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Background: Response to neoadjuvant chemotherapy (NACT), particularly pathologic complete response (pCR), is an independent predictor of favorable clinical outcome in breast cancer (BC). The accuracy of residual disease measurement and reporting is of critical importance in treatment planning and prognosis for these patients. Currently, gross pathological evaluation of the residual tumor bed is the greatest determinant for accurate reporting of NACT response. Fluorescence imaging (FI) is a new technology that is being evaluated for use in the detection of tumors in different oncological conditions. Objective: The aim of this study was to evaluate whether indocyanine green fluorescence imaging (ICG-FI) is able to detect residual breast tumor tissue after NACT in breast surgical operative specimens. Methods: Patients who underwent NACT for BC and were admitted for breast surgery were selected for participation in this study. Free ICG (0.25 mg/kg) was injected intraoperatively. Tumor-to-background fluorescence ratio (TBFR) was calculated on ex vivo samples from the surgical specimen. Results: One hundred and seventy-two samples from nine breast surgical specimens were evaluated for their fluorescence intensity. Among them, 52 were malignant (30.2%) and 120 were benign (69.8%). The mean TBFR was 3.3 (SD 1.68) in malignant samples and 1.9 (SD 0.97) in benign samples (p = 0.0002). With a TBFR cut-off value of 1.3, the sensitivity, specificity, negative predictive value, false negative rate, and false positive rate of ICG-FI to predict residual tumoral disease in breast surgical samples post-NACT were 94.2%, 31.7%, 92.7%, 5.8%, and 68.3%, respectively. If we restricted our analysis to only patients who achieved pCR, the negative predictive value for ICG-FI was 100%. Conclusions: These first observations indicate that ex vivo ICG-FI is sensitive but not sufficiently specific to discriminate between benign breast tissue and malignant residual tissue. Nevertheless, its negative predictive value seems sufficiently accurate to exclude the presence of residual breast tumor tissue on the operative specimen of patients treated by NACT, representing a potential tool to assist pathologists in the assessment of breast surgical specimens. [ABSTRACT FROM AUTHOR]

Background: EndoTAG-1, a tumor endothelial targeting agent has shown activity in metastatic triple-negative breast cancer (BC) in combination with paclitaxel. Methods: HER2-negative BC patients candidates for neoadjuvant chemotherapy were scheduled to receive 12 cycles of weekly EndoTAG-1 22mg/m2 plus paclitaxel 70mg/m2 followed by 3 cycles of FEC (Fluorouracil 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2) every 3 weeks followed by surgery. Primary endpoint was percent (%) reduction in Magnetic Resonance Imaging (MRI) estimated Gadolinium (Gd) enhancing tumor volume at the end of EndoTAG-1 plus paclitaxel administration as compared to baseline. Safety, pathological complete response (pCR) defined as no residual tumor in breast and axillary nodes at surgery and correlation between % reduction in MRI estimated tumor volume and pCR were also evaluated. Results: Fifteen out of 20 scheduled patients were included: Six patients with estrogen receptor (ER)-negative/HER2-negative and 9 with ER-positive/HER2-negative BC. Nine patients completed treatment as per protocol. Despite premedication and slow infusion rates, grade 3 hypersensitivity reactions to EndoTAG-1 were observed during the 1st, 2nd, 3rd and 6th weekly infusion in 4 patients, respectively, and required permanent discontinuation of the EndoTAG-1. Moreover, two additional patients stopped EndoTAG-1 plus paclitaxel after 8 and 9 weeks due to clinical disease progression. Two patients had grade 3 increases in transaminases and 1 patient grade 4 neutropenia. pCR was achieved in 5 of the 6 ER-/HER2- and in none of the 9 ER+/HER2- BC patients. The mean % reduction in MRI estimated tumor volume at the end of EndoTAG-1 plus paclitaxel treatment was 81% (95% CI, 66% to 96%, p<0.001) for the 15 patients that underwent surgery; 96% for patients with pCR and 73% for patients with no pCR (p = 0.04). Conclusions: The EndoTAG-1 and paclitaxel combination showed promising preliminary activity as preoperative treatment, especially in ER-/HER2- patients. Further studies are warranted with need of premedication optimization. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]