Different associations of tumor PIK3CA mutations and clinical outcomes according to aspirin use among women with metastatic hormone receptor positive breast cancer

Anne Marie Mccarthy,Beverly Moy,Andrew T Chan,Katrina Armstrong,A John Iafrate,Susan Regan,Michaela Welch,Nitya Pradeep Kumar,Aditya Bardia,Wei He

doi:10.1186/s12885-020-06810-8

Anne Marie Mccarthy, Beverly Moy + Show 8 more

Open Access

https://doi.org/10.1186/s12885-020-06810-8

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Abstract

IntroductionThe relationships among PIK3CA mutations, medication use and tumor progression remains poorly understood. Aspirin use post-diagnosis may modify components of the PI3K pathway, including AKT and mTOR, and has been associated with lower risk of breast cancer recurrence and mortality. We assessed time to metastasis (TTM) and survival with respect to aspirin use and tumor PIK3CA mutations among women with metastatic breast cancer.MethodsPatients with hormone receptor positive, HER2 negative (HR+/HER2-) metastatic breast cancer treated in 2009–2016 who received tumor genotyping were included. Aspirin use between primary and metastatic diagnosis was extracted from electronic medical records. TTM and survival were estimated using Cox proportional hazards regression.ResultsAmong 267 women with metastatic breast cancer, women with PIK3CA mutated tumors had longer TTM than women with PIK3CA wildtype tumors (7.1 vs. 4.7 years, p = 0.008). There was a significant interaction between PIK3CA mutations and aspirin use on TTM (p = 0.006) and survival (p = 0.026). PIK3CA mutations were associated with longer TTM among aspirin non-users (HR = 0.60 95% CI:0.44–0.82 p = 0.001) but not among aspirin users (HR = 1.57 0.86–2.84 p = 0.139). Similarly, PIK3CA mutations were associated with reduced mortality among aspirin non-users (HR = 0.70 95% CI:0.48–1.02 p = 0.066) but not among aspirin users (HR = 1.75 95% CI:0.88–3.49 p = 0.110).ConclusionsAmong women who develop metastatic breast cancer, tumor PIK3CA mutations are associated with slower time to progression and mortality only among aspirin non-users. Larger studies are needed to confirm this finding and examine the relationship among aspirin use, tumor mutation profile, and the overall risk of breast cancer progression.

Highlights

The relationships among PIK3CA mutations, medication use and tumor progression remains poorly understood
Among women who develop metastatic breast cancer, tumor PIK3CA mutations are associated with slower time to progression and mortality only among aspirin non-users
There was no difference in time to metastasis for aspirin users compared to non-users

Summary

Introduction

The relationships among PIK3CA mutations, medication use and tumor progression remains poorly understood. Aspirin use post-diagnosis may modify components of the PI3K pathway, including AKT and mTOR, and has been associated with lower risk of breast cancer recurrence and mortality. We assessed time to metastasis (TTM) and survival with respect to aspirin use and tumor PIK3CA mutations among women with metastatic breast cancer. With advances in generation sequencing, the application of this paradigm in breast cancer has progressed from identification of hormone receptor and HER-2 expression to genomic profiling of tumors to assess a range of gene expression levels and identify mutations in specific genes that may drive tumor progression and offer targets for therapeutic intervention [4,5,6]. Activation of PI3K has downstream effects on the AKT and mTOR pathways that control key steps in cancer progression including cell cycle and metabolism [8]. Despite the pre-clinical evidence that PIK3CA is an oncogene, clinical studies of the outcomes of breast cancer patients with and without PIK3CA mutations have had conflicting results, demonstrating worse outcomes among patients with tumor PIK3CA mutations, no differences in outcomes by mutation status, and, most recently, better outcomes for women with hormone receptor positive (HR+) tumors with PIK3CA mutations [7, 9, 10]

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