We recently reported that multidrug-resistant, P-170 glycoprotein-positive, Adriamycin-selected, human breast tumor (MCF7/ADRR) cells were resistant to the benzoquinonoid ansamycin antibiotics geldanamycin (GL) and herbimycin A (HA) and that significantly fewer hydroxyl radicals were formed in resistant cells.
To measure ABCB1 function in tumors, we performed PET experiments using both [<sup>18</sup>F]AVT-011 and [<sup>18</sup>F]FDG in mice bearing orthotopic breast tumors (n = 7-10/group) expressing clinically relevant levels of ABCB1.
In this pilot study, MDR1 expression in primary breast tumors was inversely related with the efficacy of first-line chemotherapy, and high expression level was a significant predictor of poor prognosis for patients with advanced disease.
Reduced ABCB1 protein levels in breast tumors was associated with triple-negative subtype (adjusted odds ratio [OR<sub>adj</sub>] =0.24; 95% confidence interval [CI] =0.13-0.45), lymph node status < pN2 (OR<sub>adj</sub> =0.27; 95% CI =0.10-0.71), tumor size >2 cm (OR<sub>adj</sub> =0.55; 95% CI =0.32-0.93), and hypertensive status (OR<sub>adj</sub> =0.42; 95% CI =0.24-0.73), and it was significantly associated with shorter disease-free survival, either for all breast cancer patients (<i>p</i> log-rank =0.012; hazard ratio [HR] =3.46; 95% CI =1.21-9.91) or for those with triple-negative tumors (<i>p</i> log-rank =0.007; HR =11.41; 95% CI =1.29-100.67).
Interleukin-6, multidrug resistance protein-1 expression and response to paclitaxel in women with metastatic breast cancer: results of cancer and leukemia group B trial 159806.
In this study, the mechanism of 99mTc-sestamibi uptake by nine human breast tumor cell lines was analyzed as a function of P-glycoprotein (PgP) expression.
We determined mRNA levels of BCRP, LRP, MRP1, MRP2, and MDR1 in 59 primary breast tumor specimens of patients who received chemotherapy as first-line systemic treatment after diagnosis of advanced disease.
Taken together, our data indicate that breast tumors with alveolar structures possess resistance to NAC, which is not related to high expression of MDR genes, whereas chemoresistance of tumors with trabecular structures can depend on the expression level of ABCB1.
An important result of our study is the demonstration of a correlation between P-gp expression and patients with HER2-positive breast tumors that do not express steroid receptors.
Determination of P-glycoprotein, MDR-related protein 1, breast cancer resistance protein, and lung-resistance protein expression in leukemic stem cells of acute myeloid leukemia.