Increased expression of fibroblast growth factor 8 in human breast cancer.
Fibroblast growth factor 8 (FGF8) is an important developmental protein which is oncogenic and able to cooperate with wnt-1 to produce mouse mammary carcinoma. The level of expression of FGF8 mRNA was measured in 68 breast cancers and 24 non-malignant breast tissues. Elevated levels of FGF8 mRNA were found in malignant compared to non-malignant breast tissues with significantly more malignant tissues expressing FGF8 (P=0.019) at significantly higher levels (P=0.031). In situ hybridization of breast cancer tissues and analysis of purified populations of normal epithelial cells and breast cancer cell lines showed that malignant epithelial cells expressed FGF8 mRNA at high levels compared to non-malignant epithelial and myoepithelial cells and fibroblasts. Although two of the receptors which FGF8 binds to (FGFR2-IIIc, FGFR3-IIIc) are not expressed in breast cancer cells, an autocrine activation loop is possible since expression of fibroblast growth factor receptor (FGFR) 4 and FGFR1 are retained in malignant epithelial cells. This is the first member of the FGF family to have increased expression in breast cancer and a potential autocrine role in its progression. (+info)
Mammography and 99mTc-MIBI scintimammography in suspected breast cancer.
The aim of this work has been to evaluate whether a diagnostic protocol based on the joint use of mammography and 99mTc-methoxyisobutyl isonitrile (MIBI) scintimammography is capable of reducing the number of biopsies required in patients with suspected breast cancer. METHODS: We performed prone scintimammography in 90 patients with suspected breast cancer, involving 97 lesions. In all patients, the diagnosis was established by way of biopsy. On mammography, we evaluated the degree of suspicion of malignancy and the size of the lesion (smaller or larger than 1 cm in diameter). RESULTS: The results of only 41 of the biopsies indicated malignancy. On mammography, 20 lesions (of which 1 was breast cancer) were considered to be of low suspicion of malignancy, 31 (of which 4 were breast cancer) as indeterminate and 46 (of which 36 were breast cancer) as high. Fourteen lesions (2 low probability, 2 indeterminate and 10 high) were smaller than 1 cm, whereas 83 (18 low probability, 29 indeterminate and 36 high) were larger. The sensitivity, specificity, positive predictive value and negative predictive value of scintimammography were 85%, 79%, 74% and 88%, respectively. Scintimammography was positive in all cases of breast cancer that initially had a low or indeterminate suspicion of malignancy according to mammography, as well as in 30 cases of breast cancer that initially were highly suspicious. Six false-negative scintimammography studies were obtained in lesions with a high suspicion of malignancy. CONCLUSION: We propose a diagnostic protocol with a biopsy performed on lesions that have a high suspicion of malignancy as well as those with low or indeterminate suspicion that are smaller than 1 cm or with positive scintimammography results. This would have reduced the total number of biopsies performed by 34%. More importantly, there would have been a 65% reduction in number of biopsies performed in the low and indeterminate mammographic suspicion groups. All 41 cases of breast cancer would have been detected. (+info)
The effect of the antiscatter grid on full-field digital mammography phantom images.
Computer Analysis of Mammography Phantom Images (CAMPI) is a method for making quantitative measurements of image quality. This article reports on a recent application of this method to a prototype full-field digital mammography (FFDM) machine. Images of a modified ACR phantom were acquired on the General Electric Diagnostic Molybdenum Rhodium (GE-DMR) FFDM machine at a number of x-ray techniques, both with and without the scatter reduction grid. The techniques were chosen so that one had sets of grid and non-grid images with matched doses (200 mrads) and matched gray-scale values (1500). A third set was acquired at constant 26 kVp and varying mAs for both grid conditions. Analyses of the images yielded signal-to-noise-ratio (SNR), contrast and noise corresponding to each target object, and a non-uniformity measure. The results showed that under conditions of equal gray-scale value the grid images were markedly superior, albeit at higher doses than the non-grid images. Under constant dose conditions, the non-grid images were slightly superior in SNR (7%) but markedly less uniform (60%). Overall, the grid images had substantially greater contrast and superior image uniformity. These conclusions applied to the whole kVp range studied for the Mo-Mo target filter combination and 4 cm of breast equivalent material of average composition. These results suggest that use of the non-grid technique in digital mammography with the GE-DMR-FFDM unit, is presently not warranted. With improved uniformity correction procedure, this conclusion would change and one should be able to realize a 14% reduction in patient dose at the same SNR by using a non-grid technique. (+info)
Macronutrient intake and change in mammographic density at menopause: results from a randomized trial.
To examine the effects of dietary fat intake on breast cancer risk, we are conducting a randomized trial of dietary intervention in women with extensive areas of radiologically dense breast tissue on mammography, a risk factor for breast cancer. Early results show that after 2 years on a low-fat, high-carbohydrate diet there is a significant reduction in area of density, particularly in women going through menopause. In women who went through menopause during the 2-year follow-up, the mean decreases in area of density and percentage of density in the intervention group were 11.0 cm2 and 11.0%, respectively, whereas the control group decreased 4.5 cm2 and 5.2%. The purpose of this analysis was to determine whether changes in intake of specific macronutrients could account for the observed reduction in breast density in these women. Differences between 2-year and baseline values of macronutrients (averaged over 3 nonconsecutive days of food intake) were calculated. We examined the effect of dietary variables, adjusted for changes in total calorie intake and weight and for family history of breast cancer, on changes in area of density and percentage of density using linear regression. Reduction in total or saturated fat intake or cholesterol intake was significantly associated with decreased dense area (p < or = .004). The most significant dietary variable associated with reduction in percentage of density was reduction in dietary cholesterol intake (P = 0.001), although reducing saturated fat intake was of borderline significance (P = 0.05). The effect of the membership in the intervention and control groups on change in area of density or percentage of density was reduced by models that included changes in intake of any fat, or cholesterol, or carbohydrates. The observation of an effect of diet at menopause on breast density, a marker of increased risk of breast cancer, may be an indication that exposures at this time have an enhanced effect on subsequent risk. (+info)
Inhibition of aberrant proliferation and induction of apoptosis in HER-2/neu oncogene transformed human mammary epithelial cells by N-(4-hydroxyphenyl)retinamide.
Epithelial cells from non-cancerous mammary tissue in response to exposure to chemical carcinogens or transfection with oncogenes exhibit hyperproliferation and hyperplasia prior to the development of cancer. Aberrant proliferation may, therefore, represent a modifiable early occurring preneoplastic event that is susceptible to chemoprevention of carcinogenesis. The synthetic retinoid N-(4-hydroxyphenyl)retinamide (HPR), has exhibited preventive efficacy in several in vitro and in vivo breast cancer models, and represents a promising chemopreventive compound for clinical trials. Clinically relevant biochemical and cellular mechanisms responsible for the chemopreventive effects of HPR, however, are not fully understood. Experiments were performed on preneoplastic human mammary epithelial 184-B5/HER cells derived from reduction mammoplasty and initiated for tumorigenic transformation by overexpression of HER-2/neu oncogene, to examine whether HPR inhibits aberrant proliferation of these cells and to identify the possible mechanism(s) responsible for the inhibitory effects of HPR. Continuous 7-day treatment with HPR produced a dose-dependent, reversible growth inhibition. Long-term (21 day) treatment of 184-B5/HER cells with HPR inhibited anchorage-dependent colony formation by approximately 80% (P < 0.01) relative to that observed in the solvent control. A 24 h treatment with cytostatic 400 nM HPR produced a 25% increase (P = 0.01) in G0/G1 phase, and a 36% decrease (P = 0.01) in S phase of the cell cycle. HPR treatment also induced a 10-fold increase (P = 0.02) in the sub-G0 (apoptotic) peak that was down-regulated in the presence of the antioxidant N-acetyl-L-cysteine. Treatment with HPR resulted in a 30% reduction of cellular immunoreactivity to tyrosine kinase, whereas immunoreactivity to p185HER remained essentially unaltered. HPR exposure resulted in time-dependent increase in cellular metabolism of the retinoid as evidenced by increased formation of the inert metabolite N-(4-methoxyphenyl)-retinamide (MPR) and progressive increase in apoptosis. Thus, HPR-induced inhibition of aberrant proliferation may be caused, in part, by its ability to inhibit HER-2/neu-mediated proliferative signal transduction, retard cell cycle progression and upregulate cellular apoptosis. (+info)
Benzodiazepine premedication: can it improve outcome in patients undergoing breast biopsy procedures?
BACKGROUND: Women awaiting needle-guided breast biopsy procedures may experience high anxiety levels. A randomized, double-blind, placebo-controlled study was designed to evaluate the ability of midazolam and diazepam (in a lipid emulsion [Dizac]) to improve patient comfort during needle localization and breast biopsy procedures. METHODS: Ninety women received two consecutive doses of a study medication, one before the mammographic needle localization and a second before entering the operating room. Patients were assigned randomly to receive saline, 2.0 ml intravenously, at the two time points; midazolam, 1.0 mg intravenously and 2.0 mg intravenously; or diazepam emulsion, 2.0 mg intravenously and 5.0 mg intravenously, respectively. Patients assessed their anxiety levels before the needle localization, before entering the operating room, and on arrival in the operating room. Patients completed a questionnaire evaluating their perioperative experience at the time of discharge. RESULTS: Patient satisfaction during needle localization was significantly improved in both benzodiazepine treatment groups (vs. saline). The incidence of moderate-to-severe discomfort during needle localization was lower in the midazolam (20%) and diazepam emulsion (6%) groups compared with the saline group (70%) (P<0.05). The preoperative visual analogue scale anxiety scores were similar in all three groups. In the operating room, however, anxiety scores were 55% and 68% lower after midazolam (21+/-19) and diazepam emulsion (15+/-14) compared with saline (46+/-28). Finally, there was no difference in the time to achieve home-readiness or actual discharge time among the three groups. CONCLUSIONS: Premedication with midazolam or diazepam emulsion improved patients' comfort during needle localization procedures and significantly reduced intraoperative anxiety levels before breast biopsy procedures without prolonging discharge times. Use of diazepam emulsion may be an effective alternative to midazolam in this population. (+info)
Double-phase 99mTc-sestamibi scintimammography and trans-scan in diagnosing breast cancer.
The goal of our study was to assess the value of both scintimammography with 99mTc-sestamibi (SMM) and trans-scan (T-scan) in detecting breast cancer. METHODS: A total of 121 women were evaluated by palpation, mammography, SMM and T-scan. SMM was performed in the prone, breast dependent position. Immediate and delayed views (double-phase) were obtained. T-scan is a new breast imaging method that maps noninvasively the distribution of tissue electrical impedance and capacitance. RESULTS: SMM had 88.9% sensitivity, 88.4% specificity and 88.4% accuracy in detecting breast cancer. SMM had 100% sensitivity in detecting breast tumors >1 cm and only 66% sensitivity in detecting tumors <1 cm. T-scan had 72.2% sensitivity and 67% specificity in detecting breast cancer. It detected one more breast cancer than SMM, at the expense of 27 additional false-positive results. CONCLUSION: Double-phase SMM was sensitive and specific in detecting breast cancer. This method may reduce the rate of negative breast biopsies in tumors >1 cm. T-scan was only moderately accurate in detecting breast cancer. Its addition to SMM did not improve significantly the rate of breast cancer detection. However, because of its complete noninvasiveness, large-scale applicability and low cost, T-scan deserves further refining. (+info)
N-acetyltransferase 1 genetic polymorphism, cigarette smoking, well-done meat intake, and breast cancer risk.
N-Acetyltransferase 1 (NAT1), encoded by the polymorphic NAT1 gene, has been shown to be one of the major enzymes in human breast tissue that activates aromatic and heterocyclic amines. Humans are mainly exposed to these carcinogens through cigarette smoking and consumption of well-done meat. To test the hypothesis that variations in the NAT1 gene are related to breast cancer risk, particularly among women who smoke or consume high levels of well-done meat, a nested case-control study was conducted in a prospective cohort study of 41,837 postmenopausal Iowa women. Information on cigarette smoking and other breast cancer risk factors was obtained at the baseline survey conducted in 1986. DNA samples and information on the consumption of well-done meat were obtained, in the case-control study, from breast cancer cases diagnosed from 1992 to 1994 and a random sample of cancer-free cohort members. Genomic DNA samples obtained from 154 cases and 330 controls were assayed for 11 NAT1 alleles (NAT1*3, *4, *5, *10, *11, *14, *15, *16, *17, *19, and *22). The NAT1*4 allele was the predominant allele observed in this study population, accounting for 73.2% (72.4% in cases versus 73.8% in controls) of the total alleles analyzed. Compared to controls, breast cancer cases had a slightly higher frequency of the NAT1*10 allele (18.8% in cases versus 17.3% in controls) and a substantially higher frequency of the NAT1*11 allele (3.6% versus 1.2%). In multivariate analyses, we found a 30% [95% confidence interval (CI) = 0.8-1.9] elevated risk of breast cancer associated with the NAT1*10 allele and a nearly 4-fold (95% CI = 1.5-10.5) elevated risk associated with the NAT1*11 allele. The positive association of breast cancer with the NAT1*11 allele was more evident among smokers [odds ratio (OR) = 13.2, 95% CI = 1.5-116.0] and those who consumed a high level of red meat (OR = 6.1, 95% CI = 1.1-33.2) or consistently consumed their red meat well done (OR = 5.6, 95% CI = 0.5-62.7). The association of the NAT1*10 allele with breast cancer was mainly confined to former smokers (OR = 3.3, 95% CI = 1.2-9.5). These findings are consistent with a role for the NAT1 gene in the etiology of human breast cancer. (+info)