PIK3CA Mutation and Prognosis in Early-Stage Breast Cancer


Key Points

  • Presence of PIK3CA mutation was associated with improved outcomes on univariate analysis.
  • On multivariate analysis, a significant association was observed for invasive disease–free survival, but not distant disease–free or overall survival.

In a study reported in the Journal of Clinical Oncology, Zardavas et al found that the prognostic effect of PIK3CA mutation in early breast cancer was reduced after adjustment for other prognostic factors.

Study Details

The study involved analysis of individual patient data from a pooled population of 10,319 patients from 19 studies. Median follow-up for overall survival was 6.9 years; 17% of patients received chemotherapy, 39% received endocrine monotherapy, 35% received chemotherapy and endocrine therapy, and 9% received none of these treatments or treatment was unknown.

PIK3CA mutations were found in 32% of patients; presence of mutation was significantly associated with estrogen receptor (ER) positivity, increasing age, lower tumor grade, and smaller tumor size (all P < .001). Mutations were found in 18% of ER-negative/HER2-negative cases, 22% of HER2-positive cases, and 37% of ER-positive/HER2-negative cases.

Invasive disease–free survival was the primary endpoint.

Prognostic Effect

In univariate analysis, PIK3CA mutations vs no mutations were associated with improved invasive disease–free survival (HR = 0.77, P < .001), with the beneficial effect appearing to be stronger earlier in follow-up; HRs were 0.73 (P  < .001) for 0 to 5 years, 0.82 (P = .037) for 5 to 10 years, and 1.15 (P = .38) for > 10 years (P = .02 for heterogeneity). On univariate analysis, the presence of mutations was also associated with better distant disease–free survival (HR = 0.79, 95% confidence interval [CI] = 0.72–0.86) and overall survival (HR = 0.90, 95% CI = 0.82–0.99). 

In multivariate analysis adjusting for  age, tumor size, nodal status, local grade, ER status, HER2 status, and treatment, PIK3CA mutation remained significantly associated with invasive disease–free survival (HR = 0. 88, P = .043) but not with distant disease–free survival (P = .054) or overall survival (P = .8).

The investigators concluded, “In this large pooled analysis, PIK3CA mutations were significantly associated with a better [invasive disease–free, distant disease–free, and overall survival], but had a lesser prognostic effect after adjustment for other prognostic factors.”

The study was supported by the Cancer Council Victoria, National Health and Medical Research Council of Australia; National Breast Cancer Foundation, Australia; Breast Cancer Research Foundation, New York; Swedish Research Council; and others.

Sherene Loi, MD, PhD, of Peter MacCallum Cancer Centre, University of Melbourne, is the corresponding author for the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.