
62.
Al-Saffar NM, Jackson LE, Raynaud FI, Clarke PA, Ramirez de MA, Lacal JC, Workman P, Leach MO: The phosphoinositide 3-kinase inhibitor PI-103 downregulates choline kinase alpha leading to phosphocholine and total choline decrease detected by magnetic resonance spectroscopy. Cancer Res. 2010, 70: 5507-5517. 10.1158/0008-5472.CAN-09-4476.CrossRefPubMedPubMedCentral
63.
Koul D, Shen R, Kim YW, Kondo Y, Lu Y, Bankson J, Ronen SM, Kirkpatrick DL, Powis G, Yung WK: Cellular and in vivo activity of a novel PI3K inhibitor, PX-866, against human glioblastoma. Neuro Oncol. 2010, 12: 559-569. 10.1093/neuonc/nop058.CrossRefPubMedPubMedCentral
64.
Wijnen JP, Scheenen TW, Klomp DW, Heerschap A: 31P magnetic resonance spectroscopic imaging with polarisation transfer of phosphomono- and diesters at 3 T in the human brain: relation with age and spatial differences. NMR Biomed. 2010, 23: 968-976. 10.1002/nbm.1523.CrossRefPubMed
65.
Hoeflich KP, O'Brien C, Boyd Z, Cavet G, Guerrero S, Jung K, Januario T, Savage H, Punnoose E, Truong T, Zhou W, Berry L, Murray L, Amler L, Belvin M, Friedman LS, Lackner MR: In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models. Clin Cancer Res. 2009, 15: 4649-4664. 10.1158/1078-0432.CCR-09-0317.CrossRefPubMed
Metadata
Title
Metabolic biomarkers for response to PI3K inhibition in basal-like breast cancer
Authors
Siver A Moestue
Cornelia G Dam
Saurabh S Gorad
Alexandr Kristian
Anna Bofin
Gunhild M Mælandsmo
Olav Engebråten
Ingrid S Gribbestad
Geir Bjørkøy
Publication date
01-02-2013
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2013
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3391

Other articles of this Issue 1/2013

Breast Cancer Research 1/2013 Go to the issue

Review

Tissue transglutaminase as a central mediator in inflammation-induced progression of breast cancer

Research article

HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer

Viewpoint

A functional link between FOXA1 and breast cancer SNPs

Research article

Prevalence of PALB2 mutations in Australasian multiple-case breast cancer families

Research article

Mammographic density as a predictor of breast cancer survival: the Multiethnic Cohort

Research article

The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer
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