Abstract P5-03-11: Possible role for cancer stem cells: results from a pilot neoadjuvant trial of HER-2 positive breast cancer patients treated with a combination of (Nab)-paclitaxel and lapatinib.

Abstract

Abstract Background: Lapatinib, a dual kinase inhibitor against both epidermal growth factor (EGFR) and human epidermal factor 2 (HER-2) and nanoparticle albumin bound (nab) paclitaxel was recently used by our group in a pilot study of early stage HER-2 positive breast cancer. We reported that the combination was well tolerated and showed good efficiency in this patient group. Cancer stem cells were recently identified in solid tumors including breast carcinomas. These tumor initiating stem cells are reported to be increased in HER-2 positive breast cancers. Lapatininb is postulated to reduce the percentage of breast cancer stem cells following HER-2 inhibition. This study aimed to investigate such an effect in this patient population of early stage HER-2 positive breast cancer cases uniquely treated by a combination of nab-paclitaxel and lapatininb. Design: 30 patients with stage I-III HER-2 positive breast cancer were treated in a neoadjuvant setting with lapatinib 1,000mg/day and nab-paclitaxel 260 mg/m2 every 2 weeks for 4 cycles. The expression of the stem cell markers aldehyde dehydroganase (ALDH1) (BD), CD24 and CD44 (both Santa Cruz Biotechnology) was assessed immunohistochemically in breast cancer specimens prior to treatment and at the time of definitive surgery. Staining was considered negative if < or = 1%, and positive if >1%. Results: Of the 30 patients, 28 underwent surgery and were evaluated for pathologic response. Complete pathologic response (pCR) was observed in 5/28 (17.9%) of the patients. Of the 17 patients for whom pre-treatment material was available 13 (76.5%) were positive for ALDH1 expression and 4 (23.5%) were negative. Of the 22 patients with material available for testing at the time of surgery, 5 showed pCR, 3 were negative and 14 (63.6%) were positive for ALDH-A1 expression. The CD44+/CD24- phenotype was variable and showed no difference between groups. Conclusions: 1. Combination of lapatinib and nab-paclitaxel resulted in a complete pathologic response in almost 1/5 of the HER-2 positive early stage breast cancer patients. 2. Overall, there is a reduction in the number cancer stem cells following neoadjuvant treatment with lapatinib and nab-paclitaxel. Our results support the hypothesis that lapatinib may have an effect in manipulating the numbers of cancer stem cells in patients with HER-2 positive breast cancer. Additional studies are currently under way to further characterize these findings. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-03-11.