Uncommon Breast Cancers Part One: PAGET’S DISEASE OF THE NIPPLE

Teasing Fact from Fiction

OBJECTIVE:

Paget's disease of the breast is a rare form of breast cancer in which the first clinical finding is usually a scaling of the nipple skin. It may also be associated with nipple redness and burning. It can be a serious problem because 9 out of 10 women who have it have some underlying breast cancer. The underlying breast cancer may be either an invasive ductal carcinoma (IDC) or ductal carcinoma in situ (DCIS).

Paget’s also may be associated with other forms of hormonally based cancers such as uterine, ovarian or cervical. Paget’s disease is quite rare only affecting about just over 1% all diagnosed breast cancers. It is most common in women past menopause, but can infrequently occur at a younger age or in men.

The cause of Paget's disease is unknown, but certain women seem to be at a higher risk of developing breast cancer. This includes women who have never had children or had them late in life, women who started their periods at a young age or who had a late menopause, and women who have a strong family history of breast cancer. The "good news" about Paget's disease is that it is usually a "curable cancer".

However, it is important to note that, by far, most cases of scaling and burning of the nipple are due to benign conditions, which can be easily confused with Paget's disease.

Making a Diagnosis:

The major goal of this section is to help in the detection of the early nipple changes associated with Paget's disease, and to help differentiate them from benign conditions. The first symptom is usually a scaly, red rash affecting the nipple and sometimes the dark area of skin surrounding the nipple (the areola). The rash always affects the nipple first, and may then affect the areola. It doesn't go away and may become sore. The skin of the nipple and areola may be inflamed. There may also be crusting, bleeding and ulceration. Some women have an itching or burning sensation. Fluid (discharge) may leak from the abnormal area of cells. The nipple may turn inwards (be inverted). There may or may not be a lump in the breast.

Paget’s disease can be confused with other skin conditions such as eczema, dermatitis or psoriasis, as they can look very similar. This can make Paget’s disease difficult to diagnose with BSE or CBE. Paget’s disease usually affects the nipple first and then the surrounding tissue. Other skin conditions usually affect the areola (the dark area of skin around the nipple) first, and then spread into the nipple.

The first step in evaluating any patient with a change in the skin of the nipple is to obtain a careful history and perform a careful breast examination. A diagnostic mammogram, as opposed to a screening study should follow. When performing the diagnostic mammogram, the Mammographer, following up the possibility of Paget's disease, should acquire coned magnification films of the retro nipple area to look for fine calcifications. A U/S of the breast is also a useful tool in the diagnosis of underlying breast cancer often associated with Paget’s disease. Moreover, because of the possibility of other hormonally based cancers (uterine, ovarian etc.) a U/S evaluation of the pelvis is sometimes recommended.

If the mammogram and U/S are negative and the clinical suspicion is low, it is usually suggested that the patient be placed on cortisone cream treatment applied to the nipple for two weeks. If the condition has not responded completely to the conservative treatment in two weeks, a skin biopsy should be performed. If, because of negative imaging results and good clinical results, a biopsy is not done, careful follow-up is highly recommended.

Making an accurate diagnosis of Paget's disease is actually quite easy. A simple skin tissue biopsy to remove a small piece of tissue from the area of the nipple affected by the abnormal changes is performed. This procedure takes only a few minutes to complete under local anaesthesia, and is painless. A small amount of skin and underlying tissue are removed and sent to the pathologist; these biopsies result in a 100% definitive diagnosis.

Treatment of Paget’s disease:
In the past, the standard treatment for malignant Paget's disease was a mastectomy. Currently, the treatment of choice is to save the breast. The nipple and any surrounding breast tissue that contains breast cancer are removed. If there are definitive clear surgical margins, then irradiation of the affected breast follows. The results with this approach have been excellent. In some cases, there will be more extensive involvement of the breast tissue or an underlying cancer is diagnosed. In these cases, a mastectomy is recommended usually followed by immediate reconstruction.

Images of Paget’s Disease of the Nipple

Figure 1: Above, Normal Right Nipple & below, Biopsy proven Paget's Left Nipple

Figure 2: Very Early Paget's disease

Figure 3: Advanced Paget's disease of the Nipple

Figure 4: Very Advanced Paget's disease of the left nipple

Benign Conditions of the Nipple:
Many of the women referred with a possible Paget's disease have similar changes in both nipples. There is not a documented case of Paget’s affecting both breasts; therefore, most such patients are referred to a dermatologist to evaluate the underlying cause of the nipple change. However, it would be prudent to insist that these patients have a mammogram to rule out any breast involvement that is not clinically obvious. If there are any reasons for concern about the possibility of Paget's disease diagnosis, a skin punch biopsy should be performed.

Most patients who do have a skin punch biopsy end up with a benign result. These patients simply require reassurance that there is no cancer present, and follow-up observation is all that is indicated. Sometimes a moisturizing cream is helpful to control any nipple dryness. Patients with persistent symptoms following a negative biopsy are also referred to a dermatologist for treatment.

There are a variety of conditions that can mimic Paget's disease, such as atopic dermatitis or nipple eczema, or contact dermatitis. Some Images of common benign nipple conditions follow:

Benign Conditions Affecting the Nipple:

Figure 5: Normal Prominent Montgomery Tubercles

Figure 6: Contact Dermatitis

Figure 7: Right Dermal Cyst. Left is a close-up view

Figure 8: Above: Spongiotic Dermatitis left nipple. Below: Normal right nipple

SUMMARY:
We are the ‘thin pink line’ that stands as a protection against ignorance, a source of pertinent breast health information and as a foundation for the start of treatment or diagnosis. We have the chance to be the voice of reason, to dispel myth and present fact. The more we know about signs and symptoms that affect our patients the better professionals we become.

Power is knowledge; the truth is much less scary than myth, story and insinuation.

THERMOGRAPHY AND COMPUTER THERMOGRAPHIC IMAGING: FUNDAMENTALS OF

Physics:

All objects with a temperature above absolute zero (-273 K) emit infrared radiation from their surface. The Stefan-Boltzmann Law defines the relation between radiated energy and temperature by stating that the total radiation emitted by an object is directly proportional to the object's area and emissivity and the fourth power of its absolute temperature. The emissivity of human skin is extremely high (within 1% of that of a standard black phantom), therefore, measurements of infrared radiation emitted by the human skin can be converted directly into accurate temperature values.

Equipment Considerations:

Infrared rays are found in the electromagnetic spectrum within the wavelengths of 0.75 micron - 1mm. Human skin emits infrared radiation mainly in the 2 - 20 micron wavelength range, with an average peak at 9-10 microns. State-of-the-art infrared radiation detection systems utilize ultra-sensitive infrared cameras and sophisticated computers to detect, analyze, and produce high-resolution diagnostic images of these infrared emissions. The problems encountered with first generation infrared camera systems such as improper detector sensitivity (low-band), thermal drift, calibration, analog interface, etc. have been solved for almost two decades.

Laboratory Considerations:

Thermographic examinations must be performed in a controlled environment. The primary reason for this is the nature of human physiology. Changes from a different external (non-clinical controlled room) environment, clothing, etc. produce thermal artefacts. Refraining from sun exposure, stimulation or treatment of the breasts, and cosmetics and lotions before the exam, along with 15 minutes of nude acclimation in a florescent lit, draft and sunlight-free, temperature and humidity-controlled room maintained between 18-23 degree C, and kept to within 1 degree C of change during the examination, is necessary to produce a physiologically neutral image free from artefact.

What is Thermography?

Thermography (also called thermal imaging or infrared imaging) was approved by the U.S. Food and Drug Administration (FDA) in 1982 as a supplement to mammography in helping to detect breast cancer. Thermography can help determine whether a local abnormality in breast tissue temperature is present, which may indicate the presence of disease. Though thermography is FDA approved, the exam has not gained acceptance in the medical community as a necessary or effective tool in breast cancer detection. According to the American College of Radiology, thermography has not shown value as a screening, diagnostic, or adjunctive imaging tool.

INFRARED THERMOGRAPHIC BREAST IMAGES

Figure 1: Medial Lt breast DCIS

Figure 2: Left Fibrocystic condition

Figure 3: inflammatory breast disease Rt breast

Figure 4: Normal breast tissue

Is Thermography Useful in Detecting Breast Cancer?

While thermography may be appealing to some women because it is a pain-free exam, most physicians do not recommend thermal imaging. Scientific research over the last 20 years has shown that thermography is not reliable for detecting breast cancer. In 1977, the Beahrs Committee of the National Cancer Institute (NCI) recommended that thermography be discontinued as a routine screening modality in the NCI’s Breast Cancer Detection Demonstration Project.

What is Computerized Thermal Imaging?

Figure 5: Inside view of CTI system. NB: mirrors that deflect infrared waves from breast to camera

Computerized thermal imaging (CTI) is a new, non-invasive imaging method that is being developed using the principles of traditional thermography but with the addition of digital image reconstruction. Computerized thermal imaging (CTI) is a heat sensing and processing system that uses a thermal sensitive camera to capture a digital image based on heat radiating from the body. A computer-assisted interpretation of the digital image helps to determine whether a local abnormality in breast tissue temperature is present, which may indicate the presence of disease. To date, CTI is only available for eligible women who participate in CTI clinical trials; the technology has not yet been approved by the U.S. FDA.

Currently, clinical trials are being conducted across the United States to determine whether the CTI technology may be useful as an adjunct (supplement) to mammography in the breast cancer diagnostic process.

How Does Computerized Thermal Imaging Work?

The main component of the CTI technology is the highly sensitive, high-speed infrared camera. The camera is designed to detect infrared heat given off by the body. After the radiologist has acquired images of the breast tissue, the CTI system uses sophisticated image analysis algorithms and a computer to reconstruct the images to show individual heat patterns. These images differentiate between normal and abnormal heat patterns. The CTI examination consists of the patient being positioned on a special examination bed with the breast suspended in an opening in the top of the bed. The thermal camera is located inside of the bed, focused at the examination area. The physician will use the thermal camera to take a series of images of the breast. The procedure is then repeated with the patient’s other breast. As with traditional thermography, no radiation or breast compression is used during CTI.

After the breast images have been taken, they are analyzed by a computer algorithm and displayed for interpretation by the physician. Breast images are displayed in different colors (red, orange, and yellow) on a computer monitor for the physician to review. Any suspicious area (abnormal heat area) is marked on the digital breast image. The radiologist may then decide whether further breast imaging is necessary. The CTI technology is designed to electronically store the digital breast images and provide the patient with an electronic copy of the images, which may be helpful if she visits another imaging facility.

IMAGES GENERATED BY COMPUTERIZED THERMAL IMAGING:

The left image is the raw thermal image. The right image is a magnified view of the processed image that corresponds to the area of suspicion selected by the green square in the left image. This image shows a very high probability of malignancy (cancer). This patient was rated a BIRAD 4 (suspected malignancy, biopsy recommended) by mammography and confirmed to have ductal carcinoma in situ by biopsy.

What are the Limitations to Computerized Thermal Imaging?

Though computerized thermal imaging (CTI) may provide a pain-free breast imaging exam and has the potential to detect cancer by identifying abnormal heat patterns in breast tissue, there are some limitations to the technology. Since CTI is based on the principles of thermography, it may give false-positive results as thermography often does. A false positive result indicates cancer when no cancer is present. Thermography has a false positive rate of approximately 25%. However, CTI uses more advanced technology and a different exam process than thermal imaging. Thus, clinical trials may find that false positive results are less likely with CTI.

In addition, CTI cannot detect microcalcifications (tiny calcium deposits that may indicate the presence of cancer). Tumours that contain calcifications may be more difficult to remove completely. Microcalcifications can only be seen reliably with mammography. Approximately 50% of the breast cancers detected by mammography appear as a cluster of microcalcifications. Other imaging exams, including thermography, do not provide the fine detail (spatial resolution) that is available with conventional x-ray mammography. However, adjunct exams (such as ultrasound, MRI, etc.,) may be beneficial in some cases because they provide excellent contrast resolution, which may make some abnormalities such as cysts easier to see since these areas "stand out" more from surrounding tissue.

Cost is another limitation of the CTI technology. The manufacturers of CTI technology are only seeking FDA approval for the exam to be used in addition to mammography to help screen for breast cancer. Because mammography will have to be performed regardless of whether or not thermal imaging is done, many physicians question whether CTI technology will drastically change how breast cancer is detected. Many facilities that perform breast imaging tests to screen for breast cancer may be unable or unwilling to acquire additional costly imaging technology if they do not see a significant benefit to the patient.

Current Status of Detection

Currently first-line breast cancer detection strategy still depends essentially on clinical examination and mammography. The limitations of CBE, with its reported sensitivity rate often below 65% is well-recognized, and even the proposed value of self-breast examination is now being contested. Mammography is widely accepted as the most reliable and cost-effective imaging modality, its contribution continues to be challenged, sighting persistent false-negative rates and decreasing sensitivity in patients with high mammographic density. In addition, there is recent data suggesting that denser and less informative mammography images are precisely those associated with an increased cancer risk.

With the current emphasis on earlier detection, there is now renewed interest in the parallel development of complimentary imaging techniques that can also exploit the precocious metabolic, immunological and vascular changes associated with early tumour growth. While promising, techniques such as scintimammography, Doppler ultrasound, and MRI, are associated with a number of disadvantages that include exam duration, limited accessibility, need of intravenous access, patient discomfort, restricted imaging area, difficult interpretation and limited availability of the technology. Like ultrasound, they are more suited to use as second-line options to pursue the already abnormal clinical or mammographic evaluation.

Because of thermography's unique ability to image the thermovascular aspects of the breast, extremely early warning signals have been observed in long-term studies. Consequently, thermography could be used to discover early indicators for the future development of breast cancer. It is for this reason that an abnormal infrared image could be an important marker of high risk for developing breast cancer. Thus, thermography could develop a significant place as one of the major front-line methods of breast cancer detection.

SUMMARY:

The large patient populations and long survey periods in many of the Infrared and CTI clinical studies yields a high significance to the various statistical data obtained. This is especially true for the contribution of thermography to early cancer diagnosis, as an invaluable marker of high-risk populations, and therapeutic decision making. There appears to be an unequivocal relationship between heat production and tumour doubling time.

Currently available high-resolution digital infrared imaging (Thermography) technology benefits greatly from enhanced image production, standardized image interpretation protocols, computerized comparison and storage, and sophisticated image enhancement and analysis. Over 30 years of research and 800 peer-reviewed studies encompassing well over 300,000 women participants has demonstrated thermography's abilities in the detection of breast cancer and distinguishing between low and high risk populations. Ongoing research into the thermal characteristics of breast pathologies will continue to investigate the relationships between neoangiogenesis, chemical mediators, and the neoplastic process.

Considering the contribution that thermography has demonstrated thus far in the field of cancer detection, all possibilities should be considered for promoting further technical, biological, and clinical research in this procedure. I am positive we will hear more about this new modality.

POSITRON-EMISSION MAMMOGRAPHY (PEM): New technology: Almost ready

Happy Mother's Day to all of you; I hope you had breakfast in bed, got flowers and ate candy for lunch!

May's Tech-talk is a continuation of April's discussion on PET scanning. May gets into a little more detail on Positronic Emission Mammography (PEM). New modalities are always coming down the pipe. Some are more valuable than others but all add a fuller dynamic to our tool box of diagnosis, prognosis and treatment options.

Enjoy and pass it on, keep in touch,

Anne

OBJECTIVES:

Mammography is the one breast cancer screening test proven to reduce mortality, yet on many occasions, it still does not capture the full picture. Detection using the high sensitivity of breast-MRI (magnetic resonance imaging) is very promising, yet it often casts too wide a net. For women at high risk for breast cancer or women who have breast cancer, the limitations of these two imaging techniques cause unnecessary procedures, anxiety and cost. However, many radiologists and physicians can now optimize the precision of molecular imaging through positron-emission tomography (PET) and focusing it on breast cancer detection and diagnosis.

Using PEM within the Breast Imaging Process:

Due to challenges inherent in other modalities, many ultimately unnecessary biopsies can be performed. Right now, PEM is being used as an adjunct to current breast imaging techniques. Used in concert with existing modalities, PEM should be able to reduce the number of biopsies, improve surgical planning, and better detect any recurrent disease, at least on the local level.

PEM is currently being used for patients with newly diagnosed breast cancer who are facing surgery. Before scheduled surgery is undertaken, PEM can provide physicians with one more imaging analysis to help determine whether there is multifocality and multicentricity. Multifocality means that there is more than one location of cancer along a dual system in a radial pattern. Multicentricity means that the cancer is in completely different locations, either in the same breast or the other breast. The difference between multifocal and multicentric is vital because, in most cases, multifocality means that breast conservation may be possible, where multicentricity is a contraindication to breast conservation. PEM likely will improve the quality of surgical decisions because it is very good at staging and determining the local extent of disease.

PEM systems can serve as a legitimate substitute for patients who cannot undergo breast MRI for reasons including implants, claustrophobia, or obesity. PEM has been found to be helpful in cases involving women with dense breast tissue that can make tumours hard to spot with mammography due to reduced specificity and sensitivity. Traditionally, whole breast ultrasound and breast MRI represent alternatives for very dense breast tissue. Both these modalities are useful but have their own issues with dense tissues, cost and specificity. PEM may be proving to achieve a lower false positive rate than MRI and has no issue with dense tissue.

The Procedure:

PEM involves the injection of the radiopharmaceutical FDG. A patient needs to fast for four hours before the procedure. Afterward, a serum blood sample is taken to determine blood glucose level. Then FDG is injected intravenously. Tumour cells will take up much more glucose than normal cells, and PEM imaging will reveal the FDG concentrations that suggest malignancy.

The imaging is acquired one hour after the FDG injection, when the patient’s body has had enough time to absorb the radiopharmaceutical. Images are obtained in a manner similar to mammography. Both breasts are imaged, with mediolateral oblique and craniocaudal views taken. Each view takes approximately 10 minutes to accomplish; thus imaging requires roughly 40 to 45 minutes. During imaging, the breast is immobilized but requires only slight compression.

Patients report that they tolerate the procedure very well because of this reduced amount of compression. The purpose of compression in a mammography procedure is to reduce the thickness of tissue to x-ray, which increases the sensitivity and decreases the background noise and radiation. But during a PEM procedure, the compression is more for isolation purposes. The imaging window for PEM is minutes, not seconds, so, only light compression for immobilization is necessary.

During the imaging, the PEM detectors are positioned close to the breast. As a result, image acquisition is much more efficient than regular full body PET scanning. In addition, with only a small attenuation of counts, the spatial resolution is greatly improved compared with whole-body PET imaging. Most PEM systems include an articulating arm with two parallel detectors at the end, which allows for flexibility in imaging of any small body part, although these systems are designed for breast imaging. Some PEM scanners include components and a compact design that make it useful for the imaging not only the breast but appendages such as the head, hand, or foot.

The viewing station should be highly mobile, with a small footprint, a camera and detectors. Having it situated on casters, allows it to be easily rolled into and out of a room. This mobility is significant because it allows the camera to be wheeled into a standard imaging room, next to a large, whole-body system, for example, and to be used in concert with that larger system.

PEM Proto-type:

Tissue Diagnosis: DCIS and IDC:

Figure 1:Mammography

Figure 2: PEM

Figure 3: Full Body PET

Figure 4: CT

PEM Images of Various Cancers

Figure 5: IDC with central necrosis

Figure 6: Multi focal breast Ca PEM & Mammo

Figure 7: Occult DCIS in a single duct

SUMMARY:

Since the advent of formal breast imaging for the purpose of diagnosing breast cancer we have done nothing but accept change. That is the nature of our specialty: X-ray, Xerography, film/screen Mammography, breast screening, US, Digital Mammography, MRI, PET, PET/CT and PEM; a virtual never ending stream of change. With every change we save few more lives and give a few more women a better prognosis and a better quality of life.

As breast imaging technologists we are required to adjust our work habits, learn more modalities and accept more adjustments to our specialty than any other modality in DI. With every change comes more knowledge, more understanding of our job and greater satisfaction with the outcomes of our examinations. In the end, knowledge always equals power!

Disturbing Paget Emails (Rumour Control)

There has been some disturbing emails going around about Paget's Disease of the nipple. Let me make this very clear to all:

1. Paget's is NOT some new disease, it has been diagnosed and treated for many years
2. Paget's is quite rare and although it used to be mis-diagnosed a lot the symptoms are no longer over-looked very often
3. Paget's is a problem of women over 50; it very rarely shows up in younger women or in men
4. A simple skin biopsy taken of the nipple can diagnose or rule out Paget's immediately

Paget's can be associated with breast cancers and also other hormonally based cancers like ovarian and uterine. Therefore a diagnosis of Paget's diseases of the nipple will entail other tests such as:

1. Mammograms
2. U/S of the breast and Pelvis
3. Skin, cell and tissue biopsies of the area

Although you might ignore some skin irritation symptoms for a short period, you would very shortly clue in that this irritation is different:

1. it starts on the nipple and spreads outward
2. it doesn't go away or get better with time, creams or ointments
3. it worsens, getting progressively deeper and wider
4. begins to weep and stays inflammed all the time
5. Paget's disease may or may not be associated with any breast abnormality; therefore there may be no breast symptoms at all aside from the nipple abnormalities.

Any change in the normal appearance, feel, orientation or contour of the breast that shows up during normal, monthly BSE should be noted and brought to the attention of a health care profesional. For BSE tips and instruction search for the BSE articles in the archives.

PET, PET/CT & PEM: What’s new, what’s coming?

The Spring holidays are over...Peaceful Easter, Good Passover and Happy Spring Equinox to you all. I hope you ate, sang, danced and had a glass of wine!!

This month's techtalk explores some new technologies that will help in our fight against breast cancer. We are coming closer to beating this problem but we can still use all the help we can get. The next three months will explore some possibilities of useful adjuvant modalities coming down the path. Enjoy and pass it on.

Don't forget Louise Miller and QCC is coming to Toronto in April. There are still some spaces open and some hotel rooms available. Grab them before they're gone. You can find the order form and flyer on last month's post. I will be presenting at the QCC this year and would love to see you all there. I need all the moral support I can get!

Keep in touch,

Anne

OBJECTIVES:

Positron emission tomography combined with computed tomography (PET/CT) has been receiving increasing attention during the recent years for making the diagnosis, for determining the staging and for the follow-up of various malignancies. The PET/CT findings of 58 breast cancer patients (age range: 34-79 years old, mean age: 50 years) were retrospectively compared with the PET or CT scans alone. PET/CT was found to be better than PET or CT alone for detecting small tumors or multiple metastases, for accurately localizing lymph node metastasis and for monitoring the response to chemotherapy in breast cancer patients.

How Does PET/CT Make a Difference?

• PET can show whether or not a lump in the breast is benign or malignant. PET may prove to be a very useful addition to mammography. For 70% of all women with suspicious mammograms, the expense and trauma of a breast biopsy for their final diagnosis may be unnecessary because of PET!
• PET accurately stages axillary and mammary lymph node involvement. Axillary lymph node dissection is currently a routine part of breast surgery, since it is the only way doctors who don't know about PET have of staging breast cancer. A complication of this procedure can be restricted movement of the arm, stiffness, swelling and pain. In the future, a PET scan may make this procedure unnecessary for patients who show no lymph node involvement.
• PET detects distant metastasis resulting in more accurate treatment.
• PET evaluates response to therapy. Treatment can be altered, if necessary, for better results.
• PET shows recurrent disease. Finding recurrent cancer early prolongs your life and increases your chances of beating the disease.

Primary Tumor

The ability of PET to detect breast cancer depends on the tumor's size and histology. The sensitivity of PET has been reported to be 68% for small (< 2 cm) tumors and 92% for larger (2-5 cm) tumors, and its reported overall accuracy for detecting in situ carcinomas is low (sensitivity: 2-25%). The major limitation of PET or PET/CT for breast imaging is its poor detection rate for small breast carcinomas and non-invasive breast cancers.

However, PET/CT has a role to play in a selected group of patients, such as those with dense breasts or with implants, for determining tumor multiplicity, for localizing the primary tumor in those patients with metastases of a breast origin when the mammography is indeterminate, and for those patients whom biopsy is not a desirable option. PET/CT has a potential advantage over PET for evaluating small lesions in which the uptake may be artifactually lowered due to the partial volume effect of PET because areas of mild hyperglycolytic activity can be reliably assigned to normal or abnormal anatomical structures.

Figure 1: 49 year old woman with DCIS

Figure 2: 57 year old woman with Invasive breast cancer

Regional Lymph Node Metastasis

Axillary lymph node metastasis is an important factor when determining the prognosis of patients. Breast cancer patients with four or more involved axillary lymph nodes have a significantly higher risk of recurrence. The sensitivity and specificity of axillary PET imaging in breast cancer patient have been reported as 79-94% and 86-92%, respectively. PET/CT can accurately localize and differentiate the metastatic and reactive lymph nodes when CT shows multiple enlarged lymph nodes in the axilla.

Figure 3: Lymph node Mets in 45 yr old woman with IDC

The metastasis to the internal mammary or mediastinal lymph nodes in breast cancer patients is often clinically occult. The prevalence of abnormal findings for the internal mammary or mediastinal lymph nodes by PET was about twice that of conventional CT in those patients with recurrent or metastatic breast cancer. In a study by Tatsumi et al., although the sample number was small, PET/CT appeared to be more useful than CT for evaluating the internal mammary and mediastinal lymph nodes because the smaller lymph nodes sometimes produced equivocal or negative CT findings.

Figure 4: Mediastinal node Mets post mastectomy

Distant Metastasis

Distant metastases from breast cancer are frequently found in the lungs, liver and bones. One advantage of whole-body PET imaging over conventional imaging modalities such as chest films, bone scanning, and abdominal ultrasound is its ability to detect metastasis at different sites and organs during a single examination). Moon et al. found that whole-body PET imaging had high diagnostic accuracy for patients with suspected recurrent or metastatic breast carcinoma. Based on the number of lesions, its sensitivity for detecting distant metastasis was 85% and its specificity was 79%.

Figure 5: Multiple distant Mets in 44 years old with bilateral breast Ca

Cook et al. found that PET was superior to bone scintigraphy for detecting osteolytic breast cancer metastases Fig. 6. In contrast, the osteoblastic metastases showed lower metabolic activity and they were frequently undetectable by PET alone. Yet PET/CT can overcome this limitation, and osteoblastic bone lesions, even if negative on PET scans, can be identified on CT images Fig. 7.

Figure 6: Bone Mets in a 64 yr old 36 mos. post mastectomy

Figure 7: Bone Mets in a 47 yr old with breast cancer

Breast Cancer Detection with Dedicated Positron Emission Mammography

More recently, dedicated breast positron emission mammography (PEM) units have been developed to overcome the limitations of whole-body PET and to provide a positron-emitting imaging platform capable of detection and depiction of primary breast carcinoma Fig 3a/b. In general, these systems consist of two planar detectors placed opposite a gently compressed breast. The advantages of such dedicated systems include improved geometric sensitivity, higher spatial resolution, shorter imaging time, and reduced attenuation compared with whole-body PET systems. They also have a small physical footprint, which makes their use in a breast imaging facility feasible and allows correlation of the results with those of conventional breast imaging as well as PEM-guided biopsy.

The images below demonstrate the detection of small invasive breast carcinomas with FDG PEM. Images from dedicated breast PEM units show 9-mm (circle in a) and 1.3-cm (rectangle in b) invasive carcinomas.

a:

b:

Figure 8a/b: Demonstration of small IDCs with FDG/PEM

Although preliminary data demonstrate that these systems are capable of imaging smaller primary breast carcinomas than whole-body systems, their clinical utility has not been adequately demonstrated. Certain limitations such as imaging posterior lesions, variable FDG uptake in small tumors, and false-positive findings from prior biopsy have been reported, and biopsy capability needs to be further addressed. Potential roles advocated for these systems include detection, problem solving, local staging, local recurrence, and assessing or predicting response of the primary tumor to chemotherapy. Dedicated breast PEM and PET are a promising technology to help overcome the limitations of whole-body imaging and may eventually provide a positron emission imaging platform capable of reliably imaging primary breast carcinoma.

SUMMARY:

PET imaging is a clear advance in the approach to staging and monitoring breast cancer. Positron imaging offers better accuracy than conventional imaging in the identification of metastatic disease both in the initial staging of breast cancer and in follow-up. Refinements in scanner technology and new radiopharmaceuticals will likely result in better identification of smaller lesions.

Dedicated breast PET/CT or PEM units show promise in improved detection in primary breast cancer, while also providing a method for image guided biopsy. Please stay tuned for further articles on PEM. The technology is marching on at a startling rate.

Ongoing research regarding the molecular basis of cancer will likely result in new agents that may better identify tumors currently not well imaged by FDG. Potentially, molecular therapies that target specific cell receptors or processes may be tagged with a positron and imaged, thereby allowing not only imaging but also treatment.