Comparison of HER-2/neu, ER and PCNA expression in premenopausal and postmenopausal patients with breast carcinoma

We attempted to compare the pattern of HER-2/neu, ER and PCNA in premenopausal and postmenopausal patients with breast carcinoma to identify potential biological differences. Five hundred and forty-eight samples from 318 premenopausal and 230 postmenopausal women with invasive ductal carcinoma of the breast were evaluated for HER-2/neu, ER and PCNA expression by immunohistochemistry. HER-2/neu expression showed 27.4% positivity in premenopausal and 24.8% in postmenopausal women; there was no significant difference between the two groups (p>0.05). In contrast, HER-2/neu expression was found to be significantly associated with ER negativity in the two groups (p<0.05 in premenopausal, p<0.001 in postmenopausal patients). However, it was significantly associated with PCNA expression only in the postmenopausal group (p<0.001). 54.4% showed premenopausal tumor cell ER positivity, whereas 64.3% of the postmenopausal group showed positivity. ER expression showed a significant correlation with patient menopausal status (p<0.05). The prevalence of PCNA positivity in the tumor cell components is slightly higher in postmenopausal compared to premenopausal women (p>0.20). The current study is consistent with reports from other groups regarding the correlation of HER-2/neu with adverse pathologic features and with expression of other markers in carcinoma. We also observed there was no trend toward increased HER-2/neu expression in either premenopausal or postmenopausal patients, i.e. there was similar HER-2/neu expression in the two groups. This suggests that HER-2/neu status could be used to determine assignment to specific intensive adjuvant therapy and evaluation of biological behavior in both pre- and postmenopausal patients with breast carcinoma.     

Improved survival in patients with recurrent Wilms tumor: the experience of the Seoul National University Children's Hospital

The survival in cases with relapsed Wilms tumor is dismal. Recently, however the introduction of new therapeutic agents and experimental strategies has improved the survival. We analysed the survival of patients with relapsed Wilms tumor according to the treatment period. During the early period 1983-1993, patients who had received two drugs were treated with doxorubicin and the others were treated with cisplatin and etoposide, whereas during the late period 1994-2004, patients were treated with combinations of cyclophosphamide/etoposide and carboplatin/etoposide. During the early period, 8 of 57 experienced relapse, and 8 of 41 relapsed during the late period. Only 2 patients treated during the early period survived in complete response (CR), whereas during the late period, 5 patients remained alive in CR, and 3 of those received high-dose chemotherapy (HDC) with autologous peripheral stem cell rescue (SCR). The estimated 5 yr event-free survival rate was 37.5% in the entire study group, 50% for patients in the late period, and 25% for patients in the early period (p=0.38). The survival in patients with relapsed Wilms tumor dramatically improved during the late period and HDC with SCR was one of the effective salvage strategies.     

Expression of cyclooxygenase-2, matrix metalloproteinase-2 and matrix metalloproteinase-9 in premenopausal and postmenopausal endometrial polyps

OBJECTIVES: Cyclooxygenase-2 (COX-2) and matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) are influenced by relative levels of estrogen and are involved in promoting cell proliferation and angiogenesis. The present study investigated expression of COX-2, MMP-2 and MMP-9 in endometrial polyps from premenopausal and postmenopausal women. METHODS: Premenopausal (n=18) and postmenopausal (n=22) endometrial polyps were included in the study. None of the women were using non-steroid anti-inflammatory drugs, hormone replacement therapy or any other estrogen containing pills. Immunohistochemical analysis for MMP-2, MMP-9 and COX-2 were performed on formalin fixed, paraffin-embedded tissue using the streptavidin-biotin-peroxidase technique. The cut-off value for positiviy was set to 10% and staining more than 50% was regarded as intense staining. Staining of 10-25% and 25-50% were recorded as mild and moderate, respectively. RESULTS: COX-2, MMP-2 and MMP-9 were stained in epithelial cells and stroma of premenopausal and postmenopausal endometrial polyps. Stromal expression of COX-2, MMP-2 and MMP-9 were found significantly higher in premenopausal polyps compared to postmenopausal polyps (p<0.05). There were no other significant differences in the immunohistochemical expressions in the epithelium of premenopausal and postmenopausal endometrial polyps except MMP-9. CONCLUSION: Polyps from both premenopausal and postmenopausal women express epithelial and stromal COX-2, MMP-2 and MMP-9, however immunohistochemical expression of these markers may be different due to menopausal status. This may suggest a shared pathogenesis for pre- and postmenopausal endometrial polyps.     

The effects of sulphasalazine on urinary excretion of the hydroxypyridinium crosslinks of collagen in patients with rheumatoid arthritis

Secondary osteoporosis is a feature of rheumatoid arthritis (RA). In recent years, several attempts have been made to develop specific markers for monitoring connective tissue metabolism in arthritic diseases. Our purpose, in this study was to assess pyridinium crosslinks (PYD and DPYD) excretion in relation to the activity of RA (changes related to sulphasalazine treatment). Fourty premenopausal female patients with active RA (mean age; 36.0 +/- 7.2 years), 20 postmenopausal women with active RA (mean age; 60.0 +/- 6.8 years), 23 postmenopausal women with OA (mean age; 56.1 +/- 6.6 years) and 17 premenopausal healthy subjects (mean age; 28.3 +/- 4.28 years) were enrolled in our study. All of the 40 premenopausal female patients with active RA were given sulphasalazine. The mean follow up period for these patients was 10.3 +/- 1.1 months. In all of these patients, urine samples were collected both in the active and in the inactive periods. Urine PYD and DPYD levels were measured by ELISA. Urine PYD levels were significantly higher in the active period (14.01 +/- 3.16 nmol/mmol cr) than in the inactive (8.25 +/- 4.23 nmol/mmol cr) period in patients with premenopausal RA (p < 0.05). Urine PYD levels were significantly high in postmenopausal active RA patients (19.06 +/- 3.26 nmol/mmol cr) compared to premenopausal active and ind inactive, postmenopausal inactive RA patients, osteoarthritis and healthy controls. Urine DPYD excretion was similar in patients with premenopausal RA in the active (7.46 +/- 2.13 nmol/mmol cr) and inactive periods (5.08 +/- 0.87 nmol/mmol cr) (p > 0.05). In active premenopausal RA patients, a correlation was found between PYD excretion and RAI, ESR, CRP and functional capacity (r=0.5729 p < 0.01, r=0.5953 p < 0.01, r=0.6125 p < 0.01 and r=0.6232, p < 0.01 respectively). But in the inactive period, no such correlation was was evident. In disease activity parameters did not correlate with DPYD excretion in either the active or the inactive period. As a result, urine PYD excretion was significantly high in patients with active RA. During sulphasalazine treatment, urine PYD levels decreased. This is attributed to improvement in bone destruction.     

Correlation between estrogens and serum adipocytokines in premenopausal and postmenopausal women

OBJECTIVE: The purpose of this study was to investigate the association between serum adipocytokines (adiponectin, resistin, leptin, and tumor necrosis factor alpha [TNF-alpha]) and endogenous estrogen (estrone and estradiol) levels in healthy premenopausal and postmenopausal women. DESIGN: This study included 53 healthy premenopausal women, 45 healthy postmenopausal women, and 10 postmenopausal women with the metabolic syndrome who were participating in general health examinations. A secondary analysis was performed on levels of adiponectin, resistin, leptin, TNF-alpha, estrone (E1), and estradiol (E2). RESULTS: After accounting for body mass index, TNF-alpha was significantly increased (1.5+/-0.1 vs 2.0+/-0.1 pg/mL, P<0.05) in healthy postmenopausal women as compared with healthy premenopausal women, whereas leptin was decreased (5.6+/-1.1 vs 4.0+/-1.1 ng/mL). Estrogen (E1 and E2) was positively correlated with leptin in only healthy premenopausal women, whereas estrogen did not correlate with any adipocytokine in healthy postmenopausal women. In the multiple regression analysis, only leptin significantly contributed to insulin resistance. Combining healthy premenopausal and postmenopausal women, E1 correlated negatively with TNF-alpha (r=-0.23, P<0.05) and positively with leptin (r=0.35, P<0.01) and did not correlate with resistin. E2 correlated negatively with TNF-alpha (r=-0.24, P<0.05) and positively with leptin (r=0.34, P<0.01); it did not correlate with adiponectin or resistin. Leptin might stimulate the increase of plasma gonadotropin-releasing hormone levels, which could result in a positive correlation with estrogen in premenopausal women but not in postmenopausal women. CONCLUSIONS: Estrogen deficiency resulted in increased TNF-alpha levels. Serum leptin levels correlated positively with estrogen levels in premenopausal women. However, the increase in obesity in postmenopausal women increased leptin, which increases insulin resistance.     

Prediction of response to adjuvant chemotherapy in premenopausal lymph node positive breast cancer patients with morphometry, DNA flow cytometry and HER-2/neu oncoprotein expression. Preliminary results.

The value of morphometry, DNA flow cytometry and HER-2/neu oncoprotein expression for prediction of response to adjuvant chemotherapy in premenopausal lymph node positive breast cancer patients was evaluated in a group of CMF treated patients and controls with long-term follow-up. In the treated group, the Morphometric Prognostic Index (cutpoint 1.1) was the best prognosticator (p less than 0.0001, MC = 16.9), followed by the Mitotic Activity Index, the volume percentage epithelium and the number of positive nodes. For the controls, only the % HER-2/neu oncoprotein expression revealed significant differences (p less than 0.0001, MC = 16.3). When directly comparing treated patients and controls stratified for a certain parameter, no significant differences were obtained, although a trend towards improved survival in the treated group was present for some of the subgroups for several parameters. These preliminary results indicate that morphometric features and quantitative HER-2/neu oncoprotein expression may be important factors for identifying cases that will or will not respond to adjuvant chemotherapy.     

绝经前后子宫内膜息肉中肥大细胞类胰蛋白酶及类糜蛋白酶的表达及意义

目的探讨肥大细胞类胰蛋白酶(MCT)及类糜蛋白酶(MCC)在绝经前、后子宫内膜息肉组织(EP)中的表达及临床意义。方法收集120例患者标本,其中绝经前EP组和绝经后EP组各35例,绝经前正常增生期子宫内膜组和绝经后正常萎缩性子宫内膜组各25例。采用Max VisionTM/HRP免疫组织化学染色法,检测各组中MCT及MCC阳性的肥大细胞(MCs)数量并分析临床意义。结果绝经前、后EP组和正常子宫内膜组中MCT和MCC阳性的MCs计数均值分别为高倍镜下(11.82±5.24)个和(2.94±2.20)个、(4.18±2.32)个和(2.18±1.52)个、(2.19±1.80)个和(0.49±0.60)个以及(0.35±0.32)个和(0.19±0.26)个。两两比较结果显示,绝经前、后EP组MCT和MCC阳性的MCs数量明显高于同期正常子宫内膜组(P0.05);在EP组中,MCT阳性的MCs数量在绝经前高于绝经后(P0.05),而MCC阳性的MCs数量没有明显差异(P0.05);在正常子宫内膜组中,MCT和MCC阳性的MCs数量在绝经前均高于绝经后(P0.05)。结论肥大细胞(MCs)的过度活化以及伴随的炎症性损害可能是绝经前、后子宫内膜息肉形成及发展的原因。     

乳腺癌患者Heath-Carter法体型研究

目的：探讨乳腺癌患者的体型特征。方法：应用Heath—Carter体型测量法对106例女性乳腺癌患者（未绝经57例,已绝经49例）及同期到该医院体检的106名健康妇女进行体型评定并比较。结果：未绝经的乳腺癌组平均体型5．3-3．6—2．0、对照组平均体型5．3-3．6-2．0,两组比较差异无统计学意义（P〉0．05）;已绝经的乳腺癌组平均体型5．9-4．2-1．5、对照组平均体型5．14．0-1．6,两组比较差异有统计学意义（P〈0．01）。结论：乳腺癌组的平均体型是偏中胚层的内胚层体型;绝经以后体脂的增加可能与乳腺癌的发生有一定的相关性,而绝经前没有这种相关性。     

Association between respiratory function and osteoporosis in pre- and postmenopausal women

OBJECTIVE: To investigate the relationships between respiratory function and osteoporosis, 132 premenopausal and 98 postmenopausal women were evaluated. METHODS: Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry. Pulmonary function and anthropometric parameters were measured using a spirometer and a body composition analyzer. RESULTS: Lumbar spine and proximal femur BMDs in postmenopausal women with forced expiratory volume in 1s (FEV1) > or = 92.0% averaged 0.83 +/- 0.12 g/cm2 and 0.67 +/- 0.11 g/cm2, which were significantly above the values (0.76 +/- 0.14 g/cm2 and 0.61 +/- 0.12 g/cm2, P < 0.05) in those with FEV1 <92.0%. The prevalences of osteoporosis at lumbar spine and proximal femur were 59.2 and 46.9% in the postmenopausal women with peak expiratory flow rate (PEFR) <5.12 l/s, significantly higher than those of osteoporosis at the corresponding sites in the women with > or = 5.12 l/s (36.7 and 20.4%, P < 0.05). Lumbar spine and proximal femur BMDs were positively correlated with FEV1 (r = 0.28, P < 0.05; r = 0.31, P < 0.05) and PEFR (r = 0.35, P < 0.05; r = 0.23, P < 0.05) in postmenopausal women; however, no significant correlations were observed in premenopausal women. CONCLUSION: Pulmonary function seems to be more closely associated with BMD in postmenopausal women than in premenopausal women. Poor respiratory function may be an indicator of postmenopausal women at increased risk of osteoporosis.     

Quantitative ultrasound of the proximal phalanges: reproducibility in erosive and nodal osteoarthritis of the hands

The aims of the study were to evaluate the reproducibility of quantitative ultrasound (QUS) densitometry of the hands and to verify whether this method is sensitive to phalangeal bone changes occurring in osteoarthritis patients and in erosive osteoarthritis patients. We studied 60 postmenopausal women (aged 63.8 +/- 3.2): 20 had osteoarthritis, 20 had erosive osteoarthritis, 20 were postmenopausal without local pathology of the hand and eight were premenopausal (aged 23.5 +/- 3.4). The patients were evaluated by means of a DBM Sonic 1200 which is able to evaluate ultrasound transmission velocity (amplitude-dependent speed of sound). The results indicated good intra- and interoperator reproducibility (coefficient of variation = 0.99% and 1.04%) in the premenopausal group. The ultrasound device was able to discriminate between the different groups and detected differences between the QUS values of erosive osteoarthritis patients, osteoarthritis patients and control subjects. QUS densitometry is reproducible and sensitive to bone changes occurring in patients with osteoarthritis and as well as in those with erosive osteoarthritis.     

Reporting endometrial cells in women 40 years and older: assessing the clinical usefulness of Bethesda 2001

We assessed the usefulness of revised Bethesda System reporting of exfoliated benign endometrial cells (EMs) in postmenopausal women. Cervicovaginal cytology specimens with benign EMs in postmenopausal women and "out-of-phase EMs" in premenopausal women 40 years and older were identified. Cases with histologic follow-up within 12 months were selected. There was tissue follow-up for 130 postmenopausal women: 10 (7.7%) had significant findings (endometrial adenocarcinoma, 6 [2 (33%) in asymptomatic women]; complex atypical endometrial hyperplasia [CAH], 3; leiomyosarcoma, 1); 20 were receiving hormone replacement therapy (HRT; n = 15) or tamoxifen (n = 5); 2 (10%) had significant pathology (endometrial adenocarcinoma, 1; CAH, 1). Eight not taking hormones (7.3%) had significant pathology (adenocarcinoma, 5; CAH, 2; leiomyosarcoma, 1). There were follow-up data for 96 premenopausal women; only 1 (who had vaginal bleeding) had significant pathology (CAH). The difference in incidence of preneoplastic and neoplastic conditions after a cytologic interpretation of "benign EM" between postmenopausal and premenopausal women was significant (P pound .025); There was no difference between postmenopausal women receiving or not receiving HRT (P > .05). Reporting benign EMs for premenopausal women 40 years and older has no clinical significance but does for postmenopausal women, regardless of HRT and symptoms.     

Comparison of the difference in histopathology and cell cycle kinetics among the postmenopausal endometrium treated with different progestins in sequential-combined hormone replacement therapy

OBJECTIVE: To investigate the difference in histopathology and cell cycle kinetics in the menopausal endometrium treated with sequential-combined hormone replacement therapy (HRT) using different types and doses of progestins. DESIGN: A randomized, double-blind, 1-year study was conducted. In a menopause clinic of a university hospital, 241 postmenopausal women using HRT were included for the study of histopathology and cell cycle analysis. Conjugated equine estrogens, 0.625mg/day, were administered for 25 days (days 1-25) of each month, and the following were also administered for 14 days (days 12-25): in group A ( n= 102), medroxyprogesterone acetate (MPA), 5 mg/day; in group B ( n= 66), MPA, 10mg/day; and in group C ( n= 73), dydrogesterone, 20mg/day. Endometrial sampling was performed after at least 10 months of treatment. Fifty-two premenopausal women were also enrolled for the comparative studies (group Y). The S-G2-M fractions in the cell cycle were used as the marker of proliferation. RESULTS: Most menopausal endometria were normal regardless of the regimens of HRT. Endometrial hyperplasia was only found in two cases (both in group A). The S-G2-M fractions of the endometrial cells in all three menopausal groups showed no statistically significant difference. It appeared that S-G2-M fractions increased from normal postmenopausal to normal premenopausal endometria to postmenopausal hyperplasia to premenopausal hyperplasia. The S-G2-M fractions of the normal menopausal endometrial cells were lower than those of the premenopausal controls either in normal or in hyperplastic categories. CONCLUSIONS: Our study showed that there is no difference between the effect of MPA and dydrogesterone used in sequential-combined HRT based on the cycle kinetics of the menopausal endometrium.     

Ovarian volume and menopausal status

OBJECTIVE: The purposes of this study were to (1) examine whether ovarian volume differs by age and menopausal status in healthy women; (2) evaluate whether ovarian volume could be a sensitive and specific predictor of menopausal status; and (3) assess whether ovarian volume is affected by cigarette smoke, oral contraceptives (OCs), and hormone replacement therapy (HRT). DESIGN: Each participant (527 women) completed an extensive in-home interview that assessed age, menopausal status, smoking history, OC use, and HRT use. Each participant also received a transvaginal ultrasound that measured ovarian volume. Geometric means for ovarian volume were compared between premenopausal and postmenopausal women using t tests. Tests for trends were conducted using linear regression analyses. RESULTS: Ovarian volume declined with age (p < or = 0.0001) and also differed by menopausal status; postmenopausal women had smaller ovarian volumes than premenopausal women of the same age (p < or = 0.0001). Ovarian volume was not associated with smoking history or HRT use. However, it was significantly smaller in current users of OCs compared with past users of or those who never used OCs (p < or = 0.0001). Ovarian volume was a sensitive and specific predictor of postmenopausal status. CONCLUSIONS: The data suggest that age, menopausal status, and OC use may be determinants of ovarian volume. They also suggest that ovarian volume may be useful for predicting menopausal status in women.     

Serum leptin levels in postmenopausal women: effects of transdermal hormone replacement therapy

OBJECTIVE: To evaluate serum leptin levels in postmenopausal women who are receiving hormone replacement therapy (HRT) and postmenopausal women who are not receiving HRT with similar body mass index (BMI) to determine whether estrogens exert effects on leptin secretion. DESIGN: Cross-sectional, prospective study comparing serum leptin levels in premenopausal women, postmenopausal women who were not receiving HRT (group A), and postmenopausal women who were receiving HRT (group B). RESULTS: Serum leptin levels were significantly higher in group A in comparison to group B and control women (15.82 +/- 6.6 ng/ml, 8.14 +/- 4.17 ng/ml, and 10.12 +/- 5.48 ng/ml, respectively; p < 0.05). Total fat mass (FM) was found to be significantly higher in untreated postmenopausal women in comparison to the other two groups (22.66 +/- 2.79 kg vs. 19.14 +/- 3.39 kg vs. 18.98 +/- 3.82 kg; p < 0.05). No significant difference was observed in weight, height, BMI, blood pressure, or glucose levels among the three groups. A linear correlation between BMI and serum leptin levels as well as between total FM and serum leptin levels was observed in all groups. No correlation was found between serum leptin levels and months from menopause and months of HRT. CONCLUSIONS: Our results show that serum leptin is increased in untreated postmenopausal women, possibly as a consequence of the increase in FM, and that HRT reduces serum leptin levels to premenopausal values. These data need further investigation by a broader longitudinal study.     

Body mass index is associated with USF1 haplotype in Korean premenopausal women

The upstream stimulatory factor 1 (USF1) gene has been shown to play an essential role as the cause of familial combined hyperlipidemia, and there are several association studies on the relationship between USF1 and metabolic disorders. In this study, we analyzed two single nucleotide polymorphisms in USF1 rs2073653 (306A>G) and rs2516840 (1748C>T) between the case (dyslipidemia or obesity) group and the control group in premenopausal females, postmenopausal females, and males among 275 Korean subjects. We observed a statistically significant difference in the GC haplotype between body mass index (BMI) > or =25 kg/m2) and BMI <25 kg/m2 groups in premenopausal females ( chi2=4.23, p=0.04). It seems that the USF1 GC haplotype is associated with BMI in premenopausal Korean females.     

Inhibition of bFGF gene expression and tumor angiogenesis of orth otopic implantation of human gastric carcinoma by N-desulfated heparin]

OBJECTIVE: To investigate the effect of N-desulfated heparin on tumor metastasis, tumor angiogenesis and basic fibroblast growth factor(bFGF) gene expression of orthotopically implanted human gastric carcinoma in NOD-SCID mice. METHODS: Human gastric cancer SGC-7901 tissues were orthotopically implanted into the stomach of the NOD-SCID mice. Twenty mice were randomly divided into two groups which received either intravenous injection of 0.9% NaCl solution(0.9%NaCl solution group) or 10 mg/kg N-desulfated heparin (N-desulfated heparin group) twice a week for three weeks. Mice were sacrificed six weeks after tumor implantation. Tissues from stomach and other organs were obtained for histopathological evaluation. The intratumoral microvessel density (MVD) in tumor was evaluated immunohistochemically. Real time PCR was used to detect bFGF mRNA expression. RESULTS: The tumor metastasis rates were 9/10 in 0.9% NaCl solution group and 2/10 in N-desulfated heparin group(P<0.05).MVD was 9.1+/-3.4 in 0.9% NaCl solution group and 4.7+/-1.8 in N-desulfated heparin group (t=3.617,P<0.05). bFGF mRNA expression was lower in N-desulfated heparin group(2.60+/-0.56%)than that in 0.9% NaCl solution group(30.65+/-6.84%). CONCLUSION: N-desulfated heparin can inhibit the metastasis of gastric cancer through inhibiting tumor bFGF gene expression and tumor angiogenesis with no obvious anticoagulant activity.     

Prognostic significance of peritumoral vessel invasion in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis

To assess the prognostic significance of peritumoral vessel invasion, data were examined for 1,510 women entered into the Ludwig Breast Cancer Group Trials I to IV evaluating adjuvant therapy for operable breast cancer with axillary nodal metastasis. Vessel invasion by tumor cells was identified by routine light microscopy in 59 per cent (889 of 1,510) of the patients and was equally distributed between premenopausal/perimenopausal (60 per cent, 468 of 778) and postmenopausal (58 per cent, 421 of 732) women. In logrank analyses stratified by nodal status (one to three or four or more positive nodes), the four-year disease-free survival (DFS) rate was significantly lower in patients with vessel invasion than in women without vessel invasion (50 per cent versus 65 per cent, P less than 0.0001). This DFS difference was seen for both premenopausal/perimenopausal (P = 0.0004) and postmenopausal (P = 0.0002) patients. The four-year overall survival rate was also lower in patients with vessel invasion (71 per cent versus 82 per cent, P = 0.0006), both for premenopausal/perimenopausal (P = 0.002) and postmenopausal (P = 0.04) women. The presence of vessel invasion was significantly associated with increasing numbers of positive axillary lymph nodes, rising tumor grade, nonstellate tumor border growth pattern, and higher steroid hormone receptor content of the primary tumor. The assessment of peritumoral vessel invasion continued to have prognostic significance for DFS (P less than 0.0001) and overall survival (P = 0.003) when evaluated in multivariate models controlling for treatment assigned, nodal status, tumor size, estrogen receptor status, menopausal status, and age. Depending on the subpopulation, patients with vessel invasion had a 41 per cent to 54 per cent greater risk of treatment failure than those without vessel invasion and a 29 per cent to 64 per cent greater risk of death. The percentage of treatment failures at distant sites was higher for women with than for those without vessel invasion (27 per cent versus 18 per cent, P = 0.003). In patients with axillary lymph node metastases, peritumoral vessel invasion may be a sign of increased systemic disease burden.     

The predictive value of EGFR and HER-2/neu in tumor tissue and serum for response to anthracycline-based neoadjuvant chemotherapy of breast cancer

We investigated the predictive value of HER-2/neu and epidermal growth factor receptor (EGFR) in tumor tissue and prechemotherapy serum for histopathologic response in 108 patients with breast cancer undergoing neoadjuvant anthracycline-based chemotherapy.Response to chemotherapy, assessed by histopathologic classification of regression (grade 0 [no therapy effect] to 4 [no residual tumor]), correlated significantly with prechemotherapy serum HER-2/neu levels. Median prechemotherapy serum HER-2/neu levels were significantly higher in patients with regression grades 1 through 4 compared with those in patients with regression grade 0 (9.6 vs 8.55 ng/mL; P = .011; 95% confidence interval [CI], .009-.014). Median pretreatment serum HER-2/neu levels of patients with complete pathologic response (pCR) were significantly higher than in patients with moderate or no treatment response (10.95 vs 9.1 ng/mL; P = .041; 95% CI, .036-.046). Receiver operating characteristic curve analysis revealed a serum HER-2/neu value of more than 10.3 ng/mL to predict a pCR with 80% sensitivity and 69.4% specificity. There was no significant correlation of response with HER-2/neu and EGFR scores in tumor tissue or with serum EGFR levels.Results demonstrate prechemotherapy serum HER-2/neu to be a significant predictor of response to neoadjuvant anthracycline-based chemotherapy for breast cancer.     

Auditory brainstem response in postmenopausal women treated with hormone replacement therapy: a pilot study

OBJECTIVE: To research the nongenital audiological target for gonadal steroids in postmenopausal women who are treated with hormone replacement therapy. DESIGN: Fifty postmenopausal volunteers were treated with hormone replacement therapy. Women with an intact uterus had sequential weekly transdermal estradiol plus nomegestrole acetate 5 mg orally for 12 days per month or a continuous daily oral dose of conjugated estrogen 0.625 mg and medroxyprogesterone acetate 5 mg tablet. Eighteen surgically postmenopausal women received a weekly transdermal estradiol system. Twenty-five postmenopausal volunteers-5 with a natural menopause and 10 with a surgical menopause-and 20 premenopausal normally cycling women were used as a control group. Each woman performed auditory brainstem response by auditory-evoked potentials for waves I, III, and V and for interpeak I-III, I-V, and III-V intervals. RESULTS: Women who were treated with hormone replacement therapy showed wave latencies and interpeak latencies shorter than those for postmenopausal women in the control group (p < or = 0.05), overlapping those of the premenopausal women (p > 0.05). Women who were treated with estrogen replacement therapy showed shorter time latencies than those treated with combined hormone replacement therapy (p < or = 0.05). CONCLUSIONS: Our data suggest that fluctuating hormone levels cause changes in auditory brain-stem response waves, even if the exact mechanism of activity of the gonadal steroids is not clear. However, we believe that estrogen may influence the neuronal plasticity, the metabolic levels of neurotransmitters, and thus the neuronal conduction time into the audiological system.