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Supplementary Tables 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, 19:21 authored by Marjolein J.A. Weerts, Antoinette Hollestelle, Anieta M. Sieuwerts, John A. Foekens, Stefan Sleijfer, John W.M. Martens

Supplementary Table 1: Clinicopathological variables of node-positive patients receiving adjuvant chemotherapy (FAC/FEC or CMF) (complete adjuvant cohort). Supplementary Table 2: Clinicopathological variables of the patients with recurrent disease receiving first-line chemotherapy (FAC/FEC or CMF) (complete advanced cohort). Supplementary Table 3: Patient response to first-line FAC/FEC or CMF chemotherapy after disease recurrence (advanced cohort). Supplementary Table 4: Performance of the calibration curves taken along in each plate for the used qPCR assays. Supplementary Table 5: Association between mtDNA content and chemotherapy given, either adjuvant in the adjuvant cohort, or as first-line for disease recurrence in the advanced cohort. Supplementary Table 6: Association between adjuvant chemotherapy given and clinicopathological variables of node-positive patients (adjuvant cohort). Supplementary Table 7: Association between first-line chemotherapy given and clinicopathological variables of patients with recurrent disease (advanced cohort). Supplementary Table 8: Cox regression analysis for DMFS of node-positive patients receiving FAC/FEC adjuvant chemotherapy (adjuvant cohort) limited to the 86 patients with no missing values. Supplementary Table 9: Cox regression analysis for PFS of patients receiving FAC/FEC first-line chemotherapy for their recurrent disease (advanced cohort) limited to the 70 patients with no missing values. Supplementary Table 10: Univariable Cox regression analysis of postulated markers for anthracycline sensitivity. Supplementary Table 11: Association between mtDNA content and postulated markers for anthracycline sensitivity.

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Philips Research

ERC

Netherlands Organisation for Scientific Research

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ARTICLE ABSTRACT

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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