Effect of anastrozole and tamoxifen on lipid metabolism in Japanese postmenopausal women with early breast cancer.

Endocrine therapies that profoundly decrease estrogen levels potentially have a detrimental effect on the cardiovascular system. This study evaluated the effect on lipid metabolism of one such agent, the new generation aromatase inhibitor anastrozole, compared with tamoxifen, when used as adjuvant treatment in postmenopausal Japanese women with early breast cancer. All patients had completed primary surgery and were randomized to anastrozole 1 mg once daily (n=22) or tamoxifen 20 mg once daily (n=22). Anastrozole significantly reduced levels of triglycerides and remnant-like particle cholesterol, whereas tamoxifen significantly increased these. Activity of lipoprotein lipase and levels of high-density lipoprotein cholesterol significantly increased after anastrozole treatment. In contrast, activity of hepatic triglyceride lipase, also a key enzyme of triglyceride metabolism, significantly decreased following treatment with tamoxifen. We thus conclude that in our study anastrozole had a beneficial effect on lipid profiles of postmenopausal women with early breast cancer after 12 weeks of treatment.

Correlation of KIT and EGFR overexpression with invasive ductal breast carcinoma of the solid-tubular subtype, nuclear grade 3, and mesenchymal or myoepithelial differentiation.

Although KIT and EGFR overexpressions are reported to occur in breast cancer, their pathological significance is still unclear. We examined KIT, EGFR, and c-erbB-2 overexpressions immunohistochemically in 150 cases of surgically resected breast cancer and their correlation with the histological type and grade and mesenchymal and/or myoepithelial immunophenotype of primary tumors. To facilitate the analysis, we constructed a tissue microarray comprising 2-mm diameter tissues cored from the representative tissue block of each tumor. KIT, EGFR, and c-erbB-2 overexpressions were detected in 15 (10%), 12 (8%), and 23 (15%), respectively. The KIT was more frequent in the group comprising comedo-type ductal carcinoma in situ and invasive ductal carcinomas (IDCs) of the solid-tubular subtype than in the group of other histological types (P=0.027), and the EGFR was more frequent in IDCs of solid-tubular type than in other histological types (P <0.05). KIT and EGFR overexpressions were correlated with nuclear grade 3 (P=0.0095 and 0.0005) and tended to be concurrent (P=0.005). KIT overexpression was correlated with vimentin and S-100 expression (P=0.003 and P=0.005), and EGFR overexpression was correlated with S100 expression (P=0.0001). These correlations with grade and mesenchymal/myoepithelial markers were not observed for c-erbB-2 overexpression. KIT and EGFR appeared to be indicators of high-grade breast carcinoma groups that often contain the carcinomas with mesenchymal and/or myoepithelial differentiation, which are distinct from the group with c-erbB-2 overexpression.

Optimal particle size of radiocolloid for sentinel node identification in breast cancer-electron microscopic study and clinical comparison.

BACKGROUND: Sentinel node (SN) biopsy using a radiotracer is easy to learn, reproducible, and performed by the majority of breast cancer surgeons. However, this technique raises the question: what is the optimal particle size of colloid? METHODS: Patients were injected with conventional tin colloid (median particle diameter: 700 nm) and the predominant particle size of radiocolloid retained in the SN was measured using electron microscopy. This showed a narrow distribution of colloidal size (100-150 nm). Patients were then injected with modified tin colloid having a median particle size of 100 nm. A clinical comparison was performed between conventional particle size or reduced particle size tin colloid and the SN biopsy success rate, the number of SNs, and the colloidal uptake in SNs. RESULTS: A total of 118 patients were injected with the conventional tin colloid (group I) and 124 patients with the smaller particle colloid (group II). The identification rate and the number of SN in both groups were almost equal, and the patients with low-uptake SNs were not significantly less in group I(p = 0.55). However, in the subgroup of patients 60 years of age or more, group II had significantly more SNs than group I(1.4 vs 1.9; p = 0.03) and low-uptake SNs were significantly less common than in group I(p = 0.02). CONCLUSIONS: The improvement of colloidal uptake in SNs using the smaller particle size tin colloid was confirmed, and this impact was statistically significant in the older population.

[Advances in sentinel node biopsy for breast cancer].

SN biopsy (SNB) has evolved rapidly during the past decade and has now become a standard of surgical care for patients with breast cancer. The primary purpose of SNB is to minimize patient morbidity from axillary staging, but SNB also presents research opportunities to further understand the role of the sentinel node in the natural history of breast cancer. We have attempted to highlight several issues regarding SN and its biopsy in this review, including:(1) Investigation of the optimal particle size for radiotracers. The success of SNB is, in large part, attributed to the particle size of radiolabeled tracers. Electron microscopy demonstrated significant accumulation of the tracer (tin colloid) in harvested SN, of which particle sizes were in the range of 100-150 nm. Therefore, this appeared to be a suitable particle size for SN identification. (2) Invention of a new gamma probe. A cord-and boxless handheld gamma probe was invented, which was more sensitive to radioactivity and involved a background subtraction function based on defined criteria. (3) Characterization of the immunologic response against tumor antigens. Fluorescence-activated cell sorting (FACS) analyses were performed to determine the phenotypic characteristics of B cells and T cells in SN. They revealed an increase in B cells expressing co-stimulated molecules as antigen-presenting cells in SN, compared with non-SN. With respect to T cells, a heterogeneous pattern of naive and memory T cells (TCM) was demonstrated in SN, in contrast to homogeneous pattern with TCM in non-SN. These results may support the concept that B cells play a significant role in antigen presentation required for T cell activation. Studies are currently in progress to test these possibilities.

Utility of axillary ultrasound examination to select breast cancer patients suited for optimal sentinel node biopsy.

BACKGROUND: Because sentinel node (SN) biopsy (SNB) is known to produce false-negative results, we examined the usefulness of axillary ultrasound (AUS) in selecting patients suitable for optimal SNB. METHODS: A positive AUS finding (positive AUS) was defined as an echo pattern of a homogeneously hypoechoic SN without an echo-rich center, indicating massive to extensive nodal involvement. The identification of SNs was performed, and complete axillary dissection was carried out. RESULTS: A total of 262 women were enrolled into the study (T1 disease = 94; T2 disease = 145; and T3 disease = 23). The incidence of positive AUS increased with increasing size of breast tumor (P <0.0001). The overall identification and false-negative rates were 88.2% and 10.8%, respectively. However, when limited to AUS-negative patients, SNs were identified in 205 of 208 patients (98.6%), and the false-negative rate was 1.7%. CONCLUSIONS: AUS should be included in the preoperative procedure for the selection of breast cancer patients suitable for SNB.

Clinicopathologic and technical factors associated with the uptake of radiocolloid by sentinel nodes in patients with breast cancer.

PURPOSE: Sentinel-node biopsy is becoming widely accepted in breast cancer treatment. Using the radioisotope technique, a lower risk of identification failure is related to the amount of radiocolloid in the sentinel nodes. The aim of this study was to identify the factors associated with the colloidal uptake of the sentinel nodes. METHODS: Technetium-labeled colloid was injected peritumorally, with or without subdermal injection. According to the maximum radioactivity of the sentinel nodes, patients were divided into high (>/=100 counts/s) or low (<100 counts/s) uptake groups. The uptake was compared in relation to the clinicopathologic and technical features. RESULTS: The sentinel node was identified in 183 of 186 patients (98.4%), with 60 and 123 patients in the low- and high-uptake groups (mean: 39 and 1003 counts/s), respectively. Multivariate analysis showed that an age of 65 years or older and a sentinel-node size of 8 mm or more were significantly more predominant in the low-uptake group. CONCLUSION: Care must be taken when performing sentinel-node biopsy, especially for aged patients and for those with large sentinel nodes. The optimal technique should be determined on the basis of these results.

Clinically useful detection criteria for sentinel nodes in patients with breast cancer using a radioisotope technique.

BACKGROUND: The radioisotope technique has been used to identify sentinel nodes in patients with breast cancer. However, quantitative analysis of the radioactivity for detecting the sentinel nodes was not previously examined. In this study, we considered a clinically useful criterion for detecting sentinel nodes by a detailed analysis of 312 sentinel nodes using the radioisotope technique. PATIENTS AND METHODS: Patients with T1-2, N0 breast cancer were eligible for this study. The nodes with the highest radioactivity after injection of technetium-labeled tin colloids were identified as hot nodes. The radioactivities of the hot nodes and the background counts of the axillary basin were examined in order to establish new criteria for detecting the sentinel nodes. RESULTS: Between May 1997 and December 2001, 312 hot nodes were detected in 183 of 186 patients (98.4%). Since the false-negative rate for metastasis in hot nodes was only 2.1% (1/48), they could serve as sentinel nodes to predict the nodal status. However, there was a wide distribution of the hot nodes and the background in terms of absolute counts and a criterion for the sentinel nodes could not be established in terms of the absolute counts. When we adopted the criterion of sentinel nodes with a >/=100 count ratio in relation to the background, only 169 hot nodes (54.3%) met our definition. When the criterion of a >or=10 count ratio was adopted, all hot nodes met our definition and all other nodes remained non-sentinel nodes. CONCLUSION: The criterion for defining sentinel nodes in our method is a node with a >or=10 count ratio with respect to the background. It is recommended that an analysis based on such objective data should be investigated in order to provide surgeons with more accurate and clinically useful criteria for detecting sentinel nodes.