Progesterone receptor levels are associated with time to aromatase inhibitor treatment failure in estrogen receptor-positive advanced breast cancer.
Authors: Anderson H , Hills M , A'Hern R , Smith IE , Dowsett M 
Published: December 2010

Abstract
Abstract #6051
Background: Aromatase inhibitors (AIs) play a key role in the endocrine treatment of hormone receptor-positive breast cancer, yet surprisingly little information is available on the effectiveness of AIs in advanced breast cancer according to quantitative levels of ER and PgR or HER-2 status. In this work, we assess expression of these three biomarkers in primary breast tumours of women who subsequently received an AI for advanced disease. This extends an earlier study [1], improving the statistical power and excluding patients who received neo-adjuvant therapy.&#x2028; Methods: Tissue microarrays were constructed from 177 archival FFPE primary or locally recurrent breast tumours from women, diagnosed between 1963 and 2003, who received no neo-adjuvant therapy prior to surgery and were treated with 3rd generation AI treatment for advanced disease (anastrozole n = 92; letrozole n = 82; exemestane n = 3). ER, PgR and HER-2 protein levels were assessed by IHC with FISH performed if HER-2 staining was equivocal. The study endpoint of time to AI treatment failure (TTF) was defined as time from commencement of AI treatment to progression of disease or cessation of treatment due to toxicity or death. Disease-free interval (DFI) was defined as time from date of diagnosis to date of first relapse.&#x2028; Results: 146/177 patients were assessed as ER+ by IHC. When both ER+ and ER- patients were considered, higher ER and PgR levels were associated with increased TTF (HR: 0.90; 95% CI: 0.83-0.98; p = 0.011 and HR: 0.86; 95% CI: 0.80-0.93; p &lt; 0.001 respectively) whereas HER-2 positivity was associated with decreased TTF (HR: 1.61; 95% CI: 1.01-2.59; p = 0.048). Longer DFI was also associated with increased TTF (HR: 0.79; 95% CI: 0.65-0.97; p = 0.022) with both PgR level and DFI remaining significant in multivariate analysis. When ER+ patients only were considered, higher PgR levels maintained an association with increased TTF (HR: 0.88; 95% CI: 0.81-0.97; p = 0.007) with this relationship appearing to be even stronger amongst the population considered PgR+ (HR: 0.73; 95% CI: 0.54-0.98; p = 0.037). No significant relationship was observed between ER levels and TTF in the ER+ subgroup. ER+HER-2+ patients (n = 13) showed a trend for decreased TTF compared to ER+HER-2- patients (n = 131), but this was not significant in this small subset of patients (HR: 1.34; 95% CI: 0.75-2.38; p = 0.32).&#x2028; Conclusions: Higher PgR level is significantly associated with increased TTF in ER+ patients receiving AI treatment for advanced disease, especially within the ER+PgR+ subgroup. ER+HER-2+ patients may show decreased TTF on AI treatment compared to ER+HER-2- patients. Larger prospective studies are required to confirm these data. These observations highlight the importance of PgR as a predictor of TTF even in advanced breast cancer patients.&#x2028; Supported by the Mary-Jean Mitchell Green Foundation.&#x2028; [1] Anderson H. et al., J Steroid Biochem Mol Biol 106 (2007) 49-54.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6051.