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Systemic Therapies to Reduce the Risk of Recurrence in Early Breast Cancer: New Strategies

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Breast Cancer Survivorship

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Abstract

The systemic adjuvant treatment of early breast cancer (EBC) has benefited from a multifaceted approach. Generic cytotoxic approaches, as well as a more targeted approach to the estrogen receptor or HER2 receptor are now established standards of care. Decades of innovative trials exploring bisphosphonates in breast cancer prevention and EBC for bone protection, as well as large prospective randomized trials have resulted in an overwhelming case for benefit in post menopausal women. Therapies such as everolimus and the PARP inhibitors, established in the secondary breast cancer setting, are being explored in the adjuvant setting for utility. Similarly, observational and retrospective studies have demonstrated a strong reduction in breast cancer risk with the use of metformin and aspirin, and hence large prospective randomized trials are underway.

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References

  1. Mathew A, Brufsky A. Decreased risk of breast cancer associated with oral bisphosphonate therapy. Breast Cancer (Dove Med Press). 2012;4:75–81.

    CAS  Google Scholar 

  2. Mathew A, Brufsky A. Bisphosphonates in breast cancer. Int J Cancer. 2015;137(4):753–64.

    Article  CAS  PubMed  Google Scholar 

  3. Tabane K, Vorobiof DA. Bone targeted therapies in early breast cancer. Curr Treat Options Oncol. 2011;12(4):412–23.

    Article  PubMed  Google Scholar 

  4. Coleman RE. Skeletal complications of malignancy. Cancer. 1997;80(8 Suppl):1588–94.

    Article  CAS  PubMed  Google Scholar 

  5. Bidard FC, et al. Disseminated tumor cells of breast cancer patients: a strong prognostic factor for distant and local relapse. Clin Cancer Res. 2008;14(11):3306–11.

    Article  CAS  PubMed  Google Scholar 

  6. Santini D, et al. Bisphosphonates as anticancer agents in early breast cancer: preclinical and clinical evidence. Breast Cancer Res. 2015;17(1):121.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Diel IJ, et al. Adjuvant oral clodronate improves the overall survival of primary breast cancer patients with micrometastases to the bone marrow: a long-term follow-up. Ann Oncol. 2008;19(12):2007–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Powles T, et al. Randomized, placebo-controlled trial of clodronate in patients with primary operable breast cancer. J Clin Oncol. 2002;20(15):3219–24.

    Article  CAS  PubMed  Google Scholar 

  9. Saarto T, et al. Ten-year follow-up of a randomized controlled trial of adjuvant clodronate treatment in node-positive breast cancer patients. Acta Oncol. 2004;43(7):650–6.

    Article  CAS  PubMed  Google Scholar 

  10. Paterson AH, et al. Oral clodronate for adjuvant treatment of operable breast cancer (National Surgical Adjuvant Breast and Bowel Project protocol B-34): a multicentre, placebo-controlled, randomised trial. Lancet Oncol. 2012;13(7):734–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. von Minckwitz G, et al. German adjuvant intergroup node-positive study: a phase III trial to compare oral ibandronate versus observation in patients with high-risk early breast cancer. J Clin Oncol. 2013;31(28):3531–9.

    Article  Google Scholar 

  12. Gnant M, et al. Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12. Ann Oncol. 2015;26(2):313–20.

    Article  CAS  PubMed  Google Scholar 

  13. Coleman R, et al. Adjuvant zoledronic acid in patients with early breast cancer: final efficacy analysis of the AZURE (BIG 01/04) randomised open-label phase 3 trial. Lancet Oncol. 2014;15(9):997–1006.

    Article  CAS  PubMed  Google Scholar 

  14. Coleman R, et al. Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results. Ann Oncol. 2013;24(2):398–405.

    Article  CAS  PubMed  Google Scholar 

  15. Early Breast Cancer Trialists’ Collaborative G, et al. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386(10001):1353–61.

    Google Scholar 

  16. Simmons DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev. 2004;56(3):387–437.

    Article  CAS  PubMed  Google Scholar 

  17. Ulrich CM, Bigler J, Potter JD. Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. Nat Rev Cancer. 2006;6(2):130–40.

    Article  CAS  PubMed  Google Scholar 

  18. Easty GC, Easty DM. Prostaglandins and cancer. Cancer Treat Rev. 1976;3(4):217–25.

    Article  CAS  PubMed  Google Scholar 

  19. Martinez ME, et al. Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene. Proc Natl Acad Sci U S A. 2003;100(13):7859–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Jankowski JA, Anderson M. Review article: management of oesophageal adenocarcinoma – control of acid, bile and inflammation in intervention strategies for Barrett’s oesophagus. Aliment Pharmacol Ther. 2004;20 Suppl 5:71–80; discussion 95–6.

    Article  PubMed  Google Scholar 

  21. Rothwell PM, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet. 2010;376(9754):1741–50.

    Article  CAS  PubMed  Google Scholar 

  22. Rothwell PM, et al. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011;377(9759):31–41.

    Article  CAS  PubMed  Google Scholar 

  23. Rothwell PM, et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 2012;379(9826):1602–12.

    Article  CAS  PubMed  Google Scholar 

  24. Eikawa S, et al. Immune-mediated antitumor effect by type 2 diabetes drug, metformin. Proc Natl Acad Sci U S A. 2015;112(6):1809–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ben Sahra I, et al. The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene. 2008;27(25):3576–86.

    Article  CAS  PubMed  Google Scholar 

  26. Pearce EL, et al. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature. 2009;460(7251):103–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Noto H, et al. Cancer risk in diabetic patients treated with metformin: a systematic review and meta-analysis. PLoS One. 2012;7(3):e33411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Col NF, et al. Metformin and breast cancer risk: a meta-analysis and critical literature review. Breast Cancer Res Treat. 2012;135(3):639–46.

    Article  CAS  PubMed  Google Scholar 

  29. Jiralerspong S, et al. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol. 2009;27(20):3297–302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhang P, et al. Association of metformin use with cancer incidence and mortality: a meta-analysis. Cancer Epidemiol. 2013;37(3):207–18.

    Article  PubMed  Google Scholar 

  31. Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature. 2006;441(7092):424–30.

    Article  CAS  PubMed  Google Scholar 

  32. Perez-Tenorio G, Stal O, Southeast Sweden Breast Cancer Group. Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients. Br J Cancer. 2002;86(4):540–5.

    Google Scholar 

  33. Beeram M, et al. Akt-induced endocrine therapy resistance is reversed by inhibition of mTOR signaling. Ann Oncol. 2007;18(8):1323–8.

    Article  CAS  PubMed  Google Scholar 

  34. Bender LM, Nahta R. Her2 cross talk and therapeutic resistance in breast cancer. Front Biosci. 2008;13:3906–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Tanaka C, et al. Identifying optimal biologic doses of everolimus (RAD001) in patients with cancer based on the modeling of preclinical and clinical pharmacokinetic and pharmacodynamic data. J Clin Oncol. 2008;26(10):1596–602.

    CAS  PubMed  Google Scholar 

  36. Baselga J, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012;366(6):520–9.

    Article  CAS  PubMed  Google Scholar 

  37. Ame JC, Spenlehauer C, de Murcia G. The PARP superfamily. Bioessays. 2004;26(8):882–93.

    Article  CAS  PubMed  Google Scholar 

  38. Tentori L, Graziani G. Chemopotentiation by PARP inhibitors in cancer therapy. Pharmacol Res. 2005;52(1):25–33.

    Article  CAS  PubMed  Google Scholar 

  39. Bryant HE, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434(7035):913–7.

    Article  CAS  PubMed  Google Scholar 

  40. Farmer H, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917–21.

    Article  CAS  PubMed  Google Scholar 

  41. O’Shaughnessy J, et al. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol. 2014;32(34):3840–7.

    Article  PubMed  Google Scholar 

  42. Lips EH, et al. Triple-negative breast cancer: BRCAness and concordance of clinical features with BRCA1-mutation carriers. Br J Cancer. 2013;108(10):2172–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Tutt A, 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(9737):235–44.

    Article  CAS  PubMed  Google Scholar 

  44. Sonnenblick A, et al. An update on PARP inhibitors – moving to the adjuvant setting. Nat Rev Clin Oncol. 2015;12(1):27–41.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. The Breast Unit, The Royal Marsden NHS Foundation Trust, Surrey, UK

    Narda Chaabouni

  2. Department of Medical Oncology, Guy’s and St Thomas’ Hospital, London, UK

    Christos Nikolaou & Mark Harries MA, FRCP, PhD

Authors
  1. Narda Chaabouni
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  2. Christos Nikolaou
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  3. Mark Harries MA, FRCP, PhD
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Corresponding author

Correspondence to Mark Harries MA, FRCP, PhD .

Editor information

Editors and Affiliations

  1. The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom

    Alistair Ring

  2. The Royal Marsden NHS Foundation Trust, London, United Kingdom

    Marina Parton

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© 2016 Springer International Publishing Switzerland

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Chaabouni, N., Nikolaou, C., Harries, M. (2016). Systemic Therapies to Reduce the Risk of Recurrence in Early Breast Cancer: New Strategies. In: Ring, A., Parton, M. (eds) Breast Cancer Survivorship. Springer, Cham. https://doi.org/10.1007/978-3-319-41858-2_7

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  • DOI: https://doi.org/10.1007/978-3-319-41858-2_7

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-41856-8

  • Online ISBN: 978-3-319-41858-2

  • eBook Packages: MedicineMedicine (R0)

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