Estrogen receptor (ER) and progesterone receptor (PgR), by ligand-binding assay compared with ER, PgR and pS2, by immuno-histochemistry in predictingresponse to tamoxifen in metastatic breast cancer: A Southwest Oncology Group Study

Results of estrogen receptor (ER) and progesterone receptor (PgR) ligand-bi nding assays (LBAs) are strongly correlated with ER and PgR by immuno-histo chemistry (IHC). To investigate whether ER and PgR by IHC are also strongly correlated with tamoxifen response, time to treatment failure (TTF) and ov erall survival (OS), the results of the 2 methods were directly compared in 205 patients with ER+ metastatic breast cancer treated with daily tamoxife n (Southwest Oncology Group protocol 8228) with 9 years median follow-up. p S2, another estrogen-regulated molecule, was also analyzed. Tumors were sco red for IHC from 0 to 5, according to the proportion of positively stained cells. These IHC scores for both ER and PgR were significantly associated w ith LBA levels (p < 0.001). There was a significant direct relationship bet ween higher IHC ER, PgR and pS2 and increasing response to tamoxifen, TTF a nd OS were also significantly longer for patients with higher ER or PgR, bu t not pS2, IHC scores. Low, intermediate and high ER or PgR categories show ed similar differences in response rates whether defined by LBA or IHC, In logistic regression models which included ER, PgR and pS2 by IHC; ER and Pg R by LBA; and menopausal status, only ER (IHC) and pS2 (IHC) retained signi ficance for predicting tamoxifen response (p = 0.02 and p = 0.005, respecti vely), along with menopausal status (for PgR by IHC, p = 0.09). Increasing ER and PgR by IHC, as by LBA, are thus significantly associated with a prog ressively better response and longer survival in ER+ metastatic breast canc er. pS2 is also predictive in this setting. (C) 2000 Wiley-Liss. Inc.