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Ref Type Journal Article
PMID (31088410)
Authors Yi Z, Ma F, Liu B, Guan X, Li L, Li C, Qian H, Xu B
Title Everolimus in hormone receptor-positive metastatic breast cancer: PIK3CA mutation H1047R was a potential efficacy biomarker in a retrospective study.
Journal BMC cancer
Vol 19
Issue 1
Date 2019 May 14
URL
Abstract Text Everolimus, an inhibitor of mammalian target of rapamycin (mTOR), has been shown to increase the efficacy of endocrine therapies in hormone receptor (HR)-positive metastatic breast cancer. However, because breast cancer is a highly heterogeneous disease, the responses of different patients to everolimus may vary. Therefore, we performed this study to better select patients who will benefit most from or be resistant to everolimus.Patients with HR-positive breast cancer who were treated with everolimus at the Cancer Hospital, Chinese Academy of Medical Sciences from February 2014 to March 2017 were enrolled in the present study. Mutations in ctDNA were assayed in 1021 tumor-related genes via gene panel target capture-based next-generation sequencing.In total, 120 patients with metastatic breast cancer who were treated with everolimus were enrolled in the present study. The median progression-free survival (PFS) of all patients was 5.1 months (95% confidence interval [CI] 3.9-6.3 months). No difference in survival was observed between patients who received endocrine drugs used in previous treatment regimens and patients who did not receive these drugs (median PFS 5.2 and 5.1 months, respectively, p > 0.05). Additionally, we did not find any difference in outcomes between patients who had primary resistance to previously used endocrine drugs and patients who had nonprimary resistance to previous treatments (p > 0.05). Multivariate analysis showed that < 3 metastatic sites, < 2 lines of previous endocrine therapy, < 2 lines of previous chemotherapy, and treatment with everolimus combined with fulvestrant were associated with improved survival (p < 0.05). Sixteen patients underwent ctDNA analysis before everolimus treatment. The frequency of PIK3CA gene mutations was 62.5%, and H1047R was the most frequently detected mutation. Patients with the PIK3CA/H1047R mutation had longer PFS than patients with wild-type or other mutant forms of PIK3CA, and the median PFS in these two groups of patients was 8.8 and 4.1 months, respectively (p < 0.05).Our data suggest that patients who receive more lines of chemotherapy or endocrine therapy are less likely to benefit from everolimus. For everolimus combination therapy, we can even select endocrine drugs that gave rise to primary resistance in previous treatments. Additionally, the PIK3CA/H1047R mutation may be a potential biomarker of sensitivity to everolimus.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
PIK3CA H1047R progesterone-receptor positive breast cancer predicted - sensitive Everolimus Clinical Study - Cohort Actionable In a retrospective analysis, combination of Afinitor (everolimus) and hormone therapy resulted in improved median progression-free survival (8.8 vs 4.1 months, p=0.02) in patients with hormone receptor-positive metastatic breast cancer harboring PIK3CA H1047R (n=6) compared to patients without PIK3CA H1047R (n=10) (PMID: 31088410). 31088410
PIK3CA H1047R estrogen-receptor positive breast cancer predicted - sensitive Everolimus Clinical Study - Cohort Actionable In a retrospective analysis, combination of Afinitor (everolimus) and hormone therapy resulted in improved median progression-free survival (8.8 vs 4.1 months, p=0.02) in patients with hormone receptor-positive metastatic breast cancer harboring PIK3CA H1047R (n=6) compared to patients without PIK3CA H1047R (n=10) (PMID: 31088410). 31088410