Breast Cancer

, Volume 19, Issue 3, pp 206–211 | Cite as

Eradication of breast cancer cells in patients with distant metastasis: the finishing touches?

Special Feature From improved survival to potential cure in patients with metastatic breast cancer
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Accepted:

Abstract

Cytotoxic agents are significantly active in breast cancer cells, but their usefulness has been limited in treating metastatic breast cancer (MBC). This has facilitated the development of an approach using molecular-targeted agents. Intrinsic subtypes including luminal A, luminal B, human epidermal growth factor receptor type 2 (HER2)-enriched, basal-like, and claudin-low tumors exhibit original drug responsiveness and clinical prognosis. Anti-HER2 treatments, trastuzumab or lapatinib, have demonstrated clinically significant efficacy. Poly ADP-ribose polymerase-1 inhibitors act against BRCA1-disabled breast cancer. Cancer stem cells could be the major obstacle to achieving a cure in systemic treatment. Extensive investigations are underway to develop novel agents that act on the genes or signaling of Hedgehog, Wnt, and Notch, which regulate cancer stem cells. Cancer cells undergo epithelial–mesenchymal transition (EMT) and acquire invasive properties. Breast cancer cells alter their phenotype in blood and bone marrow, e.g., circulating tumor cells or disseminated tumor cells. Cancer stem cells, like normal stem cells, may exist at niches in bone marrow. To achieve a cure for MBC, it is necessary to disrupt cancer stem cell–niche interactions or eradicate cancer stem cells. Traditional treatments with cytotoxic or endocrine agents require development in relation to intrinsic subtypes, stem cells, or EMT.

Keywords

Breast cancer CTC DTC Stem cell Epithelial–mesenchymal transition 

Abbreviations

ALDH

Aldehyde dehydrogenase

CTC

Circulating tumor cell

CXCR4

C-X-C motif chemokine receptor-4

DTC

Disseminated tumor cell

Dvl

Cytoplasmic disheveled

EMT

Epithelial–mesenchymal transition

ER

Estrogen receptor

HER2

Human epidermal growth factor receptor type 2

MBC

Metastatic breast cancer

PARP

Poly ADP-ribose polymerase

PCR

Polymerase chain reaction

PI3K

Phosphoinositide 3-kinase

PR

Progesterone receptor

Smo

Smoothened

RANK

Receptor activator for nuclear factor κ B

VEGF

Vascular endothelial growth factor

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References

  1. 1.
    Fossati R, Confalonieri C, Torri V, Ghislandi E, Penna A, Pistotti V, et al. Cytotoxic and hormonal treatment for metastatic breast cancer: a systematic review of published randomized trials involving 31, 510 women. J Clin Oncol. 1998;16:3439–60.PubMedGoogle Scholar
  2. 2.
    Ghersi D, Wilcken N, Simes J, Donoghue E. Taxane containing regimens for metastatic breast cancer. Cochrane Database Syst Rev. 2005;18:CD003366.Google Scholar
  3. 3.
    Jassem J, Carroll C, Ward SE, Simpson E, Hind D. The clinical efficacy of cytotoxic agents in locally advanced or metastatic breast cancer patients pretreated with an anthracycline and a taxane: a systematic review. Eur J Cancer. 2009;45:2749–58.PubMedCrossRefGoogle Scholar
  4. 4.
    Farquhar C, Marjoribanks J, Basser R, Hetrick S, Lethaby A. High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with metastatic breast cancer. Cochrane Database Syst Rev. 2005;20:CD003142.Google Scholar
  5. 5.
    Seidman AD, Hudis CA, Albanell J, Tong W, Tepler I, Currie V, et al. Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol. 1998;16:3353–61.PubMedGoogle Scholar
  6. 6.
    Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, et al. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of cancer and leukemia group b protocol 9840. J Clin Oncol. 2008;26:1642–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Dellapasqua S, Bertolini F, Bagnardi V, Campagnoli E, Scarano E, Torrisi R, et al. Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer. J Clin Oncol. 2008;26:4899–905.PubMedCrossRefGoogle Scholar
  8. 8.
    Kerbel RS. Improving conventional or low dose metronomic chemotherapy with targeted antiangiogenic drugs. Cancer Res Treat. 2007;39:150–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Jones D, Ghersi D, Wilcken N. Addition of drug/s to a chemotherapy regimen for metastatic breast cancer. Cochrane Database Syst Rev. 2006;3:CD003368.PubMedGoogle Scholar
  10. 10.
    Cardoso F, Bedard PL, Winer EP, Pagani O, Senkus-Konefka E, Fallowfield LJ, et al. International guidelines for management of metastatic breast cancer: combination vs sequential single-agent chemotherapy. J Natl Cancer Inst. 2009;101:1174–81.PubMedCrossRefGoogle Scholar
  11. 11.
    Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92.PubMedCrossRefGoogle Scholar
  12. 12.
    Dahabreh IJ, Linardou H, Siannis F, Fountzilas G, Murray S. Trastuzumab in the adjuvant treatment of early-stage breast cancer: a systematic review and meta-analysis of randomized controlled trials. Oncologist. 2008;13:620–30.PubMedCrossRefGoogle Scholar
  13. 13.
    Ito Y, Tokudome N, Sugihara T, Takahashi S, Hatake K. Does lapatinib, a small-molecule tyrosine kinase inhibitor, constitute a breakthrough in the treatment of breast cancer? Breast Cancer. 2007;14:156–62.PubMedCrossRefGoogle Scholar
  14. 14.
    Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355:2733–43.PubMedCrossRefGoogle Scholar
  15. 15.
    O’Shaughnessy J, Osborne C, Pippen J, Patt D, Rocha C, Ossovskaya V, et al. Final results of a randomized phase II study demonstrating efficacy and safety of BSI-201, a poly (ADP-ribose) polymerase (PARP) inhibitor, in combination with gemcitabine/carboplatin (G/C) in metastatic triple negative breast cancer (TNBC). Cancer Res. 2009;69:686s. (abstr 3122).Google Scholar
  16. 16.
    Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010;376:235–44.PubMedCrossRefGoogle Scholar
  17. 17.
    Zaremba T, Curtin NJ. PARP inhibitor development for systemic cancer targeting. Anticancer Agents Med Chem. 2007;7:515–23.PubMedGoogle Scholar
  18. 18.
    Giordano SH, Buzdar AU, Smith TL, Kau SW, Yang Y, Hortobagyi GN. Is breast cancer survival improving? Cancer. 2004;100:44–52.PubMedCrossRefGoogle Scholar
  19. 19.
    Gennari A, Conte P, Rosso R, Orlandini C, Bruzzi P. Survival of metastatic breast carcinoma patients over a 20-year period: a retrospective analysis based on individual patient data from six consecutive studies. Cancer. 2005;104:1742–50.PubMedCrossRefGoogle Scholar
  20. 20.
    Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol. 2010;28:92–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Dafni U, Grimani I, Xyrafas A, Eleftheraki AG, Fountzilas G. Fifteen-year trends in metastatic breast cancer survival in Greece. Breast Cancer Res Treat. 2010;119:621–31.PubMedCrossRefGoogle Scholar
  22. 22.
    Dawood S, Broglio K, Ensor J, Hortobagyi GN, Giordano SH. Survival differences among women with de novo stage IV and relapsed breast cancer. Ann Oncol. 2010;21:2169–74.PubMedCrossRefGoogle Scholar
  23. 23.
    Pagani O, Senkus E, Wood W, Colleoni M, Cufer T, Kyriakides S, et al. International guidelines for management of metastatic breast cancer: can metastatic breast cancer be cured? J Natl Cancer Inst. 2010;102:456–63.PubMedCrossRefGoogle Scholar
  24. 24.
    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.PubMedCrossRefGoogle Scholar
  25. 25.
    Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98:10869–74.PubMedCrossRefGoogle Scholar
  26. 26.
    Sørlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A. 2003;100:8418–23.PubMedCrossRefGoogle Scholar
  27. 27.
    Bertucci F, Houlgatte R, Benziane A, Granjeaud S, Adélaïde J, Tagett R, et al. Gene expression profiling of primary breast carcinomas using arrays of candidate genes. Hum Mol Genet. 2000;9:2981–91.PubMedCrossRefGoogle Scholar
  28. 28.
    Bergamaschi A, Kim YH, Wang P, Sørlie T, Hernandez-Boussard T, Lonning PE, et al. Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer. Genes Chromosom Cancer. 2006;45:1033–40.PubMedCrossRefGoogle Scholar
  29. 29.
    Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL, et al. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell. 2006;10:529–41.PubMedCrossRefGoogle Scholar
  30. 30.
    Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 2006;10:515–27.PubMedCrossRefGoogle Scholar
  31. 31.
    Beresford MJ, Wilson GD, Makris A. Measuring proliferation in breast cancer: practicalities and applications. Breast Cancer Res. 2006;8:216.PubMedCrossRefGoogle Scholar
  32. 32.
    Yerushalmi R, Woods R, Ravdin PM, Hayes MM, Gelmon KA. Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol. 2010;11:174–83.PubMedCrossRefGoogle Scholar
  33. 33.
    O’Brien CA, Kreso A, Jamieson CH. Cancer stem cells and self-renewal. Clin Cancer Res. 2010;16:3113–20.PubMedCrossRefGoogle Scholar
  34. 34.
    Kai K, Arima Y, Kamiya T, Saya H. Breast cancer stem cells. Breast Cancer. 2010;17:80–5.PubMedCrossRefGoogle Scholar
  35. 35.
    Abraham BK, Fritz P, McClellan M, Hauptvogel P, Athelogou M, Brauch H. Prevalence of CD44+/CD24−/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis. Clin Cancer Res. 2005;11:1154–9.PubMedGoogle Scholar
  36. 36.
    Keysar SB, Jimeno A. More than markers: biological significance of cancer stem cell-defining molecules. Mol Cancer Ther. 2010;9:2450–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Smalley MJ, Clarke RB. The mammary gland “side population”: a putative stem/progenitor cell marker? J Mammary Gland Biol Neoplasia. 2005;10:37–47.PubMedCrossRefGoogle Scholar
  38. 38.
    Fukuda S, Pelus LM. Survivin, a cancer target with an emerging role in normal adult tissues. Mol Cancer Ther. 2006;5:1087–98.PubMedCrossRefGoogle Scholar
  39. 39.
    Giménez-Bonafé P, Tortosa A, Pérez-Tomás R. Overcoming drug resistance by enhancing apoptosis of tumor cells. Curr Cancer Drug Targets. 2009;9:320–40.PubMedCrossRefGoogle Scholar
  40. 40.
    Sakariassen PØ, Immervoll H, Chekenya M. Cancer stem cells as mediators of treatment resistance in brain tumors: status and controversies. Neoplasia. 2007;9:882–92.PubMedCrossRefGoogle Scholar
  41. 41.
    Tang C, Chua CL, Ang BT. Insights into the cancer stem cell model of glioma tumorigenesis. Ann Acad Med Singap. 2007;36:352–7.PubMedGoogle Scholar
  42. 42.
    Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst. 2008;100:672–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Merchant AA, Matsui W. Targeting Hedgehog—a cancer stem cell pathway. Clin Cancer Res. 2010;16:3130–40.PubMedCrossRefGoogle Scholar
  44. 44.
    Jiang L, Li J, Song L. Bmi-1, stem cells and cancer. Acta Biochim Biophys Sin (Shanghai). 2009;41:527–34.CrossRefGoogle Scholar
  45. 45.
    Takahashi-Yanaga F, Kahn M. Targeting Wnt signaling: can we safely eradicate cancer stem cells? Clin Cancer Res. 2010;16:3153–62.PubMedCrossRefGoogle Scholar
  46. 46.
    Pannuti A, Foreman K, Rizzo P, Osipo C, Golde T, Osborne B, et al. Targeting Notch to target cancer stem cells. Clin Cancer Res. 2010;16:3141–52.PubMedCrossRefGoogle Scholar
  47. 47.
    Farnie G, Clarke RB. Mammary stem cells and breast cancer—role of Notch signalling. Stem Cell Rev. 2007;3:169–75.PubMedCrossRefGoogle Scholar
  48. 48.
    Korkaya H, Paulson A, Iovino F, Wicha MS. HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene. 2008;27:6120–30.PubMedCrossRefGoogle Scholar
  49. 49.
    Magnifico A, Albano L, Campaner S, Delia D, Castiglioni F, Gasparini P, et al. Tumor-initiating cells of HER2-positive carcinoma cell lines express the highest oncoprotein levels and are trastuzumab sensitive. Clin Cancer Res. 2009;15:2010–21.PubMedCrossRefGoogle Scholar
  50. 50.
    Chen Y, Fischer WH, Gill GN. Regulation of the ERBB-2 promoter by RBPJκ and NOTCH. J Biol Chem. 1997;272:14110–4.PubMedCrossRefGoogle Scholar
  51. 51.
    Maun HR, Wen X, Lingel A, de Sauvage FJ, Lazarus RA, Scales SJ, et al. Hedgehog pathway antagonist 5E1 binds hedgehog at the pseudo-active site. J Biol Chem. 2010;285:26570–80.PubMedCrossRefGoogle Scholar
  52. 52.
    He B, You L, Uematsu K, Xu Z, Lee AY, Matsangou M, et al. A monoclonal antibody against Wnt-1 induces apoptosis in human cancer cells. Neoplasia. 2004;6:7–14.PubMedGoogle Scholar
  53. 53.
    Wu Y, Cain-Hom C, Choy L, Hagenbeek TJ, de Leon GP, Chen Y, et al. Therapeutic antibody targeting of individual Notch receptors. Nature. 2010;464:1052–7.PubMedCrossRefGoogle Scholar
  54. 54.
    Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009;138:645–59.PubMedCrossRefGoogle Scholar
  55. 55.
    Mostert B, Sleijfer S, Foekens JA, Gratama JW. Circulating tumor cells (CTCs): detection methods and their clinical relevance in breast cancer. Cancer Treat Rev. 2009;35:463–74.PubMedCrossRefGoogle Scholar
  56. 56.
    Vincent-Salomon A, Bidard FC, Pierga JY. Bone marrow micrometastasis in breast cancer: review of detection methods, prognostic impact and biological issues. J Clin Pathol. 2008;61:570–6.PubMedCrossRefGoogle Scholar
  57. 57.
    Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781–91.PubMedCrossRefGoogle Scholar
  58. 58.
    Nakamura S, Yagata H, Ohno S, Yamaguchi H, Iwata H, Tsunoda N, et al. Multi-center study evaluating circulating tumor cells as a surrogate for response to treatment and overall survival in metastatic breast cancer. Breast Cancer. 2010;17:199–204.PubMedCrossRefGoogle Scholar
  59. 59.
    Riethdorf S, Müller V, Zhang L, Rau T, Loibl S, Komor M, et al. Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Clin Cancer Res. 2010;16:2634–45.PubMedCrossRefGoogle Scholar
  60. 60.
    Meng S, Tripathy D, Shete S, Ashfaq R, Saboorian H, Haley B, et al. uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues. Proc Natl Acad Sci USA. 2006;103:17361–5.PubMedCrossRefGoogle Scholar
  61. 61.
    Lang JE, Mosalpuria K, Cristofanilli M, Krishnamurthy S, Reuben J, Singh B, et al. HER2 status predicts the presence of circulating tumor cells in patients with operable breast cancer. Breast Cancer Res Treat. 2009;113:501–7.PubMedCrossRefGoogle Scholar
  62. 62.
    Pestrin M, Bessi S, Galardi F, Truglia M, Biggeri A, Biagioni C, et al. Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients. Breast Cancer Res Treat. 2009;118:523–30.PubMedCrossRefGoogle Scholar
  63. 63.
    Paik S, Kim C, Wolmark N. HER2 status and benefit from adjuvant trastuzumab in breast cancer. N Engl J Med. 2008;358:1409.PubMedCrossRefGoogle Scholar
  64. 64.
    Iwatsuki M, Mimori K, Yokobori T, Ishi H, Beppu T, Nakamori S, et al. Epithelial–mesenchymal transition in cancer development and its clinical significance. Cancer Sci. 2010;101:293–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Fehm T, Hoffmann O, Aktas B, Becker S, Solomayer EF, Wallwiener D. Detection and characterization of circulating tumor cells in blood of primary breast cancer patients by RT-PCR and comparison to status of bone marrow disseminated cells. Breast Cancer Res. 2009;11:R59.PubMedCrossRefGoogle Scholar
  66. 66.
    Tewes M, Aktas B, Welt A, Mueller S, Hauch S, Kimmig R, et al. Molecular profiling and predictive value of circulating tumor cells in patients with metastatic breast cancer: an option for monitoring response to breast cancer related therapies. Breast Cancer Res Treat. 2009;115:581–90.PubMedCrossRefGoogle Scholar
  67. 67.
    Aktas B, Tewes M, Fehm T, Hauch S, Kimmig R, Kasimir-Bauer S. Stem cell and epithelial–mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res. 2009;11:R46.PubMedCrossRefGoogle Scholar
  68. 68.
    Lu J, Fan T, Zhao Q, Zeng W, Zaslavsky E, Chen JJ, et al. Isolation of circulating epithelial and tumor progenitor cells with an invasive phenotype from breast cancer patients. Int J Cancer. 2010;126:669–83.PubMedCrossRefGoogle Scholar
  69. 69.
    Psaila B, Kaplan RN, Port ER, Lyden D. Priming the ‘soil’ for breast cancer metastasis: the pre-metastatic niche. Breast Dis. 2006–2007;26:65–74.Google Scholar
  70. 70.
    Kuhn NZ, Tuan RS. Regulation of stemness and stem cell niche of mesenchymal stem cells: implications in tumorigenesis and metastasis. J Cell Physiol. 2010;222:268–77.PubMedCrossRefGoogle Scholar
  71. 71.
    LaBarge MA. The difficulty of targeting cancer stem cell niches. Clin Cancer Res. 2010;16:3121–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Kaplan RN, Psaila B, Lyden D. Bone marrow cells in the ‘pre-metastatic niche’: within bone and beyond. Cancer Metastasis Rev. 2006;25:521–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Pierga J-Y, Bonneton CH, Vincent-Salomon A, de Cremoux P, Nos C, Blin N, et al. Clinical significance of immunocytochemical detection of tumor cells using digital microscopy in peripheral blood and bone marrow of breast cancer patients. Clin Cancer Res. 2004;10:1392–400.PubMedCrossRefGoogle Scholar
  74. 74.
    Benoy IH, Elst H, Philips M, Wuyts H, Van Dam P, Scharpe S, et al. Real-time RT-PCR detection of disseminated tumour cells in bone marrow has superior prognostic significance in comparison with circulating tumour cells in patients with breast cancer. Br J Cancer. 2006;94:672–80.PubMedGoogle Scholar
  75. 75.
    Bidard FC, Vincent-Salomon A, Gomme S, Nos C, de Rycke Y, Thiery JP. Disseminated tumor cells of breast cancer patients: a strong prognostic factor for distant and local relapse. Clin Cancer Res. 2008;14:3306–11.PubMedCrossRefGoogle Scholar
  76. 76.
    Perez EA, Suman VJ, Davidson NE, Gralow J, Kaufman PA, Ingle JN, et al. Results of chemotherapy alone, with sequential or concurrent addition of 52 weeks of trastuzumab in the NCCTG N9831 HER2-positive adjuvant breast cancer trial. Cancer Res. 2009; LBA. http://www.abstracts2view.com/sabcs09/view.php?nu=SABCS09L_992332&terms= (abstr 80).
  77. 77.
    Inoue K, Nakagami K, Mizutani M, Hozumi Y, Fujiwara Y, Masuda N, et al. Randomized phase III trial of trastuzumab monotherapy followed by trastuzumab plus docetaxel versus trastuzumab plus docetaxel as first-line therapy in patients with HER2-positive metastatic breast cancer: the JO17360 Trial Group. Breast Cancer Res Treat. 2010;119:127–36.PubMedCrossRefGoogle Scholar
  78. 78.
    Brewster AM, Hortobagyi GN, Broglio KR, Kau SW, Santa-Maria CA, Arun B, et al. Residual risk of breast cancer recurrence 5 years after adjuvant therapy. J Natl Cancer Inst. 2008;100:1179–83.PubMedCrossRefGoogle Scholar
  79. 79.
    O’Brien CS, Howell SJ, Farnie G, Clarke RB. Resistance to endocrine therapy: are breast cancer stem cells the culprits? J Mammary Gland Biol Neoplasia. 2009;14:45–54.PubMedCrossRefGoogle Scholar
  80. 80.
    Pinto MP, Badtke MM, Dudevoir ML, Harrell JC, Jacobsen BM, Horwitz KB. Vascular endothelial growth factor secreted by activated stroma enhances angiogenesis and hormone-independent growth of estrogen receptor-positive breast cancer. Cancer Res. 2010;70:2655–64.PubMedCrossRefGoogle Scholar
  81. 81.
    Lydon JP. Stem cells: cues from steroid hormones. Nature. 2010;465:695–6.PubMedCrossRefGoogle Scholar
  82. 82.
    Joshi PA, Jackson HW, Beristain AG, Di Grappa MA, Mote PA, Clarke CL, et al. Progesterone induces adult mammary stem cell expansion. Nature. 2010;465:803–7.PubMedCrossRefGoogle Scholar
  83. 83.
    Asselin-Labat ML, Vaillant F, Sheridan JM, Pal B, Wu D, Simpson ER, et al. Control of mammary stem cell function by steroid hormone signalling. Nature. 2010;465:798–802.PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Breast Cancer Society 2011

Authors and Affiliations

  1. 1.Department of Medical Oncology, Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyoJapan
  2. 2.Department of Breast Oncology, Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyoJapan

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