Background. Human epidermal growth factor receptor 2 (HER2) positive breast cancer is an entity with aggressive behaviour. One year of adjuvant trastuzumab significantly improves the disease free survival in the range of 40-50% and reduces the risk of dying from HER2 positive breast cancer by one third. Adjuvant treatment with trastuzumab became available in Slovenia in 2005 and the aim of this study is to explore, if the exceptional results reported in adjuvant clinical trials are achieved also in daily clinical practice.
Patients and methods. An analysis of tumour and patient characteristics, type of treatment and outcome (relapse free and overall survival) of 313 patients (median age 52 years) treated at the Institute of Oncology Ljubljana in years 2005-2009 was performed.
Results. Median follow-up was 4.4 years. Sixty-one patients relapsed and 24 died. Three and four years relapse free survival was 84.2% and 80.8% and the overall survival was 94.4% and 92.5%, respectively. Independent prognostic factors for relapse were tumour grade (HR 2.10; 95% CI 1.07-4.14; p = 0.031) and nodal stage (HR 1.35; 1.16-1.56; p < 0.0001) and for the overall survival nodal stage only (HR 1.36; 1.05-1.78; p = 0.021).
Conclusions. The outcome in patients with adjuvant trastuzumab in daily clinical practice, treated by medical oncologists, is comparable to results obtained in international adjuvant studies.
1. Schillani G, Era D, Cristante T, Mustacchi G, Richiardi M, Grassi L, et al. 5-HTTLPR polymorphism and anxious preoccupation in early breast cancer patients. Radiol Oncol 2012; 46: 321-7.
2. Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med 2009; 360: 790-800.
3. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989; 244: 707-12.
4. Tuzi A, Lombardi D, Crivellari D, Militello L, Perin T, La Grassa M, Massarut S, Veronesi A. Epirubicin and docetaxel as neoadjuvant treatment of hormone receptor positive, HER-2 negative breast cancer: findings from two successive phase II studies. Radiol Oncol 2013; 47: 57-62.
5. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235: 177-82.
6. 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.
7. Smith IE. Efficacy and safety of Herceptin in women with metastatic breast cancer: results from pivotal clinical studies. Anticancer Drugs 2001; 12(Suppl 4): S3-10.
8. Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol 2005; 23: 4265-74.
9. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005; 353: 1659-72.
10. Slamon D, Eiermann W, Robert N. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (ACT) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (ACTH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2 positive early breast cancer patients: BCIRG 006 study. [Abstract]. Breast Cancer Res Treat 2005; 94(Suppl 1): A-1.
11. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005; 353: 1673-84.
12. Gianni L, Dafni U, Gelber RD, Azambuja E, Muehlbauer S, Goldhirsch A, 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.
13. Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 2011; 365: 1273-83.
14. Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, 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.
15. Matos E, Čufer T. Adjuvant treatment of breast cancer patients with trastuzumab. Radiol Oncol 2007; 3: 115-22.
16. Ulhoa-Cintra A, Greenberg L, Geyer CE. The emerging role of lapatinib in HER2-positive breast cancer. Curr Oncol Rep 2008; 10: 10-7.
17. Blumenthal GM, Scher NS, Cortazar P, Chattopadhyay S, Tang S, Song P, et al. First FDA approval of dual anti-HER2 regimen: pertuzumab in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer. Clin Cancer Res 2013; 19: 1-6.
18. Ballantyne A, Dhillon S. Trastuzumab emtansine: first global approval. Drugs 2013; 73: 755-65.
19. Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 2013; 24: 2206-23.
20. Cancer in Slovenia 2009. Ljubljana: Institute of Oncology Ljubljana, Epidemiology and Cancer Registry, Cancer Registry of Republic of Slovenia; 2013.
21. Tjan-Heijnen VCG, Seferina SC, Lobbezoo DJA, Voogd AC, Dercksen MW, van den Berkmortel F, et al. Real-world use and effectiveness of adjuvant trastuzumab in 2665 consecutive breast cancer patients. [Abstract]. Cancer Res 2012; 72(24 Suppl): Nr P5-21-04.
22. Nahta R, O’Regan RM. Therapeutic implications of estrogen receptor signaling in HER2-positive breast cancers. Breast Cancer Res Treat 2012; 135: 39-48.
23. Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM, et al. 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.
24. Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, 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: 5685-92.
25. Pivot X, Romieu G, Bonnefoi H, Pierga J-Y, Kerbrat P, Guastalla J-P, et al. PHARE Trial results of subset analysis comparing 6 to 12 months of trastuzumab in adjuvant early breast cancer. [Abstract]. Cancer Res 2012; 72(24 Suppl): Nr S5-3.
26. Guarneri V, Frassoldati A, Bruzzi P, D’Amico R, Belfiglio M, Molino A, et al. Multicentric, randomized phase III trial of two different adjuvant chemotherapy regimens plus three versus twelve months of trastuzumab in patients with HER2- positive breast cancer (Short-HER Trial; NCT00629278). Clin Breast Cancer 2008; 8: 453-6.