Τίτλος:
Estrogen receptor and progesterone receptor as predictive biomarkers of response to endocrine therapy: A prospectively powered pathology study in the tamoxifen and exemestane adjuvant multinational trial
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Purpose The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial included a prospectively planned pathology substudy testing the predictive value of progesterone receptor (PgR) expression for outcome of estrogen receptor-positive (ER-positive) early breast cancer treated with exemestane versus tamoxifen. Patients and Methods Pathology blocks from 4,781 TEAM patients randomly assigned to exemestane versus tamoxifen followed by exemestane for 5 years of total therapy were collected centrally, and tissue microarrays were constructed from samples from 4,598 patients. Quantitative analysis of hormone receptors (ER and PgR) was performed by using image analysis and immunohistochemistry, and the results were linked to outcome data from the main TEAM trial and analyzed relative to disease-free survival and treatment. Results Of 4,325 eligible ER-positive patients, 23% were PgR-poor (Allred < 4) and 77% were PgRrich (Allred ≥ 5). No treatment-by-marker effect for PgR was observed for exemestane versus tamoxifen (PgR-rich hazard ratio [HR], 0.83; 95% CI, 0.65 to 1.05; PgR-poor HR, 0.85; 95% CI, 0.61 to 1.19; P=.88 for interaction). Both PgR and ER expression were associated with patient prognosis in univariate (PgR HR, 0.53; 95% CI, 0.43 to 0.65; P < 01; ER HR, 0.66; 95% CI, 0.51 to 0.86; P=.002), and multivariate analyses (P < .001 and P=.001, respectively). A trend toward a treatment-by-marker effect for ER-rich patients was observed. Conclusion Preferential exemestane versus tamoxifen treatment benefit was not predicted by PgR expression; conversely, patients with ER-rich tumors may derive additional benefit from exemestane. Quantitative analysis of ER and PgR expression provides highly significant information on risk of early relapse (within 1 to 3 years) during treatment. © 2011 by American Society of Clinical Oncology.
Συγγραφείς:
Bartlett, J.M.S.
Brookes, C.L.
Robson, T.
Van De Velde, C.J.H.
Billingham, L.J.
Campbell, F.M.
Grant, M.
Hasenburg, A.
Hille, E.T.M.
Kay, C.
Kieback, D.G.
Putter, H.
Markopoulos, C.
Kranenbarg, E.M.-K.
Mallon, E.A.
Dirix, L.
Seynaeve, C.
Rea, D.
Περιοδικό:
Journal of Clinical Oncology
Λέξεις-κλειδιά:
estrogen receptor; exemestane; progesterone receptor; tamoxifen, adult; article; breast cancer; cancer risk; controlled study; disease free survival; drug efficacy; female; hormonal therapy; human; image analysis; immunohistochemistry; major clinical study; outcome assessment; phase 3 clinical trial; priority journal; prognosis; protein expression; quantitative analysis; randomized controlled trial; scoring system; tissue microarray; treatment response, Androstadienes; Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Europe; Female; Humans; Immunohistochemistry; Middle Aged; Patient Selection; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Receptors, Estrogen; Receptors, Progesterone; Recurrence; Risk Assessment; Risk Factors; Selective Estrogen Receptor Modulators; Survival Analysis; Tamoxifen; Time Factors; Tissue Array Analysis; Treatment Outcome; Tumor Markers, Biological
DOI:
10.1200/JCO.2010.30.3677
