Luen, SJ, Lee, CK, Savas, P, Kammler, R, Dell’Orto, P, Biasi, OM, Demanse , D, JeBailey , J, Dolan, S, Hackl, W, Thuerlimann, B, Viale, G, Colleoni , M, Regan, MM and Loi, S (2018) Association of somatic driver alterations with prognosis in postmenopausal, hormone receptor-positive, HER2-negative early breast cancer - A secondary analysis of the BIG 1-98 randomized clinical trial. JAMA Oncology, Publis (June 1). E1-E9. ISSN n.a.

Abstract

Importance:
A range of somatic driver alterations have been described in estrogen receptor positive, HER2-negative (ER+/HER2-) early breast cancer (BC), however the clinical relevance is unknown.

Objective:
To investigate associations of driver alterations with prognosis and the role of PIK3CA mutations in prediction of benefit to endocrine therapy in postmenopausal patients with ER+/HER2- early BC treated with tamoxifen or letrozole.

Design, setting, participants, and interventions:
The BIG 1-98 trial randomized 8,010 post-menopausal patients with hormone receptor-positive operable invasive BC to monotherapy with letrozole or tamoxifen, or a sequential strategy for 5 years. Driver alterations were characterized using next generation sequencing in primary tumors from a subset of 764 patients from 7329 eligible ER+/HER2- patients, with 841 distant recurrences after 8.1 years median follow-up. To correct for the over-sampling of distant recurrences, weighted analysis methods were used.

Main outcomes and measures:
We analyzed the prevalence of driver alterations, associations with 5 clinicopathological factors, distant recurrence-free interval, and treatment interactions. Multivariable analyses were performed to adjust for clinicopathological factors.

Item Type:	Article
Keywords:	ER-positive breast cancer, BIG1-98, Letrozole, somatic driver lesions
Date Deposited:	03 Jul 2018 00:45
Last Modified:	03 Jul 2018 00:45
URI:	https://oak.novartis.com/id/eprint/36023