Evaluation of TNBC genome stability traits from clinical trials and drug adapted cell lines. (A) Schematic flow diagram of method t establish the chemoresistant cell lines. (B) Distance relapse free survival of neoadjuvant doxorubicin and docetaxel treated patients stratified for triple negative breast cancer subtype versus the remaining subtypes (GSE25066; 310 patients in total). P = 1.8e-6 Log-rank Mantel-Cox test. (C) In an independent dataset, the breast cancer dataset from The Cancer Genome Atlas (TCGA), the molecular signature derived from GSE25066 (see Methods and Supplementary Table 1) perfectly separates all 173 basal breast cancer samples from all 703 luminal samples. Subtypes were defined according to the PAM50 classifier. Mann-Whitney U test p-values as shown. (D) Molecular signatures Database curated gene set comparing TNBC to other subtypes for gene expression changes in molecular functions ranked based on gene numbers and statistical significance following neoadjuvant doxorubicin and docetaxel chemotherapy (GSE25066). Mann–Whitney U test P-values as shown. (E) Patient samples compared for genes expression induced in response to chemotherapy combination doxorubicin and docetaxel profile compared to Homologous recombination deficiency measured using a gene expression signature, based on the expression of 230 genes (HRD_score), as previously reported (46). (F) Chromosome count of metaphase spreads comparing MDA-M-231 sensitive and resistant cell lines. (G) BT549, (H) Hs578t and (I) MDA-MB-468 (***P < 0.0001, **P < 0.001 paired Student t-test, ± SEM of three independent experiments). (J) Heat map of IC50 values derived from dose curves for each matched sensitive (SENS) and drug adapted (RES) TNBC cell lines for docetaxel monotherapy, in combination with doxorubicin and with the addition of P-glycoprotein pump inhibitor (PGPi). IC50 (nM) indicated from three independent experiments. (J) Correlation between IC₅₀ of docetaxel and the average loss of chromosome number observed in the matched resistant cell line. r² = 0.9376 Pearson correlation coefficient, *P = 0.034 paired student t-test. (K) As above in (I), heat map utilizing doxorubicin monotherapy in combination with docetaxel and with the addition of P-glycoprotein pump inhibitor (PGPi). (L) Correlation between IC50 of doxorubicin and the average loss of chromosome number observed in the matched resistant cell line. r² = 0.7466 Pearson correlation coefficient, ns.