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Response to neo-adjuvant exemestane in post-menopausal breast cancer patients: correlation with biological factors measured by real-time quantitative RT-PCR (QRT-PCR).

538 Background: The effects of aromatase inhibitors on tumor biological factors in the neo-adjuvant setting are still not well documented and predictive factors of response are needed in addition to hormone receptor status.


METHODS
41 postmenopausal women with estrogen and/or progesterone receptor (ER, PR) positive operable breast cancer received neoadjuvant exemestane 25 mg once daily, during 16 weeks. Frozen and formalin-fixed tumor tissues were collected before treatment and at surgery for pathological and biological markers measured by immunohistochemistry (IHC) and QRT-PCR. We analyzed ERα, PgR, Ki67, HER2 at the protein and mRNA level (IHC and QRT-PCR) and ERβ, aromatase and COX-2 (QRT-PCR).


RESULTS
QRT-PCR was performed on pre-treatment biopsies in 31 cases. The median quantity of total RNA was 4,5 μg (range: 0.3-22,7). For each target gene, median and range mRNA values relative to the TBP reference gene were : ERα : 306 (48-893) ; ERβ: 34.6 (3.5-278.5) ; PgR: 263 (2-2738) ; Ki67: 18.5 (3.3-66.5) ; HER2: 532.5 (2-10467); Aromatase: 515.5 (55-3608); COX-2: 5.1 (1-59.2). There was a statistically significant positive correlation between IHC and QRT-PCR measurements of PgR, Ki-67 and HER2 (r=0.81 p<0.0001; r=0.56 p=0.001; r=0.53 p=0.002). Aromatase mRNA expression was positively correlated with COX-2 (0.51 p=0.001) and ERβ mRNA (0.39 p=0.02). A clinical response was observed in 31 patients (75.6%) ; a pathological response (Sataloff score>50%) in 6 patients (17.6%). No significant relation was found between any initial biological factor and clinical or histological response. Exemestane treatment was associated with no change in ERα expression and a significant reduction in PgR and Ki-67 expression (IHC and QRT-PCR).


CONCLUSIONS
Quantitative assessment of gene expression at the mRNA level is feasible and reproducible on small biopsies by QRT-PCR. So far, no correlation was found between pre-treatment biological factors and response; post-treatment QRT-PCR measurements will be compared to pre-treatment data and response. No significant financial relationships to disclose.