Phosphorylation of the oestrogen receptor alpha at serine 305 and prediction of tamoxifen resistance in breast cancer
2009 (English)In: JOURNAL OF PATHOLOGY, ISSN 0022-3417, Vol. 217, no 3, 372-379 p.Article in journal (Refereed) Published
Phosphorylation of oestrogen receptor a at serine 305 (ER alpha S305-P) induces tamoxifen resistance in experimental studies, but does not influence response to other endocrine agents, such as fulvestrant. We evaluated ER alpha S305-P using immunohistochemistry in 377 breast carcinomas from premenopausal participants of a randomized trial (n = 248) and patients with advanced disease (n = 129). Among the premenopausal patients, adjuvant tamoxifen improved recurrence-free survival (RFS) for ER alpha S305-P-negative tumours (multivariate HR = 0.53, 95% CI 0.32-0.86, p = 0.010), but not for ER alpha S305-P-positive tumours (multivariate HR = 1.01, 95% CI 0.33-3.05, p = 0.99) (interaction p = 0.131). Notably, ER alpha S305-P was not significantly associated with RFS in patients not treated with tamoxifen (multivariate HR = 0.64, 95% CI 0.30-1.37, p = 0.248), indicating that ER alpha S305-P is a marker for treatment outcome rather than tumour progression. Given the direct experimental link between ER alpha S305-P and tamoxifen resistance and these first clinical data suggesting that premenopausal patients with ER alpha S305-P-positive breast cancer are resistant to adjuvant tamoxifen, further research is encouraged to study whether alternative endocrine treatment should be considered for this subgroup.
Place, publisher, year, edition, pages
2009. Vol. 217, no 3, 372-379 p.
breast, breast cancer, immunohistochemistry, oestrogen receptor, phosphorylation, tamoxifen, drug resistance, predictive marker
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-16848DOI: 10.1002/path.2455OAI: oai:DiVA.org:liu-16848DiVA: diva2:174391