PIK3CA mutations and first-line outcomes in endocrine-resistant HR+/HER2- metastatic breast cancer: A multicentric real-world study.

BACKGROUND: Outcomes and characteristics of endocrine-resistant, PIK3CA-mutated HR+ /HER2- advanced breast cancer patients in real-world are poorly investigated. Here, we explored the role of circulating PIK3CA mutations in endocrine-resistant patients in the ongoing prospective, multicentric CHAMBER study. METHODS: PIK3CA was analyzed by NGS panel covering the full exonic region of PIK3CA gene. Endocrine resistance was defined as: i) primary: relapse during the first 2 years of adjuvant ET, or ii) secondary: relapse after 2 years of starting or within 1 year of completing ET. Overall survival (OS) was calculated from the start of first-line to death from any cause. Progression free survival 1 (PFS1) was calculated from the start of first-line to progression or death. RESULTS: Among the overall CHAMBER population, 22 % patients met the criteria for endocrine-resistance (74/337). The study population consisted in 95 % women and 5 % men; median age at diagnosis was 50 years (IQR 44-63); 75 % of the women was postmenopausal;86 % of the total population presented with a secondary endocrine-resistance, 64 % had visceral relapse, 74 % had less than 3 metastatic sites, 79 % had received first-line CDK4/6 inhibitor. PIK3CA status was available for 63/74 pts, with a 29 % prevalence of mutation. PIK3CAmut was a negative prognostic factor for OS (median 65 [wt] vs 36 months [mut], log-rank p 0.024 HR 2.61 [95 % CI 1.10-6.22]) and PFS1 (median 22 [wt] vs 10 months [mut], log-rank p 0.012, HR 2.24 [95 % CI 1.18-4.26]). CONCLUSION: The co-occurrence of endocrine-resistance and PIK3CAmut identifies a population with unfavorable prognosis, reinforcing the rationale of escalated therapies.