The California State Legislature passed a bill last Friday requiring doctors to inform women if they have dense breasts after a mammogram, making California the second state this summer and the third state so far to have passed a so-called breast density law.

The bill, SB 791, passed the state Senate 35-1, and is now going before Gov. Jerry Brown to get signed.

When he signs it, starting next year, Calif. radiologists will have to send women with dense breasts, as determined by an American College of Radiology-developed system, this text:

Because your mammogram demonstrates that you have dense breast tissue, which could hide small abnormalities, you might benefit from supplementary screening tests, depending on your individual risk factors. A report of your mammography results, which contains information about your breast density, has been sent to your physician’s office and you should contact your physician if you have any questions or concerns about this notice.

Texas Gov. and Republican presidential hopeful Rick Perry signed into law a similar bill, Texas Act HB 2102, or Henda’s Law, in June. And breast density legislation was also passed in Connecticut in 2009.

New Hampshire, Massachusetts, New York and Florida all have similar legislation pending.

The American College of Radiology Imaging Network says that around 40 percent of women getting screening mammograms have dense breasts, with younger women typically having denser breasts.

Dense breasts are less fatty, with more connective tissue. The connective tissue appears white on a mammogram, just like the cancer, making it harder to diagnose, according to Are You Dense, an advocacy group.

A January 2011 study by the Mayo Clinic found three-quarters of cancers in women with dense breasts are missed by mammograms.

“When it comes to your health, ignorance is not bliss. What you don’t know can hurt you,” State Sen. Joe Simitian, a Democrat from Palo Alto who authored the bill, said in a statement.

The idea for the bill came from by Amy Colton, a registered nurse who had breast cancer not discovered by a mammogram, and who learned she had dense breasts only after her cancer was diagnosed, according to Are You Dense. She suggested the bill in Simitian’s “There Oughta Be a Law” contest.

However, the bill met some opposition from the California Medical Association. Writing about an earlier incarnation of the bill, SB 173, the CMA warned that it could bring legal and practical problems for Calif. doctors.

“Because the scope of who must receive the notice is so broad, women will be ‘scared’ into thinking they need these expensive additional screenings when it isn’t at all warranted, leading to increased costs and pressures on a physician’s practice,” the group wrote in a notice on its website. “Moreover, because the grading of the condition that may/may not lead to their receipt of the prescribed notice is subjective in nature, the absence of the notice could lead to lawsuits against doctors if a patient is later diagnosed with breast cancer.”

But the bill was backed by several other groups, including the California Nurses Association, the Breast Cancer Fund, the California Association of Health Underwriters and California NOW.

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

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.

J OANN  G. E LMORE , M.D., M.P.H., M ARY  B. B ARTON , M.D., M.P.P., V ICTORIA  M. M OCERI , P H .C., S ARAH  P OLK , B.A., P HILIP  J. A RENA , M.D.,  AND  S UZANNE  W. F LETCHER , M.D.

A BSTRACT Background The cumulative risk of a false positiveresult of a breast-cancer screening test is unknown. Methods We performed a 10-year retrospective co-hort study of breast-cancer screening and diagnosticevaluations among 2400 women who were 40 to 69years old at study entry. Mammograms or clinicalbreast examinations that were interpreted as indeter-minate, aroused a suspicion of cancer, or promptedrecommendations for additional workup in women inwhom breast cancer was not diagnosed within thenext year were considered to be false positive tests. Results A total of 9762 screening mammogramsand 10,905 screening clinical breast examinationswere performed, for a median of 4 mammograms and5 clinical breast examinations per woman over the 10-year period. Of the women who were screened, 23.8percent had at least one false positive mammogram,13.4 percent had at least one false positive breast ex-amination, and 31.7 percent had at least one falsepositive result for either test. The estimated cumula-tive risk of a false positive result was 49.1 percent (95percent confidence interval, 40.3 to 64.1 percent) after10 mammograms and 22.3 percent (95 percent confi-dence interval, 19.2 to 27.5 percent) after 10 clinicalbreast examinations. The false positive tests led to870 outpatient appointments, 539 diagnostic mam-mograms, 186 ultrasound examinations, 188 biopsies,and 1 hospitalization. We estimate that among wom-en who do not have breast cancer, 18.6 percent (95percent confidence interval, 9.8 to 41.2 percent) willundergo a biopsy after 10 mammograms, and 6.2 per-cent (95 percent confidence interval, 3.7 to 11.2 per-cent) after 10 clinical breast examinations. For every$100 spent for screening, an additional $33 was spentto evaluate the false positive results.

To read the rest of the study, click here to download the PDF.

© 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.

Head JF, Wang F, Elliott RL.

Source

Elliott Mastology Center, Baton Rouge, Louisiana 70816.

Abstract

Our recent retrospective analysis of the clinical records of patients who had breast thermography demonstrated that an abnormal thermogram was associated with an increased risk of breast cancer and a poorer prognosis for the breast cancer patient. This study included 100 normal patients, 100 living cancer patients, and 126 deceased cancer patients. Abnormal thermograms included asymmetric focal hot spots, areolar and periareolar heat, diffuse global heat, vessel discrepancy, or thermographic edge sign. Incidence and prognosis were directly related to thermographic results: only 28% of the noncancer patients had an abnormal thermogram, compared to 65% of living cancer patients and 88% of deceased cancer patients. Further studies were undertaken to determine if thermography is an independent prognostic indicator. Comparison to the components of the TNM classification system showed that only clinical size was significantly larger (p = 0.006) in patients with abnormal thermograms. Age, menopausal status, and location of tumor (left or right breast) were not related to thermographic results. Progesterone and estrogen receptor status was determined by both the cytosol-DCC and immunocytochemical methods, and neither receptor status showed any clear relationship to the thermographic results. Prognostic indicators that are known to be related to tumor growth rate were then compared to thermographic results. The concentration of ferritin in the tumor was significantly higher (p = 0.021) in tumors from patients with abnormal thermograms (1512 +/- 2027, n = 50) compared to tumors from patients with normal thermograms (762 +/- 620, n = 21). Both the proportion of cells in DNA synthesis (S-phase) and proliferating (S-phase plus G2M-phase, proliferative index) were significantly higher in patients with abnormal thermograms. The expression of the proliferation-associated tumor antigen Ki-67 was also associated with an abnormal thermogram. The strong relationships of thermographic results with these three growth rate-related prognostic indicators suggest that breast cancer patients with abnormal thermograms have faster-growing tumors that are more likely to have metastasized and to recur with a shorter disease-free interval.

Circadian rhythm chaos: a new breast cancer marker.

Keith LG, Oleszczuk JJ, Laguens M.

Source

Department of Obstetrics and Gynecology, Northwestern University Medical School, Chicago, Illinois, USA.

Abstract

The most disappointing aspect of breast cancer treatment as a public health issue has been the failure of screening to improve mortality figures. Since treatment of late-stage cancer has indeed advanced, mortality can only be decreased by improving the rate of early diagnosis. From the mid-1950s to the mid-1970s, it was expected that thermography would hold the key to breast cancer detection, as surface temperature increases overlying malignant tumors had been demonstrated by thermographic imaging. Unfortunately, detection of the 1-3 degrees C thermal differences failed to bear out its promise in early identification of cancer. In the intervening two-and-a-half decades, three new factors have emerged: it is now apparent that breast cancer has a lengthy genesis; a long-established tumor-even one of a certain minimum size-induces increased arterial/capillary vascularity in its vicinity; and thermal variations that characterize tissue metabolism are circadian (”about 24 hours”) in periodicity. This paper reviews the evidence for a connection between disturbances of circadian rhythms and breast cancer. Furthermore, a scheme is proposed in which circadian rhythm “chaos” is taken as a signal of high risk for breast cancer even in the absence of mammographic evidence of neoplasm or a palpable tumor. Recent studies along this line suggest that an abnormal thermal sign, in the light of our present knowledge of breast cancer, is ten times as important an indication as is family history data.

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.