No abstract

Purpose: After apparently successful excision of breast cancer, risk of local recurrence remains high mainly in the area surrounding the original tumor, indicating that wound healing processes may be implicated.The proportional reduction of this risk by radiotherapy does not depend on the extent of surgery, suggesting that radiotherapy, in addition to killing tumor cells, may influence the tumor microenvironment. Experimental Design: We studied how normaland mammary carcinoma cell growth and motility are affectedby surgical wound fluids (WF), collectedover 24 hfollowingbreast-conserving surgery in 45 patients, 20 of whomhadreceivedadditionalTARGeted Intraoperative radioTherapy (TARGIT), immediately after the surgical excision. The proteomic profile of the WF and their effects on the activation of intracellular signal transduction pathways of breast cancer cells were also analyzed. Results: WF stimulated proliferation, migration, and invasion of breast cancer cell lines.The stimulatory effect was almost completely abrogated when fluids from TARGIT-treated patients were used. These fluids displayed altered expression of several cytokines and failed to properly stimulate the activation of some intracellular signal transduction pathways, when compared with fluids harvested from untreated patients. Conclusions: Delivery of TARGIT to the tumor bed alters the molecular composition and biological activity of surgical WF. This novel antitumoral effect could, at least partially, explain the very low recurrence rates found in a large pilot study using TARGIT. It also opens a novel avenue for identifying new molecular targets and testing novel therapeutic agents.

Thallium-201 breast scans were performed preoperatively in 72 female patients with breast abnormalities detected by mammography and/or ultrasonography (7.5-13 MHz), in order to differentiate benign from malignant breast disease. Informed consent was obtained from each patient. Scintigraphy consisted of anterior and oblique planar images of the affected breast and axilla at 10 min and 3 h following the injection of 201Tl chloride (110 MBq). All 201Tl scans were interpreted without prior knowledge of surgery data. Pathological features of breast malignancies, such as tumour size, axillary lymph node metastases, tumour grading, lymphatic vascular channel invasion and receptor status, were analysed for their association with 201Tl uptake by tumour cells. A total of 76 breast lesions were assessed in the study. On final histological diagnosis, there were 56 malignant tumours, 14 benign nodules (9 fibroadenomas, two cases of adenosis, two cases of focal fibrosis and one case of epitheliosis) and six atypical lesions (atypical ductal or lobular hyperplasia). Thallium scintigraphy was shown to have high accuracy (92%) in detecting breast cancer, better than mammography (74%) and ultrasonography (84%). Almost all (51/56) breast cancers showed greater 201Tl activity than surrounding normal breast tissue while there was no significant increase in 201Tl activity above background in all but one (19/20) case of non-malignant disease. 201Tl activity within breast tumours, calculated as tumour/background (T/B) ratio, ranged between 1.2 and 2.5 with a mean value of 1.45. In our experience the concentration of thallium in the breast cancer seems to be primarily dependent on vascularity and tumour size rather than tumour grading, lymphatic/vascular invasion or receptor status. 201Tl scan sensitivity was 97% for malignant lesions larger than 1.5 cm (n = 35) and 80% for lesions of 1.5 cm or less (n = 21); however, five of the eight breast cancers smaller than 1.0 cm were also detectable by 201Tl scintigraphy, compared with five out of seven by mammography. Thallium scintigraphy would not be useful in evaluating the axilla for lymph node metastases (sensitivity 27%, specificity 77%).

The neoadjuvant treatment was active and well tolerated, but the incidence of pathologic complete remissions was relatively low.