Estrogen receptor (ER) and progesterone receptor (PgR), by ligand-binding assay compared with ER, PgR and pS2, by immuno-histochemistry in predicting response to tamoxifen in metastatic breast cancer: a Southwest Oncology Group Study.
Results of estrogen receptor (ER) and progesterone receptor (PgR) ligand-binding assays (LBAs) are strongly correlated with ER and PgR by immuno-histochemistry (IHC). To investigate whether ER and PgR by IHC are also strongly correlated with tamoxifen response, time to treatment failure (TTF) and overall survival (OS), the results of the 2 methods were directly compared in 205 patients with ER(+) metastatic breast cancer treated with daily tamoxifen (Southwest Oncology Group protocol 8228) with 9 years median follow-up. pS2, another estrogen-regulated molecule, was also analyzed. Tumors were scored 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 with LBA levels (p < 0.001). There was a significant direct relationship between higher IHC ER, PgR and pS2 and increasing response to tamoxifen. TTF and OS were also significantly longer for patients with higher ER or PgR, but not pS2, IHC scores. Low, intermediate and high ER or PgR categories showed 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 PgR by LBA; and menopausal status, only ER (IHC) and pS2 (IHC) retained significance for predicting tamoxifen response (p = 0. 02 and p = 0.005, respectively), 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 progressively better response and longer survival in ER(+) metastatic breast cancer. pS2 is also predictive in this setting.
Elledge
R M
RM
Baylor College of Medicine, Houston, TX, USA. relledge@bcm.tmc.edu
Green
S
S
Pugh
R
R
Allred
D C
DC
Clark
G M
GM
Hill
J
J
Ravdin
P
P
Martino
S
S
Osborne
C K
CK
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001667:Binding, Competitive; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D016015:Logistic Models; D011237:Predictive Value of Tests; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D015206:Southwestern United States; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D020847:Estrogen Receptor Modulators; D008024:Ligands; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen