• Author
    Niharika Duggirala
  • Discovery PI

    Marla Lipsyc-Sharf

  • Project Co-Author

  • Abstract Title

    ​Clinical and Molecular Features of Patients with PIK3CA-mutant (PIK3CAm) ER+/HER2- Breast Cancer with Detectable Circulating Tumor DNA (ctDNA) in early breast cancer (eBC)

  • Discovery AOC Petal or Dual Degree Program

    Basic, Clinical, & Translational Research

  • Abstract

    Keywords: Breast Cancer, Liquid Biopsy

    Background: 

    We ​previously ​​​reported that ~35% of ER+/HER2-​ ​eBC ​patients ​with a ctDNA-positive (ctDNA+) test​ result​ after surgery had a PIK3CAm primary tumor. Of patients with +ctDNA testing, those with PIK3CAm eBC had worse outcomes (versus PIK3CA-wild type​​)1​​. However, the impact of ctDNA dynamics during treatment ​​​of​ PIK3CAm eBC remains understudied.

    Methods: 

    We conducted a retrospective analysis of patients at our institution with ER+/HER2- breast cancer (BC) ​who had​ >1 ctDNA+ test​ result​ via a personalized, tumor-informed 16-plex mPCR-NGS ctDNA assay (SignateraTM, Natera, Inc.). ​​PIK3CA​m status was determined by analysis of the Signatera whole exome sequencing data. ​Clinical data were obtained by review of electronic medical records.  

    ​​​Results: 

    41 patients with ER+/HER2- BC and tumor PIK3CAm with >1 ctDNA+ test were identified. 35/41 (85.4%) patients had eBC at time of initial diagnosis; 16/35 (45.7%) of these had a positive ctDNA test in the adjuvant treatment (AT) setting. Median follow up for this cohort is 61.5 months. Among eBC patients that were ctDNA+ in the AT setting, 7/16 (43.8%) patients received chemotherapy, 12/16 (75.0%) received adjuvant endocrine therapy, and 3/16 (18.8%) received adjuvant CDK4/6 inhibitor therapy. The median time from surgery to first ctDNA test for these patients in the AT setting was 15.4 months. The initial ctDNA test was positive for 11/16 (68.8%) patients; 5/16 (31.3%) had a negative initial ctDNA test and later had a ctDNA+ test. 5/16 (31.3%) patients had clearance in the AT setting. 3/5 (60.0%) cleared ctDNA on adjuvant endocrine therapy +/- CDK4/6i and 2/5 (40.0%) cleared ctDNA in the absence of therapy. None of the 5 patients with ctDNA clearance have had distant metastatic recurrence with a median follow up after +ctDNA test of 15.8 months. Median time from first ctDNA+ test to ctDNA clearance was 57 days in the AT setting. 11/16 (68.8%) did not clear ctDNA; 7/11 (63.6%) of these patients had a distant recurrence and 1/11 (9.1%) had a local recurrence. 3/11 (27.3%) did not have recurrence, with a median follow up after first ctDNA+ test of 14.4 months. Of patients with distant metastatic recurrence, the median time from first ctDNA+ to distant recurrence was 6.0 months. 

    ​​​Conclusions: 

    This analysis explores ctDNA dynamics and clinical features during treatment for eBC in patients with +ctDNA and tumor PIK3CA mutations. These data indicate that ctDNA clearance is associated with better prognosis even in this high-risk population of patients with PIK3CAm tumors and +ctDNA testing. These data may inform further research and practice in treating ER+/HER2- PIK3CAm early breast cancers. 

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