Background: Triple-negative breast cancer (TNBC) patients (pts) without pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) have an unfavourable prognosis. ABCSG trials 14 and 24 defined 6 cycles of epirubicin/docetaxel (+/- capecitabine) as active NAC regimen; pts without pCR commonly received another 4-8 cycles of adjuvant CMF. Different studies suggested that breast tumours harbouring BRCA-1 germline mutations were resistant to taxane-based therapy while sensitivity to DNA-damaging agents was retained. BRCA-1 mutations are rare in sporadic BC; BRCA-1 promotor methylation (PM), however, is frequently observed. We hypothesized that pts with TNBC harbouring BRCA1 PM would benefit from adjuvant CMF salvage therapy. Methods: For this analysis, we included all pts with TNBC refractory to taxane-based NAC who received adjuvant CMF. DNA was extracted from formalin-fixed paraffin-embedded tissue samples, purified and bisulfite-converted. The TaqMan assay was used in order to perform a quantitative methylation-specific PCR. Actin-b was used as reference gene to normalise the amount of provided DNA; bisulfite-converted, artificially methylated DNA was used as positive control. Results: Twenty-four pts, median age 47 years, were available for this analysis. In 9/24 pts (37.5%), BRCA-1 PM was detected. At a median follow-up of 27.5 months, 1/9 pts (11.1%) with BRCA-1 PM had a disease-free survival (DFS) event, as compared to 10/15 (66.6%) in the non-methylated group (p = 0.013; Fisher’s exact test). Kaplan Meier estimation of DFS in the non-methylated group was 24 months (95% CI 14.06-33.94) and was not reached in the methylated group (n.s.). Conclusions: In TNBC refractory to taxane-based NAC, adjuvant CMF is of limited efficacy. In tumours harbouring BRCA-1 PM, however, a significant decrease of DFS events was observed. Therefore, tumours harbouring defects in genetic repair mechanism might be exceptionally sensitive to drugs causing DNA-damage. Further clinical investigation of this concept is warranted.