The AR, E-Cadherin and Ki 67 expression in 45 patients TNBC.

<p>Legend: [A, B] negative/positive AR staining; [C, D] E-cadherin negative/positive staining; [E, F] Ki-67 level < or ≥ 20%.</p

Univariate and multivariate analysis.

<p>Univariate and multivariate analysis.</p

Estimated Overall Survival Curves for AR and Ki67.

<p>The AR and Ki-67 expression are independent variables associated with overall survival.</p

AR, E-Cadherin and Ki 67 expression.

<p>AR, E-Cadherin and Ki 67 expression.</p

Additional file 1: Table S1. of Response and survival of breast cancer intrinsic subtypes following multi-agent neoadjuvant chemotherapy

Cox model DRFS analyses including intrinsic subtype in all patients from the MDACC-based cohort (GSE25066). Table S2. Cox model DRFS analyses including ROR-P in all patients from the MDACC-based cohort (GSE25066). Table S3. Cox model DRFS analyses including intrinsic subtype in patients that achieved a pCR from the MDACC-based cohort (GSE25066). Table S4. Cox model DRFS analyses including ROR-P in patients that achieved a pCR from the MDACC-based cohort (GSE25066). Table S5. Cox model DRFS analyses including ROR-P in patients with residual disease from the MDACC-based cohort (GSE25066). Table S6. Distribution of the PAM50 subtypes within the TNBCtype groups and vice versa. Table S7. Association of the TNBCtype subtypes with chemotherapy response in triple-negative breast cancer. Figure S1. CONSORT diagram of the various cohorts evaluated in this study. Figure S2. Kaplan-Meier distant relapse-free survival analysis in MDACC-based (GSE25066 [13]) dataset set. (A) Survival outcomes of the ROR-P groups in all patients. (B) Survival outcomes of the ROR-P groups in patients with clinically node-negative disease. Figure S3. Levels of ESR1 across TNBCtype ESR1-low group, TNBCtype ESR1-high group and ER+ group. Median expression of ESR1 in the PAM50 training dataset reported in Parker et al. [24] has been set to zero. Figure S4. Distribution of the TNBCtype subtypes and ESR1-high group within the PAM50 subtypes in TNBC. Figure S5. Distribution of the TNBCtype subtypes and ESR1-high group within the PAM50 + Claudin-low subtypes in TNBC. Figure S6. Training and testing gene expression-based models predictive of pCR in all patients. Figure S7. Training and testing gene expression-based models predictive of pCR in patients with Basal-like disease. Figure S8. Training and testing gene expression-based models predictive of pCR in patients with luminal (A/B) disease. (DOCX 819 kb

Additional file 2: of Response and survival of breast cancer intrinsic subtypes following multi-agent neoadjuvant chemotherapy

Supplemental data. (XLSX 897 kb

Sequential and combination treatment of the MDA-MB-231-BR cell line with ABT-888 and non-liposomal doxorubicin (NonL-doxo).

<p>(<b>A</b>) Percentage of viable cells treated in each of three treatment arms (72 hours [h] ABT-888 followed by 72 h NonL-doxo [blue], 72 h NonL-doxo followed by 72 h ABT-888 [red], and 72 h concurrent schedule of NonL-doxo and ABT-888 in combination [green]). (<b>B</b>) Combination index (CI) analysis in each arm compared to treatment with single agents. Note: CI <0.1–0.9, synergy; CI 0.9–1.1, additivity; CI >1.1, antagonism.</p

Bioluminescence imaging of TNBC intracranial tumor model.

<p>(<b>A</b>) Dynamic changes in intracranial tumor growth after treatment as measured by bioluminescence imaging in photons/second. Groups are as follows: Control (black), non-liposomal doxorubicin (NonL-doxo, green), PEGylated liposomal doxorubicin [PLD] (blue), ABT-888 (purple), NonL-doxo/ABT-888 (yellow) and PLD/ABT-888 (red). The median fold changes are connected over time for each treatment group. The vertical bars indicate the interquartile rages (25^th–75^th percentiles). Points are only plotted when there were at least 2 animals in a treatment group. (<b>B</b>) Representative images of intracranial bioluminescence by treatment group 14 days post-treatment initiation.</p

Efficacy Studies in an intracranial model of breast cancer.

<p>(<b>A</b>) Median survival (from the time of intracranial cell line injection) of animals treated with control (PBS, black), non-liposomal doxorubicin (NonL-doxo, green) 6mg/kg IV weekly and PEGylated liposomal doxorubicin (PLD, blue) 6mg/kg IV weekly in a murine model of intracranial breast cancer. (<b>B</b>) Median survival of animals treated with control (PBS, black), NonL-doxo 4.5 mg/mg IV weekly plus ABT-888 25 mg/kg OG daily (yellow) versus PLD (red) 4.5mg/mg IV weekly plus ABT-888 25 mg/kg OG daily in a murine model of intracranial breast cancer.</p

Sum Total Doxorubicin Concentrations from NonL-doxo.

<p>Individual and mean sum total doxorubicin concentration in plasma, brain tumor, contralateral non-tumor brain, and peri-tumoral brain of female athymic nude (nu/nu) mice bearing intracranial MDA-MB-231-BR human triple-negative breast cancer xenografts following administration of nonliposomal doxorubicin (NonL-doxo) at 6 mg/kg IV ×1. Samples (n = 3 mice at each time point) were obtained at 0.083, 1, 3, 6, 24, 72 and 96 hours following administration of NonL-doxo. Concentrations were undetectable after 3 hours (contralateral non-tumor brain), 6 hours (peri-tumoral brain), and 24 hours (plasma and tumor) of administration. (<b>A</b>) 0–96 h; (<b>B</b>) 0–6 h.</p