January 14, 2008

Inflammatory Breast Cancer — PET/CT Takes on a Tough Challenge
By Kathy Hardy
Radiology Today
Vol. 9 No. 1 P. 14

A rare, aggressive form of breast cancer with a five-year survival rate of only 25% to 50% deserves an equally aggressive approach to discovering a timely diagnosis. That was the impetus behind a study of whether F-18 fluorodeoxyglucose (FDG)-PET/CT scans can improve the chances of survival for patients diagnosed with inflammatory breast cancer (IBC) by detecting the systemic spread of the disease.

“All aspects of treating IBC, including staging, diagnosis, and therapy, are vastly different from other breast cancers,” says Selin Carkaci, MD, assistant professor of diagnostic radiology at The University of Texas M. D. Anderson Cancer Center in Houston. “It requires prompt treatment due to the rapid pace of disease progression. Staging should be fast and accurate to increase the efficacy of system treatments in eradicating occult microscopic disease.”

Carkaci presented the results of this study at RSNA 2007 in Chicago in November. Participating in the study were 41 women with IBC, with metastases found in 20 of those patients. Overall, the study revealed that FDG-PET/CT is 95% accurate in identifying distant metastases and 98% accurate in identifying regional lymph node metastases.

“Findings of IBC on FDG-PET/CT are scarce or not available in the published literature,” Carkaci says. “We, therefore, wanted to evaluate the use of this relatively new and promising imaging modality in the initial staging of this deadly form of breast cancer.”

According to the American Cancer Society, IBC accounts for 1% to 5% of all breast cancer cases in the United States and strikes patients aged 45 to 55. Approximately 20% of patients with IBC have gross distant metastases when they are first diagnosed, Carkaci says, which is roughly twice the percentage of other newly diagnosed breast cancer patients.

She points out that one reason for these grim statistics is that IBC does not present with the same symptoms as other breast cancers, making initial diagnoses more difficult. With IBC, patients experience rapid breast swelling, with the overlying skin developing peau d’orange (skin texture like that of an orange), local tenderness, induration, and warmth. Also, the disease can present with or without a palpable breast mass. With that, tissue diagnosis is problematic due to the difficulty in defining an area for biopsy.

Systemic Disease
Another characteristic of IBC—and a reason why early detection is critical—is that it is a systemic disease, sometimes spreading rapidly to other parts of the body such as the lymph nodes or bone marrow.

Unfortunately, not all imaging techniques are effective for detecting IBC. Mammography can miss IBC in that it detects lumps in the breast tissue; ultrasound can be helpful for evaluating lymph nodes and localizing primary tumors, Carkaci says, particularly to facilitate biopsy and evaluate regional lymph nodes. MRI is currently considered by many to be the most sensitive method for detecting breast cancer, but Carkaci says that while IBC requires a clinical diagnosis, breast MRI can be useful in determining the extent of the disease and evaluating a patient’s response to cancer treatments.

“The bottom line is, in nearly one half of these patients, we identify systemic disease,” says study coauthor Homer A. Macapinlac, MD, chair and professor of nuclear medicine at M. D. Anderson. “You don’t expect to see that. Even up front, when patients present, they have evidence of systemic spread of the disease. Not all imaging modalities detect cancer that has become widespread.”

PET and CT have been staples of oncology imaging, used separately for more than 20 years, but only in the past few years have the two modalities been combined. Carkaci says PET is routinely used in clinical practice and has been considered effective for detecting cancers in the lung, head and neck, colon, esophagus, breast, thyroid, cervix, pancreas, and brain, as well as lymphomas and melanomas.

“It has proven particularly valuable in providing a road map for staging for biopsies, using endobronchial ultrasound in lieu of mediastinoscopy in non–small-cell lung cancer,“ she says. “PET/CT is also found useful in detection of the primary disease site in patients who present with metastatic lesions with unknown origin.”

PET scans detect a metabolic signal of actively growing cancer cells by tracking radiotracers injected into a patient’s body, producing 3D images of where those substances have settled.

A CT scan produces multiple images, providing a detailed picture of the internal anatomy, including the location of cancerous growths. Combining the results of both imaging methods into one picture can provide more complete information on the location of cancerous growths and their metabolism.

“The fusion of the two [modalities] yields more information than do the two separately,” Carkaci says. “Over the past few years, fused PET/CT scans have been proven invaluable in helping oncologists make more accurate diagnosis and staging assessments, choose the most appropriate therapies, and determine whether a therapy is effective against a cancer.”

Adding FDG as a tracer adds a finer point to the exact location of where the cancer has spread, according to Macapinlac. “FDG is known to pick up very aggressive and more systemic cancers,” he says. “It’s not currently approved by CMS [Centers for Medicare & Medicaid Services] for diagnosis of breast cancer, but in IBC, it appears promising as an important modality for detecting the extent of the cancer.”

As a tracer used for the PET scan, FDG is a short-lived radioactive glucose absorbed by cells in the body. Cancer cells are known to have a higher rate of glucose utilization and absorb glucose faster than other cells. They also appear as brighter images on PET scans, hence its effectiveness.

“FDG-PET/CT detects cancer spread in its earliest stages, when changes are happening at a functional and cellular level,” Carkaci says. “This differs from other modalities, which detect disease when there is distortion of the normal structure of the organs.”

In this study, FDG-PET/CT detected the spread of cancer in 40 of the 41 patients. Detecting the far reaches of where this aggressive form of breast cancer has spread is a key in improving survival rates for IBC patients, according to Carkaci. Also, the sensitivity and specificity of PET/CT for detecting distant metastasis was 95% on a per-patient basis, she says, and for detecting regional nodal metastasis, sensitivity was 97% with a specificity of 100%. Only two false positives were noted for distant metastasis. Macapinlac adds that while these are good numbers, it’s difficult to extrapolate considering the number of patients who participated in the study. “That needs to be verified with a larger group,” he says.

“Everyone is enthusiastic about the findings,” he adds. “They’re realizing that PET/CT is a good way to identify systemic disease.”

At M. D. Anderson, PET/CT is routinely the imaging modality of choice for staging IBC patients, Carkaci says. With the results of this study and subsequent larger-scale trials addressing the clinical benefits of PET/CT, she hopes to see this imaging method become more mainstream in routine diagnostics and follow-up protocols for patients with IBC.

A key to the study’s success—and ultimately the prognosis of patients with IBC—is continued work with FDG-PET/CT. Follow-ups will be conducted with the study patients to determine if their current treatment methods have generated positive results. Also, more patients may be included in the study. Macapinlac adds that more data needs to be gathered to determine if this type of imaging contributes to a better outcome for patients with a poor prognosis.

“We would like to find if PET/CT has an impact on the overall survival of the IBC patients by identifying the distant metastasis and locoregional disease early in the course of the disease and by serving as an early predictor of chemotherapy response,” Carkaci says.

Physicians at M. D. Anderson perform an average of approximately 60 PET/CT scans per day, Carkaci says. In addition, experts from many centers have focused efforts to develop unique tracer techniques that can show processes other than glucose metabolism and more sophisticated imaging instrumentation “to yield further insight into the behavior, growth, and treatment of tumors,” she says.

Important to the IBC study, M. D. Anderson last year created what is considered the first clinic and research program dedicated to this aggressive form of breast cancer. The clinic’s goal has been to reach an understanding of why IBC is different from other forms of breast cancer and develop treatments that will improve the outcome for patients diagnosed with the disease.

“We at M. D. Anderson felt that because IBC strikes younger patients in the prime of their productivity, because it is so aggressive, that it was important to establish a clinic specifically for IBC,” Macapinlac says. “IBC is aggressive, so we thought we should be equally aggressive and combine resources to find better detection/response evaluation methods with novel therapies to potentially increase survival rates for patients with IBC.”

— Kathy Hardy is a freelance writer and editor based in Phoenixville, Pa.