Medical Oncology

, 35:48 | Cite as

Predictive markers for efficacy of everolimus plus exemestane in patients with luminal HER2-negative metastatic breast cancer

  • Misato Okazaki
  • Yoshiya Horimoto
  • Masahiko Tanabe
  • Yuko Ichikawa
  • Emi Tokuda
  • Atsushi Arakawa
  • Toshiyuki Kobayashi
  • Mitsue Saito
Original Paper


Metastatic breast cancer (MBC) is essentially incurable despite recent improvements in systemic therapies. We often encounter difficulties in choosing the most appropriate treatments, with optimal timing, for individual patients. Everolimus, one of the mTOR inhibitors, is usually used with endocrine therapy for MBC. Identification of predictive markers for everolimus-based treatment remains a major issue, but to date, no predictive markers have been established. We retrospectively investigated predictive markers for treatments with everolimus plus exemestane in patients with ER-positive and HER2-negative breast cancer. Clinicopathological features of 18 patients, with locally advanced disease or MBC given everolimus plus exemestane treatments, were examined in relation to treatment effects. Also, primary breast cancer specimens, all ER positive and HER2 negative, were immunohistochemically investigated for phospho-S6 (pS6) and PTEN, to evaluate the mTOR and PIK3CA/Akt pathways. Those showing a good clinical response had a significantly lower Ki67 labeling index than the poor responders. A similar trend was observed in pS6 level but without statistical significance. Interestingly, there was no correlation between the Ki67 labeling index and pS6, and when both indexes were low, the good clinical response rate was high. The median progression-free survival was longer in the group showing a low Ki67 labeling index (109 weeks) than in that with high Ki67 (19 weeks). There was no trend between PTEN expression and treatment effects. Our results suggest that the primary tumor in luminal HER2-negative breast cancer patients with a low Ki67 labeling index and pS6 level has the potential to respond well to everolimus plus exemestane.


Metastatic breast cancer Everolimus Biomarker Ki67 pS6 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

12032_2018_1112_MOESM1_ESM.xlsx (10 kb)
Supplementary material 1 (XLSX 10 kb)
12032_2018_1112_MOESM2_ESM.pptx (2.9 mb)
Supplementary figure 1. Representative images of pS6 and PTEN immunohistochemistry. Representative images of pS6 (stained in the cytoplasm) and PTEN (stained on cell membrane) immunohistochemistry are shown. Supplementary figure 2. Kaplan-Meier curve for PFS of the 18 patients. The median PFS was 21 weeks. Supplementary figure 3. The scatter diagram for the Ki67 labelling index and pS6. The scatter diagram revealed that there was no correlation between the Ki67 labelling index and pS6 expression, with the correlation coefficient being -0.06 (PPTX 2982 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Breast OncologyJuntendo University School of MedicineTokyoJapan
  2. 2.Department of Pathology and OncologyJuntendo University School of MedicineTokyoJapan
  3. 3.Department of Breast and Endocrine Surgery, Graduate School of MedicineThe University of TokyoTokyoJapan
  4. 4.Department of Human PathologyJuntendo University School of MedicineTokyoJapan

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