Factors associated with negative margins of lumpectomy specimen: potential use in selecting patients for intraoperative radiotherapy.

BACKGROUND: Lumpectomy followed by radiation is standard treatment for early breast cancer. Recently, the use of partial breast intraoperative radiation (IORT) has been developed, and patients selected for IORT should not have positive margins. This study's purpose was to identify factors predicting negative margins after lumpectomy. METHODS: Patient age, preoperative investigations, surgery, final pathology, and margin status were examined using a prospective database between 1999 and 2005. Univariate and multivariate logistic regression analysis were performed to identify patient and tumor factors predicting an increased rate of negative margins. The results were used to generate a patient selection algorithm. RESULTS: The rate of positive margins at first resection was 17% in 730 lumpectomies (708 patients). Multivariate analysis revealed that older age (P = .0006), smaller tumor size (P < .0025), type of surgery (OR = 3.4 for ultrasound vs mammogram-guided wire localization, P = .003), and having a core needle biopsy (CNB) with preoperative cancer diagnosis (P < .0001) were predictive for having a negative margin. Patients older than age 50 with a preoperative CNB showing invasive cancer less that 3 cm that can be localized under ultrasound had a negative margin rate of 98% (n = 178). These patients would be ideal for consideration of IORT. CONCLUSIONS: Negative margin rates after lumpectomy are predicted by age, tumor size, preoperative investigations, and localization technique. These variables can be used to select patients for IORT with a 2.2% chance of positive margins.

Microdissection and molecular genetic analysis of HER2/neu in breast carcinoma.

Precise correlation of histomorphology with molecular genetic analysis is difficult in tissues composed of heterogeneous cell populations. We describe here a novel microdissection technique employed to correlate HER2/neu (HER2) immunohistochemical staining with HER2 genetic analysis in formalin-fixed, paraffin-embedded breast tissue. Fourteen invasive ductal carcinomas were selected from the pathology files of Memorial Sloan-Kettering Cancer Center that had been immunostained for HER2. Seven tumors showed typical membrane immunoreactivity and seven were negative. A dissecting microscope was then used to isolate minute (< or = 1 mm x 1 mm) areas of invasive carcinoma and normal breast tissue for molecular study. To document the type of cell sample submitted for polymerase chain reaction (PCR) analysis, each microdissected piece of tissue was photographed prior to removal from the glass slide. A preliminary study of four cases compared the results of PCR and genetic analysis using microdissected hematoxylin and eosin (H & E)-stained tissue, unstained dewaxed tissue, and destained dewaxed tissue in four specimens. Similar results were obtained with all three tissue preparations. Thereafter, H & E stained sections were selected as the tissue preparation of choice because tissue details were seen more clearly. There was complete correlation of immunohistochemical staining and HER2 analysis by PCR in all 14 cases. In the final 10 cases, the PCR product was resolved by gel electrophoresis and quantified by optical densitometry. Fourfold to eightfold amplification of HER2 was found in the five tumor specimens that immunohistochemically stained for HER2. A single copy of HER2 was found in all HER2-negative tumors and in normal breast tissue. We conclude that it is possible to quantify gene amplification of HER2 in minute samples of H & E-stained normal and malignant breast tissue. This microdissection technique can be applied to correlative histologic--molecular genetic analysis in a wide variety of tumor types.

Displacement of carcinomatous epithelium in surgical breast specimens following stereotaxic core biopsy.

A variety of needling procedures in the breast may lead to dislodgment and displacement of fragments of breast carcinoma into tissue outside the target lesion of the needling procedure. To assess how frequently displaced fragments of carcinoma are seen in surgical breast specimens following stereotaxic core needle biopsies, slides were reviewed from 43 consecutive cases of breast carcinoma in which surgical excision and/or mastectomy had been performed following an initial diagnostic stereotaxic 14-gauge core biopsy procedure. In 12 of 43 (28%) cases, displaced carcinomatous fragments were identified outside of the main tumor mass. These patients were subjected to other needling procedures that included local anesthetic injection at the time of core biopsy (43 cases), needle localization (22 of 43 cases), suture placement (18 of 43 cases), and fine-needle aspiration (1 of 43 cases). Attributing carcinomatous displacement solely to the core needle biopsy is complicated by these additional needling procedures. In 18 instances, local anesthetic injection by 25-gauge needle was the only needling procedure other than the core biopsy. In 7 of these 18 (39%) cases, fragments of displaced carcinoma were observed outside the main tumor mass. The authors have previously observed only one case in which a 25-gauge needle was associated with epithelial displacement, suggesting that the core biopsy was more likely to have been the cause of displaced epithelium in these cases. Long-term clinical follow-up will be necessary to determine the biologic and clinical significance of these findings.

Epithelial displacement in surgical breast specimens following needling procedures.

Lesional breast tissue is often subjected to various needling procedures prior to resection and formal histologic examination. In this article, we describe a series of 29 surgical breast specimens in which histologic examination revealed fragments of benign or malignant epithelium displaced in breast stroma or in lymphovascular channels, associated with the traumatic effects of a needling procedure. Follow-up revealed that a variety of different interventions, including needle localization, fine-needle aspiration, infiltration with local anesthetic, core biopsy, and suture placement, preceded the surgical resection in these instances. The displaced epithelial fragments mimic stromal invasion to a variable degree and may represent a potential source of misdiagnosis. The incidence and biological significance of epithelial displacement in this context are as yet unknown.

Modulation of positive inotropy and metabolic coronary dilatation by myocardial alpha-adrenoceptors.

Cardiac hyperactivity and its consequent metabolically induced coronary vasodilation (MCD) were studied in isolated, perfused, electrically paced rat hearts. The alpha-adrenoceptor agonists, phenylephrine and methoxamine, produced a concentration-dependent inhibition of the inotropic responses to noradrenaline, dobutamine, isoprenaline, tyramine, and glucagon, while relatively potentiating their MCD reactions. This inhibition was unrelated to the alpha-agonists' known inotropic action and was not affected by catecholamine depletion of the heart. Withdrawal of the alpha-agonists or administration of the alpha-adrenoceptor antagonists phentolamine, phenoxybenzamine, or prazosin returned the inotropic and MCD reactions to normal. Neither the MCD response to electrically induced tachycardia nor the inotropic reactions produced by calcium chloride were affected by alpha-adrenoceptor agonists or antagonists. Alone, alpha-adrenoceptor antagonists were shown to potentiate the inotropic responses to noradrenaline and isoprenaline while the MCD was relatively diminished. The responses to glucagon were unaltered by alpha-antagonists. We postulate that myocardial reactivity to sympathetic stimulation can be modulated through alpha-adrenoceptors by the inhibition of processes that mediate cardiostimulation at post-beta-adrenoceptor sites, together with facilitation of those leading up to MCD. Accordingly, this modulation would act to prevent ischaemic damage to the heart by acting to limit the inotropic responses to increasing sympathetic stimulation while maximizing the blood supply to the myocardium.