Patterns of biomarker expression in patients treated with primary endocrine therapy – a unique insight using core needle biopsy tissue microarray

Abstract

Purpose: Prediction of response to primary endocrine therapy (PET) in older women is based on measurement of oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor (HER)-2. This study uses a unique method for construction of core needle biopsy (CNB) tissue microarray (TMA), to correlate expression of a panel of 17 biomarkers with clinical outcome, in patients receiving PET. Methods: Over 37 years (1973–2010), 1758 older (≥ 70 years) women with operable primary breast cancer were managed in a single institution. Of these, 693 had sufficient good-quality CNB to construct TMA, of which 334 had ER-positive tumours treated by PET with a minimum of 6-month follow-up. A panel of biomarkers was measured by immunohistochemistry (ER, PgR, HER2, Ki-67, p53, CK5/6, CK 7/8, EGFR, BCL-2, MUC1, VEGF, LKB1, BRCA1, HER3, HER4, PTEN and AIB1). Expression of each biomarker was dichotomised into ‘low’ or ‘high’ based on breast cancer-specific survival (BCSS). Results: From the panel of biomarkers, multivariate analysis showed:High ER (p = 0.003) and PgR (p = 0.002) were associated with clinical benefit of PET at 6 months, as opposed to progressive disease.High ER (p = 0.0023), PgR (p < 0.001) and BCL-2 (p = 0.043) and low LKB1 (p = 0.022) were associated with longer time to progression.High PgR (p < 0.001) and low MUC1 (p = 0.021) were associated with better BCSS. Expression of other biomarkers did not show any significant correlation. Conclusions: In addition to ER and PgR; MUC1, BCL-2 and LKB1 are important in determining the outcome of PET in this cohort.