Mitochondrial DNA Content as a Potential Marker to Predict Response to Anthracycline in Breast Cancer Patients

  • Hsu C
  • Yin P
  • Lee H
 et al. 
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Abstract

Mutations and reduced mitochondrial DNA (mtDNA) content are commonly
observed in breast cancer, yet their functional significance is not
clear. This study aimed to determine whether the mtDNA content in
breast cancer plays an important role in modulating the response
to anthracycline treatment in vivo and in vitro. The mtDNA content
in tumor cells was analyzed using quantitative polymerase chain reaction
in 60 Taiwanese breast cancer patients to correlate with their survival.
In addition, human breast cancer MDA-MB-231 cells were treated with
ethidium bromide to decrease mtDNA copy number. Cell survival was
determined by trypan blue exclusion assay and intracellular reactive
oxygen species (ROS) were determined by flow cytometry. After an
anthracycline-based regimen, the disease-free survival of patients
with higher mtDNA content breast cancer was significantly lower than
that of patients with lower mtDNA content breast cancer (p = 0.03).
Moreover, the MDA-MB-231 cells with low copies of mtDNA had higher
sensitivity to doxorubicin treatment and increased ROS production
when compared with higher mtDNA parental cells. Our results suggest
that the level of mtDNA copy number in breast cancer may be a potential
biomarker for prediction of the response to anthracycline-containing
regimens in breast cancer patients.

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Authors

  • C W Hsu

  • P H Yin

  • H C Lee

  • C W Chi

  • L M Tseng

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