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The aim of this prospective trial was to evaluate if 3-D ultrasound (US) brings any advantage to breast diagnostics. A total of 65 women with breast lesions (42 malignant, 23 benign) were examined preoperatively with 2-D and 3-D US. The impact of the use of the 3-D coronal plane for the visualization of the infiltrative zone in comparison to 2-D US was evaluated. Additionally, 3-D surface imaging and volumetry were performed. The coronal plane was of benefit when the infiltrative zone was unclear (6 of 8 cases) or not visible (17 of 39 cases; 43.6%) using 2-D imaging. The surface mode was advantageous for imaging complex structures (e.g., a multinodular fibroadenoma). Volumetry yielded a highly significant correlation between 2-D and 3-D US. 3-D US of breast lesions as adjunct to 2-D sonography can offer a better assessment of the infiltrative zone. Moreover, it enables accurate documentation of data.

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PURPOSE: Large-core needle biopsy (LCNB) has become a more widely used technique in the evaluation of breast lesions. This study was undertaken to access the accuracy of percutaneous LCNB on breast lesions and the impact on further proceeding. METHODS: A retrospective review of imaging-guided LCNB of 159 breast lesions was done. 143 LCNB were taken with ultrasound guided automated spring gun biopsy and 16 stereotactic-guided with vacuum-assisted biopsy device. Histology and morphobiological parameters were compared with subsequent material from surgery. RESULTS: In 113 core biopsies (71%), an infiltrating breast cancer was diagnosed, 5 biopsies (3%) yielded in-situ/atypical lesions and a benign lesion was shown in 38 cases (24%). In 3 cases, insufficient/necrotic material was obtained. 108 patients underwent subsequent surgery. In 100/108 cases (93%), histology on LCNB and surgery was identical. LCNB was false negative in 5 core biopsies (5%). Immunhistochemical stains of hormone receptors, bcl-2, c-erbB-2, p53 and MIB-1 was comparable on LCNB and on surgical material. Based on the results of LCNB, 17/113 patients (15%) with infiltrating carcinoma were primarily treated with hormones or with neoadjuvant therapy. 32/38 patients (84%) with benign lesions were followed up by imaging control. CONCLUSIONS: In patients with benign lesions on imaging, open biopsies can be avoided by LCNB. In patients with biopsy proven carcinoma, therapy planning is improved. The addition of morphobiological parameters allows early individual treatment.

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OBJECTIVE: Interventional techniques allow a microinvasive diagnostic of breast lesions. We examined the reliability of large core needle biopsies for histologic diagnosis on breast lesions. MATERIAL AND METHODS: 143 ultrasound guided automated spring gun biopsies and 16 stereotactic guided vacuum-assisted device biopsies were analyzed. Indications included confirmation of malign or benign lesions and diagnosis of suspicious lesions. RESULTS: In 113 biopsies (71%) an invasive breast carcinoma was diagnosed, in 5 biopsies (3%) in situ/atypical lesions were seen and 38 cases (24%) showed benign lesions. Based on the bioptic results, 108 patients underwent subsequent surgery. An identical histology was seen in 100/108 patients (93%), 5 biopsies were false negative (5%) and 3 specimens yielded necrotic/insufficient material. The immunohistochemical results of percutaneous biopsies and surgical specimens were comparable. 17 out of 113 patients (15%) with biopsy proven carcinoma were treated with neoadjuvant therapy. 32/38 patients with benign lesions were follow-up clinically. CONCLUSION: Ultrasound- or stereotactic guided percutaneous biopsies are methods to confirm histological diagnosis. Based on the biopsy results the, number of surgical excisions can be reduced and treatment of biopsy proven carcinoma can be improved by individual presurgical planing.

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Long-term i.m. or s.c. injections of interferon-alpha, beta, and gamma(IFN) in patients with chronic myelogenous leukemia (CML) can cause severe, long-lasting cutaneous complications consistent with necrotizing vasculitis. The purpose of this study was to describe the cutaneous lesions and the course of illness in 7 well-documented patients with Philadelphia chromosome-positive (Ph+) CML treated with IFN. We reviewed 7 patients diagnosed with Ph+ CML at M.D. Anderson Cancer Center between 1983 and 1994 who experienced cutaneous lesions at the injection site after treatment with i.m. or s.c. IFN (3 patients treated with IFN-alpha, 3 with combined IFN-alpha and IFN-gamma, and 1 with IFN-beta). According to pathology reports available for 3 patients, the cutaneous lesions seem to be consistent with necrotizing vasculitis. The skin reactions occurred independent of the IFN type, administration modality (i.m. or s.c.), duration of previously received IFN therapy (3-108 months), stage of disease, and cytogenetic response to IFN treatment. Of 7 patients, 4 developed low-grade fever during the occurrence of skin reactions, but all cultures taken from the abscesslike lesions were negative for bacterial or fungal infection. These lesions either did not resolve and required surgical debridement (5 patients) or resolved slowly with conservative management that included discontinuation of IFN at the specific, involved site. Independent of the IFN type or i.m. or s.c. injections, IFN can cause painful and long-lasting cutaneous lesions that frequently require surgical intervention. Whether this is a result of the high concentration of IFN at the injection site, the diluent, or an immunologic reaction remains unclear.

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This study was performed to analyze the relevance of iliac crest biopsy in patients with primary breast cancer with regard to metastases of the primary tumor and osteogenic disease. We performed intraoperative bilateral biopsy of the anterior iliac crests in 1465 patients with primary breast cancer. The bone specimens were histologically evaluated with regard to quality of the biopsy, tumor involvement, and osteogenic and hematogenic disease. Accurate and clear evaluation of the iliac crest biopsies was possible in 1365 patients (93%). Osteopenia was diagnosed in 48 patients (3.5%); 24 patients (1.7%) showed histological evidence of tumor involvement of the skeletal system. All these 24 patients received systemic (adjuvant) therapy after surgery. Ten patients had micrometastases, although in 5 of them both the postoperative bone scan and X-rays showed no pathological results. In 10 women with histologically negative bone biopsies, metastases to the bone were diagnosed by bone scan and radiological methods. Random perioperative iliac bone biopsy cannot be recommended in patients with primary breast cancer. Iliac crest biopsy is relevant in certain scenarios (e.g. suspected recurrence, doubtful bone scan).

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Patients with an elevated level of urokinase plasminogen activator (uPA) in breast cancer tissue have an adverse prognosis. This study evaluated the prognostic relevance of uPA detection in disseminated tumour cells in bone marrow. Bone marrow was sampled intraoperatively from both iliac crests in 280 patients with primary breast cancer. Interphase cells were enhanced and stained immunocytologically with two antibodies: 2E11, which detects TAG 12--a tumour-associated glycoprotein typically expressed by almost all breast cancer cells--and the anti-uPA antibody HD-UK9. Thirty-five of the 2E11-positive women (n = 132, 47%) developed metastatic disease (median follow-up time 44 months). Of these, most were uPA positive (n = 23, 65%) and only 12 were uPA negative. Patients with uPA-positive cells in bone marrow (n = 98, 35%) had a significantly shorter metastasis-free interval (36 months) than women who were uPA negative (44.5 months). The worst prognosis was seen in patients positive for both markers (29.5 months), followed by those who were uPA negative and 2E11 positive (37 months). The detection of uPA on disseminated tumour cells characterizes a subgroup of patients with an even worse prognosis, who should undergo more aggressive adjuvant systemic therapy. For the first time, it was possible to evaluate an important qualitative parameter involved in the process of breast cancer metastases.

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The antigen levels of urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor (PAI) 1, as detected in tumor extracts by ELISA, have been reported to be correlated with a poor prognosis in primary breast cancer. In the present study we have characterized a novel PAI-2-specific ELISA, designed to measure PAI-2 antigen levels in tumor cytosols. We determined PAI-2 antigen levels along with those of uPA and PAI-1 in 1012 routinely prepared tumor cytosols of patients with primary breast cancer (median follow-up, 71 months). In the overall population there was no significant association between the level of PAI-2 and prognosis, while in tumors with high uPA values, PAI-2 (test for trend) was associated with a prolonged relapse-free survival, metastasis-free survival, and overall survival (for all analyses, P < 0.02). In Cox's multivariate analysis for relapse-free survival, metastasis-free survival, and overall survival in tumors with high uPA values (including patient's age, menopausal status, lymph node status, tumor size, estrogen and progesterone receptor status, uPA, and PAI-1), PAI-2 either dichotomized or, as a continuous variable, was independently associated with a favorable relapse-free survival, metastasis-free survival, and overall survival. We conclude that the PAI-2-specific ELISA described herein is well suited for the measurement of PAI-2 levels in cytosols routinely prepared for analysis of steroid hormone receptors. We speculate that PAI-2 may serve as an inhibitor for uPA in human primary breast cancers.

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