Treatment of recurrent breast cancer following breast conserving surgery.

Patients with isolated ipsilateral breast cancer recurrence face completion mastectomy in the majority of cases. Selected patients may derive good outcomes from repeat breast conservation surgery and indeed repeat irradiation may be employed using one of many different modalities. Tumor biology rather than salvage surgery method is likely to influence outcome. Patients with isolated breast tumor recurrence are treated in the majority of cases with completion mastectomy, when for selected patients there exists little evidence that more radical surgery provides better outcomes in terms of further recurrence and overall survival, than repeated breast conserving surgery. Literature search identifying articles addressing the issue of repeat breast conserving surgery for ipsilateral breast tumor recurrence, and repeat radiotherapy(search terms include: repeat breast conserving surgery, salvage mastectomy, salvage breast conserving surgery,salvage radiotherapy, reirradiation). Thirty-five articles discussed the outcomes of repeat breast conserving surgery versus salvage mastectomy, methods of repeat breast irradiation, repeat sentinel lymph node biopsy and related factors. Repeat breast conserving surgery may represent a safe and feasible treatment method for isolated ipsilateral breast tumor recurrence.

Short-term effects of axillary lymph node clearance surgery on lymphatic physiology of the arm in breast cancer.

It is not known why some women develop breast cancer-related lymphedema (BCRL) of the arm, whereas others having similar treatment do not. We speculated that increased uptake of protein into local blood may protect against BCRL. Sixteen women were given bilateral subcutaneous hand webspace injections of polyclonal immunoglobulin (HIgG), (99m)Tc-HIgG on one side and (111)In-HIgG on the other, before and 3 mo after axillary clearance surgery. The rates of clearance of activity from the depot (k) and accumulation in central blood (b(contra)) were measured using a scintillation probe and bilateral antecubital vein blood sampling, respectively. Activity accumulating in blood ipsilateral to the injected side, in excess of central blood activity (b(ipsi)) was also calculated as a measure of local vascular uptake. The k correlated with b(contra), but neither changed in response to surgery. However, b(ipsi) for injections of (99m)Tc-HIgG into the affected arm increased in all seven patients in whom data were available (0.018 +/- 0.006 to 0.038 +/- 0.007%/min; P < 0.05); indeed, in five of these seven, b(ipsi) paradoxically exceeded b(contra), and none developed BCRL at 3-yr follow-up. We conclude that uptake of protein into local blood and/or proteolysis increases after axillary surgery and may protect against BCRL.

Local vascular access of radioprotein injected subcutaneously in healthy subjects and patients with breast cancer-related lymphedema.

UNLABELLED: The aim of the study was to use dual-isotope lymphoscintigraphy in healthy volunteers and women with breast cancer-related lymphedema (BCRL) to detect and quantify transport of radiolabeled protein from a subcutaneous injection depot to local blood vessels as a potential mechanism of protection against edema resulting from treatment to the axilla. METHODS: A total of 29 subjects and 18 women with a history of BCRL received bilateral subcutaneous injections of human IgG (HIgG) in the second dorsal web space of each hand, (99m)Tc-HIgG on one side and (111)In-HIgG on the other. In 8 further healthy subjects, epinephrine was administered with the labeled HIgG. Radioactivity at each depot was measured at regular intervals for a total of 3 h using a collimated sodium iodide scintillation detector, and radioactivity in venous blood sampled from both arms was measured using an automatic sample counter. Ipsilateral blood time-concentration curves were corrected for recirculating activity by subtraction of the simultaneous contralateral concentration, to define the component of ipsilateral blood resulting from local vascular access of radioprotein. Accumulation of activity in blood was expressed in relation to injected activity and activity that had left the depot and was calculated as a function of time-in systemic blood, by multiplying contralateral concentrations by an estimate of the subject's blood volume, and in ipsilateral blood, by using indicator dilution theory and an assumed forearm blood flow of 20 mL/min. RESULTS: (99m)Tc-HIgG and (111)In-HIgG behave almost identically with respect to depot clearance and accumulation in contralateral venous blood, with or without epinephrine, which reduced both depot clearance and blood accumulation rate. Moreover, a side-to-side correlation with respect to contralateral accumulation was present in healthy subjects, was not abolished by epinephrine, and was maintained in the face of asymmetric accumulation in BCRL. Contralateral accumulation of radioprotein was reduced in BCRL after injection into the affected side only when the hand was involved. In contrast to contralateral sampling, ipsilateral time-concentration and accumulation profiles were consistent with instability of (111)In-HIgG and rapid local vascular access of small amounts of protein-free (111)In. Experiments based on precipitation of protein with trichloroacetic acid confirmed relatively high levels of unbound ipsilateral (111)In, especially in samples obtained early after injection. Substantial accumulation of protein-bound (99m)Tc was observed in ipsilateral blood, with a time course similar to that of contralateral accumulation. Positive correlation between ipsilateral and contralateral blood (99m)Tc activity was observed at all time points, often significantly, in contrast to (111)In, for which it was negative at all time points. Ipsilateral accumulation of (99m)Tc adjusted for activity that had left the depot was unchanged with respect to the affected arm in BCRL patients. CONCLUSION: Whereas (111)In-HIgG and (99m)Tc-HigG are interchangeable for measurement of depot clearance and contralateral venous accumulation rates, ipsilateral sampling is much more sensitive to protein-free radionuclide and detects significant differences resulting from some instability of (111)In-HIgG. On the basis of (99m)Tc data, there appears to be substantial local vascular access of radioprotein within the arm, both in healthy subjects and in patients with BCRL, through either lymphaticovenous communications or direct transendothelial transport.

Side-to-side symmetry of radioprotein transfer from tissue space to systemic vasculature following subcutaneous injection in normal subjects and patients with breast cancer.

Quantitative lymphoscintigraphy can be used for investigation of unilateral lymphatic disease of the limbs, such as breast cancer-related lymphoedema (BCRL). Previous studies have compared lymphatic function in the affected limb with that in the unaffected contralateral limb. This study aims to confirm that the assumption of pre-morbid symmetry, never previously demonstrated, is valid. A dual-isotope technique, with bilateral subcutaneous hand injection of polyclonal human immunoglobulin G (HIgG) labelled with either technetium-99m or indium-111, was performed on a total of 37 subjects. The use of two different labels, one for each limb, enabled comparison not only of the rate of clearance from the injection depot, but also of the rate of appearance in venous blood. Results demonstrate clear symmetry between the two arms with respect to both depot clearance and blood appearance rates, as well as the coupling between these two variables. In unilateral lymphatic disease, results of quantitative lymphoscintigraphy should be expressed in relation to the normal arm rather than to an independent control population.

Quantification of lymphatic function for investigation of lymphedema: depot clearance and rate of appearance of soluble macromolecules in blood.

UNLABELLED: The object of this study was to develop a new technique for the quantitative measurement of lymphatic function. The rate of clearance of radiolabeled protein from a subcutaneous depot is supplemented by measurement of the appearance of the protein in venous blood. This initial study was performed on normal arms, with a view to subsequent clinical application such as in the investigation of women with breast cancer--related lymphedema (BCRL). METHODS: Fourteen healthy volunteers (12 women, 2 men) and 8 women awaiting surgery for breast cancer were recruited for the study. Each received subcutaneous depot injection of protein solution in the second dorsal web space of each hand, labeled with (111)In on one side and with (99m)Tc on the other side. Human serum albumin (HSA) was the protein used in the first 8 subjects and human polyclonal immunoglobulin G (HIgG) was used thereafter. The activity at each depot was measured at regular intervals using a collimated sodium iodide scintillation detector, and the activity in venous blood sampled from both arms was measured in an automatic sample counter. RESULTS: (99m)Tc-HSA cleared from the depot consistently faster than (111)In-HSA (P = 0.001). The proportions of radionuclide remaining bound to protein in venous blood were higher for (99m)Tc than for (111)In. HIgG displayed improved labeling stability for both nuclides, reflected in equal rates of clearance. Blood activity rose steadily after an early latent phase and for HIgG correlated strongly with the rate of clearance from the depot (P < 0.001). Marked variation between individuals was observed. CONCLUSION: A dual-isotope technique relies on identical behavior of the 2 radiopharmaceuticals used. This study shows that this is the case with respect to HIgG but not HSA. (99m)Tc-HSA cleared faster than (111)In-HSA and yet displayed better in vivo labeling stability. We conclude that (111)In dissociates from HSA in the depot but then becomes locally bound. Using HIgG, a close correlation was observed between the rates of clearance from the depot and the appearance in venous blood. This finding suggests that HIgG would be a suitable marker for subsequent dual-isotope studies on women with BCRL.