Abstract
Abstract Background: In patients with HER-2 over-expressing breast cancer, predictors of trastuzumab response and resistance remain unclear and unvalidated. In an exploratory analysis within a phase II trial, we evaluated various biologic markers as predictors of response or resistance to a trastuzumab containing neoadjuvant chemotherapy regimen. Methods: A tissue microarray (TMA) was constructed from formalin-fixed paraffin-embedded tumor tissue samples obtained prior to neoadjuvant chemotherapy in 21 (from a total of 30) HER-2 positive stage II-III patients. Protocol treatment consisted of 4 cycles of 5-Fluorouracil, Epirubicin and Cyclophosphamide (FEC100) followed by 4 cycles of Docetaxel, Carboplatin (AUC 6) and Trastuzumab (TCH). Immunohistochemical (IHC) analyses of estrogen receptor (ER), progesterone receptor (PR), HER-2, Ki67, EGFR and PTEN were performed utilizing previously published protocols and cut-offs. HER-2 equivocal (2+) by IHC cases was confirmed by prior FISH analysis. Fisher's exact test was used for statistical analysis. Results: 21 patients had sufficient tumour for analysis. Median age at diagnosis was 49 years old, 67% were pre-menopausal, and biomarker expression was as follows: 43% ER positive, 29% PR positive, and 100% HER-2 positive. 14 patients (67%) had pathologic complete response (pCR) following the completion of neoadjuvant chemotherapy and trastuzumab. In general, tumour samples showed high Ki67 (>14%) staining (62%), low EGFR positivity (14%), and high PTEN expression (71%). Neither high Ki67 expression (p=0.65), any EGFR expression (p=0.26), nor PTEN loss (p=0.60) was associated with higher or lower rates of pCR respectively. Conclusion: In our small cohort of locally advanced HER-2 over-expressing tumours, baseline expression of Ki67, EGFR and PTEN were not associated with pCR to a neoadjuvant sequential anthracycline and taxane/trastuzumab combination regimen. Additional biomarkers for an activated PI3K pathway and for p95 will be attempted. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-25.
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