Use of Everolimus in Advanced ER-Positive, HER2-Negative Breast Cancer: Molecular Features Influence Prognosis

By: Celeste L. Dixon
Posted: Wednesday, May 29, 2024

Results of a 71-patient study emphasized that among all patients with advanced estrogen receptor (ER)-positive, HER2-negative breast cancer, the mTOR inhibitor everolimus may be preferentially beneficial in those whose disease harbors an activated state of the PIK3CA/AKT/mTOR pathway. Paul Cottu, MD, PhD, of Institut Curie, Paris, and colleagues reported their findings in The Journal of Pathology: Clinical Research.

“Most interestingly, [is that this] activation of the PIK3CA/AKT/mTOR pathway…is tightly associated with prognosis with regard to both progression-free survival and overall survival,” the study authors noted.

The 71 heavily pretreated patients (44 primary tumors and 27 metastatic tissues; median age, 63 years) were treated with everolimus and endocrine therapy between 2012 and 2014 in two cancer centers. Targeted sequencing examined mutations in PIK3CA, ESR1, and AKT1. Further, an immunochemical analysis evaluated expression of PTEN, INPP4B, STK11, p4EBP1, and pS6.

Progression-free survival was found to be longer in patients with a pS6 or p4EBP1 histoscore of at least a median value (6.6 vs 3.7 months; P = .037) and in patients with a PTEN histoscore of a median value or less (7.1 vs 5.3 months; P = .02). Further, overall survival was found to be longer in patients with pS6 of at least 3rd quartile (27.6 vs 19.3 months; P = .038) and in patients with any mutation in the PIK3CA/AKT/mTOR pathway (27.6 vs 19.3 months; P = .011).

Most patients’ samples showed cytoplasmic expression of the PIK3CA pathway proteins, Dr. Cottu and co-investigators noted. “A mutation in the PIK3CA pathway was observed in 32 samples (PIK3CA exons 10 and 21 and AKT1 exon 4 in 15.5%, 24.0%, and 5.6% of samples) and in ESR1 in 5 samples (7.0%), respectively,” they wrote.

Disclosure: The study authors’ disclosure information can be found at pathsocjournals.onlinelibrary.wiley.com.

The Journal of Pathology: Clinical Research