BACKGROUND: Estrogen receptor (ER) expression predicts tamoxifen response, which halves the risk of breast cancer recurrence. We examined clinical factors associated with concordance between ER expression at diagnosis and centralized re-assay, and the association of concordance with breast cancer recurrence. MATERIAL AND METHODS: We used immunohistochemistry to assess ER expression on archived fixed, paraffin-embedded breast carcinoma tissue excised from women aged 35-69 years, diagnosed 1985-2001 in Jutland, Denmark. We calculated the percentage agreement, positive predictive value (PPV) and negative predictive value (NPV) of ER status at diagnosis and re-assay. We used logistic regression to investigate factors associated with concordance, and its association with recurrence (odds ratios (OR) and associated 95% confidence intervals (95%CI)). RESULTS: ER was re-assayed in 91% of patients (n = 1530). Concordance was better in ER + than ER- tumors (PPV = 94% vs. NPV = 75%). Factors associated with concordance included menopausal status, tumor size, surgical procedure, diagnostic period, lymph node status and time to recurrence. ER + women at diagnosis who re-assayed ER + were less likely to have recurrent disease (OR = 0.49, 95% CI = 0.28, 0.86) than those who re-assayed ER-. In originally ER- women, concordance was not associated with recurrence (OR = 0.97, 95% CI = 0.66, 1.42). CONCLUSIONS: Several clinical factors were associated with ER assay concordance. Some women were ineffectively treated with tamoxifen, or required but did not receive tamoxifen. We observed almost exactly the protective effect of endocrine therapy among tamoxifen-treated ER + women whose tumors expressed the ER on re-assay, compared with those ER- on re-assay. Diagnostic pathology results for ER + tumors appear a valid and useful resource for research studies. However, those for ER- tumors have lower validity. Study-specific considerations regarding the aims, diagnostic period, and consequences of including ER- patients with truly ER + disease ought to be examined when using diagnostic pathology results for ER- tumors in research studies.
BACKGROUND:Estrogen receptor (ER) expression predicts tamoxifen response, which halves the risk of breast cancer recurrence. We examined clinical factors associated with concordance between ER expression at diagnosis and centralized re-assay, and the association of concordance with breast cancer recurrence. MATERIAL AND METHODS: We used immunohistochemistry to assess ER expression on archived fixed, paraffin-embedded breast carcinoma tissue excised from women aged 35-69 years, diagnosed 1985-2001 in Jutland, Denmark. We calculated the percentage agreement, positive predictive value (PPV) and negative predictive value (NPV) of ER status at diagnosis and re-assay. We used logistic regression to investigate factors associated with concordance, and its association with recurrence (odds ratios (OR) and associated 95% confidence intervals (95%CI)). RESULTS:ER was re-assayed in 91% of patients (n = 1530). Concordance was better in ER + than ER- tumors (PPV = 94% vs. NPV = 75%). Factors associated with concordance included menopausal status, tumor size, surgical procedure, diagnostic period, lymph node status and time to recurrence. ER + women at diagnosis who re-assayed ER + were less likely to have recurrent disease (OR = 0.49, 95% CI = 0.28, 0.86) than those who re-assayed ER-. In originally ER- women, concordance was not associated with recurrence (OR = 0.97, 95% CI = 0.66, 1.42). CONCLUSIONS: Several clinical factors were associated with ER assay concordance. Some women were ineffectively treated with tamoxifen, or required but did not receive tamoxifen. We observed almost exactly the protective effect of endocrine therapy among tamoxifen-treated ER + women whose tumors expressed the ER on re-assay, compared with those ER- on re-assay. Diagnostic pathology results for ER + tumors appear a valid and useful resource for research studies. However, those for ER- tumors have lower validity. Study-specific considerations regarding the aims, diagnostic period, and consequences of including ER- patients with truly ER + disease ought to be examined when using diagnostic pathology results for ER- tumors in research studies.
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