A New Imaging Technology Brings New Hope for Women with Inflammatory Breast Cancer

Judith Greif, RN, MS, APNC

^*Family Nurse Practitioner, East Brunswick, New Jersey.
Address correspondence to: Judith Greif, RN, MS, APNC, Family Nurse Practitioner, 50 Central Avenue, East Brunswick, NJ 08816. E-mail: grifcommedical@aol.com.

Data from the US Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute reveal that breast cancer is the second most common form of cancer among women (after skin cancer), and that it is a leading cause of mortality (ranking as the sixth most common cause of death overall for women and resulting in nearly 41 000 deaths annually).¹ Now scientists and researchers may be able to use a cutting-edge imaging technique, positron emission tomography coupled with computed tomography (PET/CT) scans to improve the odds for women suffering from a type of breast malignancy that is more deadly than most: inflammatory breast cancer (IBC).

What is Inflammatory Breast Cancer?
Inflammatory breast cancer is a rare and extremely aggressive form of primary epithelial cancer that accounts for 1% to 6% of all breast cancers.² Symptoms are atypical for breast cancer, and therefore, a delay in diagnosis may occur resulting in a poor prognosis. Furthermore, this type of cancer metastasizes rapidly; approximately 20% to 30% of patients have distant metastases at the time of diagnosis,² and 70% have infiltration of lymph nodes.³ The 3-year overall survival rates for IBC range from 32% to 42%.⁴ IBC is marked by redness and/or rapid swelling of the breast, with a characteristic "peau d'orange" or "orange-peel" texture. The breast may be painful, unusually firm (indurated), and warm—sometimes mimicking other types of breast diseases, such as mastitis or locally advanced breast cancer with secondary skin involvement. Frequently, there is no palpable tumor.⁵ Epidemiologically, IBC is more prevalent among younger women (<50 years of age) and among black women.³

Mammography alone is not an optimal method of diagnosing IBC.⁵ Recently, Wei T. Yang, MD, and his associates at the University of Texas MD Anderson Cancer Center evaluated several imaging modalities for their role in diagnosing IBC to determine whether they may be helpful in tracking issues, such as metastasis, response to therapy, or disease recurrence. These included mammography, ultrasound, magnetic resonance imaging (MRI), and PET/CT scans.² PET scans are of particular interest because they examine tissues and disease processes at the cellular level and are capable of identifying areas of inflammation. They are a functional—not merely an anatomical—tool, and they evaluate the entire body rather than just the site of disease.

How Do PET Scans Work?
It has long been known that cancer cells have increased metabolic activity compared with normal cells, and in 1931, 2 scientists, Warburg and Dickens, discovered that tumor cells carry out more glycolysis⁶ (the breakdown of a simple sugar, glucose, to produce adenosine triphosphate, an energy source needed for rapidly-dividing cells). This knowledge has been applied to PET scan technology in that it capitalizes on the increased uptake of glucose to track oncologic activity. A PET scan is a high-resolution CT imaging modality that uses radionuclides that emit positrons as they decay. A positron is a positively charged particle of the same mass as an electron, and substances altered to emit positrons have the same chemical properties as their parent element. As positrons interact with electrons, they produce annihilation photons that leave a biologic trace that can be mapped. Therefore, the PET scan will detect malignant cells at multiple sites within the body, depending on where there is increased uptake of a tagged form of glucose, 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG) that contains the positron emitter, ¹⁸F (Figure).⁷ Again, because tumor cells use more glucose, FDG accumulates at diseased sites before structural changes (such as tumor growth) will become evident on traditional scans (such as mammography, ultrasound, or MRI). Furthermore, they will identify sites of metastasis, in addition to primary cancers, because of the ability to detect abnormal activity anywhere in the body. However, the downside to this is that PET scans may identify areas of inflammation, infection, or regions of normally increased metabolic activity as cancerous, because of their increased uptake of glucose. This may lead to false-positive tests.⁷

Figure. PET/CT Image Revealing Hypermetabolic Foci in the Breast, Liver, and Femur

A, PET/CT shows multicentric hypermetabolism in the right breast (arrow) associated with hypermetabolic diffuse skin thickening. B, PET/CT shows a solitary focal hypermetabolic focus in the right lobe of the liver (arrows) that showed a maximum SUV of 5.7. Corresponding CT of the liver shows a focal hypoechoic mass with indistinct margins. C, PET/CT shows a solitary focal hypermetabolic focus in the left proximal femur (arrows) that showed a maximum SUV of 7.7. Corresponding CT of the proximal femur shows this area of hypermetabolism to be within the marrow (whole body bone imaging was negative in this patient).
CT = computed tomography; PET = positron emission tomography; SUV = standardized uptake values.
Reprinted with permission from Yang et al. Breast Cancer Res Treat. 2007; [Epub ahead of print].²

Applications of PET/CT Scan Technology to Diagnosis and Treatment of IBC
The first use of PET scan technology among patients with breast cancer was reported in 1989. The authors of the study were able to detect primary breast cancer 100% of the time for tumors bigger than 5 cm. However, the study only involved 10 women, and tumor size was not that small.⁸ Other studies followed, in several cases identifying tumors that had been missed on mammography (eg, due to dense breast tissue.) Whereas smaller, earlier studies reported sensitivities of 96% to 100% and were able to identify smaller tumors in addition to multifocal disease, the largest study by Avril et al in 2000 of 144 patients was not as promising.⁹ The overall sensitivity ranged from 64% to 80% and specificity ranged from 76% to 94%, with better accuracy for larger tumors, suggesting that PET scanning is not an effective screening tool—especially because it is costly, time-consuming, and requires ionizing radiation.⁹ Since then, PET scans have been studied for a variety of other applications related to breast cancer, including assessment of axillary node status, evaluation of distant metastases, looking for recurrent disease, and monitoring of response to therapies—especially chemotherapeutic agents that work by reducing the ability of tumor cells to conduct glycolysis. It seems that these latter applications may be more appropriate uses of the technology.⁷

New Study Brings New Hope
For example, in the case of the particularly lethal inflammatory breast cancer, a new study by Dr Yang et al presented at the annual meeting of the Radiological Society of North America reports that PET scan combined with CT scan technology may allow clinicians to accurately determine the location of metastases earlier than with other imaging methods and to deliver the appropriate treatment sooner, perhaps allowing for a better prognosis for these women. PET/CT imaging also may be used to monitor the effectiveness of the treatment and to make alterations in the regimen based on results. The study of 41 women (mean age, 50 years) with newly diagnosed IBC, all of whom underwent a whole-body FDG-PET/CT scan, discovered metastases in nearly half (49%) of the participants. The 20 patients whose scans indicated that the cancer had spread beyond the primary site underwent biopsy and supplementary imaging to confirm the results, and only 2 false-positives were found. FDG-PET/CT scanning for IBC was 95% accurate in detecting distant metastases and 98% accurate in detecting lymph node involvement. As one of the physicians involved in the study, Selin Carkaci, MD, points out, this is exciting news for patients diagnosed with this form of breast cancer. "What's exciting about PET/CT is that it is able to detect disease in its earliest stages, when changes are happening at a functional and cellular level. This is quite different from other imaging modalities that identify disease when there is destruction of normal anatomy." This study, as well as other future investigations into the application of the PET/CT scan for diagnosis, staging, and treatment monitoring, may pave the road for the future with hope for those suffering the pain and disability of inflammatory breast cancer.

References
1. US Cancer Statistics Working Group. United States cancer statistics: 2004 incidence and mortality. Atlanta, GA: Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute; 2007. Available at: http://www.cdc.gov/print.do?url=http%3A%2F%2Fwww.cdc.gov%2Fcancer%2Fbreast%2Fstatistics%2F. Accessed March 14, 2008.

2. Yang WT, Le-Petross HT, Macapinlac H, et al. Inflammatory breast cancer: PET/CT, MRI, mammography, and sonography findings. Breast Cancer Res Treat. 2007; [Epub ahead of print].

3. Wingo PA, Jamison PM, Young JL, Gargiullo P. Population-based statistics for women diagnosed with inflammatory breast cancer (United States). Cancer Causes Control. 2004;15:321-328.

4. Chang S, Parker SL, Pham T, et al. Inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program of the National Cancer Institute, 1975-1992. Cancer. 1998;82:2366-2372.

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6. Warburg OH, Dickens F, eds. The Metabolism of Tumours. New York, NY: Richard R. Smith; 1931.

7. Byrne AM, Hill AD, Skehan SJ, et al. Positron emission tomography in the staging and management of breast cancer. Br J Surg. 2004;91:1398-1409.

8. Minn H, Soini I. [18F]fluorodeoxyglucose scintigraphy in diagnosis and follow up of treatment in advanced breast cancer. Eur J Nucl Med. 1989;15:61-66.

9. Avril N, Rose CA, Schelling M, et al. Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations. J Clin Oncol. 2000;18:3495-3502.