Purpose: In this study, we aimed to explore whether low levels of mitochondrial DNA (mtDNA) content in the primary tumor could predict better outcome for breast cancer patients receiving anthracycline-based therapies. We hypothesized that tumor cells with low mtDNA content are more susceptible to mitochondrial damage induced by anthracyclines, and thus are more susceptible to anthracycline treatment.<br /><br />Experimental Design: We measured mtDNA content by a quantitative PCR approach in 295 primary breast tumor specimens originating from two well-defined cohorts: 174 lymph node-positive patients who received adjuvant chemotherapy and 121 patients with advanced disease who received chemotherapy as first-line palliative treatment. The chemotherapy regimens given were either anthracycline-based (FAC/FEC) or methotrexate-based (CMF).<br /><br /><br />Results: In both the adjuvant and advanced setting, we observed increased benefit for patients with low mtDNA content in their primary tumor, but only when treated with FAC/FEC. In multivariable Cox regression analysis for respectively distant metastasis-free survival and progression-free survival, the hazard ratio for the FAC/FEC treated mtDNA low group in the adjuvant setting was 0.46 (95% confidence interval (CI) 0.24-0.89, P = 0.020) and in the advanced setting 0.49 (95% CI 0.27-0.90, P = 0.022) compared to the FAC/FEC treated mtDNA high group. We did not observe these associations in the patients treated with CMF.<br /><br /><br />Conclusions: In our two study cohorts, breast cancer patients with low mtDNA content in their primary tumor have better outcome from anthracycline-containing chemotherapy. The frequently observed decrease in mtDNA content in primary breast tumors may be exploited by guiding chemotherapeutic regimen decision-making.
- Received January 5, 2017.
- Revision received April 7, 2017.
- Accepted April 11, 2017.
- Copyright ©2017, American Association for Cancer Research.