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Inflammatory breast cancer (IBC) is an aggressive BC subtype with poor outcomes. A targetable somatic  PIK3CA  mutation is reported in 30% of IBC, allowing for treatment by PI3Kα-specific inhibitors, such as alpelisib. The aim of this study was to evaluate the detection rate of circulating  PIK3CA  mutation in locally-advanced IBC (LAIBC) patients harbouring a  PIK3CA  mutation on initial biopsy. This monocentric retrospective study was based on available stored plasma samples and tumour biopsies at diagnosis from all LAIBC patients treated with neo-adjuvant chemotherapy (NCT) between 2008 and 2018 at the Centre Henri Becquerel.  PIK3CA  mutations (E542K, E545K, H1047R/L) were assessed by droplet digital PCR (ddPCR) in plasma samples and tumoral tissue at diagnosis. A total of 55 patients were included. Overall, 14/55 patients (25%) had a  PIK3CA  mutation identified on baseline biopsy (H1047R = 8; H1047L = 3; E545K = 2; E542K = 1). Among them, 11 (79%) patients had enough DNA for circulating DNA analyses, and corresponding circulating  PIK3CA  mutations were found in 6/11 (55%). Among the 41 patients without  PIK3CA  mutations on biopsy, 32 (78%) had enough DNA for circulating DNA analysis, and no circulating  PIK3CA  mutation was identified. Our results revealed no prognostic or predictive value of  PIK3CA  mutations at the diagnosis of non-metastatic IBC but highlighted the prognostic value of the cfDNA rate at diagnosis. Our study showed that a corresponding circulating  PIK3CA  mutation was identified in 55% of LAIBC patients with  PIK3CA -mutated tumours, while no circulating mutation was found among patients with  PI3KCA  wild-type tumours.

Circulating PIK3CA mutation detection at diagnosis in non-metastatic inflammatory breast cancer patients