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Adjuvant Molecular Therapies in Breast Cancer

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Breast Cancer Management for Surgeons

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Abstract

Adjuvant therapies (radiotherapy, chemotherapy, endocrine and targeted agents) in patients with localised cancer are aimed at the elimination of putatively present micrometastatic disease. The underlying concept being that this minimal amount of disease is more amenable to definitive eradication as compared to macroscopic disease. The history of adjuvant therapy in breast cancer originated with the introduction of combination chemotherapy with CMF (cyclophosphamide, methotrexate, 5-fluorouracil) in the 1970s by the Milan group. Initially this was introduced for patients with node-positive disease. Subsequently its benefit was also demonstrated in unselected patients with breast cancer without nodal involvement.

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References

  1. Bonadonna G, Brusamolino E, Valagussa P, et al. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976;294:405–10.

    Article  CAS  PubMed  Google Scholar 

  2. Fisher B, Anderson S, Tan-Chiu E, Wolmark N, Wickerham DL, Fisher ER, Dimitrov NV, Atkins JN, Abramson N, Merajver S, Romond EH, Kardinal CG, Shibata HR, Margolese RG, Farrar WB. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001;19(4):931–42.

    Article  CAS  PubMed  Google Scholar 

  3. Early Breast Cancer Trialists’ Collaborative Group. Ovarian ablation in early breast cancer: overview of the randomised trials. Lancet. 1996;348:1189–96.

    Article  Google Scholar 

  4. Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet. 1998;351:1451–67.

    Article  Google Scholar 

  5. Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.

    Article  CAS  PubMed  Google Scholar 

  6. Sørlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98(19):10869–74.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Goldhirsch A, Ingle JN, Gelber RD, et al. Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2009. Ann Oncol. 2009;20:1319–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Coates AS, Winer E, Goldhirsch A, et al. Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol. 2015;26:1533–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Perez EA, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med. 2015;373(21):2005–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Piccart M, Rutgers E, Van’t Veer L, Slaets L, Delaloge S, Viale G et al; Primary analysis of the EORTC 10041/ BIG 3-04 MINDACT study: a prospective, randomized study evaluating the clinical utility of the 70-gene signature (MammaPrint) combined with common clinical-pathological criteria for selection of patients for adjuvant chemotherapy in breast cancer with 0 to 3 positive nodes. AACR 2016, # CT 039.

    Google Scholar 

  11. Sestak I, Cuzick J, Dowsett M, et al. Prediction of late distant recurrence after 5 years of endocrine treatment: a combined analysis of patients from the Austrian breast and colorectal cancer study group 8 and arimidex, tamoxifen alone or in combination randomized trials using the PAM50 risk of recurrence score. J Clin Oncol. 2015;33(8):916–22.

    Article  CAS  PubMed  Google Scholar 

  12. Davies C, Pan H, Godwin J, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381(9869):805–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Francis PA, Regan MM, Fleming GF, et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015;372(5):436–46.

    Article  PubMed  Google Scholar 

  14. Goss PE, Ingle JN, Pritchard KI, et al. Extending aromatase-inhibitor adjuvant therapy to 10 years. N Engl J Med. 2016;375:202.

    Article  Google Scholar 

  15. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  CAS  PubMed  Google Scholar 

  16. Weidner N, Folkman J, Pozza F, et al. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst. 1992;84:1875–87.

    Article  CAS  PubMed  Google Scholar 

  17. Holmgren L, O’Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med. 1995;1:149–55.

    Article  CAS  PubMed  Google Scholar 

  18. Dirix LY, Van Dam PA, Prove AM, Vermeulen PB. Bevacizumab in the treatment of patients with advanced breast cancer: where have we landed? Ther Adv Med Oncol. 2010;2(5):331–443.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Miles DW, Chan A, Dirix LY, et al. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010;28:3239–47.

    Article  CAS  PubMed  Google Scholar 

  20. Cameron D, Brown J, Dent R, et al. Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial. Lancet Oncol. 2013;14:933–42.

    Article  CAS  PubMed  Google Scholar 

  21. Miller K, O’Neill AM, Dang CT, et al. Bevacizumab (Bv) in the adjuvant treatment of HER2-negative breast cancer: final results from Eastern Cooperative Oncology Group E5103. J Clin Oncol. 2014;32:500.

    Google Scholar 

  22. Slamon DJ, Swain SM, Buyse M, et al. Primary results from BETH, a phase 3 controlled study of adjuvant chemotherapy and trastuzumab ± bevacizumab in patients with HER2-positive, node-positive or high risk node-negative breast cancer. Cancer Res. 2013;73:S01–3.

    Article  Google Scholar 

  23. Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31:3997–4013.

    Article  PubMed  Google Scholar 

  24. Slamon DJ, Leyland-Jones B, Shak S, 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.

    Article  CAS  PubMed  Google Scholar 

  25. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659–72.

    Article  CAS  PubMed  Google Scholar 

  26. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84.

    Article  CAS  PubMed  Google Scholar 

  27. Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365:1273–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gianni L, Dafni U, Gelber RD, et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol. 2011;12:236–44.

    Article  CAS  PubMed  Google Scholar 

  29. Perez EA, Romond EH, Suman VJ, et al. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011;29:3366–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Slamon DJ, Eiermann W, Robert NJ, et al. Ten year follow-up of BCIRG-006 comparing doxorubicin plus cyclophosphamide followed by docetaxel (AC→T) with doxorubicin plus cyclophosphamide followed by docetaxel and trastuzumab (AC→TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2+ early breast cancer. SABCS. 2016:(S5–04).

    Google Scholar 

  31. Perez EA, Suman VJ, Davidson NE, et al. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011;29(34):4491–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Baselga J, Bradbury I, Eidtmann H, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012;379:633–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Piccart-Gebhart M, Holmes E, Baselga J, et al. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III adjuvant lapatinib and/or trastuzumab treatment optimization trial. J Clin Oncol. 2015;34:1034–42.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Robidoux A, Tang G, Rastogi P, et al. Evaluation of lapatinib as a component of neoadjuvant therapy for HER2+ operable breast cancer: 5-year outcomes of NSABP protocol B-41. J Clin Oncol. 2016;34. (suppl; abstr 501).

    Google Scholar 

  35. Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, et al. for the Herceptin Adjuvant (HERA) Trial Study Team. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013;382(9897):1021–8.

    Article  CAS  PubMed  Google Scholar 

  36. Chan A, Delaloge S, Holmes FA, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17:367–77.

    Article  CAS  PubMed  Google Scholar 

  37. Burstein HJ, Sun Y, Dirix LY, et al. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer. J Clin Oncol. 2010;28:1301–7.

    Article  CAS  PubMed  Google Scholar 

  38. Joensuu H, Bono P, Kataja V, et al. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial. J Clin Oncol. 2009;27(34):5685–92.

    Article  CAS  PubMed  Google Scholar 

  39. Pivot X, Romieu G, Deblet M, et al. 6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial. Lancet Oncol. 2013;14(8):741–8.

    Article  CAS  PubMed  Google Scholar 

  40. Kramar A, Bachelot T, Madrange N, et al. Trastuzumab duration effects within patient prognostic subgroups in the PHARE trial. Ann Oncol. 2014;25:1563–70.

    Article  CAS  PubMed  Google Scholar 

  41. Mavroudis D, Saloustros E, Malamos N, et al. Six versus twelve months of adjuvant trastuzumab in combination with dose-dense chemotherapy for women with HER2-positive breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG). Ann Oncol. 2015;26:1333–40.

    CAS  PubMed  Google Scholar 

  42. O’Sullivan, Bradbury I, Campbell C, Spielmann M, et al. Efficacy of adjuvant trastuzumab for patients with human epidermal growth factor 2-positive early breast cancer and tumors < 2 cm: a meta-analysis of the randomized trastuzumab trials. J Clin Oncol. 2015;33:2600–8.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Gonzalez-Angulo AM, Litton JK, Broglio KR, et al. High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor-2 positive , node negative tumors 1 cm or smaller. J Clin Oncol. 2009;27:5700–6.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Joerger M, Thürlimann B, Huober J. Small HER2-positive, node-negative breast cancer: who should receive systemic adjuvant treatment ? Ann Oncol. 2011;22:17–31.

    Article  CAS  PubMed  Google Scholar 

  45. Tolaney SM, Barry WT, Dang CT, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. NEJM. 2015;372:134–41.

    Article  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Breast Unit-Medical Oncology, Sint-Augustinus Cancer Centre, Iridium Network, Antwerp, Belgium

    A. Prove

  2. Medical Oncology, EUSOMA Breast Unit, Sint-Augustinus, Oosterveldlaan 24, Wilrijk, Antwerp, Belgium

    L.-A. Teuwen & L. Dirix

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  1. A. Prove
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  2. L.-A. Teuwen
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  3. L. Dirix
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Editor information

Editors and Affiliations

  1. The Medical School Department of Oncology, University of Sheffield, Sheffield, United Kingdom

    Lynda Wyld

  2. Athens University Medical School, Athens, Greece

    Christos Markopoulos

  3. Helsinki University Hospital, Helsinki, Finland

    Marjut Leidenius

  4. Department of Oncology & Radiotherapy, Gdańsk Medical University Department of Oncology & Radiotherapy, Gdańsk, Poland

    Elżbieta Senkus-Konefka

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Prove, A., Teuwen, LA., Dirix, L. (2018). Adjuvant Molecular Therapies in Breast Cancer. In: Wyld, L., Markopoulos, C., Leidenius, M., Senkus-Konefka, E. (eds) Breast Cancer Management for Surgeons. Springer, Cham. https://doi.org/10.1007/978-3-319-56673-3_37

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  • DOI: https://doi.org/10.1007/978-3-319-56673-3_37

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  • Publisher Name: Springer, Cham

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  • Online ISBN: 978-3-319-56673-3

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