American Association for Cancer Research
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Supplementary Figure 1 from Low Tumor Mitochondrial DNA Content Is Associated with Better Outcome in Breast Cancer Patients Receiving Anthracycline-Based Chemotherapy

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posted on 2023-03-31, 19:22 authored by Marjolein J.A. Weerts, Antoinette Hollestelle, Anieta M. Sieuwerts, John A. Foekens, Stefan Sleijfer, John W.M. Martens

Study design (REMARK diagram) for the adjuvant (left) and advanced cohort (right).


Philips Research


Netherlands Organisation for Scientific Research



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.Experimental Design: We measured mtDNA content by a qPCR 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).Results: In both the adjuvant and advanced settings, 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 HR 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 with the FAC/FEC-treated mtDNA high group. We did not observe these associations in the patients treated with CMF.Conclusions: In our two study cohorts, breast cancer patients with low mtDNA content in their primary tumor had 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. Clin Cancer Res; 23(16); 4735–43. ©2017 AACR.

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