Impact of Topoisomerase IIα, PTEN, ABCC1/MRP1, and KI67 on triple-negative breast cancer patients treated with neoadjuvant chemotherapy

Fouzia Guestini, Katsuhiko Ono, Minoru Miyashita, Takanori Ishida, Noriaki Ohuchi, Saki Nakagawa, Hisashi Hirakawa, Kentaro Tamaki, Yasuyo Ohi, Yoshiaki Rai, Yasuaki Sagara, Hironobu Sasano, Keely May Mcnamara

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


Purpose: Triple-negative breast cancer (TNBC) patients with residual disease following neoadjuvant chemotherapy (NAC) harbor higher risk of relapse, and eventual demise compared to those who achieve pathologic complete response. Therefore, in this study, we assessed a panel of molecules involved in key pathways of drug resistance and tumor progression before and after NAC in TNBC patients, in order to clarify the underlying mechanisms. Methods: We studied 148 TNBC Japanese patients treated with anthracycline/taxane-based NAC. KI67, Topoisomerase IIα (TopoIIα), PTEN, p53, Bcl2, vimentin, ABCG2/BCRP1, ABCB1/MDR1, and ABCC1/MRP1 were immunolocalized in surgical pathology materials before and after NAC. Results: The status of vimentin and increasing labeling index (LI) of TopoIIα and KI67 in biopsy specimens were significantly associated with those who responded to NAC treatment. The abundance of p53 (p = 0.003), ABCC1/MRP1 (p = 0.033), ABCB1/MDR1 (p = 0.022), and a loss of PTEN (p < 0.0001) in surgery specimens following treatment were associated with pathologic parameters. TopoIIα, PTEN, and ABCC1/MRP1 status predicted pathologic response. In addition, the status of PTEN, ABCC1/MRP1, ABCB1/MDR1, Bcl2, and vimentin in surgical specimens was also significantly associated with adverse clinicopathological factors in surgery specimens, suggesting that these alterations could be responsible for tumor relapse in TNBC patients. Conclusion: KI67, TopoIIα, PTEN, and ABCC1/MRP1 status could predict treatment response and/or eventual clinical outcomes. These results could also provide an insight into the mechanisms of drug resistance and relapse of TNBC patients receiving NAC.

Original languageEnglish
Pages (from-to)275-288
Number of pages14
JournalBreast Cancer Research and Treatment
Issue number2
Publication statusPublished - 2019 Jan 30


  • Drug resistance
  • Mechanistic markers
  • Neoadjuvant chemotherapy
  • Outcomes
  • Residual disease
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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