Skip to main content

Advertisement

SpringerLink
Log in

What’s new in metastatic breast cancer?

  • review
  • Published:
memo - Magazine of European Medical Oncology Aims and scope Submit manuscript

Abstract

Overall, breast cancer mortality has declined due to advances in systemic adjuvant treatment in recent years; still, metastatic breast cancer remains an incurable disease. Due to novel treatment options, however, survival was prolonged even in patients with advanced-stage disease. In hormone-receptor positive breast cancer, endocrine therapy is the mainstay of treatment. Currently, different strategies are being evaluated to overcome resistance to anti-hormonal interventions, with the aim to prolong the chemotherapy-free interval. In Her2-positive breast cancer, anti-Her2 targeted therapies such as trastuzumab or lapatinib have improved patients’ outcome. Further substances—antibodies or novel tyrosine-kinase inhibitors—will increase therapeutic options in the future. Limited progress was achieved in the triple-negative sub-type. Bevacizumab, a monoclonal antibody targeting the vascular endothelial growth factor, is currently the only biological agent available in this sub-type. In combination with paclitaxel or capecitabine, bevacizumab offers clinically meaningful activity in metastatic breast cancer patients. Other strategies, such as treatment with DNA-damaging agents or the inhibition of DNA-repair mechanisms were not successful so far in a general triple-negative population. This article reviews recent developments and future trends in the field of metastatic breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Brewster AM, Hortobagyi GN, Broglio KR, et al. Residual risk of breast cancer recurrence 5 years after adjuvant therapy. J Natl Cancer Inst. 2008;100(16):1179–83.

    Article  PubMed  Google Scholar 

  2. O’Shaughnessy J. Extending survival with chemotherapy in metastatic breast cancer. Oncologist. 2005;10(Suppl. 3):20–9.

    Article  PubMed  Google Scholar 

  3. Beslija S, Bonneterre J, Burstein HJ, et al. Third consensus on medical treatment of metastatic breast cancer. Ann Oncol. 2009;20(11):1771–85.

    Article  CAS  PubMed  Google Scholar 

  4. Riggio M, Polo ML, Blaustein M, et al. PI3K/AKT pathway regulates phosphorylation of steroid receptors, hormone independence and tumor differentiation in breast cancer. Carcinogenesis 2012; [Epub ahead of print]. PMID: 22180571.

  5. Bartlett JMS, Brookes CL, van de Velde CJH, et al. Final results of a prospectively planned biomarker analysis: HER1-3 as predictive markers of benefit from early treatment with aromatase inhibitors versus tamoxifen in the TEAM pathology sub-study. Cancer Res. 2010;70(Suppl. 2):Abst. S2-4.

    Google Scholar 

  6. Johnston S, Pippen J Jr, Pivot X, et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009;27(33):5538–46.

    Article  CAS  PubMed  Google Scholar 

  7. Osborne CK, Neven P, Dirix LY, et al. Gefitinib or placebo in combination with tamoxifen in patients with hormone receptor-positive metastatic breast cancer: a randomized phase II study. Clin Cancer Res. 2011;17(5):1147–59.

    Article  CAS  PubMed  Google Scholar 

  8. Baselga J, Semiglazov V, van Dam P, et al. Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer. J Clin Oncol. 2009;27(16):2630–7.

    Article  CAS  PubMed  Google Scholar 

  9. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2011;[Epub ahead of print]. PMID: 22149876.

  10. Gianni L, Lladó A, Bianchi G, et al. Open-label, phase II, multicenter, randomized study of the efficacy and safety of two dose levels of pertuzumab, a human epidermal growth factor receptor 2 dimerization inhibitor, in patients with human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010;28(7):1131–7.

    Article  CAS  PubMed  Google Scholar 

  11. Schneeweiss A, Chia S, Hickish T, et al. Neoadjuvant pertuzumab and trastuzumab concurrent or sequential with an anthracycline-containing or concurrent with an anthracycline-free standard regimen: a randomized phase II study (TRYPHAENA). Cancer Res. 2011;71(Suppl. 3):Abst. S5-6.

    Google Scholar 

  12. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25–32.

    Article  CAS  PubMed  Google Scholar 

  13. Baselga J, Cortés J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109–19.

    Article  CAS  PubMed  Google Scholar 

  14. Burris III HA, Rugo HS, Vukelja SJ, et al. Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. J Clin Oncol. 2011;29(4):398–405.

    Article  Google Scholar 

  15. Perez EA, Dirix L, Kocsis J, et al. Efficacy and safety of trastuzumab-DM1 versus trastuzumab plus docetaxel in HER2-positive metastatic breast cancer patients with no prior chemotherapy for metastatic disease: preliminary results of a randomized, multicenter, open-label phase 2 study (TDM4450G). Ann Oncol. 2010;21(Suppl. 8):LBA3.

    Google Scholar 

  16. ClinicalTrials. http://www.clincialtrials.gov. Accessed 2 Feb 2012.

  17. Cortés-Funes H, Mendiola C, Manso L, Ciruelos E. Neratinib, an irreversible pan erB receptor tyrosine kinase inhibitor active for advanced HER2+ breast cancer. Breast Cancer Res. 2009;11(Suppl. 1):S19.

    Article  PubMed  Google Scholar 

  18. Martin M, Bonneterre J, Geyer Jr CE, et al. A Phase 2, Randomized, Open-Label, Study of Neratinib (HKI-272) vs lapatinib plus capecitabine for 2nd/3rd-line treatment of HER2+ locally advanced or metastatic breast cancer. Cancer Res. 2011;71(Suppl. 3):Abst. S5-7.

    Google Scholar 

  19. Hickish T, Wheatley D, Lin N, et al. Use of BIBW 2992, a novel irreversible EGFR/HER1 and HER2 tyrosine kinase inhibitor to treat patients with HER2-positive metastatic breast cancer after failure of treatment with trastuzumab. Cancer Res. 2009;96(Suppl. 3):Abst. 5060.

    Article  Google Scholar 

  20. Gianni L, Bianchini G, Kiermaier A, et al. Neoadjuvant pertuzumab (P) and trastuzumab (H): biomarker analyses of a 4-Arm randomized phase II study (NeoSphere) in patients (pts) with HER2-positive breast cancer (BC). Cancer Res. 2011;71(Suppl. 3):Abst. S5-1.

    Google Scholar 

  21. Xu B, Guan Z-Z, Shen Z-Z, et al. Association of PTEN loss and PIK3CA mutations on outcome in HER2+ metastatic breast cancer patients treated with first-line lapatinib plus paclitaxel or paclitaxel alone. Cancer Res. 2011;71(Suppl. 3):Abst. S3-3.

    Google Scholar 

  22. Folkman J, Klagsbrun M. Angiogenic factors. Science. 1987;235(6141):442–7.

    Article  CAS  PubMed  Google Scholar 

  23. Laughner E, Taghavi P, Chiles K, Mahon PC, Semenza GL. HER2 (neu) signaling increases the rate hypoxia-induceable factor 1α (HIF-1 α) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. Mol Cell Biol. 2001;21(12):3995–4004.

    Article  CAS  PubMed  Google Scholar 

  24. Gianni L, Romieu G, Lichinitser M, et al. First results of AVEREL, a randomized phase III trial to evaluate bevacizumab (BEV) in combination with trastuzumab (H) + docetaxel (DOC) as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer (LR/mBC). Cancer Res. 2011;71(Suppl. 3):Abst. S4-8.

    Google Scholar 

  25. Bergh J, Greil R, Voytko N, et al. Sunitinib (SU) in combination with docetaxel (D) versus D alone for the first-line treatment of advanced breast cancer (ABC). J Clin Oncol. 2010;28(Suppl. 18):Abst. LBA1010.

    Google Scholar 

  26. Crown J, Dieras V, Staroslawska E, et al. Phase III trial of sunitinib (SU) in combination with capecitabine (C) versus C in previously treated advanced breast cancer (ABC). J Clin Oncol. 2010;28(Suppl. 18):Abst. LBA1011.

    Google Scholar 

  27. Baselga J, Roche H, Costa F, et al. SOLTI-0701: a multinational double-blind, randomized phase 2b study evaluating the efficacy and safety of sorafenib compared to placebo when administered in combination with capecitabine in patients with locally advanced or metastatic breast cancer (BC). Cancer Res. 2009;69(Suppl. 24):Abst. 45.

    Article  Google Scholar 

  28. Birgisdottir V, Stefansson OA, Bodvarsdottir SK, Hilmarsdottir H, Jonasson JG, Eyfjord JE. Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer. Breast Cancer Res. 2006;8(4):R38.

    Article  PubMed  Google Scholar 

  29. Turner N, Tutt A, Ashworth A. Hallmarks of “BRCAness” in sporadic cancers. Nat Rev Cancer. 2004;4(10):814–9.

    Article  CAS  PubMed  Google Scholar 

  30. Gelmon KA, Hirte HW, Robidoux A, et al. Can we define tumors that will respond to PARP inhibitors? A phase II correlative study of olaparib in advanced serous ovarian cancer and triple-negative breast cancer. J Clin Oncol. 2010;25(Suppl. 18):Abst. 3002.

    Google Scholar 

  31. Sirohi B, Arnedos M, Popat S, et al. Platinum-based chemotherapy in triple-negative breast cancer. Ann Oncol. 2009;19(11):1847–52.

    Article  Google Scholar 

  32. Byrski T, Huzarski T, Dent R, et al. Response to neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat. 2009:115(2):359–63.

    Article  CAS  PubMed  Google Scholar 

  33. Serra V, Markman B, Scaltriti M, et al. NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer Res. 2008;68(19):8022–30.

    Article  CAS  PubMed  Google Scholar 

  34. Baselga J, Gomez P, Awada A, et al. The addition of cetuximab to cisplatin increases overall response rate (ORR) and progression free survival (PFS) in metastatic triple-negative breast cancer (TNBC): Results of a randomized phase II study (BALI-1). Ann Oncol. 2010;21(Suppl. 8):Abst. 274O.

    Google Scholar 

  35. Hankinson SE, Willett WC, Colditz GA, et al. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet. 1998;351(9113):1393–6.

    Article  CAS  PubMed  Google Scholar 

  36. Nahta R, Yuan LX, Zhang B, Kobayashi R, Esteva FJ. Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res. 2005;65(23):11118–28.

    Article  CAS  PubMed  Google Scholar 

  37. Citri A, Kochupurakkal BS, Yarden Y. The achilles heel of ErbB-2/HER2: regulation by the Hsp90 chaperone machine and potential for pharmacological intervention. Cell Cycle. 2004;3(1):51–60.

    Article  CAS  PubMed  Google Scholar 

  38. Modi S, Stopeck A, Linden H, et al. HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab. Clin Cancer Res. 2011;17(15):5132–9.

    Article  CAS  PubMed  Google Scholar 

  39. Wiedermann U, Wiltschke C, Jasinska J, et al. A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study. Breast Cancer Res Treat. 2010;119(3):673–83.

    Article  CAS  PubMed  Google Scholar 

  40. Mohebtash M, Tsang KY, Madan RA, et al. A pilot study of MUC-1/CEA/TRICOM poxviral-based vaccine in patients with metastatic breast and ovarian cancer. Clin Cancer Res. 2011;17(22):7164–73.

    Article  CAS  PubMed  Google Scholar 

  41. Lobell RB, Omer CA, Abrams MT, et al. Evaluation of farnesyl:protein transferase and geranylgeranyl:protein transferase inhibitor combinations in preclinical models. Cancer Res. 2001;61(24):8758–68.

    Google Scholar 

  42. Johnston SR, Semiglazov VF, Manikhas GM, et al. A phase II, randomized, blinded study of the farnesyltransferase inhibitor tipifarnib combined with letrozole in the treatment of advanced breast cancer after antiestrogen therapy. Breast Cancer Res Treat. 2008;110(2):327–35.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

Rupert Bartsch has received lecture honoraria, travel support and research support from Roche Austria, the manufacturer of bevacizumab, pertuzumab, T-DM 1, and trastuzumab; lecture honoraria from Glaxo Smith Kline, the manufacturer of lapatinib; travel support from Boehringer-Ingelheim, the manufacturer of afatinib.

Author information

Authors and Affiliations

  1. Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Waehringer Guertel 18–20, 1090, Vienna, Austria

    Rupert Bartsch MD

  2. Comprehensive Cancer Centre Vienna, Medical University of Vienna, Waehringer Guertel 18–20, 1090, Vienna, Austria

    Rupert Bartsch MD

Authors
  1. Rupert Bartsch MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bartsch, R. What’s new in metastatic breast cancer?. memo 5, 110–115 (2012). https://doi.org/10.1007/s12254-012-0004-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12254-012-0004-5

Keywords

Search

Navigation