Trastuzumab plus Paclitaxel or Docetaxel in HER‐2–Negative/HER‐2 ECD–Positive Anthracycline‐ and Taxane‐Refractory Advanced Breast Cancer

Trastuzumab is considered effective against human epidermal growth factor receptor (HER)‐2–positive breast cancer as assessed by immunohistochemistry (IHC) and fluorescence or chromogenic in situ hybridization (FISH/CISH) on biopsy material. Trastuzumab is now approved in both the adjuvant and metastatic settings for this patient population. Because HER‐2 extracellular domain (ECD) levels have been correlated with disease progression in the metastatic setting, we considered trastuzumab salvage therapy plus a taxane in heavily pretreated trastuzumab‐naive relapsed breast cancer patients with high serum levels of HER‐2 ECD (≥15 ng/ml). All patients had previously failed at least two lines of anthracycline‐ and taxane‐based regimens and were HER‐2 negative by IHC and FISH/CISH prior to a centralized reanalysis, and were serum positive for HER‐2 ECD (≥15 ng/ml) at baseline. Regular serum accounts of HER‐2 ECD were recorded and compared with response and survival outcomes. Twenty‐two patients were finally eligible for salvage therapy. Minor responses were observed in five (23%) and stable disease (SD) was observed in 11 patients, leading to a clinical benefit rate of 73% (16 of 22 patients). The median time to progression and overall survival time were 5 (6.5 months in minor responders and SD) and 12 months, respectively; 11 and eight patients remained progression free for >6 and >12 months, respectively. Eleven and seven patients were alive at 12 and 15 months, respectively, after treatment start. Furthermore, in total, 13 (59.1%) patients obtained a biochemical response. In our study, patients with conventionally HER‐2–negative disease but with expression of HER‐2 ECD above the normal limit (≥15 ng/ml) displayed a rapid response, both biochemically and clinically, to the trastuzumab–taxane combination. This is the first study assessing anti‐HER‐2–based treatment in HER‐2–negative advanced breast cancer according to HER‐2 ECD positivity; if our results are confirmed, additional patients with “hidden” HER‐2–positive breast cancer might benefit from anti‐HER‐2 treatment. This study considers trastuzumab salvage therapy plus a taxane in heavily pretreated trastuzumab‐naive relapsed breast cancer patients with high serum levels of HER‐2 extracellular domain (ECD). This is the first study assessing anti‐HER‐2–based treatment in HER‐2–negative advanced breast cancer patients according to HER‐2 ECD positivity.