The role of PIK3CA mutation in lobular breast cancer in the era of precision oncology – A systematic review

Background

Ιnvasive lobular carcinoma (ILC) is a distinct subtype of breast cancer with unique clinical and molecular features. Although ILC generally responds to endocrine therapy, it tends to exhibit lower chemotherapy sensitivity, underscoring the need for tailored therapeutic approaches. PIK3CA mutations are frequently observed in ILC. This systematic review evaluates the prevalence of PIK3CA mutations in ILC and examines their prognostic and predictive significance.

Methods

We searched PubMed and Scopus for studies reporting PIK3CA mutations in lobular breast cancer. Inclusion criteria encompassed studies on stage I–III ILC examining mutation frequency, prognosis, or predictive value. Data on mutation prevalence in ILC (and comparisons to invasive ductal carcinoma, IDC) and associated outcomes were extracted. Meta-analyses were performed with assessment of heterogeneity and publication bias.

Results

Ten relevant studies (nine cohorts) were included. The prevalence of PIK3CA mutations in ILC ranged from ∼30 % to ∼50 %. Statistic analysis showed that nearly half of ILCs harbor PIK3CA mutations. Mutation rates in ILC were generally higher than in IDC. No significant association between PIK3CA mutation status and patient prognosis was observed in the available studies. There were limited data ontreatment response.

Conclusions

PIK3CA is a commonly mutated gene in ILC, but current evidence does not demonstrate a clear impact on prognosis or definite predictive value for therapy response in this subtype. Nonetheless, the high mutation frequency provides a rationale for targeted therapeutic approaches. PIK3CA testing may be considered in advanced ILC to identify candidates for PI3K inhibitor therapy, although further research is needed.