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Background and Importance Alterations in components of the PI3K pathway are frequently observed in oestrogen receptor (ER) positive. Mutations in PIK3CA (PIK3CA+), which encodes the alpha isoform of the catalytic subunit of PI3K, are detected in over 40% of ER+ breast cancers (BC).Aim and Objectives To develop a systematic review of therapies for advanced and metastatic BC with PIK3CA-mutated (PIK3CA+).Material and Methods Based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology, a search was conducted in PubMed database until September 2025. Filter ‘Randomised Controlled Trial’ was combined with the following search terms: [PI3K AND breast cancer AND treatment]. Inclusion criteria: randomised clinical trials (RCTs) enrolling patients diagnosed with ER+, HER2- and PIK3CA+ advanced and/or metastatic BC. The study population could be previously at least one endocrine-based regimen treated patients. Efficacy outcomes considered were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). The following data were recorded: publication date, study design, tumour stage, sample size, population follow-up, treatments and efficacy results.Results Seventy-three studies were reviewed and 11 met the inclusion criteria. Publication dates were between May 2016 and October 2024. Study design: seven randomised phase III and four randomised phase II. All studies were placebo-controlled. Patients with advanced BC were included in 18.2% of CTs and advanced or metastatic disease in 81.8%. The sample sizes comprised between 28-516 patients. Median follow-up ranged from 8 to 54 months. Treatments assessed: alpelisib plus fulvestrant, buparlisib with paclitaxel, buparlisib plus fulvestrant, capivasertib with paclitaxel, capivasertib plus fulvestrant, ipatasertib with paclitaxel, pictilisib plus fulvestrant and taselisib with fulvestrant. The highest numerical efficacy results were obtained with alpelisib plus fulvestrant [OS=39.3 months (95% CI 24.4-44.9); PFS=11.0 months (95% CI 7.5-14.5); ORR=not available] and capivasertib plus fulvestrant [OS=38.9 months (95% CI 23.3-50.7); PFS=12.8 months (95% CI 6.6-18.8); ORR=not available]. Buparlisib plus fulvestrant presented the next best numerical efficacy [OS=33.6 months (95% CI 23.8-40.0); PFS=7.0 months (95% CI 5.0-10.0); ORR=18.4% (95% CI 10.9-28.1)].Conclusion and Relevance Eight regimens with combinations of drugs for the treatment of advanced or metastatic BC with PIK3CA+ were found. Capivasertib plus fulvestrant and alpelisib plus fulvestrant suggested a similar efficacy result.Conflict of Interest No conflict of interest