Effect of estrogen receptor beta expression (ERße) in triple-negative breast cancer (TNBC) patients treated in the neoadjuvant GeparTrio trial.

Abstract

1069 Background: TNBC is defined as tumor that lack expression of estrogen receptor (ER), progesterone receptor (PgR) and HER2. Pts with TNBC have a relatively poor prognosis but usually respond well to chemotherapy-the only systemic treatment option- but those who achieve a pathological complete response (pCR) have an excellent prognosis. Numerous efforts have been undertaken to further characterize this group. ER-α is assessed routinely in pathological work-up. Another subtype of ER, ER beta has been described, but conflicting results have been published. We investigated the impact of ERße in neoadjuvant treated TNBC pts. Methods: Tissue microarrays from core biopsies of 93 TNBC pts recruited to the phase III GeparTrio trial, receiving 6-8 cycles neoadjuvant TAC/NX chemotherapy, were centrally stained immunohistochemically for ER-α, ER-beta (clone 14C8), PgR and HER2. ERße was assessed using the immunoreactive score: low (IRS: 0-4) or high (IRS>4). Pts received no neoadjuvant tamoxifen. Results: Nuclear and cytoplasmic ERße was high in 54.8% and 5.4%, respectively, but neither cytoplasmic nor nuclear ERße was found to be correlated with tumor size, nodal status, grading or histology. Due to low cytoplasmic expression, further analyses were restricted to nuclear expression. pCR rate was 34% in the TNBC group with 27% in the ERße high and 40% in the ERße low group (p=0.2). After a median follow-up of 56 months, 23 pts (24.7%) had relapsed (14/93 pts (15.0%) with low and 9/93 (9.6%) with high ERße) and 14 pts (15.1%) have died (6/93 pts (6.5%) with low and 8/93 (8.6%) with high ERße). 5 year overall- and progression-free survival rates were not significantly different between patients with low and high nuclear ERße, 85.8 months vs 83.6 months (p=0.78) and 65.6 months vs 77.3 months, (p=0.12), respectively. Conclusions: An apparently high proportion of pts with TNBC showed high nuclear ERße. Impact of nuclear ERße on pCR rates and survival rates was not distinctive in TNBC pts, thus prognostic relevance of ERße seems to be minimal in TNBC at most. Tamoxifen might alter the prognosis of TNBC pts whose tumors express ER beta.