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.