Adjuvant systemic therapy for HER2-positive breast cancer
- Harold Burstein, MD, PhD
Harold Burstein, MD, PhD
- Section Editor — Breast Cancer
- Associate Professor of Medicine
- Harvard Medical School
Globally, breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in females. In the United States, breast cancer is the most common female cancer, the second most common cause of cancer death in women, and the main cause of death in women ages 40 to 49 years. The lifetime probability of developing invasive breast cancer is one in eight.
Breast cancer is a heterogeneous, phenotypically diverse disease composed of several biologic subtypes that have distinct behavior. Amplification or overexpression of the human epidermal growth factor receptor 2 (HER2) oncogene is present in approximately 18 to 20 percent of primary invasive breast cancers. Women with early-stage breast cancer that meet criteria for HER2 positivity are treated with chemotherapy and trastuzumab as adjuvant treatment.
This topic review will cover the use of adjuvant trastuzumab plus chemotherapy in patients with HER2-positive early stage breast cancer (stage I to III (table 1)). Principles of testing for HER2 expression on breast cancer tumor tissue is discussed elsewhere, as is adjuvant chemotherapy in other populations.
- 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.
- 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.
- 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.
- Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 2011; 365:1273.
- Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 2006; 354:809.
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), Breast Cancer (version 1.2014). http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf (Accessed on January 28, 2014).
- Tolaney SM, Barry WT, Dang CT, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med 2015; 372:134.
- Curigliano G, Viale G, Bagnardi V, et al. Clinical relevance of HER2 overexpression/amplification in patients with small tumor size and node-negative breast cancer. J Clin Oncol 2009; 27:5693.
- 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.
- Chia S, Norris B, Speers C, et al. Human epidermal growth factor receptor 2 overexpression as a prognostic factor in a large tissue microarray series of node-negative breast cancers. J Clin Oncol 2008; 26:5697.
- Livi L, Meattini I, Saieva C, et al. Prognostic value of positive human epidermal growth factor receptor 2 status and negative hormone status in patients with T1a/T1b, lymph node-negative breast cancer. Cancer 2012; 118:3236.
- 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 2016; 34:1034.
- 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.
- Ismael G, Hegg R, Muehlbauer S, et al. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol 2012; 13:869.
- Pivot X, Gligorov J, Müller V, et al. Preference for subcutaneous or intravenous administration of trastuzumab in patients with HER2-positive early breast cancer (PrefHer): an open-label randomised study. Lancet Oncol 2013; 14:962.
- Moja L, Tagliabue L, Balduzzi S, et al. Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev 2012; :CD006243.
- Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol 2014; 32:3744.
- http://www.acccessdata.fda.gov/drugsatfda_docs/label/2015/103792s5327lbl.pdf (Accessed on May 10, 2015).
- 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; 27:5685.
- Pivot X, Romieu G, Debled 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; 14:741.
- Pivot X, Suter T, Nabholtz JM, et al. Cardiac toxicity events in the PHARE trial, an adjuvant trastuzumab randomised phase III study. Eur J Cancer 2015; 51:1660.
- Cameron D, Piccart-Gebhart MJ, Gelber RD. 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet 2017.
- 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.
- Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, et al. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet 2013; 382:1021.
- 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.
- 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 2015; S5-04.
- Goss PE, Smith IE, O'Shaughnessy J, et al. Adjuvant lapatinib for women with early-stage HER2-positive breast cancer: a randomised, controlled, phase 3 trial. Lancet Oncol 2013; 14:88.
- Bowles EJ, Wellman R, Feigelson HS, et al. Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J Natl Cancer Inst 2012; 104:1293.
- Perez EA, Suman VJ, Davidson NE, et al. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol 2011; 29:4491.
- Smith I, Procter M, Gelber RD, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007; 369:29.
- Martín M, Esteva FJ, Alba E, et al. Minimizing cardiotoxicity while optimizing treatment efficacy with trastuzumab: review and expert recommendations. Oncologist 2009; 14:1.
- PATIENT ELIGIBILITY
- Indications for small HER2-positive tumors
- HER2-DIRECTED AGENTS
- TREATMENT OVERVIEW
- TRASTUZUMAB-BASED THERAPY
- Prescribing information
- Treatment duration
- Choice of chemotherapy
- - Anthracycline-based therapy
- - Nonanthracycline-based therapy
- - Preferred regimen for small HER2-positive tumors
- SPECIAL POPULATIONS
- Male breast cancer
- Breast cancer in pregnancy
- Patients with cardiac risk factors
- Patients who were treated with neoadjuvant therapy
- ASSESSING RISKS AND BENEFITS OF TREATMENT
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS