Fig. 3

Clonal multiple PIK3CAmut samples exhibit fewer RTK and non-PIK3CA PI3K pathway gene alterations. A Summary diagram of pathway-level alteration rates in baseline ctDNA from SANDPIPER participants shows a significantly lower prevalence of alterations in genes associated with receptor tyrosine kinase (RTK) signaling in those samples with clonal vs subclonal multiple PIK3CAmut (p = 0.0317); (B & C), tile plot of sample-level pathway co-alteration analysis. Summary diagrams of pathway-level alteration rates in a larger dataset of (D) ERBB2 non-amplified metastatic breast cancer (BC) tumor tissue samples and (E) any BC tumor tissue samples from the Foundation Medicine database harboring clonal multiple PIK3CAmut exhibit a lower prevalence of alterations in RTK-related genes (p = 0.0233 and p = 4.01 × 10^–5, respectively) and in non-PIK3CA PI3K-pathway genes (p = 0.0119 and p = 5.09 × 10^–4, respectively) compared to samples harboring subclonal multiple PIK3CAmut. A higher proportion of alterations in MAPK pathway genes was observed in breast cancer samples with clonal multiple PIK3CAmut vs those with subclonal multiple PIK3CAmut (p = 9.34 × 10^–3) (E). p-values were obtained from a Fisher’s Exact Test. KEYS: For the summary pathway co-alteration analyses, pink and lavender bars represent samples with clonal or subclonal multiple PIK3CAmut, respectively. For alteration type specifications, distinct from “multiple PIK3CAmut”, orange boxes represent samples with multiple alteration types identified in one gene