A new phase 2 clinical trial is one of the first to investigate the use of hormonal therapy without chemotherapy as a neoadjuvant strategy for patients with HER2-positive breast cancer (Rimawi MF, et al. J Clin Oncol. 2013;31:1726-1731). Of patients with overexpressed HER2, 50% are also estrogen receptor (ER)-positive. The HER2 receptor is an ideal target for monoclonal antibody therapy. Trastuzumab is an effective inhibitor of HER2 but is a weak inhibitor of HER2 heterodimers with HER1 and HER3, which lead to the downstream inhibition of the PI3K/PTEN pathway. Lapatinib is a dual kinase inhibitor of HER1 and HER2 and therefore inhibits the HER receptors more completely than trastuzumab alone.
This study included 66 patients with stage II or III HER2-positive breast cancer who were stratified by ER status. All patients received oral lapatinib 1000 mg daily and trastuzumab in a 4-mg/kg loading dose, followed by 2 mg/kg weekly for 12 weeks. In addition, all ER-positive patients received oral letrozole 2.5 mg daily (with a luteinizing hormone–releasing hormone antagonist for premenopausal status).
The overall pathologic response rate was 49%, with 54% in the ER-positive group and 40% in the ER-negative group. The overall complete pathologic response rate was 22%. Overall, 89% of the patients proceeded to surgery. The treatment was generally well tolerated, with only 6% of patients discontinuing therapy. The most common adverse effects were diarrhea, rash, fatigue, nausea, and elevated liver function tests.
These results show that a nonchemotherapy neoadjuvant targeted hormonal therapy can produce complete remission in a relatively high number of patients with large primary breast cancer tumors. The study shows a high pathologic response to targeted hormonal therapy without systemic chemotherapy, indicating that some patients may be spared the cost and the toxicity of chemotherapy.
