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INTRODUCTION: The unexpected diagnosis of breast cancer following total duct excision is distressing for patients. Despite advances in radiology and the description of suspicious nipple discharge, pre-operative diagnosis of malignancy still evades us. The aim of this study was to review the pathological findings of total duct excision and microdochectomy with reference to pre-operative symptoms, ultrasound, or mammographic findings and identify features associated with increased likelihood of malignant disease. METHODS: Data were collected retrospectively of all patients who underwent total duct excision surgery in a single centre (2011-2017). Pre-operative demographics, symptoms, and imaging findings were recorded and correlated with subsequent pathology. RESULTS: 214 patients underwent total duct excision; data were available for 211. Median age was 53 years. 175/211 (82.9%) patients had benign pathology (duct ectasia, papilloma without atypia, fibrocystic change) on final histological examination, 21/211 (10%) had "risk" lesions (papilloma with atypia, atypical ductal hyperplasia), and 15/211 (7.1%) had malignancy (ductal carcinoma in situ). Of the 15 patients with malignant lesions, 6/15 (40%) had normal imaging (M1, U1). 71/211 (33.6%) had normal imaging (M1, U1): 60/71 (84.5%) had benign disease, 5/71 (7%) had "risk" lesions, and 6/71 (8.5%) had malignant lesions. 83/211 (39.3%) patients presented with bloody discharge: 64/83 (77.1%) had benign pathology, 9/83 (10.8%) risk, and 10/83 (12%) malignancy. 38/211 (18%) patients presented with non-bloody discharge: 32/38 (84.2%) had benign disease, 4/38 (10.5%) risk, and 2/38 (5.3%) malignant lesions. CONCLUSION: Neither imaging nor presenting symptoms correlate with the likelihood of malignant disease being present at final pathology. Even with advances in pre-operative diagnosis, total duct excision remains an essential diagnostic and therapeutic procedure.
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OBJECTIVE: The aim of this study was to describe the pharmacokinetics of 3 different single doses of fulvestrant-a new estrogen receptor (ER) antagonist that downregulates the ER with no known agonist effects-administered as a prolonged-release IM formulation. METHODS: Pharmacokinetic data were obtained in a randomized, partially blinded, placebo-controlled, parallel-group, Phase I/II multicenter trial involving postmenopausal women with primary breast cancer (clinical stages T1-T3, with tumors that were ER positive or of unknown ER status) awaiting curative-intent surgery. Patients received either IM fulvestrant (50, 125, or 250 mg), oral tamoxifen (20 mg, once daily), or oral placebo (once daily). Treatment started 2 to 3 weeks before surgery and blood was taken at various times up to 12 weeks after fulvestrant administration to assess pharmacokinetic variables. RESULTS: A total of 200 patients entered the trial, of whom 58 took part in the pharmacokinetic analysis (50 mg, n = 20; 125 mg, n = 16; 250 mg, n = 22). Following single IM injections of fulvestrant, the median time to maximum concentration was 6.98, 6.98, and 6.96 days in the 50-, 125,- and 250-mg dose groups, respectively, with an overall range of 2 to 19 days). The plasma concentration-time profiles were primarily controlled by the rate of absorption from the injection site; post-peak plasma concentrations declined over time and were measurable up to 84 days after administration of fulvestrant 125 and 250 mg. Plasma concentrations at 28 days were 2- to 5-fold lower than the maximum value. Plasma concentration data for the 250-mg dose were best described by a 2-compartment pharmacokinetic model, with an apparent terminal phase half-life of approximately 49 days, beginning approximately 3 weeks after administration. Mean area under the plasma concentration-time curve for days 0 through 28 (AUC 0-28) was proportional for fulvestrant 50, 125, and 250 mg. For a doubling of the dose, an analysis of covariance model of the pharmacokinetic data projected an estimated increase in AUC 0-28 of a factor of 1.84 (95% CI, 1.67 to 2.04). CONCLUSIONS: The IM formulation of fulvestrant used in this study had predictable, dose-linear pharmacokinetics. The prolonged-release properties of this formulation suggested that it may be well suited for the once-monthly dosing schedule intended for clinical use.
