J Clin Oncol 2014 Oct 2;32(29):3307-29. Epub 2014 Sep 2.
Ann H. Partridge, Dana-Farber Cancer Institute; Steven E. Come, Beth Israel Deaconess Medical Center; Beverly Moy, Massachusetts General Hospital, Boston, MA; R. Bryan Rumble, American Society of Clinical Oncology, Alexandria; Michael A. Danso, Virginia Oncology Associates, Norfolk, VA; Lisa A. Carey, University of North Carolina, Chapel Hill, NC; Nancy E. Davidson, University of Pittsburgh Cancer Institute/University of Pittsburgh Medical Center, Pittsburgh, PA; Angelo Di Leo, Sandro Pitigliani Medical Oncology Unit, Prato, Italy; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Gabriel N. Hortobagyi, The University of Texas MD Anderson Cancer Center, Houston, TX; Douglas Yee, University of Minnesota/Masonic Cancer Center, Minneapolis, MN; Shelley B. Brundage, Patient Representative, Washington, DC; Maggie Wilcox, Independent Cancer Patients' Voice; and Ian E. Smith, Royal Marsden Hospital, London, United Kingdom.
Purpose: To identify optimal chemo- and targeted therapy for women with human epidermal growth factor 2 (HER2)- negative (or unknown) advanced breast cancer.
Methods: A systematic review of randomized evidence (including systematic reviews and meta-analyses) from 1993 through to current was completed. Outcomes of interest included survival, progression-free survival, response, quality of life, and adverse effects. Guideline recommendations were evidence based and were agreed on by the Expert Panel via consensus.
Results: Seventy-nine studies met the inclusion criteria, comprising 20 systematic reviews and/or meta-analyses, 30 trials on first-line treatment, and 29 trials on second-line and subsequent treatment. These trials form the evidence base for the guideline recommendations.
Recommendations: Endocrine therapy is preferable to chemotherapy as first-line treatment for patients with estrogen receptor-positive metastatic breast cancer unless improvement is medically necessary (eg, immediately life-threatening disease). Single agent is preferable to combination chemotherapy, and longer planned duration improves outcome but must be balanced against toxicity. There is no single optimal first-line or subsequent line chemotherapy, and choice of treatment will be determined by multiple factors including prior therapy, toxicity, performance status, comorbid conditions, and patient preference. The role of bevacizumab remains controversial. Other targeted therapies have not so far been shown to enhance chemotherapy outcome in HER2-negative breast cancer.