SACRAMENTO, Calif. (AP) — It took seven years of annual mammograms and a cancer diagnosis for Amy Colton to learn something her doctors had realized from the beginning: Her breast tissue is so dense that it could have masked tumors on earlier exams.

“I requested a copy of the report sent from my radiologist to my primary care physician, and every single one said, ‘Patient has extremely dense breast tissue,’” the registered labor and delivery nurse said. “I was really outraged that I didn’t know this.”

About 40 percent of women over 40 have breast tissue dense enough to mask or mimic cancers on mammograms, but many of them don’t know it. Mammogram providers in California will be required to notify those patients, and suggest that they discuss additional screenings with their doctors based on their individual risk factors, if Gov. Jerry Brown signs a bill that the Legislature passed this month. Similar laws have passed in Texas and Connecticut in the past two years but no data is available yet from either state on the effect of the legislation.

“The notice in the bill is a two-sentence notice that gets added to a letter,” said the bill’s author, Democratic state Sen. Joe Simitian of Palo Alto. “I believe these two sentences can save thousands of lives.”

Brown has not given his opinion about the bill, but many doctors oppose it. Researchers studying breast density, a relatively young field, said such requirements may end up causing undo anxiety in millions of women and lead to unnecessary and expensive ultrasound or MRI screenings.

The California Medical Association, which represents 35,000 doctors, recommended a public education campaign instead of individual notifications, and said there isn’t enough evidence to support the idea the extra money spent on additional screenings will save more lives.

Those tests could cost the state more than $1 billion, and many women wouldn’t be able to afford them, said Dr. Karen Lindfors, a professor of radiology and chief of breast imaging at the University of California, Davis Medical Center in Sacramento. She testified against the bill before a legislative committee.

“I just don’t think that at this point we have the ability to meet the kind of demand either financially or in terms of manpower that this is going to create, and we also don’t have proof that it’s going to save lives,” she said.

The women who would receive the notifications have more tissue than fat in their breasts. As women age, their breasts become more fatty. Fat appears black on a mammogram, making it easier to spot cancer, which shows up as white.

Doctors agree that high breast density is an increased risk factor for cancer, but researchers say the issue needs more study to determine whether the risk is great enough to justify a higher level of screenings for women who have it.

Pre-menopausal women are more likely to have dense tissue, regardless of whether they are at high risk for breast cancer, said Celine Vachon, an associate professor of epidemiology at the Mayo Clinic in Rochester, Minn. She said women who get the notifications required by the California bill could be frightened into seeking additional screenings, such as MRIs or ultrasounds, which can pick up false positives and cost thousands of dollars.

“If women want their breast density information, that’s their right,” Vachon said. “However, breast density is not yet a risk factor that’s used clinically, so what women will do with this information is not clear. We need improved density measurements as well as models that do a better job of predicting women’s risk. Everyone wants density to be this silver bullet, but to date, it’s not.”

Colton, who got the California legislation rolling by contacting Simitian’s office, said women ought to be told whether their breast density could make cancer difficult to detect.

She said she practiced self-exams monthly, had no family history of breast cancer and thought she was among the lucky cohort of women at a low risk for breast cancer. But five surgeries, six weeks of daily radiation and 15 rounds of chemotherapy later, she is angered that she went years without being told about her dense breast tissue.

“I don’t want anyone to think this is a rare story. There are countless women like me, and many with worse diagnoses,” she said.

Dr. Judy Dean, a diagnostic radiologist in Santa Barbara who specializes in breast imaging, supports the effort. She said 20 of her patients have found cancers through ultrasounds after she informed them that their dense tissue might be hiding tumors in a mammogram.

“Negative doesn’t mean negative; you could still be positive,” she said.

All radiologists agree that a mammogram — an X-ray image of the breast — is the best way for a woman to discover whether she has dense tissue, but few agree on how to proceed with that information.

Researchers have been experimenting with new breast imaging techniques that might provide the same answers as an MRI or ultrasound for women with a high risk for cancer, but with less expense. 3-D X-ray images known as “stereo mammograms” and molecular breast imaging are two techniques that are better than traditional mammograms at spotting cancers and cost much less than MRIs.

Some say a notice about the hidden risks of dense tissue should be sent to all women receiving the results of their mammogram, not just those with dense tissue. That way, everyone can be armed with the available information, said California state Assemblywoman Linda Halderman, a former breast cancer surgeon.

She said the bill would end up giving women with low breast tissue density false assurances they are not at risk for cancer.

“We’re offering something to women that doesn’t help improve their care or shed any light on the best way to assess their risk for breast cancer,” said Halderman, a Republican from Fresno. “Unfortunately, breast density is just one of those things we don’t know about yet.”

Peter C Gøtzsche and Karsten Juhl Jørgensen of the Nordic Cochrane Centre urge for “more honesty” from the NHS BSP (Breast Screening Programme). They believe that harm has been understated, and that information issued to the public has in general been unaffected by “repeated criticism and pivotal research” which has expressed reservations regarding screening benefits and registered considerable over-diagnosis.

Their paper, “The Breast Screening Programme and Misinforming the Public”, is published in the Journal of the Royal Society of Medicine.

The authors say:
“Spokespeople for the Program have stuck to the beliefs about benefit that prevailed 25 years ago and continue to question the issue of over-diagnosis.

Women therefore cannot make an informed choice whether to participate in screening based on the information the Program provides. This must be changed.”

The report explains that information is largely embellished, regarding the lives that have been saved through the screening program.

Professor Peter Gøtzsche, co-author of the paper and Director of the Nordic Cochrane Center, explains:
“The claim that death rates have fallen ‘in part from earlier diagnosis associated with screening’ is astonishingly misleading.

Deaths from breast cancer are falling because treatment is improving. There’s been a similar fall in the age-groups not invited to screening. In this respect, and many others, the Program persists in misinforming the public. It was forced to revise its leaflet inviting women for mammography but the new leaflet and their latest Annual Review continue to repeat incorrect mortality estimates.”

The program estimates that one breast cancer death for every 400 women is prevented by being screened on a regular basis over a ten year period – arguing against this the authors say:
“(the figure) is wrong by a factor of five. We have been unable to find any evidence for this estimate in reports from the Program or elsewhere. The 1993 meta-analysis of the Swedish trials reported that one breast cancer death was avoided for every 1000 invited women after ten years. The number is 2000 if we use the more realistic estimates of a 15% reduction in breast cancer mortality.”

They also stress that contradictory information about over-diagnosis is being provided by the NHS BSP.
“The (2010) Review has reverted to repeating the much too low estimate regarding over-diagnosis from the 2006 Review, but it is obscure as to where this figure comes from. The new leaflet never uses the term over-diagnosis, and although it talks a lot about ‘benefits’ it does not use the equivalent term ‘harms’ but just speaks about ‘downsides’, which is far less negative.”

In the report they explain that “the only hint at over-diagnosis” in the invitation leaflet is the sentence ‘Screening can find cancers which are treated but which may not otherwise have been found during your lifetime’. They believed this is vague and readers may understand that screening can only be good, as it detects cancers which would otherwise be hard to find.

The researchers tried out the sentence on a group of fourth year medical students – by this time in their training they still would now have had lectures about screening. They discovered almost half did not understand the sentence and one third believed it was bad for women to have these cancers detected.

The researchers said:
“There is no quantification of over-diagnosis in the leaflet and no estimate of the balance between benefit and harm.”

The Programs 2010 Annual Review was criticized by the authors for using sentences, such as..:
“If a breast cancer is found early, you are less likely
to have a mastectomy.”

..claiming that the program encouraged belief that screening will reduce the chances of the women needing to have a mastectomy. The authors express:
“But such claims are seriously misleading. Danish data has demonstrated that because of over-diagnosis, screening increases the use of mastectomies substantially.”

Written by Grace Rattue

Dr. Mercola – Breast Thermography

Thermography at the Natural Health Center

Thermography Video from Fox 10

Special Report: Beating Breast Cancer with Thermography

Special Report: Hot and Cold Diagnosis

Thermography Helps ID Breast Cancer

KTTV Fox 11 – A Better Way to Detect Breast Cancer?

Dr. Peter Leando – Meditherm, Inc.

Computer-aided detection (CAD) technology, which analyzes mammography images and marks suspicious areas for radiologists to review, has been widely hyped and pushed on women as a way to insure invasive breast cancer is spotted on mammograms. And it has grown into a huge industry, adding millions of dollars to the cost of healthcare.

The problem is, CAD simply doesn’t work — at all. That’s right. Despite the fact CAD is now applied to the large majority of screening mammograms in the U.S. with annual direct Medicare costs exceeding $30 million (according to a 2010 study in the Journal of the American College of Radiology), new research by University of California at Davis (UC Davis) scientists shows the expensive technology is ineffective in finding breast tumors.

But it does something extremely well. It causes enormous stress by greatly increasing a woman’s risk of being called back for more costly testing following a CAD analyzed mammogram.

The new research, just published in the Journal of the National Cancer Institute, used data from the Breast Cancer Surveillance Consortium to analyze 1.6 million mammograms. Entitled “Effectiveness of Computer-Aided Detection in Community Mammography Practice,” the study specifically looked at screening mammograms performed on more than 680,000 women at 90 mammography facilities in seven U.S. states, between the years of 1998 and 2006.

The results are being hailed as the most definitive findings to date on whether the super popular mammography tool is effective in locating cancer in the breast. The findings? CAD is a waste of time and money.

The false-positive rate increased from 8.1 percent before CAD to 8.6 percent after CAD was installed at the medical centers in the study. What’s more, the detection rate of breast cancer and the stage and size of breast cancer tumors were similar regardless of whether or not CAD was used.

“In real-world practice, CAD increases the chances of being unnecessarily called back for further testing because of false-positive results without clear benefits to women,” Joshua Fenton, assistant professor in the UC Davis Department of Family and Community Medicine, said in a statement to the media. “Breast cancers were detected at a similar stage and size regardless of whether or not radiologists used CAD.”

This isn’t the first time the CAD technology has been questioned by researchers. The current study follows a previous study of the computer aided mammography tool that was published by Dr. Fenton in the New England Journal of Medicine in 2007.

That examination of mammography screening results in 43 facilities, including seven that used CAD, found that CAD was actually linked to reduced accuracy of mammogram screenings and produced no difference in the detection rate of invasive breast cancer.

“In the current study, we evaluated newer technology in a larger sample and
over a longer time period,” Fenton noted in a statement to the press. “We also looked for the first time at cancer stage and cancer size, which are critical for understanding how CAD may affect long-term breast cancer outcomes, such as mortality.”

CAD software was first approved by the Food and Drug Administration back in 1998, but its use only skyrocketed after Medicare began covering it in 2001. According to 2009 Medicare data, using CAD adds another $12 to the costs of having a mammogram (about $81 for film mammography and $130 for digital mammography), representing a 9 percent to 15 percent additional cost for CAD use.

© 2003 Wiley-Liss, Inc.

Publication of the International Union Against Cancer

Infrared imaging has frequently been used in the past to detect changes in skin surface temperature associated with breast cancer. Usually a 1–2° C elevation in skin surfacet em-perature is observed at the tumour periphery, and it has been proposed that this change is due to hypervascularity resulting from tumour-associated angiogenesis. In our study, we used the rat mammary adenocarcinoma 13762 MAT, a tumour that has been used to identify antiangiogenic drugs, to investigate whether infrared imaging can detect angiogenesis in malignant tumours. If successful, it was hoped that this technique would represent a simple, noninvasive, procedure for monitoring the activity of antiangiogenic drugs.  To read the rest of this article, click here to download the PDF file of this study.

M Salhab, W Al Sarakbi and K Mokbel

St George’s and The Princess Grace Hospitals, London, UK

International Seminars in Surgical Oncology 2005, 2:8doi:10.1186/1477-7800-2-8

The electronic version of this article is the complete one and can be found online at: http://www.issoonline.com/content/2/1/8

© 2005 Salhab et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

It is now recognised that the breast exhibits a circadian rhythm which reflects its physiology. There is increasing evidence that rhythms associated with malignant cells proliferation are largely non-circadian and that a circadian to ultradian shift may be a general correlation to neoplasia.

Cancer development appears to generate its own thermal signatures and the complexity of these signatures may be a reflection of its degree of development.

The limitations of mammography as a screening modality especially in young women with dense breasts necessitated the development of novel and more effective screening strategies with a high sensitivity and specificity. Dynamic thermal analysis of the breast is a safe, non invasive approach that seems to be sensitive for the early detection of breast cancer.

This article focuses on dynamic thermal analysis as an evolving method in breast cancer detection in pre-menopausal women with dense breast tissue. Prospective multi-centre trials are required to validate this promising modality in screening.

The issue of false positives require further investigation using molecular genetic markers of malignancy and novel techniques such as mammary ductoscopy.

Keywords:

Circadian rhythm; breast cancer; screening and dynamic thermal analysis

Introduction

Breast cancer is one of the most common cancers, it is estimated that one in eight women in the USA will develop breast cancer during their lifetime [1-4]. Furthermore, 25–30% of breast cancers are found in pre-menopausal women [1]. Currently mammography is the best available approach for the early detection of breast cancer in the general population with a sensitivity of 75–90% [2]. However, the positive predictive value is only 25% [3,4].

In addition to mammography, non invasive new modalities have been developed to allow the early detection of breast cancer in all age groups and more importantly in young women with dense breast tissue and women who have high risk of developing breast cancer such as, women with strong family history and carriers of BRCA1 and/or BRCA2 genes.

Currently, magnetic resonance imaging (MRI) is being studied for the early detection of breast cancer. Its sensitivity in high risk women has been found to be much higher than mammography but with a lower specificity [5,6]. Kriege et al observed a higher sensitivity for MRI in detection of breast cancer in women with a genetic predisposition or at high risk compared to (71% vs. 41 %) but with lower specificity (90% vs. 95%) [6].

Electrical impedance scanning (EIS) is another modality under development for breast cancer detection especially in young women with dense breasts [7]. The basic science behind its use is the fact that malignant tumours have lower electrical impedance than the surrounding normal tissue. However, separation between malignant and benign lesions needs further investigations [8].

Furthermore, mammary ductoscopy (MD) and visualization of mammary ducts and proteomics of nipple aspirate fluid (NAF) and serum are promising screening modalities that require further evaluation [9,10].

The limitations of mammography as a screening modality especially in young women with dense breasts necessitated the development of novel and more effective screening strategies with a high sensitivity and specificity.

This article focuses on the dynamic thermal analysis as an evolving non invasive and a safe method in breast cancer detection in pre-menopausal women with dense breast tissue and women at high risk due to family history or genetic predisposition.

Breast and circadian rhythm [1]

It is now recognised that the establishment and growth of a tumour depend on neovascularization. This successful recruitment of new blood vessels into a tumour; also known as angiogenesis is dependent on angiogenic growth factors produced by the tumour cells [11]. Such new vessels grow adjacent to the tumour presumably to increase its nutrient supply [12]. These new vessels lack smooth muscles rendering them unreceptive to control by epinephrine [13,14]. The lack of receptivity produce a more constant blood flow, thus increasing the local temperature.

Earlier technology for assessing thermal abnormalities in the breast focussed on the presence of the abnormal temperature as a crucial marker [15-17]. In a study conducted by Gantherine et al, 21.3% of patients who had abnormal thermograms but no abnormality on physical examination and mammography developed breast cancer within the next 3 years [17]. In another study of women who had thermal abnormalities on initial examination using infrared technology, long term follow up (2–10 years) revealed that 33% of these women developed breast cancer, a rate six times higher than that expected in the normal population [18]. This relationship between breast skin temperature and breast cancer was thoroughly examined by Gros et al [15,16]. They found that the differences between the characteristics of rhythmic changes in skin temperature of clinically healthy and cancerous breasts were real and measurable. Despite these interesting observations thermography as a general screening tool for the detection of women at risk of breast cancer did not find a wide spread acceptance due to low sensitivity of the test and the subjective nature of the test interpretations.

The superficial thermal patterns measured on the surface of the breast seem to be related to tissue metabolism and vascularization within the underlying tissue. Such thermal patterns change significantly as a result of normal phenomena including menstrual cycle, pregnancy and more importantly the pathologic process itself. Additionally, cancer development represents the summation of a large number of mutations that occur over years, each with its own particular histologic phenotype [19-23].

Such changes appear to generate their own thermal signature and the complexity of these signatures may be a reflection of their degree of development [24-28].

Temperature in a normal breast increases from the skin into the deep tissue and heat conductivity in the healthy breasts is constant in most cases and generally can be characterized in terms of circadian rhythm periodicity [29]. In contrast, the rhythms associated with malignant cells proliferation are largely non circadian and suggest that a circadian to ultradian shift may be a general correlation to neoplasia. Heat production by the tumour under the influence of angiogenesis should be therefore re-examined in terms of absence of normal circadian fluctuations. Due to the increased blood flow and the lack of receptivity in the newly formed vessels in malignancy, temperature production exhibits circadian rhythmic variations to a far lesser degree than is evident in the healthy breasts [13]. It has been found that independent of a tumour’s size, relatively small tumours (>/= 0.5 cm in diameter), poorly vascularized rapidly growing tumors can produce increases in regional heat. The explanation for this effect is unclear but it may be due to the chronic inflammatory response around developing breast tumours. With increasing evidence that inflammation can enhance tumor growth and is associated with a poor prognosis, this suggestion implies that thermal analysis may have considerable value [30].

Furthermore, the unique relationship between the thermal circadian rhythm and mitotic activity could be considered as a first warning of tumour development, which can be detected using a safe and non-invasive technology. The genes that drive the circadian rhythm are emerging as central players in gene regulation throughout the organism, particularly for cell-cycle regulatory genes and the genes of apoptosis [31].

Dynamic thermal analysis

Recent technological advances have facilitated the recording of circadian rhythm variations of the breast and analysing the recorded data using highly complicated computer statistical software. A miniaturized microprocessor has been developed to record and store thermal information collected from eight separate sites of each breast. Sensors are placed in anatomically critical positions elicited by data obtained from tumour registries as to where cancers are most likely to develop.

In the First Warning System (FWS, Lifeline Biotechnologies, Florida, USA), thermal data are collected every five minutes for a period of 48 hours during which time women are encouraged to maintain their daily activities. 9000 pieces of data are recorded by microprocessors during the test period and analysed using specially developed statistical software. Temperature points from each contralateral sensor are plotted against each other to form a thermal motion picture of a lesion’s physiological activity.

Such a technology was first used by Farrar et al who examined a cohort of 138 women who had been scheduled for open breast biopsies based on the finding of physical examination and mammography [14]. A total of 23 women (17%) were found to have breast cancer, of these, 20 (87%) were characterized by the monitor as being high risk. The other 3 patients (13%) who were missed by the monitor had ductal carcinoma. Mammography was positive or suspicious in only 19 patients (83%). Of the 4 cancers missed by mammography (3 of them were pre menopausal), the monitor correctly characterized 3 women as being high risk. Figures 1 and 2 demonstrate the thermal graphs in two patients with a fibroadenoma (Fig. 1) and a T1 breast cancer (Fig. 2). A neural net algorithm was subsequently developed and evaluated by the authors because of its value in analysing the non-linear data such as these recorded by the breast’s monitors. Using this neural net algorithm reduced the number of false positives (18% vs. 30%)) and improved sensitivity (91% vs. 87%).

One of the main challenges to this technology is the false positive cases; confusion could be created in these women who are characterized as being positive or high risk by dynamic thermal analysis in the absence of physical and mammographical signs. This group of women may or may not have cancer in its earliest stages. Further retrospective analysis of the thermal data using a refined neural net algorithm may increase the sensitivity and reduce the number of false positives. Also this group of patients may well benefit from the new advances in the nipple aspirate fluid analysis and proteomic profiling technologies. Research is currently ongoing on this subject and the initial results are promising [9].

The Future

Dynamic thermal analysis of the breast is a safe, non invasive approach that seems to be sensitive for the early detection of breast cancer especially in young women where the conventional mammography is of limited value. Such a technology could become the initial breast screening test in pre-menopausal women and those who are classified as positive can then be selected for anatomical imaging with mammography, MRI and/or ultrasonography. Further refinement of the neural net algorithm is required in order to shorten the period of data recording and improve specificity. Prospective multi-centre trials are then required to validate these promising observations. The issue of false positives require further investigation using molecular genetic markers of malignancy and novel techniques such as mammary ductoscopy [10].

Finally, a better understanding of the circadian rhythm biology [1,30] and clearer definition of the thermal activity boundaries for various pathological conditions of the breast will open the door to a new and more precise screening method for breast cancer.

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Advanced integrated technique in breast cancer thermography.

Ng EY, Kee EC.

Source

School of Mechanical and Aerospace Engineering, College of Engineering, Nanyang Technological University, 639798, Singapore. mykng@ntu.edu.sg

Abstract

Thermography is a passive and non-contact imaging technique used extensively in the medical arena, but in relation to breast care, it has not been accepted as being on a par with mammography. This paper proposes the analysis of thermograms with the use of artificial neural networks (ANN) and bio-statistical methods, including regression and receiver operating characteristics (ROC). It is desired that through these approaches, highly accurate diagnosis using thermography techniques can be achieved. The suggested method is a multi-pronged approach comprising of linear regression, radial basis function network (RBFN) and ROC analysis. It is a novel, integrative and powerful technique that can be used to analyse large amounts of complicated measured data such as temperature values extracted from abnormal and healthy breast thermograms. The use of regression allows the correlation between the variables and the actual health status of the subject, which is decided by other traditional means such as the gold standard of mammography for breast cancer detection. This is important as it helps to select the appropriate variables to be used as inputs for building the neural network. RBFN is next trained to produce the desired outcome that is either positive or negative. When this is done, the RBFN possess the ability to predict the outcome when there are new input variables. The advantages of using RBFN include fast training of superior classification and decision-making abilities as compared to other networks such as backpropagation. Lastly, ROC is applied to evaluate the sensitivity, specificity and accuracy of the outcome for the RBFN test files. The proposed technique has an accuracy rate of 80.95%, with 100% sensitivity and 70.6% specificity in identifying breast cancer. The results are promising as compared to clinical examination by experienced radiologists, which has an accuracy rate of approximately 60-70%. To sum up, technological advances in the field of infrared thermography over the last 20 years warrant a re-evaluation of the use of high-resolution digital thermographic camera systems in the diagnosis and management of breast cancer. Thermography seeks to identify the presence of a tumour by the elevated temperature associated with increase blood flow and cellular activity. Of particular interest would be investigation in younger women and men, for whom mammography is either unsuitable or of limited effectiveness. The paper evaluated the high-definition digital infrared thermographic technology and knowledge base; and supports the development of future diagnostic and therapeutic services in breast cancer imaging. Through the use of integrative ANN and bio-statistical methods, advances are made in thermography application with regard to achieving a higher level of consistency. For breast cancer care, it has become possible to use thermography as a powerful adjunct and biomarker tool, together with mammography for diagnosis purposes.

Elmore JG, Armstrong K, Lehman CD, Fletcher SW.

Source

Department of Medicine, University of Washington School of Medicine, Seattle, USA. jelmore@u.washington.edu

Abstract

CONTEXT:

Breast cancer screening in community practices may be different from that in randomized controlled trials. New screening modalities are becoming available.

OBJECTIVES:

To review breast cancer screening, especially in the community and to examine evidence about new screening modalities.

DATA SOURCES AND STUDY SELECTION:

English-language articles of randomized controlled trials assessing effectiveness of breast cancer screening were reviewed, as well as meta-analyses, systematic reviews, studies of breast cancer screening in the community, and guidelines. Also, studies of newer screening modalities were assessed.

DATA SYNTHESIS:

All major US medical organizations recommend screening mammography for women aged 40 years and older. Screening mammography reduces breast cancer mortality by about 20% to 35% in women aged 50 to 69 years and slightly less in women aged 40 to 49 years at 14 years of follow-up. Approximately 95% of women with abnormalities on screening mammograms do not have breast cancer with variability based on such factors as age of the woman and assessment category assigned by the radiologist. Studies comparing full-field digital mammography to screen film have not shown statistically significant differences in cancer detection while the impact on recall rates (percentage of screening mammograms considered to have positive results) was unclear. One study suggested that computer-aided detection increases cancer detection rates and recall rates while a second larger study did not find any significant differences. Screening clinical breast examination detects some cancers missed by mammography, but the sensitivity reported in the community is lower (28% to 36%) than in randomized trials (about 54%). Breast self-examination has not been shown to be effective in reducing breast cancer mortality, but it does increase the number of breast biopsies performed because of false-positives. Magnetic resonance imaging and ultrasound are being studied for screening women at high risk for breast cancer but are not recommended for screening the general population. Sensitivity of magnetic resonance imaging in high-risk women has been found to be much higher than that of mammography but specificity is generally lower. Effect of the magnetic resonance imaging on breast cancer mortality is not known. A balanced discussion of possible benefits and harms of screening should be undertaken with each woman.

CONCLUSIONS:

In the community, mammography remains the main screening tool while the effectiveness of clinical breast examination and self-examination are less. New screening modalities are unlikely to replace mammography in the near future for screening the general population.

It took 12 years and a creation of a highly sophisticated transgenic mouse, but researchers at Kimmel Cancer Center at Jefferson have finally proven a long suspected theory: Inflammation in the breast is key to the development and progression of breast cancer.

In Cancer Research, the scientists say they can now definitively show that an inflammatory process within the breast itself promotes growth of breast cancer stem cells responsible for tumor development.

They also demonstrate that inactivating this inflammation selectively within the breast reduced activity of these stem cells, and stopped breast cancer from forming.

“These studies show for the first time that inactivating the NFKB inflammatory pathway in the breast epithelium blocks the onset and progression of breast cancer in living animals,” says Richard G. Pestell, M.D., Ph.D., Director, Kimmel Cancer Center and Chairman of Cancer Biology.

“This finding has clinical implications,” says co-author Michael Lisanti, Leader of the Program in Molecular Biology and Genetics of Cancer at Jefferson. “Suppressing the whole body’s inflammatory process has side effects. These studies provide the rationale for more selective anti-inflammatory therapy directed just to the breast.”

Dr. Pestell and his colleagues show the “canonical” NFKB pathway promotes breast cancer development: the first “insult” is provided by the HER2 oncogene, which then activates NFKB (nuclear factor kappa-light-chain-enhancer of activated B cells). NFKB turns on inflammation via tumor-associated macrophages (TAM), which produce tumor growth promoting factors.

Although inflammation, mediated by NFKB, has long been thought to be important in breast cancer development, the theory had been untestable because NF-?B is essential to embryonic development, Dr. Pestell says. “When you try to knock out NFKB genes in mice, they die.”

He addressed this problem by creating a mouse in which the inflammatory system within the adult animal’s normal breast could be regulated. This allows selective inactivation of NFKB in different cell types and took 12 years to accomplish, Dr. Pestell says. “These mice have five co-integrated transgenes.”

The mice are programmed to develop breast cancer, but the researchers found that if they selectively blocked inflammation just in the breast, tumors would not develop. “This is a very novel finding,” Dr. Pestell says.

They then demonstrated that this inactivation also reduced the number of cancer stem cells in the breast. “That told us that inflammation, through the action of NF-?B, is important to the growth and activity of cancer stem cells,” Dr. Pestell says. “The transgenic mice are a new technology that can be used by the scientists and the pharmaceutical industry to understand the role of NFKB in different diseases including heart disease, neurodegeneration and other cancers.”

Notes:

The study was funded by support from the National Institutes of Health, the Dr. Ralph and Marian C. Falk Medical Research Trust, and a grant from the Pennsylvania Department of Health.

Researchers from the Nigata University of Pharmacy and Applied Life Sciences in Japan, the National Cancer Institute, the University of Western Australia, and the Lombardi Comprehensive Cancer Center at Georgetown University Medical School contributed to the study.

The authors declare no conflicts of interest.

Source:
Ed Federico
Thomas Jefferson University

When Dr. Deborah Rhodes orders a diagnostic test that involves radiation, she consults a chart in her office that lists the amount of radiation exposure from each test. She considers the patient’s total past exposure, and then carefully weighs the risks and benefits of each test and any alternative approaches she can take.

Two new studies appearing in Tuesday’s issue of the journal Radiology suggest more physicians should take this approach. One study found that certain nuclear-based breast imaging exams that involve injecting radioactive material into patients expose women to far higher doses of radiation than regular mammography, increasing their risk of cancer in vulnerable organs beyond the breast, like the kidneys, bladder or ovaries.

Over all, the United States population’s annual radiation dose from medical procedures increased sevenfold between 1980 and 2006, a second paper reports.

“I’m a radiation phobe — I’ll come right out and say this,” said Dr. Rhodes, an internist at the Mayo Clinic who is doing research to develop screening technologies that require less radiation exposure to the patient. “I’m constantly monitoring radiation doses in my patients.”

Unfortunately, she said, “this is something that isn’t well understood, not just by the public — but by physicians who order the tests.”

R. Edward Hendrick, a physicist who has studied breast imaging for almost 30 years, said he was motivated to quantify the radiation exposure from nuclear breast imaging technologies in a published paper because of similar concerns.

“I would go to the international breast meeting and the big radiology meetings, and nobody had a clue what the doses and risks were,” Dr. Hendrick said. “They’re treating all the tests as if they have the same radiation dose and risk as mammography, and the truth is they have a much, much higher risk. The point of the paper was to say that not all the breast imaging procedures have comparable risks and doses.”

Dr. Hendrick, a clinical professor of radiology at the University Colorado-Denver School of Medicine in Aurora, Colo., is a consultant to G.E. Healthcare regarding digital breast tomosynthesis, another breast imaging technique, and is on the medical advisory boards of Koning and Bracco, which make other imaging technologies.

The nuclear technologies breast-specific gamma imaging (B.S.G.I.) and positron emission mammography (P.E.M.) are meant to be used as complements or adjuncts to mammography and ultrasound, once there is concern about a cancerous lesion, and not for routine screening. These technologies are also more useful in women who have very dense breast tissue, when mammography often does not provide clear images.

But a single breast-specific gamma imaging or positron emission mammography exam exposes patients to a risk of radiation-induced cancer that is comparable to the risk from an entire lifetime of yearly mammograms starting at 40, according to Dr. Hendrick’s study.

While digital mammography has an average lifetime risk of inducing 1.3 fatal breast cancers per 100,000 women aged 40 at exposure, a single B.S.G.I. exam was estimated to involve a lifetime risk 20 to 30 times greater in women aged 40, and the lifetime risk of a single P.E.M. was 23 times greater.

Moreover, mammography only increases a woman’s risk for breast cancer while B.S.G.I. and P.E.M. increase the risk of cancer in other organs, such as the intestines, kidneys, bladder, gallbladder, uterus, ovaries and colon, the study said.

There is also a concern that use of the imaging technologies will become more widespread and casual. “B.S.G.I. and P.E.M. are great tools for problem solving, if you have a patient with an abnormal mammogram and you’re not really sure,” said Dr. Rhodes. “The problem is these tests are now being considered and even being used in some cases as screening tests, and this is not appropriate.”

“I’m not saying ‘Don’t do the test,’ I’m just saying ‘Don’t prescribe these tests willy-nilly like you would an ultrasound exam,’ ” Dr. Hendrick said.

In another paper in the same issue of Radiology, William R. Hendee, a distinguished professor of radiology, radiation oncology, biophysics and bioethics at the Medical College of Wisconsin in Milwaukee, called on radiologists to spearhead a campaign to reduce overuse of imaging technologies that expose patients to radiation unnecessarily and drive up health costs in the process

Suggested proposals for curbing excessive use of imaging include developing national evidence-based appropriateness criteria for imaging, educating referring physicians and the public, curbing the physician practice of self-referral and finding ways to reduce duplicate exams.

Companies that make the two nuclear-based breast imaging exams did not argue with the assessment of radiation exposure, but said the comparison with mammography — which exposes patients to very low levels of radiation, equivalent to about two months of natural background radiation — was inappropriate because the tests are used differently.

“The comparison to mammography is a bit like comparing apples to oranges,” said Doug Kieper, vice president of science and technology for Dilon Technologies Inc., which developed the B.S.G.I. technology. “This is not being used as a screening procedure for the general asymptomatic population who have no indication of disease.” He added that studies were already under way to see if the same results could be obtained using lower doses of radiation.

Guillaume Bailliard, vice president for marketing for Naviscan, which makes the P.E.M. scanner, said it should never be used as a tool for routine screening. “It is true that P.E.M. provides a higher dose than mammography,” he said, “but physicians balance the risk-to-benefit when making decisions.”