title: Combined treatment with everolimus and fulvestrant reversed anti-HER2 resistance in a patient with refractory advanced breast cancer: a case report.
abstract: BACKGROUND
  Everolimus, an inhibitor of the mammalian target of rapamycin, shows promising antitumor activity when combined with trastuzumab and chemotherapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer or when combined with endocrine agents for hormone receptor (HR)-positive tumors. However, data are limited regarding the effect of everolimus in combination with endocrine drugs in HER2-positive advanced breast cancer regardless of the HR status.
  
  
  METHODS
  A 44-year-old female was diagnosed with recurrent HER2-positive breast cancer. The primary tumor was HR positive; however, the metastatic tumor was HR negative. The patient was resistant to classical chemotherapeutic agents and anti-HER2 treatment. Thus, the combination of everolimus and fulvestrant, a selective estrogen receptor downregulator, was chosen to reverse the resistance to anti-HER2 therapy. Indeed, the patient experienced long-term disease stabilization. Adverse events associated with the treatment were manageable by dose adjustments. We performed genetic testing of the metastatic tumor, which harbored a PIK3CA gene mutation but was positive for phosphatase and tensin homologue expression, which might result in resistance to the mammalian target of rapamycin inhibitor.
  
  
  CONCLUSIONS
  This case study indicates that combined treatment with everolimus and fulvestrant might be a viable option for the treatment of metastatic breast cancer patients who are HER2 positive and carry a PIK3CA gene mutation but are resistant to anti-HER2 therapy and classical chemotherapeutic agents. Further prospective randomized trials are needed to confirm this finding.
authors.affiliation: Department of Radiotherapy.
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Radiotherapy.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Radiotherapy.
authors.forename: Shikai
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Radiotherapy.
authors.forename: Xiangying
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Breast Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China.
authors.forename: Santai
authors.initials: S
authors.lastname: Song
keywords: PI3K Akt mTOR pathway; PIK3CA gene; genetic testing; mTOR inhibitor