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Screening
International Journal of Surgery November 2014:
Evaluation of digital infra-red thermal imaging as an adjunctive screening method for breast carcinoma.

by Rassiwala M, Mathur P, Mathur R, Farid K, Shukla S, Gupta PK, and Jain B.

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The American Journal of Surgery October 2008 Article:
Effectiveness of a noninvasive digital infrared thermal imaging system in the detection of breast cancer.
by Nimmi Arora, M.D., Diana Martins, B.S., Danielle Ruggerio, B.S., Eleni Tousimis, M.D., Alexander J. Swistel, M.D., Michael P. Osborne, M.D., Rache M. Simmons, M.D.

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Dynamic infrared imaging for the detection of malignancy.
by Button TM., Li H., Fisher P., Rosenblatt R.. Dulaimy K., Li S., O'Hea B., Salvitti M., Geronimo V.,
Geronimo C., Jambawalikar S., Carvelli P., Weiss R.
2004

Department of Radiology, State University of New York at Stony Brook, Stony Brook, NY 11794, USA. tbutton@radiol.som.sunysb.edu

The potential for malignancy detection using dynamic infrared imaging (DIRI) has been investigated in an animal model of human malignancy. Malignancy was apparent in images formed at the vasomotor and cardiogenic frequencies of tumor bearing mice. The observation of malignancy was removed by the administration of an agent that blocks vasodilation caused by nitric oxide (NO). Image patterns similar to those that characterize malignancy could be mimicked in normal mice using an NO producing agent. Apparently DIRI allows for cancer detection in this model through vasodilation caused by malignancy generated NO. Dynamic infrared detection of vasomotor and cardiogenic surface perfusion was validated in human subjects by a comparison with laser Doppler flowmetry (LDF). Dynamic infrared imaging technology was then applied to breast cancer detection. It is shown that dynamic infrared images formed at the vasomotor and cardiogenic frequencies of the normal and malignant breast have image pattern differences, which may allow for breast cancer detection.

 
Risk Evaluation
 
Application of Second Generation Infrared Imaging with Computerized Image Analysis to Breast Cancer Risk Assessment

by Jonathan F. Head, Ph.D., Charles A. Lipari, Ph.D., Fen Wang, M.D., Ph.D., JamesE. Davidson, B.Ar., Robert L. Elliot, M.D., Ph.D.
1996

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Cancer Risk assessment with a second generation infrared imaging system
by Jonathan F. Head, Ph.D., Charles A. Lipari, Ph.D., Fen Wang, M.D., Ph.D., Robert L. Elliot, M.D., Ph.D
1997

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A reappraisal of the use of infrared thermal image analysis in medicine.
by Jones BF.
1998

School of Computing, University of Glamorgan, Pontypridd, UK. bfjones@glam.ac.uk

Infrared thermal imaging of the skin has been used for several decades to monitor the temperature distribution of human skin. Abnormalities such as malignancies, inflammation, and infection cause localized increases in temperature which show as hot spots or as asymmetrical patterns in an infrared thermogram. Even though it is nonspecific, infrared thermology is a powerful detector of problems that affect a patient's physiology. While the use of infrared imaging is increasing in many industrial and security applications, it has declined in medicine probably because of the continued reliance on first generation cameras. The transfer of military technology for medical use has prompted this reappraisal of infrared thermology in medicine. Digital infrared cameras have much improved spatial and thermal resolutions, and libraries of image processing routines are available to analyze images captured both statically and dynamically. If thermographs are captured under controlled conditions, they may be interpreted readily to diagnose certain conditions and to monitor the reaction of a patient's physiology to thermal and other stresses. Some of the major areas where infrared thermography is being used successfully are neurology, vascular disorders, rheumatic diseases, tissue viability, oncology (especially breast cancer), dermatological disorders, neonatal, ophthalmology, and surgery.

 
Assessment of physiologic and pathologic radiative heat dissipation using dynamic infrared imaging.
by Anbar M.
2002

Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, University at Buffalo (SUNY), New York 14214, USA. amara@adelphia.net

This paper reviews the mechanism and assessment of regulated radiative heat dissipation, involving the circulatory system and the skin. It describes the quantitative assessment of skin temperature modulation. The main regulating process, which can be quantitatively monitored by fast and sensitive dynamic infrared imaging, involves autonomic nervous control of cutaneous and subcutaneous perfusion. This control is significantly affected by a variety of local or systemic pathologic conditions, including cancer and certain neuropathies. A potential clinical application that objectively assesses local attenuation of temperature modulation in the presence of breast cancer is described in some detail. Systemic aberrations in skin temperature modulation can be clinically useful also in neurology. It can be used also in psychology and psychiatry to evaluate transient effects of mental stress on the autonomic nervous system.

 
Breast cancer : new technologies for risk assessment and diagnosis.
by Wright T., McGechan A.
2003

Adis International Inc., Yardley, Pennsylvania, USA.

In the US, one in every eight women will develop breast cancer in her lifetime. Despite the advances made in treating breast cancer, the causal mechanisms underlying this disease have yet to be fully elucidated; 85% of breast cancer cases occur sporadically without any known genetic mutation.Too little is known about the pathogenesis of breast cancer for primary prevention to be feasible in the near- to mid-term. Secondary prevention through screening offers an alternative that has been widely adopted. For decades, breast self-examination has been touted as a technique for the early identification of breast cancer. However, it has been recently suggested that this technique is a waste of time and resources for both doctors and patients. Mammography finds breast cancer earlier than breast self-examination, and will reduce the risk of death from breast cancer by approximately 30% in women over 50 years old. Mammography is limited in that cancer, like breast tissue, appears white on the x-ray; therefore lesions may be difficult to detect in women with very dense breasts, and a tumor may not cast a significant shadow until it is quite large. Some cancers are so aggressive that they can spread quickly, before routine screening can detect them. Despite these limitations, mammography is still viewed as the best tool currently available for screening and early diagnosis. Improved methods to detect and diagnose breast cancer early, when it is most curable, are required if a significant impact on morbidity and mortality from breast cancer is to be made. Various new and innovative technologies are being investigated for improving the early detection and diagnosis of breast cancer. About 85% of breast cancers begin in the milk ductal system of the breast. As cancer develops in the breast, abnormalities occur, including atypical hyperplasia, ductal carcinoma in situ, and invasive breast carcinoma. Thus, the early screening of ductal cells can provide a parallel benefit to the 'Pap' smear, which is used virtually universally to identify the abnormal cells that can lead to cervical cancer. Two technologies to monitor for atypical ductal epithelial cells are Cytyc Corporation's FirstCyte trade mark Ductal Lavage system and Nastech Pharmaceutical Company's Mammary Aspiration Cytology Test. Matritech, Inc. is searching for biomarkers linked to breast cancer. Researchers at Matritech have detected the presence of nuclear matrix protein (NMP) in the blood of women at the early stage of breast cancer, which is absent in the blood of healthy women, as well as those with fibroadenoma, a benign breast disease. NMP66 has been selected as a marker for further development and clinical trials of a test for use in the detection and monitoring of women with, or at risk for, breast cancer have been initiated. Technologies developed by the US Department of Defense are under investigation as breast cancer screening. Advanced Image Enhancement, Inc. has licensed naval sonar technology for digital image enhancement of mammograms. New thermography applications are also being investigated in two separate projects sponsored by the US Department of Defense using military thermal surveillance tools adapted for cancer detection. Both are enhancements of older thermal imaging technology based on the principle that heat equates to unwanted activity, in the case of breast cancer, abnormal cell proliferation.

 
Computerized breast thermography: study of image segmentation and temperature cyclic variations.
by Ng EY., Chen Y., Ung LN.

2001

School of Mechanical and Production Engineering, Nanyang Technological University, Singapore. mykng@ntu.edu.sg

Breast cancer is a common and dreadful disease in women. The surface temperature and the vascularization pattern of the breast could indicate breast diseases. Establishing the surface isotherm pattern of the breast and the normal range of cyclic variations of temperature distribution can assist in identifying the abnormal infrared images of diseased breasts. This paper investigates the cyclic variation of temperature and vascularization of the normal breast thermograms under a controlled environment. More than 50 Asian women, were examined and some of them have been examined continuously for two month. All together, not less than 800 thermograms were obtained. Before these thermograms can be analyzed objectively via a computer algorithm, they must be digitized and segmented. The authors present a method to segment thermograms and extract the useful region from the background. After the image processing, these thermograms can be analyzed and then the best time to perform an examination can be chosen. All these results are important for establishing a data bank of normal breast thermography, to choose the best time for an examination and as a systematic methodology for evaluating and analyzing the abnormal breast thermography in the future.

 
From tanks to tumors.
by Paul JL., Lupo JC.
2002

Applied Research Associates, Alexandria, Virginia, USA.

"Tanks to Tumors" succeeded in bringing several different communities together--medical, military, academic, industrial, and engineering. They worked together in panels to determine how the United States might adopt thermal imaging diagnostic technology in an orderly and demonstrable way for the early detection of breast cancer and other conditions. The panel recommendations will serve to guide the transition of military technology developments in ATR, the VDL, and IR sensors to the civilian medical community. The result will be a new tool in the war against breast cancer--a major benefit to the military and civilian population. A CD of the workshop proceedings is available at no cost through Advanced Concepts Analysis, Falls Church, Virginia; +1 703 914 9237; e-mail: diakides@erols.com.

 
Infrared imaging technology and biological applications.
by Kastberger G., Stachl R.
2003

Institute of Zoology, University of Graz, Graz, Austria. gerald.kastberger@uni-graz.at

Temperature is the most frequently measured physical quantity, second only to time. Infrared (IR) technology has been utilized successfully in astronomy (for a summary,see Hermans-Killam, 2002b) and in industrial and research settings (Gruner, 2002; Madding, 1982, 1989; Wolfe & Zissis, 1993) for decades. However, fairly recent innovations have reduced costs, increased reliability, and resulted in non contact IR sensors offering mobile, smaller units of measurement (EOI, 2002; Flir, 2000, 2001,2002). The advantages of using IR imaging are (1) rapidity in the millisecond range, facilitating measurement of moving targets, (2) non contact procedures, allowing measurements of hazardous or physically inaccessible objects, (3) no interference and no energy lost from the target, (4) no risk of contamination, and (5) no mechanical effect on the surface of the object. All these factors have led to IR technology's becoming an area of interest for new kinds of applications and users. In both manufacturing and quality control, temperature plays an important role as an indicator of the condition of a product or a piece of machinery (EOI, 2002; Flir, 2000, 2001, 2002; Raytek, 2002). In medical and veterinary applications, IR thermometry is increasingly used in organ diagnostics, in the evaluation of sports injuries and the progression of therapy, in disease evaluation (e.g, breast cancer, arthritis, and SARS; Flir, 2003), and in injury and inflammation examinations in horses, livestock (Tivey & Banhazi, 2002), and zoo animals (Hermans-Killam, 2002a; Thiesbrummel, 2002). Lastly, physiological expressions of life processes in animals (Kastberger, Winder, & Steindl, 2001; Stabentheiner, Kovac, & Hagmuller, 1995; Stabentheiner, Kovac, & Schmaranzer, 2002; Stabentheiner & Schmarnzer, 1987) and plants (Bermadinger-Stabentheiner & Stabentheiner, 1995) can be monitored. The most recent field in which IR technology has been applied is animal behavior. This article focuses on the practical options for non contact IR thermometry--in particular, in biological applications.

 
Numerical computation as a tool to aid thermographic interpretation.
by Ng EY., Sudharsan NM.
2001

School of Mechanical and Production Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798.

Thermography is an non-invasive and a painless tool for the detection of breast cancer. However, performing and interpreting thermograms requires meticulous training. It was found that women with an abnormal thermogram are at a higher risk and have a poorer prognosis. One of the main drawbacks of the thermogram is the high incidence of false-positive results. The authors believe that the fault lies in misinterpretation of the thermogram, rather than the thermogram itself. The paper aims to show that computer simulations could be an adjunct tool to help the clinician in the interpretation. This would greatly reduce the false-positive diagnosis.

 
Relationship between microvessel density and thermographic hot areas in breast cancer.
by Yahara T., Koga T., Yoshida S., Nakagawa S., Deguchi H., Shirouzu K.
2003

Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.

PURPOSE: This study was conducted to evaluate the validity of thermography in breast examination. METHODS: We performed contact thermography and measured the direct temperature by inserting a needle-type thermometer into the tissue. The core temperature of the tumor (dTt) and the temperature of the tissue surrounding the tumor (dTs) were compared with normal tissue. The microvessel density (MVD) and the MIB-1 labeling index (MIB-1 LI) of the tumor were examined immunohistochemically. The subjects were 48 women with primary invasive ductal carcinoma. The area of the tumor was diagnosed pathologically, and the hot area was measured using thermography. RESULTS: The dTt was significantly higher than the dTs. Both the dTt and dTs were significantly higher when the thermographical hot area was positive, or when more than four lymph node metastases were found. The dTs was correlated with MVD. A correlation between MVD and tumor temperature measured directly was also confirmed. A higher dTs was related to the dissociated wide area of the thermogram. CONCLUSION: These findings suggested a relationship between dTs and the high-risk group of breast cancer. We also found that abnormalities in temperature were reflected in thermography and that a higher dTs was related to the dissociated wide area of the thermogram.

 
Role of cancer thermography for detection of breast cancer.
by Yokoe T., Ishida T., Ogawa T., Iino Y., Kawai T., Izuo M.
1990

2nd Dept. of Surgery, Gunma Univ. School of Med.

Out of one hundred and sixty-two patients that examined by contact thermography, forty-five cases involving 55 cancers were assessed for malignancy. The sensitivity and the specificity of this method of testing were 81.5% and 83.5%, respectively. False negative cases included early stage, small sized and papillotubular carcinomas. Twenty-five per cent of the fibroadenoma and mastopathy cases showed false positive findings. Further, half of the phyllodes tumor and mastitis cases also showed false positive findings. Two of six T0, Tis cases (33.3%) were diagnosed as malignant tumors by thermography. Contact thermographic examinations will be more widely used in the near future.

 
Adjuvant Diagnostics
 
Efficacy of computerized infrared imaging analysis to evaluate mammographically suspicious lesions.
by Parisky YR., Sardi A., Hamm R., Hughes K., Esserman L., Rust S., Callahan K.
2003

USC/Norris Cancer Center, 1441 Eastlake Ave., Los Angeles, CA 90033, USA.

The purpose of this clinical trial was to determine the efficacy of a dynamic computerized infrared imaging system for distinguishing between benign and malignant lesions in patients undergoing biopsy on the basis of mammographic findings. SUBJECTS AND METHODS: A 4-year clinical trial was conducted at five institutions using infrared imaging of patients for whom breast biopsy had been recommended. The data from a blinded subject set were obtained in 769 subjects with 875 biopsied lesions resulting in 187 malignant and 688 benign findings. The infrared technique records a series of sequential images that provides an assessment of the infrared information in a mammographically identified area. The suspicious area is localized on the infrared image by the radiologist using mammograms, and an index of suspicion is determined, yielding a negative or positive result. RESULTS: In the 875 biopsied lesions, the index of suspicion resulted in a 97% sensitivity, a 14% specificity, a 95% negative predictive value , and a 24% positive predictive value. Lesions that were assessed as false-negative by infrared analysis were microcalcifications, so an additional analysis was performed in a subset excluding lesions described only as microcalcification. In this restricted subset of 448 subjects with 479 lesions and 110 malignancies, the index of suspicion resulted in a 99% sensitivity, an 18% specificity, a 99% negative predictive value, and a 27% positive predictive value. Analysis of infrared imaging performance in all 875 biopsied lesions revealed that specificity was statistically improved in dense breast tissue compared with fatty breast tissue. CONCLUSION: Infrared imaging offers a safe noninvasive procedure that would be valuable as an adjunct to mammography in determining whether a lesion is benign or malignant.

 
Computer simulation in conjunction with medical thermography as an adjunct tool for early detection of breast cancer.
by Ng EY., Sudharsan NM.
2004

School of Mechanical and Production Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore. mykng@ntu.edu.sg

Mathematical modeling and analysis is now accepted in the engineering design on par with experimental approaches. Computer simulations enable one to perform several 'what-if' analyses cost effectively. High speed computers and low cost of memory has helped in simulating large-scale models in a relatively shorter time frame. The possibility of extending numerical modeling in the area of breast cancer detection in conjunction with medical thermography is considered in this work. METHODS: Thermography enables one to see the temperature pattern and look for abnormality. In a thermogram there is no radiation risk as it only captures the infrared radiation from the skin and is totally painless. But, a thermogram is only a test of physiology, whereas a mammogram is a test of anatomy. It is hoped that a thermogram along with numerical modeling will serve as an adjunct tool. Presently mammogram is the 'gold-standard' in breast cancer detection. But the interpretation of a mammogram is largely dependent on the radiologist. Therefore, a thermogram that looks into the physiological changes in combination with numerical simulation performing 'what-if' analysis could act as an adjunct tool to mammography. RESULTS: The proposed framework suggested that it could reduce the occurrence of false-negative/positive cases. CONCLUSION: A numerical bio heat model of a female breast is developed and simulated. The results are compared with experimental results. The possibility of this method as an early detection tool is discussed.

 
Combination of thermographic and ultrasound methods for the diagnosis of female breast cancer.
by Ramlau C., Sledzikowski J.
1993

Oncological Clinic, Medical Academy in Poznan, Poznan Polytechnic's Research Center.

The experiment leads to the formulation of a non-invasive and highly efficient method for the detection of the female breast cancer. The proposed method is a combination of the results of ultrasound and thermography tests of the breast. The study is expected to produce the principles of test results analysis offering a 90% success rate in detecting breast cancer.

 
Recent trends in U.S. breast cancer incidence, survival, and mortality rates.
by Chu KC., Tarone RE., Kessler LG., Ries LA., Hankey BF., Miller BA., Edwards BK.
1997

Special Population Studies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Clinical trials have demonstrated that use of mammographic screening and advances in therapy can improve prognosis for women with breast cancer. PURPOSE: We determined the trends in breast cancer mortality rates, as well as incidence and survival rates by extent of disease at diagnosis, for white women in the United States and considered whether these trends are consistent with widespread use of such beneficial medical interventions. METHODS: We examined mortality data from the National Center for Health Statistics and incidence and survival data by extent of disease from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute, all stratified by patient age, using statistical-regression techniques to determine changes in the slope of trends over time. RESULTS: The age-adjusted breast cancer mortality rate for U.S. white females dropped 6.8% from 1989 through 1993. A significant decrease in the slope of the mortality trend of approximately 2% per year was observed in every decade of age from 40 to 79 years of age. Trends in incidence rates were also similar among these age groups: localized disease rates increased rapidly from 1982 through 1987 and stabilized or increased more slowly thereafter; regional disease rates decreased after 1987; and distant disease rates have remained level over the past 20 years. Three-year relative survival rates increased steadily and significantly for both localized and regional disease from 1980 through 1989 in all ages, with no evidence of an increase in slope in the late 1980s. IMPLICATIONS: The decrease in the diagnosis of regional disease in the late 1980s in women over the age of 40 years likely reflects the increased use of mammography earlier in the 1980s. The increase in survival rates, particularly for regional disease, likely reflects improvements in systemic adjuvant therapy. Statistical modeling indicates that the recent drop in breast cancer mortality is too rapid to be explained only by the increased use of mammography; like wise, there has been no equivalent dramatic increase in survival rates that would implicate therapy alone. Thus, indications are that both are involved in the recent rapid decline in breast cancer mortality rates in the United States.

 
Role and evaluation of mammography and other imaging methods for breast cancer detection, diagnosis, and staging.
by Feig SA.
1999

Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.

Mammographic screening of women age 40 and older can reduce breast cancer deaths by at least 30% to 40%. However, not all cancers are detected by mammography. Although a new supplementary modality for screening could, in theory, fill in this detection gap, such utilization must be based on rigorous demonstration of its ability to consistently and frequently find early cancers missed by mammography, such as those occurring in dense breasts or rapidly growing interval cancers that surface clinically between mammographic screens. After an abnormality is found at mammographic screening, supplementary mammographic views and/or ultrasound are now used to match the finding with an ACR BIRADS final diagnostic assessment category to indicate the relative likelihood of a normal, benign, or malignant diagnosis so that routine screening, short interval follow-up, or biopsy can then be advised. Appropriate categorization will maximize early cancer detection and minimize false-positive biopsies. Application of a new imaging method to this type of diagnostic evaluation requires well-designed studies to determine its effectiveness for this purpose.

 
Skin reactions after breast-conserving therapy and prediction of late complications using physiological functions.
by Sekine H., Kobayashi M., Honda C., Aoki M., Nakagawa M., Kanehira C.
2000

Department of Radiology, Division of Radiotherapy, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan.

The temperature of the skin remains elevated long after breast-conserving treatment with irradiation, perhaps because evaporative cooling is impaired. We investigated physiological changes of the irradiated skin and reevaluated the radiosensitivity of sweat glands on a functional basis to determine whether severe complications can be predicted. METHODS: Breast and auxiliary skin temperatures were measured with thermography and sweat production in response to local thermal stimuli was measured on the basis of changes in electrical skin resistance with a bridge circuit in 45 women before, during, and after breast irradiation for breast cancer. RESULTS: Breast and auxiliary skin temperatures were significantly increased after irradiation. In response to cutaneous thermal stimuli, the electric skin resistance of non irradiated areas decreased significantly because of sweating, but that of irradiated areas was unchanged. CONCLUSION: Impairment of sweating may play an important role in skin damage after irradiation. Although glandular tissue is not usually radiosensitive, the results of our functional assessment suggest that sweat glands are more radiosensitive than expected.

 
Statement from the National Cancer Institute on the National Cancer Advisory Board Recommendations on Mammography.
by National Cancer Institute
1997

The National Cancer Institute (NCI) accepts the recommendations of the National Cancer Advisory Board on screening mammography. As a result, NCI will recommend that:

Women in their 40s should be screened every one to two years with mammography.
Women aged 50 and older should be screened every one to two years.
Women who are at higher than average risk of breast cancer should seek expert medical advice about whether they should begin screening before age 40 and the frequency of screening.

The board also stated that because of mammography's limitations, it is important that a clinical breast examination by a health care provider be included as part of regular, routine health care. NCI will include that statement in its recommendations. Richard Klausner, M.D., NCI director, expressed his gratitude to the board for coming to closure on the issue quickly and for helping to bring clarity to this important issue. He said the board also made important recommendations for future research on breast cancer screening and education, and that NCI would address those research recommendations. Klausner said the institute will immediately begin to develop new educational materials to communicate the screening recommendations and to help women and health professionals determine an individual's breast cancer risk. He said that NCI also will work with the American Cancer Society, other government agencies, advocacy organizations, cancer centers, and other groups to educate the public and health professionals about the benefits, limitations, and risks of screening mammography.

 
Switch to the angiogenic phenotype during tumorigenesis.
by Folkman J., Hanahan D.
1991

Department of Surgery, Children's Hospital, Boston, Massachusetts.

Tumor growth and metastasis are angiogenesis-dependent. Virtually all solid tumors are neovascularized by the time they are detected. However, there is a prevascular phase during early tumor development where few or no tumor cells are angiogenic and expansion of the tumor is restricted to a few mm3. When enough tumor cells become angiogenic, the tumor can expand progressively and shed metastatic cells. This angiogenic switch has recently been quantitated for human breast cancer, as well as for prostate cancer. We have studied the problem of how tumors switch to the angiogenic phenotype by using transgenic mice in which tumors develop at a predictable time and in discrete prevascular and vascular stages. When the transgene is the bovine papilloma virus (BPV) genome, angiogenic fibrosarcomas develop from non-angiogenic precursors called fibromatoses. The fibrosarcomas secrete growth factors for capillary endothelial cells. In contrast, the fibromatoses do not secrete endothelial cell growth factors. When t he transgene consists of the large "T" antigen of SV40 under the control of the rat insulin promoter, 70% of pancreatic islets become hyperplastic and 4-10% of these become angiogenic at 6-7 weeks. Tumors arise from these neovascularized hyperplastic islets and reach > 1000 x the volume of the preangiogenic islets. The onset of angiogenic activity coincides with the secretion of acidic fibroblast growth factor (aFGF) and other growth factors not fully identified at this writing. These studies help to explain the switch to the angiogenic phenotype during tumorigenesis and provide models to discover antiangiogenic therapies directed at the source of angiogenic activity. Such therapy, when developed, may be co-administered with currently available angiogenesis inhibitors which are directed at the target of angiogenic activity, vascular endothelial cells.

 
The effectiveness of the Gail model in estimating risk for development of breast cancer in women under 40 years of age.
by MacKarem G., Roche CA., Hughes KS.
2001

Breast Cancer Treatment Center and the Department of General Surgery, Lahey Hitchcock Medical Center, Burlington, Massachusetts, USA.

Epidemiologic studies have provided information on risk factors for breast cancer. Gail and associates identified five risk factors using the Breast Cancer Detection Demonstration Project (BCDDP) population and developed a model to calculate a composite relative risk (RR). This model is commonly used to counsel women regarding their risk for breast cancer and was used by the National Surgical Adjuvant Breast Project (NSABP) for eligibility for the Breast Cancer Prevention Trial. Because the BCDDP population was composed almost entirely of women 40 years of age or older, our purpose was to evaluate the effectiveness of the Gail model in estimating the risk of breast cancer for women under 40 in the clinical setting. The Gail risk factors were assessed for 124 patients under the age of 40 treated for either ductal carcinoma in situ (DCIS) or invasive breast cancer at the Lahey Hitchcock Medical Center between 1983 and 1995. The RR was calculated using the Gail model. For comparison, two cohorts of women un der the age of 40 were used: 107 randomly selected patients who underwent a breast biopsy because of a benign condition and 129 nurses from our institution who responded to a questionnaire that included reproductive and family history information as used in the Gail model. The RR calculated was the RR that existed at the time of the surgical consultation for a suspicious breast lesion. The Tarone-Ware method was used to analyze statistical significance of differences between distribution. Contingency tables were analyzed using Miettinen's modification of Fisher's exact test. No differences were found between the median RR for all groups. Only 2 of the 124 patients with breast cancer had a RR of 5 or more (the RR required to enter the Breast Cancer Prevention Trial). The distribution of age at menarche (AGEMEN) was the same for each group. No difference was found for the distribution of age at first live birth (AGEFLB) between those with breast cancer and those with a benign biopsy or the control group. The number of breast biopsies (NBIOPS) was higher in patients with a benign breast biopsy. No difference was found in the distribution of number of first-degree relatives with breast cancer (NUMREL). Overall the Gail model failed to differentiate those women about to have cancer diagnosed from two control populations. The Gail model is not useful in identifying immediate risk of breast cancer in women under 40 and should not be used for that purpose.

 
Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma.
by Weidner N., Semple JP., Welch WR., Folkman J.
1991

Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115.

BACKGROUND. Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, we counted microvessels (capillaries and venules) and graded the density of microvessels within the initial invasive carcinomas of 49 patients (30 with metastases and 19 without). METHODS. Using light microscopy, we highlighted the vessels by staining their endothelial cells immunocytochemically for factor VIII. The microvessels were carefully counted (per 200x field), and their density was graded (1 to 4+), in the most active areas of neovascularization, without knowledge of the outcome in the patient, the presence or absence of metastases, or any other pertinent variable. RESULTS. Both microvessel counts and density grades correlated with metastatic disease. The mean (+/- SD) count and grade in the patients with metastases were 101 +/- 49.3 and 2.95 +/- 1.00 vessels, resp ectively. The corresponding values in the patients without metastases were significantly lower--45 +/- 21.1 and 1.38 +/- 0.82 (P = 0.003 and P less than or equal to 0.001, respectively). For each 10-microvessel increase in the count per 200x field, there was a 1.59-fold increase in the risk of metastasis (95 percent confidence interval, 1.19 to 2.12; P = 0.003). The microvessel count and density grade also correlated with distant metastases. For each 10-microvessel increase in the vessel count per 200x field, there was a 1.17-fold increase in the risk of distant metastasis (95 percent confidence interval, 1.02 to 1.34; P = 0.029). CONCLUSIONS. The number of microvessels per 200x field in the areas of most intensive neovascularization in an invasive breast carcinoma may be an independent predictor of metastatic disease either in axillary lymph nodes or at distant sites (or both). Assessment of tumor angiogenesis may therefore prove valuable in selecting patients with early breast carcinoma for aggressive therapy.

 
Treatment Monitoring
 
Use of digital infrared imaging in enhanced breast cancer detection and monitoring of the clinical response to treatment
by Francis Arena M.D, Clement Barone M.D, Thomas DiCicco
2003

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Dynamic infrared imaging of newly diagnosed malignant lymphoma compared with with gallium-67 and fluorine-18 fluorodeoxyglucose (fdg) positron emission tomography.
by Milos J. Janicek, M.D, Ph.D, George Memetri, M.D, Milos R. Janicek, Kitt Shaffer, M.D, Ph.D, Mark A. Fauci, B.S.S., M.B.A.
2003

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Multi-modality data fusion aids early detection of breast cancer using conventional technology and advanced digital infrared imaging .
by Francis Arena M.D., Thomas DiCicco, Azad Anand M.D.
2004

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Infrared Imaging as a Useful Adjunct to Mammography
by Oncology News International
1997

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