Tumor clearance of technetium 99m-sestamibi as a predictor of response to neoadjuvant chemotherapy for locally advanced breast cancer

Purpose: Since we have previously shown that the efflux rate of technetium 99m (^99mTc) sestamibi, a transport substrate of P-glycoprotein (Pgp), is directly correlated with Pgp levels in untreated breast carcinoma, we tested whether tumor clearance of ^99mTc-sestamibi may be predictive of therapeutic response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. Patients and Methods: Thirty-nine patients with stage III disease, median tumor diameter 5.8 cm (range, 3 to 10) were enrolled onto this prospective clinical trial and underwent ^99mTc-sestamibi scan before neoadjuvant chemotherapy. Patients were injected intravenously (IV) with 740 MBq of ^99mTc-sestamibi; a 15-minute dynamic study was performed, and static planar images were obtained at 0.5, 1, 2, and 4 hours. The time to half clearance of ^99mTc-sestamibi was calculated in each patient from decay corrected time-activity curves using a monoexponential fitting. Patients were treated with epirubicin 150 mg/m² IV every 2 weeks for three courses and then underwent surgery within 3 weeks from the completion of chemotherapy. Residual tumor was assessed by pathologic examination of mastectomy specimens. Results: Seventeen of 39 patients showed a rapid tumor clearance of ^99mTc-sestamibi (time to half clearance [t( 1/4 )] ≤ 204 minutes) and 15 of these 17 (88%) showed a highly cellular macroscopic residual tumor at histology that indicated lack of tumor response to neoadjuvant chemotherapy. In contrast, only eight of 22 (36%) with prolonged retention of ^99mTc-sestamibi (t( 1/4 ) > 204 minutes) showed residual macroscopic tumor at histology (Fisher's exact test, P <.01). Conclusion: A rapid tumor clearance of ^99mTc-sestamibi may predict lack of tumor response to neoadjuvant chemotherapy with drugs affected by the multidrug- resistant phenotype in patients with locally advanced breast carcinoma.