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Dissecting the predictive value of MAPK/AKT/estrogen-receptor phosphorylation axis in primary breast cancer to treatment response for tamoxifen over exemestane: a Translational Report of the Intergroup Exemestane Study (IES)-PathIES.
- Source :
-
Breast cancer research and treatment [Breast Cancer Res Treat] 2019 May; Vol. 175 (1), pp. 149-163. Date of Electronic Publication: 2019 Jan 24. - Publication Year :
- 2019
-
Abstract
- Purpose: The prognostic and predictive values of the MAPK/AKT/ERα phosphorylation axis (pT202/T204MAPK, pT308AKT, pS473AKT, pS118ERα and pS167ERα) in primary tumours were assessed to determine whether these markers can differentiate between patient responses for switching adjuvant endocrine therapy after 2-3 years from tamoxifen to exemestane and continued tamoxifen monotherapy in the Intergroup Exemestane Study (IES).<br />Methods: Of the 4724 patients in IES, 1506 were managed in a subset of centres (N = 89) participating in PathIES. These centres recruited 1282 (85%, 1282/1506) women into PathIES of whom 1036 had phospho-marker data. All phospho-markers were analysed by immunohistochemistry staining. Multivariable Cox proportional hazards models of the phospho-markers for disease-free survival (DFS) and overall survival (OS) were adjusted for clinicopathological factors. Treatment effects on the biomarker expression were determined by interaction tests. Benjamini-Hochberg adjustment for multiple testing with a false discovery rate of 10% was applied (p <subscript>BH</subscript> ).<br />Results: Phospho-T202/T204MAPK, pS118ERα and pS167ERα were all found to be correlated (p <subscript>BH</subscript> = 0.0002). These markers were not associated with either DFS or OS when controlling for the established clinicopathological factors. Interaction terms between the phospho-markers and treatment strategies for either DFS or OS were not statistically significant (p <subscript>BH</subscript> > 0.05 for all).<br />Conclusions: This PathIES study confirmed previously described associations between the phosphorylation site markers of AKT, MAPK and ERα activity in postmenopausal breast cancer patients. No prognostic correlations between the phosphorylation markers and clinical outcome were found, nor were they predictive for clinical outcomes among patients who switched therapy over those treated with tamoxifen alone.
- Subjects :
- Adult
Aged
Androstadienes administration & dosage
Androstadienes adverse effects
Antineoplastic Agents administration & dosage
Antineoplastic Agents adverse effects
Antineoplastic Agents therapeutic use
Breast Neoplasms mortality
Breast Neoplasms pathology
Female
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Middle Aged
Neoplasm Grading
Neoplasm Staging
Phosphorylation
Prognosis
Tamoxifen administration & dosage
Tamoxifen adverse effects
Treatment Outcome
Androstadienes therapeutic use
Breast Neoplasms drug therapy
Breast Neoplasms metabolism
Mitogen-Activated Protein Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
Receptors, Estrogen metabolism
Tamoxifen therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1573-7217
- Volume :
- 175
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Breast cancer research and treatment
- Publication Type :
- Academic Journal
- Accession number :
- 30680659
- Full Text :
- https://doi.org/10.1007/s10549-018-05110-x