Fatty Breast Tissue Research Articles

Field nonuniformity correction for quantitative analysis of digitized mammograms.

Several factors, including the heel effect, variation in distance from the x-ray source to points in the image and path obliquity contribute to the signal nonuniformity of mammograms. To best use digitized mammograms for quantitative image analysis, these field non-uniformities must be corrected. An empirically based correction method, which uses a bowl-shaped calibration phantom, has been developed. Due to the annular spherical shape of the phantom, its attenuation is constant over the entire image. Remaining nonuniformities are due only to the heel and inverse square effects as well as the variable path through the beam filter, compression plate and image receptor. In logarithmic space, a normalized image of the phantom can be added to mammograms to correct for these effects. Then, an analytical correction for path obliquity in the breast can be applied to the images. It was found that the correction causes the errors associated with field nonuniformity to be reduced from 14% to 2% for a 4 cm block of material corresponding to a combination of 50% fibroglandular and 50% fatty breast tissue. A repeatability study has been conducted to show that in regions as far as 20 cm away from the chest wall, variations due to imaging conditions and phantom alignment contribute to <2% of overall corrected signal.

In vivo breast tissue backscatter measurements with 7.5- and 10-MHz transducers

Measurements of the ultrasound (US) backscatter coefficient (BSC) of fibroglandular and fatty breast tissues in vivo from 5.25 through 13 MHz, using the reference phantom method, are presented. Radiofrequency echo data were collected at a series of locations in the left breasts of 16 adults, age 46 to 84, and in a custom-built phantom calibrated for backscatter and attenuation. Matched regions of interest (ROIs) were then selected in these images, from which the backscatter coefficient and the backscatter frequency dependence were ratiometrically estimated, after compensation for attenuation. The mean results in fibroglandular tissues were 78.9 × 10 −3/cm, sr at 7.2 MHz ( n ROI = 43, n = 13) and 146 × 10 −3/cm, sr at 10.3 MHz ( n ROI = 19, n = 10) with frequency dependencies of f 2.28 and f 3.25. The corresponding results in subcutaneous fat were 2.59 × 10 −3/cm, sr at 7.2 MHz ( n ROI = 56, n = 16) and 7.08 × 10 −3/cm, sr at 10.3 MHz ( n ROI = 57, n = 16) with frequency dependencies of f 3.49 and f 3.43. These findings are discussed and compared to similar measurements in the literature. (E-mail: martin.anderson@seas.rochester.edu)

In-Utero and Lactational Exposure of 3,3',4,4',5-Pentachlorobiphenyl Modulate Dimethlbenz[a]anthracene-Induced Rat Mammary Carcinogenesis.

While polychlorinated biphenyls (PCB) are fat-soluble environmental pollutants stored breast fatty tissue and secreted in milk; the precise evidence of breast carcinoma from exposure to PCBs remains unclear. The aim of this study was to investigate the dose-response relationship in-utero and lactational exposure of PCBs congener for dimethlbenz[a]anthracene (DMBA)-induced rat mammary carcinogenesis. Female SD rats were injected (i.g.) with 25 pg, 2.5 ng, 250 ng, 7.5 μg of 3,3',4,4',5-pentachlorobiphenyl (PCB126)/kg, or the vehicle, on days 13 to 19 post-conception. Fifty-day-old female offspring were injected (i.g.) with 20 mg DMBA. The concentration of PCB in the liver of the 50-day-old was compared to the vehicle-group, found to be 530-fold higher in the 7.5 μg-group, nearly 21-fold higher in the 250 ng-group, nearly 2.4-fold in the 2.5 ng-group, and nearly 1.2-fold in the 25 pg-group. The expression of CYP1A1 in the liver of the 50-day-old was intensive in the 7.5 μg- and 250 ng-groups, and slight in the 2.5 ng-group, and not observed in the other groups. The observation was terminated when the pups were 170-day-old or the tumor size reached 20mm in diameter. The 7.5 μg-group showed a reduction of mammary carcinogenesis, but the 250 ng- and 2.5 ng-groups revealed increases incidence of carcinoma, while the 25 pg-group showed a similar incidence of the vehicle-group. The time course of tumor development of the 7.5 μg-group was significantly lower than that of the other groups, but that of the 250 ng-group was significantly higher, and that of the 2.5 ng- and 25 pg-groups was similar to that of the vehicle-group. Moreover, the tumors of the 250 ng-group showed the highest cell proliferation, anuploid tumor index, and nuclear grade when compared to those of the other groups. The present studies indicate that in-utero and lactational exposure of relatively low dose PCB acts as an enhancing agent toward DMBA-induced rat mammary carcinogenesis, but that of high dose PCB acts as an inhibiting agent. This effect partly may be due to the in vivo difference at the day of DMBA exposure (50-day-old); between the concentration of PCB and the expression of phase I drug-metabolize enzymes (CYP1A1) converting DMBA into the ultimate carcinogen.

Saline-enhanced radiofrequency ablation of breast tissue: an in vitro feasibility study.

The feasibility of radiofrequency (RF) ablation for the treatment of breast tumors was investigated in vitro. The best parameters for ablation of breast tissue were chosen. Saline-enhanced RF ablation was performed in human breast tissue specimens and cow udder tissue. Temperature profiles were measured depending on RF power (20, 28, 36 W) and NaCl infusion rate (15, 30, 60 mL/h) using eight thermocouples. Lesion development was monitored by ultrasound. Thermolysis efficiency was measured by tissue weight determinations before and after ablation. After RF ablation of tissue samples, 73.6% turned into a fat/saline emulsion. Ultrasound monitoring showed a cone-shaped hyperechoic area during the first 2 minutes of RF ablation, followed by an irregular expansion of the area. Time-dependent spatial temperature curves were more homogeneous at low infusion rates (15 mL/h). Peak temperatures up to 160 degrees C were measured. Controlled RF ablation of breast tissue is feasible. The irregular expansion of RF lesions in fatty breast tissue is due to liquefied fat. Low saline interstitial infusion rates result in better control of lesioning.

Effect of age and breast density on screening mammograms with false-positive findings.

The objective of this study was to examine the effect of breast density and age on screening mammograms with false-positive findings. The study sample was taken from the Washington State Mammography Tumor Registry, which links data from participating radiologists with the Puget Sound Cancer Surveillance System and the Washington State Cancer Registry. Participants (n = 73,247) were women 35 years old and older who underwent screening mammography for which an assessment and a four-category density rating were coded. A total of 46,340 mammograms were sampled to avoid interpreter bias. In this study of false-positive mammograms, only women with no diagnosis of breast cancer within 12 months of the index mammogram were included. Logistic regression was used to estimate the odds ratios of a false-positive mammogram being associated with each category of breast density or age, adjusting for the other factor as a covariate. After controlling for breast density, we found that the risk of a false-positive mammogram was not affected by age (p = 27). However, the trend of increasing risk of a false-positive mammogram with increasing breast density was highly significant (p < .001). Women with extremely dense breast tissue were almost two times more likely to have a false-positive mammogram than were women with fatty breast tissue. This effect persisted after controlling for age. Breast density, not age, is an important factor when predicting risk of a false-positive mammogram. Breast density should be considered when educating individual women on the risks and benefits of screening mammography.

Two-dimensional near-infrared transillumination imaging of biomedical media with a chromium-doped forsterite laser

Transillumination images of objects hidden in normal and cancerous human breast tissues and bovine, porcine, and gallinaceous (chicken) tissues as well as model-random-scattering media were recorded with 1250-nm light from a chromium-doped forsterite laser. A Fourier space gate and a polarization gate were used to sort out image-bearing photons and discriminate against multiply scattered image-blurring photons. Better contrast, higher spatial resolution, and deeper penetration of samples were achieved for imaging with 1250-nm light than those obtained at shorter wavelengths, such as 1064 nm from a neodymium-doped yttrium aluminum garnet (YAG) laser. Better contrast and higher resolution were also obtained when the object was imaged through normal human breast tissue than through cancerous breast tissue. Images with marked distinction between fatty and fibrous human breast tissues were obtained when the Cr:forsterite laser was tuned to 1225 nm, a wavelength that resonates with an optical absorption band of breast fat tissues. Imaging with linearly polarized light revealed that the image quality depends significantly on the orientation of the polarization of the incident light with respect to the fibers in the bovine tissue.

3,3',4,4'-tetrachlorobiphenyl (TCB) can enhance DMBA-induced mammary carcinogenesis in the rat.

Polychlorinated biphenyls (PCBs) are fat-soluble environmental pollutants which can be stored in the fatty tissue of breast and secreted in milk. Previous studies have shown that PCBs can influence liver carcinogenesis in animal models but no such studies have been reported in breast. These experiments aimed to determine whether a PCB congener could influence mammary carcinogenesis using the rat DMBA-induced mammary tumour model system. 3,3',4,4'-Tetrachlorobiphenyl (TCB) enhanced the development of DMBA-induced mammary tumours in young female rats and did so in animals fed either a low-fat (5% w/w corn oil) or a high-fat (20% w/w corn oil) diet. The combination of TCB and high-fat diet resulted in tumours growing so fast that the experiment had to be terminated at 10.5 weeks for humane reasons. At termination the total numbers of tumours in each group of 20 rats were: 4 in the low-fat group, 22 in the low-fat plus TCB group, 25 in the high-fat group and 50 in the high-fat plus TCB group. Histopathological analysis confirmed that 98% of the tumours were mammary carcinomas, predominantly in situ ductal carcinomas, but, in addition, revealed that 13 of the tumours had an invasive phenotype of which 12/13 had all arisen in TCB-treated animals. This demonstrates, for the first time, that a PCB congener can influence mammary carcinogenesis.

Diffusion imaging of human breast

It is shown that diffusion-weighted imaging is possible in the human breast. Diffusion constants were measured in the breast parenchyma of four volunteers with no known breast lesions. The apparent diffusion constant of water measured in regions of interest chosen in normal human breast fibroglandular tissue was 1.64 +/- 0.19 x 10(-5) cm2/S and that measured in the area of fatty breast tissue was 0.32 +/- 0.18 x 10(-5) cm2/S. The resulting images indicate that fibroglandular tissue and fat can be clearly distinguished in diffusion-weighted as well as in absolute diffusion images of the breast. Potential future applications of this technology for the study of breast pathologies are suggested.

Analysis of parenchymal density on mammograms in 1353 women 25-79 years old.

This study was undertaken to determine the frequency and distribution of dense mammograms. Factors that may affect parenchymal density of breasts among the diverse age groups of women who undergo mammography were also studied. Mammograms of 1353 women between 25 and 79 years old who were grouped in 5-year age cohorts were reviewed. Breast density and the presence of benign calcifications were analyzed. Parenchymal density on mammograms decreased progressively in the patient cohorts 25-29 years old through 75-79 years old (Spearman correlation, p < .01). In the cohort of 25- through 29-year-old patients, 38% had predominantly (> 50%) fatty breasts. In the cohort of 75- through 79-year-old patients, 76% had predominantly fatty breasts. Increased parenchymal density mammograms were more common in women who had smaller breasts, had had fewer than two pregnancies, and underwent hormone replacement (p < .01). Forty-nine percent of women 50-79 years old undergoing hormone replacement had predominantly dense breasts, a percentage similar to that (48%) of the patient cohort of women 40-44 years old. Prevalence of benign calcifications also increased with age, from 8% at ages 25-29 to 86% at ages 75-79 (p < .01). In our study, a significant percentage (38%) of women who were 25-39 years old had predominantly fatty breast tissue that should not impede selective mammographic screening or diagnostic efforts in this age group.

On the significance of in situ production of oestrogens in human breast cancer tissue

We have previously shown that human breast cancer is autonomous in the regulation of its intra-tissue oestradiol concentration. Breast fatty tissue does not have this capacity, but rather reflects changes in the peripheral oestradiol concentration. To further evaluate the relative contribution of breast cancer and fatty tissue to the maintenance of tumour oestradiol we investigated whether a tumour-directed gradient in aromatase activity and oestrogen levels existed in mastectomy specimens. No such gradient was found, however, for aromatase, oestrone, oestradiol and their sulphates. Aromatase activity (expressed per gram of tissue) and the concentrations of oestradiol, oestradiol sulphate and oestrone sulphate were higher in tumour than in breast fatty tissue. Fatty tissue had a higher oestrone concentration. It is tentatively concluded that breast tumour aromatase activity is more important for the maintenance of tumour oestradiol levels than aromatase in breast fatty tissue.

Estrogens in plasma and fatty tissue from breast cancer patients and women undergoing surgery for non-oncological reasons.

Breast cancer tissue is able to maintain the tissue estradiol level in spite of the massive decrease in plasma estradiol associated with menopause, whereas fatty tissue from breasts with malignancies more closely reflects the changes in plasma. In the present study estrone and estradiol levels in fatty tissues from different origins were compared to evaluate the capacity of distant fatty tissues to act as estrogen reservoirs. Abdominal fat was obtained from 25 premenopausal and 20 postmenopausal women who underwent surgery for non-oncological reasons. Estrone and estradiol levels in these tissues were compared to those in breast fatty tissue from breast cancer patients. Plasma estrogen levels were not different in the two groups. In both groups, median plasma estradiol levels dropped sharply with menopause (from 363 to 40 pmol/l in breast cancer patients; from 280 to 45 pmol/l in the non-oncological patients; p less than 0.002), whereas a significant decrease in plasma estrone was observed only in the breast cancer patients (from 238 to 140 pmol/l; p less than 0.02). In premenopausal women, median estrone and estradiol levels in breast fatty tissue (1135 and 375 fmol/g, respectively) and abdominal tissue (1390 and 470 fmol/g, respectively) were not different. In postmenopausal women, however, significantly higher estrone levels (663 vs. 508 fmol/g; p less than 0.01) and estradiol levels (245 vs. 187 fmol/g; p less than 0.02) were found in abdominal fatty tissue. In view of the absolute estrogen levels in breast and abdominal fatty tissue and in plasma, we conclude, however, that it is unlikely that remote fat contributes substantially to the maintenance of estrogen levels in breast cancer tissue.

Endogenous oestrogens and androgens in normal and malignant endometrial and mammary tissues

Because of a well-established mechanism of action, tissue concentrations of steroid hormones are thought to be more closely related than blood levels to the biological effects exerted by these hormones.The results of studies on oestrogen and androgen concentrations in malignant and normal breast tissues are presented. Normal fatty and epithelial breast tissues and malignant tumour samples which had been obtained from pre- and postmenopausal women of two countries (Poland and The Netherlands) differing in the incidence of this malignancy were studied. In both countries highly comparable oestradiol concentrations in the breast were found. The median hormone levels in tumour tissue of 0.65 pmol/g tissue did not change with age. They were significantly higher than in normal epithelial (0.48 and 0.25 pmol/g in pre- and postmenopausal women) and fatty tissues (0.54 and 0.19 pmol/g respectively). Particularly in postmenopausal women, hormone levels in tumour tissue were much higher than plasma concentrations, which are comparable in both populations. Oestrone levels decreased with age in normal and malignant breast tissues. In both countries median levels in normal and fatty tissues of premenopausal women were similar (1.10 pmol/g tissue) but higher than those in postmenopausal patients (0.45 pmol/g tissue. Significantly lower levels were found in the malignant tissue samples of Polish premenopausal women (0.70 pmol/g) than in Dutch women (1.05 pmol/g); similarly, after menopause the tissue concentrations were higher in Dutch (0.55 pmol/g) than in Polish (0.31 pmol/g) patients. Thus lower oestrone tissue levels were observed in tumours from the country with the lower incidence for breast cancer.In a comparable study of uterine tissues, obtained from pre- and postmenopausal women, higher oestradiol concentrations than in the breast were found, whereas estrone levels were very similar. The levels in the uterus did not correlate with those in the plasma; no relation with histology was observed.The results of androgen measurements in breast tissues were in agreement with the concept that, particularly, androstenedione and testosterone could play a role as substrates for local aromatization. Lower concentrations were observed in the tumours than in the normal and fatty tissues.More extensive investigations will be needed to clarify the role of local formation (aromatization, hydrolysis by sulphatase) of oestrogens in tissues and of the interconversion of less active (oestrone) to more active (oestradiol) oestrogens.