WBRT combined with TMZ did not significantly improve local control and survival in patients with BMs from breast cancer. CLINICALTRIALS.GOV: NCT00875355.

Tumor hypoxia is a hallmark of malignant tumors, and is a major factor in the resistance to anti-cancer therapies, particularly radiotherapy. Indeed, tumor blood flow often fluctuates, and thus the oxygen supply is often reduced, thereby inducing tumor hypoxia. We decided to explore whether post-occlusive reactive hyperemia, a physiological reaction known to occur in normal tissues, could be induced through a malignant tumor, basal cell carcinoma (BCC), in which angiogenesis occurs, as in all malignant tumors. Skin blood flow was measured in twelve patients with BCC, using Laser Speckle Contrast Imaging to determine BCC perfusion after three minutes of vascular occlusion, induced by limb tourniquet for limb tumors (4 BCC), and/or by clamping the pedicle of a skin flap with the BCC at its center, for other tumor locations (12 BCC). We demonstrated for the first time that post-occlusive reactive hyperemia occurs in malignant tumors in humans. BCC perfusion curves were similar to those of healthy skin, characterized by a peak of hyperemia after reperfusion followed by a progressive return to the pre-occlusion perfusion level. Induction of post-occlusive reactive hyperemia in malignant tumors is therefore a novel investigational approach that could lead to a new adjuvant tool to increase the efficacy of chemotherapy and radiotherapy, respectively through the synchronized temporary increase of tumor perfusion and oxygenation.

Objectives : A French multicenter study was promoted by the national French cancer federation (Unicancer R&D) to assess the potential of [18F]FLT (positron emission tomography (PET) biomarker of proliferation)to manage breast cancer neoadjuvant chemotherapy (NAC). The main objective was to compare changes in tumor [18F]FLT uptake to histopathological changes induced by NAC, assuming an arrest of tumor growth related to the effectiveness of NAC. Methods : 97 patients (age 48.6 +/- 10.2 y.) were included in 13 nuclear medicine centers. All patients were eligible to anthracycline-based NAC for a de novo unifocal breast cancer (ductal n = 84, lobular = 11, other type = 2; stage II n = 75, stage III n = 21 et stage IV n = 1). 90 patients underwent a baseline PET before the onset of NAC (PET1) and a final PET after the end of NAC and before surgery (PET3). PET acquisitions were performed 60±7min after FLT injection. SUVmax (maximum standardized uptake value), SUVpeak (1 cm3 ROI including pixel max) and SUV41 (isocontour 41% of pixel max) were computed. Changes in SUV on PET3 vs PET1 were analyzed in relation to histopathological findings at the end of NAC (Sataloff criteria). Results : Tumor FLT uptake decreased markedly between TEP1 and TEP3 (SUVmax = 6.2±4.8 vs 1.3±1.2 respectively; SUVpeak = 4.6±3.2 vs 0.9±0.9; SUV41 = 3.6±2.8 vs 0.8±0.7). Total or near-total therapeutic effect (grade A) were obtained in 20 patients, more than 50% therapeutic effect but less than total or near-total effect (grade B) in 37 patients, less than 50% therapeutic effect but visible effect (grade C) in 22 patients, or no therapeutic effect (grade D) in 11 patients. SUVmax decreased dramatically (87.5%) to background levels in all patients with a complete response (grade A). Overall, changes in SUV differed depending on the type of histological response (p<0.01) i.e. SUVmax changes were more pronounced as pathological responses were good: 61% for grade D; 65.7% grade C and 69.8% grade B. The same results were obtained with the two other SUV types. Conclusions : Pathologic response to NAC in breast cancer can be assessed accurately by FLT. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-05.

Purpose: Neoadjuvant hormone therapy (HT) promotes breast-conserving surgery (BCS) and minimizes treatment-related toxicities for oestrogen receptor (ER)-positive HER2 negative breast cancer (BC). We aimed to evaluate the response rates to an AI (anastrozole) or an antioestrogen (fulvestrant) and to identify specific biomarkers of sensitivity to both treatments. Patients and Methods: A phase II multicentre, open-label trial was conducted to evaluate the efficacy of anastrozole and fulvestrant. 116 postmenopausal patients (pts) with ER positive, HER2 negative, operable BC were recruited in 6 centers and randomly assigned to receive either neoadjuvant anastrozole (arm A; 1mg/day) or fulvestrant (arm B; 500mg, with a loading dose during first month then q4w) for 4 months (mo). Pts with a good clinical response estimated by the clinician at 4 mo were allowed to pursue treatment for 2 more mo (i.e. up to 6 mo). The primary endpoint was to evaluate the best clinical response (by palpation) by RECIST criteria at 6 mo (or 4 mo). US and MR imaging were performed at baseline, after 1 mo treatment, and before surgery. Pathological response was evaluated using Sataloff classification. Follow-up is planned for 5 yrs. Results: Between Oct 2007 and Apr 2011, 59 pts were randomized to arm A and 57 to arm B. Main baseline characteristics were well-balanced between the 2 arms: Median age was 68 yrs-old (53–91) in arm A and 74 yrs-old (51–88) in arm B. Histological grades were EE I-II in 53 pts (89 %) and 49 pts (86%) and median clinical size before treatment was 41.5 mm and 42.3 mm in arm A and B respectively. Neither SAE nor grade 3/4 toxicity was reported. The most common treatment-related AEs were grade1/2 hot flushes (27% and 12% of pts in arm A and B respectively), and musculoskeletal symptoms (20% and 21%). 35 pts in arm A and 29 pts in arm B continued assigned treatment up to 6 mo depending on the clinical response evaluated at 4 mo. Also, the clinical response rate was estimated at 4 mo orat 6 mo. 1 death post-surgery was reported in arm B with no proven relationship with treatment. Overall clinical response rates (CR + PR) at 4 or 6 mo were 62% (CI 95% [49–75]) in arm A and 46% (CI 95% [32–59]) in arm B. Clinical response rate amelioration at 6 mo was observed among 15% of pts in each arm. BCS was performed in 59% of pts in arm A and 49% in arm B. (1 pt from arm B refused surgery). Pathological response according to Sataloff classification: TA and TB tumor responses were observed in 17/59 pts (29%) in arm A vs 12/57 (21%) in arm B respectively. Conclusions: Both anastrozole and fulvestrant show excellent efficacy and tolerability as neoadjuvant therapy in post-menopausal pts with endocrine-dependent, HER2-negative BC. Objective response rates and improvement in surgical outcome seem to be more frequent with anastrozole. However disease stabilization and tolerability are in favour of fulvestrant. Our data suggest that neo-adjuvant HT improves surgical options for HR+ post-menopausal women. Correlation between clinical & pathological responses and outcome as well as the identification of markers of sensitivity to both treatments will be also studied. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD07-04.