Genomic spectrum of acquired driver alterations.

A) The circle graph represents for each case (n = 74) the proportion of driver mutations detected in primary and/or metastatic tumor samples. Outer numbers represent mutations of eBC, inner numbers represent mutations of mBC. B) Cumulative frequency of the difference (Δ) between number of mutations in metastatic vs. primary tumor samples (Δ vs. metastatic tumor; Δ > 0, number of driver mutations in the primary sample lower than in the metastatic sample. C) Non-linear relationship between the difference of driver mutations in metastasis/primary pair (Δ, x-axis), and DRFS hazard ratio of Schoenfeld residuals (y-axis). The analysis is adjusted for T/N status, Ki67, menopausal status and tumor grade. The solid line represents a penalized spline fit of the predicting variables, while the dashed lines show 95% confidence intervals. D) Functional analysis of Gene Ontology (GO) terms associated to cell cycle, DDR, epigenetic regulation, androgen receptor activity and WNT signaling pathway. The size of the dots is inversely proportional to the p values of estimated hazard ratio (x-axis) displayed in log10 scale. P values are reported in S5 Table.</p

Association between <i>MAP3K</i> alterations and clinical outcome.

Kaplan Meier curves displaying distant relapse-free survival (DRFS) (A) and overall survival (OS) (B) in patients with MAP3K gene alteration (red curves) as compared with patients with wild-type MAP3K status (blue curves). Forest plots indicating the hazard ratios for DRFS (C) and OS (D), and the corresponding confidence intervals, in MAP3K-altered and MAP3K-wild type patients. Multivariable Cox analysis is adjusted for tumor size, lymph node involvement, Ki67, menopausal status and tumor grade of the primary tumor.</p

(Sequencing Gene Content, Gene Targets and BED file of the design).

(XLSX)</p

(Associations between gene alteration and ET, broad classes).

(TIF)</p

Demographic and clinical characteristics of the study cohort.

Demographic and clinical characteristics of the study cohort.</p

(Supplementary methods).

(DOCX)</p

(Detailed Patient-Level Clinical and Treatment Data for the Study Cohort).

(XLSX)</p